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Gilda SANDRI
Ricercatore Universitario
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto
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Pubblicazioni
2024
- Assessing hand grasp in patients with systemic sclerosis using the 16-grasp test: Preliminary results from a multidisciplinary study group
[Articolo su rivista]
Sandri, Gilda; Spinella, Amelia; Sartini, Silvana; Caselgrandi, Francesco; Schiavi, Margherita; Bettelli, Valentina; Gherardini, Francesco; Amati, Gabriele; Lumetti, Federica; Mascia, Maria Terasa; Secchi, Ottavio; Giuggioli, Dilia
abstract
Background: Reports on hand dysfunction and rehabilitation in SSc are quite scarce in the literature and mainly focus on functional assessment tools, such as the Duruoz Hand Index and the HAMIS test for evaluating hand mobility by simulating specific grasps with nine different objects. Purpose of the study: This study aimed to provide an adequate assessment methodology for hand grasp dysfunctions in patients suffering from systemic sclerosis (SSc) through the 16-grasp test. Study design: Case-control study. Methods: Ninety-seven consecutive SSc patients were recruited at our Scleroderma Unit, where a 16-grasp test was performed by all patients and supervised by an experienced hand therapist. Sixteen different patterns of grasp have been divided into power grasps and precision pinch and two more modalities: static and dynamic prehension evaluation on scale from 0 to 4. We also compared previous evaluations on 19 of patients recruited. Results: The majority of SSc patients (84 females and 13 males; mean age 56.0±12.0 years; mean disease duration 8.0±6.0 years) displayed grasp dysfunctions; in particular 48% and 54% reported slight difficulty in the right and left grasps respectively, 6% medium difficulty in both hands, and only 3% and 1% experienced severe difficulty respectively, while 31.5% had no issues in either hand. Our results showed that the limited cutaneous subset (lcSSc) scored a lower deficit for either grasp compared to diffuse form (dcSSc). No statistically significant differences in total grasp deficit had been noticed when comparing patients having a disease duration < 5 years or longer. In the retrospective study on 19 of these patients, 8 out of 10 lcSSc patients showed no significant changes, while in 2 out of 10, slight improvements were observed in both hands. However, in the dcSSc group, 4 out of 9 worsened bilaterally while the grasp scores for 5 of them remained unchanged. Conclusion: Our study reported hand involvement in both lcSSc and dcSSc forms, more significantly in dcSSc patients. This test is intended to be a more objective means of assessing grasp alterations linked to scleroderma hand deformities. Furthermore, thanks to its intuitiveness, the test may be useful for engineers designing personalized ergonomic assistive devices.
2024
- Factors associated of long-term retention rate of Janus kinase inhibitors in a multi-failure rheumatoid arthritis population
[Articolo su rivista]
Sebastiani, Marco; Zabotti, Alen; Biasi, Bruno; Cacioppo, Sofia; Sandri, Gilda; Giovannini, Ivan; Manfredi, Andreina; Quartuccio, Luca
abstract
Objectives: We aimed to retrospectively evaluate retention rate and causes of discontinuation of JAKi in RA patients with particular regards to difficult-to-treat subgroups. Methods: The diffusion of Janus kinase inhibitors (JAKi) for the treatment of rheumatoid arthritis (RA) has rapidly increased in recent years due to their effectiveness, even in difficult-to-treat subgroups of patients. After the publication of the Oral Surveillance study, the labelling of JAKi was modified, advising against their use in elderly patients and those at risk for cardiovascular events and malignancies. Demographic, clinical, serological and therapeutic characteristics of RA patients treated with JAKi were recorded, including smoking habit and comorbidities. Results: Three hundred and thirty consecutive RA patients were enrolled in the study. Among them, 50.3% patients had previously failed at least two biologic DMARDs. Risk factors for the use of JAKi were reported in 75.5% of patients, 41.5% of them were older than 65 years, 37.6% had smoked, while 48.8% had increased cardiovascular or cancer risk. Anticitrullinated peptide antibodies (ACPA) and combination therapy with conventional synthetic DMARDs were associated with a longer drug persistence and ACPA remained independently associated to a higher retention rate of JAKi also in the subgroup of difficult-to-treat patients. Conclusions: In conclusion, our study supports the clinical effectiveness of JAKi in RA, even in the multi-failure subgroup of patients, where the risk/benefit ratio overcomes the safety risk. The presence of ACPA and the concurrent use of + cs-DMARD may increase the survival on JAKi in the long term.
2023
- Metabolic Profile of Whole Unstimulated Saliva in Patients with Sjögren's Syndrome
[Articolo su rivista]
Setti, Giacomo; Righi, Valeria; Mucci, Adele; Panari, Lucia; Bernardelli, Giuditta; Tarentini, Elisabetta; Gambini, Anna; Consolo, Ugo; Generali, Luigi; Magnoni, Cristina; Meleti, Marco; Sandri, Gilda; Bellini, Pierantonio
abstract
: Primary Sjögren's Syndrome (pSS) is a multi-system autoimmune disease that involves the exocrine glands. Lymphocytes infiltrate the gland tissue, leading to anatomical modification and hypofunction. Even if the prognosis of pSS is favorable, quality of life is typically reduced due to the diverse manifestations of the disease. The aim of this study is to compare the salivary metabolomes of pSS with healthy controls (HCs). Seven cases were selected from a cohort of pSS patients, and six age- and sex-matched HCs were recruited from a cohort of volunteers. Whole unstimulated saliva was collected for NMR analysis. Our metabolomic analysis focused on 360 ms total echo 1D 1H NMR CPMG spectra. Metabolites detected with CPMG NMR spectra were assigned through 2D NMR spectra (COSY, TOCSY, and HSQC). About 50 metabolites were detected and assigned. Unsupervised exploratory PCA returned partial clustering, and PLS-DA improved the separation between pSS and HCs, highlighting a pool of metabolites distinctly describing each group. Despite the limited number of samples, the presented preliminary data are promising. PLS-DA indicated well-defined group separation, suggesting that the application of 1H-NMR metabolomics is suitable for the study of pSS.
2023
- Predictors of DAPSA Response in Psoriatic Arthritis Patients Treated with Apremilast in a Retrospective Observational Multi-Centric Study (2023-02-07)
[Articolo su rivista]
Becciolini, Andrea; Parisi, Simone; Del Medico, Patrizia; Farina, Antonella; Visalli, Elisa; Biagio Molica Colella, Aldo; Lumetti, Federica; Caccavale, Rosalba; Scolieri, Palma; Andracco, Romina; Girelli, Francesco; Bravi, Elena; Colina Alessandro Volpe, Matteo; Ianniello, Aurora; Chiara Ditto, Maria; Nucera, Valeria; Franchina, Veronica; Platè, Ilaria; Di Donato, Eleonora; Amato, Giorgio; Salvarani, Carlo; Bernardi, Simone; Lucchini, Gianluca; De Lucia, Francesco; Molica Colella, Francesco; Santilli, Daniele; Mansueto, Natalia; Ferrero, Giulio; Marchetta, Antonio; Arrigoni, Eugenio; Foti, Rosario; Sandri, Gilda; Bruzzese, Vincenzo; Paroli, Marino; Fusaro, Enrico; Ariani, Alarico
abstract
Background: To date, only a few real-world-setting studies evaluated apremilast effectiveness in psoriatic arthritis (PsA). The aims of this retrospective observational study are to report long-term Disease Activity Index for Psoriatic Arthritis (DAPSA) response of apremilast in PsA patients and to analyze the predictors of clinical response. Methods: All PsA consecutive patients treated with apremilast in fifteen Italian rheumatological referral centers were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline, 6 months, and 12 months were recorded. The Mann–Whitney test and chi-squared tests assessed the differences between independent groups, whereas the Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. Logistic regressions verified if there were factors associated with achievement of DAPSA low disease activity or remission at 6 and 12 months. Results: DAPSA low disease activity or remission rates at 6 and 12 months were observed, respectively, in 42.7% (n = 125) and 54.9% (n = 161) patients. Baseline DAPSA was inversely associated with the odds of achieving low disease activity or remission at 6 months (odds ratio (OR) 0.841, 95% confidence interval (CI) 0.804–0.879; p < 0.01) and at 12 months (OR 0.911, 95% CI 0.883–0.939; p < 0.01). Conclusions: Almost half of the PsA patients receiving apremilast achieved DAPSA low disease activity or remission at 6 and 12 months. The only factor associated with achievement of low disease activity or remission at both 6 and 12 months was baseline DAPSA.
2022
- Adalimumab and ABP 501 in the Treatment of a Large Cohort of Patients with Inflammatory Arthritis: A Real Life Retrospective Analysis
[Working paper]
Becciolini, Andrea; Parisi, Simone; Caccavale, Rosalba; Bravi, Elena; Lumetti, Federica; Andracco, Romina; Volpe, Alessandro; Gardelli, Lucia; Girelli, Francesco; Di Donato, Eleonora; Santilli, Daniele; Lucchini, Gianluca; Ditto, Maria Chiara; Platè, Ilaria; Arrigoni, Eugenio; Mozzani, Flavio; Riva, Michele; Marchetta, Antonio; Fusaro, Enrico; Sandri, Gilda; Salvarani, Carlo; Paroli, Marino; Ariani, Alarico
abstract
The recent introduction of ABP 501, an adalimumab biosimilar, in the treatment of rheumatic diseases was supported by a comprehensive comparability exercise with its originator. On the other hand, observational studies comparing adalimumab and ABP 501 in inflammatory arthritis are still lacking. The main aim of this study is to compare the clinical outcomes of the treatment with adalimumab, both the originator and ABP 501, in a large cohort of patients affected by autoimmune arthritis in a real life setting. We retrospectively analysed the baseline characteristics and the retention rate in a cohort of patients who received at least a course of adalimumab (originator or ABP 501) from January 2003 to December 2020. We stratified the study population according to adalimumab use: naive to original (oADA), naive to ABP 501 (bADA) and switched from original to ABP 501 (sADA). The oADA, bADA and sADA groups included, respectively, 724, 129 and 193 patients. In each group, the majority of patients had a diagnosis of rheumatoid arthritis. The total observation period was 9805.6 patient-months. The 18-month retentions rate in oADA, bADA and sADA was, respectively, 81.5%, 84.0% and 88.0% (p > 0.05). The factors influencing the adalimumab retention rate were an axial spondylarthritis diagnosis (Hazard Ratio (HR) 0.70; p = 0.04), switch from oADA to ABP 501 (HR 0.53; p = 0.02) and year of prescription (HR 1.04; p = 0.04). In this retrospective study, patients naive to the adalimumab originator and its biosimilar ABP 501 showed the same retention rate. Patients switching from the originator to biosimilar had a higher retention rate, even though not statistically significant, when compared to naive.
2022
- Analysis of cryoproteins with a focus on cryofibrinogen: a study on 103 patients
[Articolo su rivista]
Natali, Patrizia; Debbia, Daria; R Cucinelli, Maria; Trenti, Tommaso; Amati, Gabriele; Spinella, Amelia; Giuggioli, Dilia; Mascia, Maria Teresa; Sandri, Gilda
abstract
2022
- Apremilast retention rate in clinical practice: observations from an Italian multi-center study
[Articolo su rivista]
Ariani, A1; Parisi, S2; Del Medico, P3; Farina, A4; Visalli, E5; Molica Colella, Ab6; Lumetti, F7; Caccavale, R8; Scolieri, P9; Andracco, R10; Girelli, F11; Bravi, E12; Colina, M13; Volpe, A14; Ianniello, A15; Franchina, V16; Platè, I12; Di Donato, E1; Amato, G5; Salvarani, C17; Lucchini, G1; De Lucia, F5; Molica Colella, F18; Santilli, D1; Ferrero, G19; Marchetta, A14; Arrigoni, E12; Mozzani, F1; Foti, R5; Sandri, G; Bruzzese, V9; Paroli, M8; Fusaro, E2; Becciolini, A1
abstract
Objective There are few real-world setting studies focused on apremilast efectiveness (i.e., retention rate) in psoriatic
arthritis (PsA). The main aim of this retrospective observational study is the assessment of apremilast 3-year retention ratein real-world PsA patients. Moreover, the secondary objective is to report the reasons of apremilast discontinuation and thefactors related to treatment persistence.
Methods In ffteen Italian rheumatological referral centers, all PsA consecutive patients who received apremilast were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline were recorded. The Kaplan–Meier curve and the Coxanalysis computed the apremilast retention rate and treatment persistence-related risk factors. A p-value<0.05 was considered statistically
signifcant.
Results The 356 enrolled patients (median age 60 [interquartile range IQR 52–67] yrs; male prevalence 42.7%) median
observation period was 17 [IQR 7–34] months (7218 patients-months). The apremilast retention rate at 12, 24, and 36 months was, respectively, 85.6%, 73.6%, and 61.8%. The main discontinuation reasons were secondary inefcacy (34% of interruptions), gastro-intestinal intolerance (24%), and primary inefcacy (19%). Age and oligo-articular phenotype were related to
treatment persistence (respectively hazard ratio 0.98 IQR 0.96–0.99; p=0.048 and 0.54 IQR 0.31–0.95; p=0.03).
Conclusion Almost three-ffths of PsA patients receiving apremilast were still in treatment after 3 years. This study confrmed its efectiveness and safety profle. Apremilast appears as a good treatment choice in all oligo-articular PsA patients and in those ones burdened by relevant comorbiditie
2022
- Diagnosi di crioproteinemia: preziosa collaborazione tra laboratorio e clinica
per la corretta gestione di una patologia rara
[Articolo su rivista]
Natali, Patrizia; Debbia, Daria; Sheldon, Joanna; Bari, Alessia; Basile, Umberto; Lavatelli, Francesca; Patel, Dina; Galli, Massimo; Villa, Erica; Salvarani, Carlo; Palladini, Giovanni; Mascia, Maria Teresa; Sandri, Gilda
abstract
Cryoglobulinemia is a rare pathologic condition that can be difficult to diagnose both clinically and in the laboratory,
which is why close collaboration between the clinic and laboratory is essential. The laboratory needs the skills and
experience to interpret the laboratory tests and the clinician should not hesitate to contact the laboratory when the
result is not supported by the clinical signs. To strengthen this collaboration, the Protein Study Group of the Italian
Society of Clinical Biochemistry (SIBioC) in collaboration with the Italian Association for the Fight against
Cryglobulinemia (ALCRI) under the patronage of the University of Modena and Reggio Emilia, organised a
conference in Modena on September 2021 entitled "Cryoglobulinemia: laboratory and clinic, a virtuous collaboration
for the correct management of a rare pathology". This collective paper is aimed to summarize the topics discussed
during the meeting. The conference consisted of two parts: the first aimed at highlighting the critical components of
the pre-, intra- and post-analytical phases of cryoglobulin investigation. Cryoprotein testing remains totally manual
and operator dependent so it was important to identify areas where best practice guidance or even harmonisation of
the laboratory investigation would be beneficial. The second part of the conference focused on clinical aspects and
the effects of therapies, including antiviral drugs with direct action against HCV. These drugs are able to eradicate the
virus, but the elimination of HCV-related cryoglobulins is seen in only about half of cases. Finally, the clinical
consequences of the diagnosis of cryoglobulinemia and the multidisciplinary implications that this entails were
highlighted, underlining how the continuous dialogue between the laboratory and clinic is crucial for the correct
management of the patient.
2022
- Early Occupational Therapy Intervention: Patients’ Occupational Needs
[Capitolo/Saggio]
Schiavi, M.; Volta, B.; Sandri, G.; Kelling, E.; Mascia, Mt
abstract
The occupational therapy management involves the assessment of the individual’s specific needs. This kind of assessment facilitates the therapeutic relationship and boosts the person’s motivation, as he or she feels valued and heard. Early-stage collection of information about meaningful activities for the individual helps them project themselves outside the context of illness. Collecting occupational need at an early stage, permits “Engagement”, which means participating in activities even without actually doing them. An occupational therapy model called “Personal Environment Occupation Model” suggests that already at an early stage we should make the environment and occupations meaningful to the person in order to maximise the patient’s performance. An observational study on stroke patients shows how people have personal occupational needs beyond simple self-care, including productive life and leisure time, already in the subacute phase. A further study is underway to demonstrate the effectiveness of early occupational therapy intervention, including complex patients regardless of diagnosis and taking into account their need for care and disability in order to promote their participation and maximise their autonomy.
2022
- Efficacy and Drug Survival after Switching from Etanercept to the Biosimilar SB4: A Real-Life Long-Term Study
[Articolo su rivista]
Parisi, S.; Becciolini, A.; Ditto, M. C.; Rozza, D.; Zanetti, A.; Lagana, A.; Peroni, C. L.; Centanaro Di Vittorio, C.; Degiovanni, R.; Realmuto, C.; Scire, C. A.; Priora, M.; Di Donato, E.; Santilli, D.; Mozzani, F.; Lucchini, G.; Ariani, A.; Gardelli, L.; Girelli, F.; Arrigoni, E.; Plate, I.; Bravi, E.; Paroli, M.; Caccavale, R.; Salvarani, C.; Sandri, G.; Lumetti, F.; Volpe, A.; Marchetta, A.; Fusaro, E.
abstract
We evaluated the 3-year drug survival and efficacy of the biosimilar SB4/Benepali in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients, pre-viously treated with etanercept (ETA). Drug survival rate was calculated using the Kaplan–Meier method and Cox proportional hazard models were developed to examine predictors of SB4 discontin-uation. 236 patients (120 RA, 80 PsA and 36 AS), aged 60.7 ± 13.8 years and with an ETA duration of 4.1 ± 3.4 years were included. The 3-year retention rate for SB4 was 94.4%, 88% and 86% in AS, RA and PsA patients, respectively, with no difference between groups. Patients without comorbid disease had higher retention rates vs. patients with comorbid disease (90% vs. 60%, p < 0.0001). Disease activity, as measured by DAS28, DAPSA and BASDAI remained stable over the 3 years. Comorbid disease (hazard ratio; HR: 4.06, p < 0.0001) and HAQ at baseline (HR: 2.42, p = 0.0024) significantly increased the risk of SB4 discontinuation, while previous ETA duration was negatively associated with SB4 discontinuation (HR: 0.97, p = 0.0064). Forty-one (17.4%) patients left the study due to the interruption of the SB4 treatment, 31 (75.6%) discontinued due to inefficacy and 10 (24.4%) due to adverse events. This real-life study confirms the similar efficacy profile of ETA with long-term retention and a good safety profile in inflammatory arthritis patients.
2022
- Endothelial Dysfunction in Acute Hepatic Porphyrias
[Articolo su rivista]
Ricci, Andrea; Sandri, Gilda; Marcacci, Matteo; Di Pierro, Elena; Granata, Francesca; Cuoghi, Chiara; Marchini, Stefano; Pietrangelo, Antonello; Ventura, Paolo
abstract
Background Acute hepatic porphyrias (AHPs) are a group of rare diseases caused by
dysfunctions in the pathway of heme biosynthesis. Although acute neurovisceral attacks are the
most dramatic manifestations, patients are at risk of developing long-term complications, several of
which are of a vascular nature. The accumulation of non-porphyrin heme precursors is deemed to
cause most clinical symptoms. AimWe measured the serum levels of endothelin-1 (ET-1) and nitric
oxide (NO) to assess the presence of endothelial dysfunction (ED) in patients with AHPs. Forty-six
patients were classified, according to their clinical phenotype, as symptomatic (AP-SP), asymptomatic
with biochemical alterations (AP-BA), and asymptomatic without biochemical alterations (AP-AC).
Results Even excluding those under hemin treatment, AP-SP patients had the lowest NO and highest
ET-1 levels, whereas no significant differences were found between AP-BA and AP-AC patients.
AP-SP patients had significantly more often abnormal levels of ED markers. Patients with the highest
heme precursor urinary levels had the greatest alterations in ED markers, although no significant
correlation was detected. Conclusions ED is more closely related to the clinical phenotype of AHPs
than to their classical biochemical alterations. Some still undefined disease modifiers may possibly
determine the clinical picture of AHPs through an effect on endothelial functions.
2022
- Photobiomodulation Therapy: A New Light in the Treatment of Systemic Sclerosis Skin Ulcers
[Articolo su rivista]
Spinella, Amelia; de Pinto, Marco; Galluzzo, Claudio; Testoni, Sofia; Macripò, Pierluca; Lumetti, Federica; Parenti, Luca; Magnani, Luca; Sandri, Gilda; Bajocchi, Gianluigi; Starnoni, Marta; De Santis, Giorgio; Salvarani, Carlo; Giuggioli, Dilia
abstract
Introduction: Skin ulcers (SU) represent one of the most frequent manifestations of systemic sclerosis (SSc), occurring in almost 50% of scleroderma patients. SSc-SU are often particularly difficult to treat with conventional systemic and local therapies. In this study, a preliminary evaluation of the role and effectiveness of blue light photobiomodulation (PBM) therapy with EmoLED® in the treatment of scleroderma skin ulcers (SSc-SU) was performed. Methods: We retrospectively analyzed 12 consecutive SSc patients with a total of 15 SU on finger hands. All patients were treated with adequate systemic therapy and local treatment for SU; after a standard skin ulcer bed preparation with debridement of all lesions, EmoLED® was performed. All patients were locally treated every week during 2 months of follow-up; SU data were collected after 4 weeks (T4) and 8 weeks (T8). Eight SSc patients with comparable SU were also evaluated as controls. Results: The application of EmoLED® in addition to debridement apparently produced faster healing of SU. Complete healing of SU was recorded in 41.6% cases during EmoLED® treatment. Significant improvements in SU area, length, and width, wound bed, and related pain were observed in EmoLED® patients from T0 to T8. Control subjects treated with standard systemic/local therapies merely showed an amelioration of SU area and width at the end of the follow-up. No procedural or post-procedural adverse events were reported. Conclusions: The positive clinical results and the absence of side effects suggest that EmoLED® could be a promising tool in the management of SSc-SU, with an interesting role to play in the healing process in addition to conventional systemic and local treatments.
2021
- EULAR guidelines on ANCA-associated vasculitis in the real life
[Articolo su rivista]
Marvisi, Chiara; Galli, Elena; Manzini, Carlo Umberto; Sandri, Gilda; Salvarani, Carlo
abstract
Anti-neutrophil cytoplasmic antibodies-associated vasculitides
(AAVs) are a heterogenous group of inflammatory diseases which
primarily involve small vessels and include granulomatosis with
polyangiitis (GPA), microscopic polyangiitis (MPA) and
eosinophilic granulomatosis with polyangiitis (EGPA). They present heterogeneous clinical manifestations, while their diagnosis and
management still remain a challenge for clinicians.
Nowadays, the treatment is based on two different regimens:
the remission-induction treatment and the remission-maintenance
treatment.
The therapeutic armamentarium has grown over the years, with
the aim to lessen adverse effects, improve quality of life of patients
and maintain the disease under control. Biological treatments are
the future: they act on different pathogenic pathways and may offer
in the future a personalized management approach tailored to actual
clinical manifestations.
The latest guidelines were published in 2015 by the European
League Against Rheumatism (EULAR) and still represent the vade
mecum for the management of AAVs.
In this review, we will focus on the principal strategies to treatAAVs. We discuss the remission-induction therapy and the remission-maintenance therapy; we have also distinguished the management of GPA and MPA from that of EGPA, because of their different clinical pictures
2021
- On- and off-label use of rituximab in rheumatic diseases
[Articolo su rivista]
Sandri, Gilda; Manzini, Carlo Umberto; Salvarani, Carlo
abstract
Steadily growing knowledge about pathogenetic mechanisms in autoimmune rheumatic diseases (RDs) has paved the way to different therapeutic approaches. In particular, the availability of biologics on the market has dramatically modified the natural history of rheumatic chronic inflammatory diseases with a meaningful impact on patients’ quality of life. Among the wide spectrum of available biological treatments, rituximab (RTX), initially used in the treatment of non- Hodgkin’s lymphoma, was later approved for rheumatoid arthritis and anti-neutrophil cytoplasmic antibodies-associated vasculitis. Currently, in rheumatology, RTX is also used with off-label indications in patients with systemic sclerosis, Sjögren’s syndrome and systemic lupus erythematosus. RTX is a monoclonal antibody targeted to CD20 molecules expressed on the surface of pre-B and mature B lymphocytes. It acts by causing apoptosis of these cells with antibody- and complement-dependent cytotoxicity. As inflammatory responses to cell-associated immune complexes are key elements in the pathogenesis of several autoimmune RDs, such an approach might be effective in these patients. In fact, RTX promotes a rapid and long-term depletion of circulating and lymphoid tissue-associated B cells, thus leading to a lower recruitment of these effector cells at sites of immune complex deposition, therefore reducing inflammation and tissue damage. RTX is extremely interesting for rheumatologists, as it represents an important additional therapeutic approach. Therefore, the advent in clinical practice of approved RTX biosimilars, such as CT-P10, may help in improving treatment access as well as reducing costs
2021
- Susceptibility to COVID-19 in Patients Treated With Antimalarials: A Population-Based Study in Emilia-Romagna, Northern Italy
[Articolo su rivista]
Salvarani, C.; Mancuso, P.; Gradellini, F.; Viani, N.; Pandolfi, P.; Reta, M.; Carrozzi, G.; Sandri, G.; Bajocchi, G.; Galli, E.; Muratore, F.; Boiardi, L.; Pipitone, N.; Cassone, G.; Croci, S.; Marata, A. M.; Costantini, M.; Giorgi Rossi, P.
abstract
Objective: To evaluate the susceptibility to coronavirus disease 2019 (COVID-19) in patients with autoimmune conditions treated with antimalarials in a population-based study. Methods: All residents treated with chloroquine (CQ)/hydroxychloroquine (HCQ) from July through December 2019 and living in 3 provinces of Regione Emilia-Romagna were identified by drug prescription registries and matched with the registry containing all residents living in the same areas who have had swabs and tested positive for severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results: A total of 4,408 patients were identified. The prevalence of patients receiving antimalarials was 0.85 per 1,000 men and 3.3 per 1,000 women. The cumulative incidence of testing during the study period was 2.7% in the general population and 3.8% among those receiving CQ or HCQ, while the cumulative incidence of testing positive was 0.55% in the general population and 0.70% among those receiving CQ/HCQ. Multivariate models showed that those receiving CQ/HCQ had a slightly higher probability of being tested compared to the general population (OR 1.09 [95% CI 0.94–1.28]), the same probability of being diagnosed as having COVID-19 (OR 0.94 [95% CI 0.66–1.34]), and a slightly lower probability of being positive once tested (OR 0.83 [95% CI 0.56–1.23]). None of the differences were significant. Conclusion: Our findings do not support the use of antimalarials as a prophylactic treatment of COVID-19.
2021
- The management of large vessel vasculitides
[Articolo su rivista]
Galli, Elena; Marvisi, Chiara; Sandri, Gilda; Manzini, Carlo Umberto; Salvarani, Carlo
abstract
2020
- Correction: PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability (Modern Pathology, (2020), 33, 7, (1398-1409), 10.1038/s41379-020-0497-0)
[Articolo su rivista]
Giuffrida, P.; Arpa, G.; Grillo, F.; Klersy, C.; Sampietro, G.; Ardizzone, S.; Fociani, P.; Fiocca, R.; Latella, G.; Sessa, F.; D'Errico, A.; Malvi, D.; Mescoli, C.; Rugge, M.; Nesi, G.; Ferrero, S.; Furlan, D.; Poggioli, G.; Rizzello, F.; Macciomei, M. C.; Santini, D.; Volta, U.; De Giorgio, R.; Caio, G.; Calabro, A.; Ciacci, C.; D'Armiento, M.; Rizzo, A.; Solina, G.; Martino, M.; Tonelli, F.; Villanacci, V.; Cannizzaro, R.; Canzonieri, V.; Florena, A. M.; Biancone, L.; Monteleone, G.; Caronna, R.; Ciardi, A.; Elli, L.; Caprioli, F.; Vecchi, M.; D'Inca, R.; Zingone, F.; D'Odorico, A.; Lenti, M. V.; Oreggia, B.; Bonetti, L. R.; Astegiano, M.; Biletta, E.; Cantoro, L.; Giannone, A. G.; Orlandi, A.; Papi, C.; Perfetti, V.; Quaquarini, E.; Sandri, G.; Silano, M.; Usai, P.; Barresi, V.; Ciccocioppo, R.; Luinetti, O.; Pedrazzoli, P.; Pietrabissa, A.; Viglio, A.; Paulli, M.; Corazza, G. R.; Solcia, E.; Vanoli, A.; Di Sabatino, A.
abstract
Author ‘Marco Vincenzo Lenti’ was listed in the original article as given name: ‘Marco’, family name: ‘Vincenzo Lenti’. However, this should be listed as given name: ‘Marco Vincenzo’, family name: ‘Lenti’. This has been addressed by means of this correction article as well as an update to the original article.
2020
- Frequency and Results of Cryoglobulin Retesting in 4,963 Patients: Comment on the Article by Kolopp-Sarda et al
[Articolo su rivista]
Natali, Patrizia; Galassi, Giuliana; Debbia, Daria; Chester, Johanna; Trenti, Tommaso; Sandri, Gilda; Mascia, Maria T
abstract
Cryoglobulinemia is a rare pathology which is difficult to diagnose both clinically and in the laboratory. Symptoms vary and there are many difficulties in the detection of cryoglobulins (CRG), beginning with the necessity of maintaining the sample at 37°C during the pre‐analytic phase until centrifugation in laboratory. To improve analytical accuracy, some authors have suggested the repetition of sample examinations, especially with persistent clinical suspicion, to avoid false‐negative results.
2020
- INTERSTITIAL LUNG DISEASE RELATED TO RHEUMATOID ARTHRITIS. WHAT DO WE DON’T KNOW? THE LIRA STUDY (LUNG INVOLVEMENT IN RHEUMATOID ARTHRITIS)
[Articolo su rivista]
Sebastiani, M.; Vacchi, C.; Cassone, G.; Salvarani, C.; Sandri, G.; Atzeni, F.; Biggioggero, M.; Carriero, A.; Erre, G. L.; Fedele, A. L.; Furini, F.; Tomietto, P.; Venerito, V.; Atienza-Mateo, B.; Della Casa, G.; Cerri, S.; Palermo, A.; Galli, E.; Pancaldi, F.; González-Gay, M. A.; Manfredi on behalf of LIRA Study Group, A.
abstract
Background: Interstitial lung disease (ILD) is one of the more frequent and potentially severe extra-articular manifestation of rheumatoid arthritis (RA). ILD significantly decreases the survival and quality of life of patients and influences the treatment approach to the patient.
Despite its clinical relevance, the prevalence, incidence and survival of RA-ILD is unknown and supposed on the base of retrospective data or registry-based studies.
Objectives: For the first time, the Lung Involvement in Rheumatoid Arthritis (LIRA) study aims to investigate epidemiology, features and prognosis of RA-ILD patients in a prospective international multicentre study.
Methods: All RA patients referring to the involved centres will be evaluated every six months with a digital stethoscope and a software able to identify velcro crackles with a diagnostic accuracy of 83.9% (VECTOR). In fact, velcro crackles are virtually identified in all stages of fibrosing alveolitis like RA-ILD, and their search is as a simple and reliable method to screening patients to be undergone to high resolution computed tomography (HRCT).
For each patient, clinical and serological data are recorded at baseline and every six months; when velcro crackles or other conditions suspicious for ILD, such as cough or dyspnoea, are detected, a HRCT is requested to confirm ILD. Patients with ILD periodically perform pulmonary function tests to monitor lung function evolution.
Results: At now, 205 RA patients have been enrolled (female/male 161/44, mean age 64.8±12.9 years, mean disease duration 14.2±8.9 years), anti-citrullinated peptides antibodies (ACPA) and rheumatoid factor (RF) were positive in 77.1% and 78.1%, respectively. The prevalence of ILD was 21% (43 patients). In other 13 patients the HRCT is ongoing; therefore, we could suppose up to a prevalence of 27.3%. Patients with ILD were symptomatic in 53.5% of cases (23 patients), they are more frequently males and were older than patients without ILD (mean age 73.2±7.4 and 62.7±13.2; p<0.0001, female/male ratio 139/23 vs 22/21; p<0.0001) without significant differences regarding disease duration, positivity for ACPA or RF.
Conclusion: The prevalence and the incidence of RA-ILD is still not well defined. Preliminary data of our study confirm a prevalence of ILD higher than 20%, patients are asymptomatic in almost the half of cases and more frequently males and elderly. Our study can help to define the clinical history of these patients, the possible association with clinical and serological features and the supposed role of some drugs.
2020
- NATURAL HISTORY OF CRYOGLOBULINEMIA FROM 2000 TO 2018 FROM THE
LABORATORY POINT OF VIEW: AN ANALYSIS OF CRYOGLOBULIN
CHARACTERISTICS IN A SINGLE CENTER.
[Abstract in Atti di Convegno]
Sandri, Gilda; Spinella, A; Bari, A; Fontana, F; Trenti, ; Natali, Mascia MT P.; Debbia, D.; Campioli, D.; Amati, G.; Galassi, G.; Mazzoli, M.; Alfano, G.
abstract
2020
- PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability
[Articolo su rivista]
Giuffrida, P.; Arpa, G.; Grillo, F.; Klersy, C.; Sampietro, G.; Ardizzone, S.; Fociani, P.; Fiocca, R.; Latella, G.; Sessa, F.; D'Errico, A.; Malvi, D.; Mescoli, C.; Rugge, M.; Nesi, G.; Ferrero, S.; Furlan, D.; Poggioli, G.; Rizzello, F.; Macciomei, M. C.; Santini, D.; Volta, U.; De Giorgio, R.; Caio, G.; Calabro, A.; Ciacci, C.; D'Armiento, M.; Rizzo, A.; Solina, G.; Martino, M.; Tonelli, F.; Villanacci, V.; Cannizzaro, R.; Canzonieri, V.; Florena, A. M.; Biancone, L.; Monteleone, G.; Caronna, R.; Ciardi, A.; Elli, L.; Caprioli, F.; Vecchi, M.; D'Inca, R.; Zingone, F.; D'Odorico, A.; Lenti, M. V.; Oreggia, B.; Reggiani Bonetti, L.; Astegiano, M.; Biletta, E.; Cantoro, L.; Giannone, A. G.; Orlandi, A.; Papi, C.; Perfetti, V.; Quaquarini, E.; Sandri, G.; Silano, M.; Usai, P.; Barresi, V.; Ciccocioppo, R.; Luinetti, O.; Pedrazzoli, P.; Pietrabissa, A.; Viglio, A.; Paulli, M.; Corazza, G. R.; Solcia, E.; Vanoli, A.; Di Sabatino, A.
abstract
Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn’s disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 expression was correlated with several clinico-pathological features, such as the etiology, microsatellite instability status, and tumor-infiltrating lymphocyte (TIL) density. The prevalence of PD-L1 positivity according to combined positive score (CPS) was 26% in the whole cohort of SBAs, with significantly (p = 0.001) higher percentage (35%) in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs (5%). CPS ≥ 1 SBAs were significantly (p = 0.013) more frequent in MSI-H cases (41%) than in non-MSI-H ones (18%); however, 15 CPS ≥ 1 microsatellite stable SBAs were also identified. CPS ≥ 1 SBAs showed higher TIL and PD-1+ immune cell density, more frequently medullary histotype, as well as a better outcome in comparison with CPS < 1 cases. This study demonstrates an increased proportion of PD-L1+ cases in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs. In addition, the identification of a subset of PD-L1+ microsatellite stable SBAs supports the need to ascertain additional biomarkers of response to immune checkpoint inhibitors along with MSI-H.
2020
- RETENTION RATE OF ADALIMUMAB AND ABP 501 IN THE TREATMENT OF A LARGE COHORT OF PATIENTS WITH INFLAMMATORY ARTHRITIS: A REAL LIFE RETROSPECTIVE ANALYSIS
[Poster]
Lumetti, F.; Sandri, G.; Becciolini, A.; Caccavale, R.; Parisi, S.; Giordano, S.; Bravi, E.; DI Donato, E.; Andracco, R.; Ditto, M. C.; Santilli, D.; Lucchini, G.; Volpe, A.; Marchetta, A.; Mozzani, F.; Girelli, F.; Arrigoni, E.; Fusaro, E.; Paroli, M.; Ariani, A.
abstract
Background: The recent introduction of ABP 501, an adalimumab biosimilar, in treatment of rheumatic diseases was supported by a comprehensive comparability exercise with its originator. On the other hand observational studies comparing adalimumab and ABP 501 in inflammatory arthritis are still lacking.
Objectives: To compare the clinical outcomes of the treatment with adalimumab, both originator and biosimilar, in a large cohort of patients affected by autoimmune arthritis in a real life setting.
Methods: We retrospectively analysed the baseline characteristics and the retention rate in a cohort of patients who received at least a course of adalimumab (originator or biosimilar ABP 501) in eight Rheumatology Units from January 2003 to January 2020. We stratified the study population according to biosimilar use. Descriptive data are presented by medians (interquartile range [IQR]) for continuous data or as numbers (percentages) for categorical data. Drug survival distribution curves were computed by the Kaplan-Meier method and compared by a stratified log-rank test. P values ≤0.05 were considered statistically significant.
Results: 764 patients (53.4% female, median age 55 [44-65] years, median disease duration 60 [25-149] months) treated with adalimumab were included in the analysis. 308 (40.3%) were affect by rheumatoid arthritis, 244 (31.9%) by psoriatic arthritis, and 212 (27.7%) by axial spondylarthritis. 558 (73%) were treated with adalimumab originator and 206 (27%) with ABP 501. Among the biosimilars 60 (29.1%) patients were naïve to adalimumab treatment. The overall 6-month retentions rate was 93.1%. The 6-month retention rate for adalimumab and ABP 501 were 93.3% and 91.2% respectively, without significant differences between the groups (p=0.541). Patients switching from originator to biosimilar showed and overall higher treatment survival when compared to naive (6-month retention rate 95% vs 90-4%), although it was not significant (p=0.179).
Conclusion: In our retrospective study adalimumab originator and its biosimilar ABP 501 showed the same effectiveness. Patients switching from originator to biosimilar showed an higher retention rate when compared to naive.
2020
- Ultrasonographic and clinical assessment of peripheral enthesitis and arthritis in an Italian cohort of inflammatory bowel disease patients
[Articolo su rivista]
Bertolini, E.; Macchioni, P.; Rizzello, F.; Salice, M.; Vukatana, G.; Sandri, G.; Bertani, A.; Ciancio, G.; Govoni, M.; Zelante, A.; Malavolta, N.; Beltrami, M.; Salvarani, C.
abstract
Aims: To evaluate the prevalence of clinical and ultrasonographic musculoskeletal involvement in Italian patients with inflammatory bowel disease (IBD). Methods: In this cross-sectional multicenter study, 148 consecutive patients with IBD were evaluated by a gastroenterologist and a rheumatologist. All patients underwent a B-mode and power Doppler ultrasonographic examination of 6 pairs of entheses and of knee and ankle joints. Results: A positive history for at least one musculoskeletal manifestation was reported by 40.5% of patients, more frequently in ulcerative colitis (UC) (p = 0.033). Inflammatory back pain was reported by 13.5% of patients, and a past history of peripheral arthritis by 14.9%, entheseal inflammation by 14.2% and dactylitis by 2.7%. At clinical examination, arthritis was observed in 19.6% of patients and enthesitis in 33%. Oligoarthritis and enthesitis at clinical examination were more frequently observed in UC than in Crohn disease (CD). 37.8% of total IBD patients fulfilled ASAS classification criteria for axial and/or peripheral spondyloarthritis, 8.1% ASAS classification criteria for axial spondyloarthritis, and 29.7% ASAS classification criteria for peripheral spondyloarthritis. With ultrasonographic examination, signs of entheseal involvement were observed in 87.8% of patients, while at power Doppler, ≥1 abnormality was observed in 27.1%. ASAS+ patients compared to those ASAS- had a significantly higher frequency at ultrasonography of acute entheseal abnormalities, power Doppler entheseal positivity and joint involvement. These abnormalities at ultrasonography were also observed in 34%, 13% and 12% of ASAS- patients. Conclusions: Musculoskeletal manifestations occur frequently in patients with IBD. Ultrasonographic entheseal and joint involvement were also observed in asymptomatic patients.
2019
- Buerger's disease or thromboangiitis obliterans: description of two cases
[Articolo su rivista]
Manzini, Carlo; Sandri, Gilda; Sebastiani, Marco
abstract
2019
- Diagnostic accuracy of a velcro sound detector (VECTOR) for interstitial lung disease in rheumatoid arthritis patients: The InSPIRAtE validation study (INterStitial pneumonia in rheumatoid ArThritis with an electronic device)
[Articolo su rivista]
Manfredi, A.; Cassone, G.; Cerri, S.; Venerito, V.; Fedele, A. L.; Trevisani, M.; Furini, F.; Addimanda, O.; Pancaldi, F.; Della Casa, G.; D'Amico, R.; Vicini, R.; Sandri, G.; Torricelli, P.; Celentano, I.; Bortoluzzi, A.; Malavolta, N.; Meliconi, R.; Iannone, F.; Gremese, E.; Luppi, F.; Salvarani, C.; Sebastiani, M.
abstract
Background: Interstitial lung disease (ILD) is a severe systemic manifestation of rheumatoid arthritis (RA). High-resolution computed tomography (HRCT) represents the gold standard for the diagnosis of ILD, but its routine use for screening programs is not advisable because of both high cost and X-ray exposure. Velcro crackles at lung auscultation occur very early in the course of interstitial pneumonia, and their detection is an indication for HRCT. Recently, we developed an algorithm (VECTOR) to detect the presence of Velcro crackles in pulmonary sounds and showed good results in a small sample of RA patients. The aim of the present investigation was to validate the diagnostic accuracy of VECTOR in a larger population of RA patients, compared with that of the reference standard of HRCT, from a multicentre study. Methods: To avoid X-ray exposure, we enrolled 137 consecutive RA patients who had recently undergone HRCT. Lung sounds of all patients were recorded in 4 pulmonary fields bilaterally with a commercial electronic stethoscope (ES); subsequently, all HRCT images were blindly evaluated by a radiologist, and audio data were analysed by means of VECTOR. Results: Fifty-nine of 137 patients showed ILD (43.1%). VECTOR correctly classified 115/137 patients, showing a diagnostic accuracy of 83.9% and a sensitivity and specificity of 93.2 and 76.9%, respectively. Conclusions: VECTOR may represent the first validated tool for the screening of RA patients who are suspected for ILD and who should be directed to HRCT for the diagnosis. Moreover, early identification of RA-ILD could contribute to the design of prospective studies aimed at elucidating unclear aspects of the disease.
2019
- Salivary 1H-NMR Metabolomics in Primary Sjögren Syndrome. Preliminary Results of a Pilot Case-Control Study
[Abstract in Rivista]
Setti, G.; Sandri, G.; Tarentini, E.; Panari, L.; Mucci, A.; Righi, V.; Meleti, M.; Magnoni, C.; Consolo, U.; Bellini, P.
abstract
2018
- Cryoglobulin evaluation: analysis of intra-laboratory and inter-laboratory variability
[Abstract in Atti di Convegno]
Campioli, Daniele; Natali, P; Debbia, D; Spinella, A; Sandri, G; Cerami, C; Scichilone, L; Fontana, F; Mascia, Mt
abstract
Background Cryoglobulins (CRG) are immunoglobulins that precipitate in serum at temperatures below 37°C and resolubilize upon warming. The main reasons of interest of a clinical pathologist in the study of cryoglobulinemia are: 1) lack of standardisation in the preanalytical, analytical and postanalytical phases of the process (classification and reporting); 2) peculiarities of physiopathological mechanism 3) important clinical consequences. Vermeersch et al. studied these issues in 2008. To assess current practice in the detection, analysis, and reporting of cryoglobulins, a questionnaire was sent to 140 laboratories. They showed that only 36% of laboratories used standard procedures of analysis. Consequently, they concluded that standardisation was needed for cryoglobulin detection to avoid missed diagnoses and improve the comparability of results. Sargur et al. in 2010 reviewed the classification and clinical features of cryoglobulins and suggested “best practice” guidelines for laboratory detection and identification of cryoglobulins. They particularly highlighted the relevance of preanalytical and analytical phases: maintenance of the sample at a stable temperature of 37°C, especially throughout the initial steps (collection and transportation); centrifugation and separation methods; cryoprecipitate quantification; cryoprecipitate washing techniques; immunocharacterization of cryoprecipitates especially through immunofixation techniques (considered the “gold standard”).
Objectives To verify and assess the variability of laboratory processes of CRG.
Methods We checked laboratory databases of Hospital and University (Lab A and B) of Modena with long tradition in the cryoglobulin analysis (more than 6000 tests from 2002 to 2017). Concerning CRG testing, 734 patient samples were studied in both laboratories. We compared our results according to Brouet classification into subgroups: type I, II and III. Therefore, we evaluated intra-laboratory variability, compared to previous or more frequent results. Finally, we studied inter-laboratory variability based on non-concordant laboratory reports.
Results In the following table, we have represented the comparison between labs about the same patient cohort in 734 patient samples:Conclusions No data about variability in CRG analysis are reported in literature. National and international guidelines are not explicative enough. Furthermore, many doubts about classifications are established. Our experience is unique but limited in two laboratories. Given the variability of testing conditions used in different laboratories and the lack of test standards and reference values, we confirm the need of further investigations into standardisation of CRG testing. New guidelines are fundamental, in order to optimise all phases of CRG research (pre and post analysis) and to ensure correct diagnosis and adequate treatments of the associated diseases.
2018
- The New Test for Monitoring Infliximab Therapy: From Laboratory to Clinical Practice
[Articolo su rivista]
De Santis, Elena; Melegari, Alessandra; Bonaguri, Chiara; Sandri, Gilda; Mascia, Maria Teresa; Gaiani, Federica; Pecoraro, Valentina; De Angelis, Gianluigi; Trenti, Tommaso
abstract
Biological agents for anti-tumor necrosis factor-α therapy have revolutionized treatments for autoimmune diseases; however, approximately 20% of rheumatology and 40% of gastroenterology patients do not respond to the therapy, or they show reduced drug efficacy because of anti-drug antibody (ADA) formation.
2018
- The prevalence of asymptomatic early sacroiliitis in Crohn’s disease patients: The single experience of an Italian tertiary care centre
[Abstract in Atti di Convegno]
DI GIROLAMO, Maria; Campomori, F; Spinella, A; Sartini, A; Sandri, G; Bertani, A; Verga, C; Merighi, A; Villa, E
abstract
Background
The inflammatory involvement of sacroiliac joint is one of the most frequent and underestimated extra-intestinal manifestation in patients with inflammatory bowel disease. The early recognition of a sacroiliitis can prevent their progression to definite spondyloarthritis with worsening of quality of patients’ life. The use of magnetic resonance imaging might be useful to detect early and asymptomatic sacroiliitis. The aim of this study is to assess the prevalence of early sacroiliitis in asymptomatic patients affected by Crohn’s disease who undergo to abdominal magnetic resonance imaging for the staging of bowel disease.
Methods
The retrospective study included 121 patients affected by Crohn’s disease who refer to the Department of Gastroenterology and undergo consecutively to the abdominal magnetic resonance imaging for the staging of the bowel disease, enrolled from January 2012 to January 2017. The assessment of sacroiliitis and Crohn’s disease by magnetic resonance imaging was made using T1-weighted spin-echo [TISE], short tau inversion recovery [STIR] and fat-saturated T2-weighted sequences.
Results
At the abdominal magnetic resonance imaging, 35 (28.9 %) of patients have an asymptomatic bone marrow oedema of the sacroiliac joint. At the logistic regression, the previous surgical therapy is a statistical significant predictive factor of sacroiliitis (OR 3.27, 95% CI 1.45–7.41, p = 0.004) and the previous biological therapy with anti-TNF seems to be a protective factor (OR 0.79, 95% CI 0.26 - 2.36, p = 0.67).Conclusions
Our study underlines the presence of an asymptomatic and early sacroilitiis in patients affected by Crohn's disease and the need for tight control of Crohn's patients using also cross-sectional methods for a complete control of disease and an integrated multidisciplinary approach in order to identify a therapeutic strategy, especially in the era of the new biologic therapies.
2018
- Tocilizumab for the treatment of patients with rheumatoid arthritis and interstitial lung diseases: a case series
[Articolo su rivista]
Manfredi, A.; Sebastiani, M.; Cassone, G.; Colaci, M.; Sandri, G.; Ferri, C.
abstract
na
2017
- EXPERIMENTAL USE OF 3D PRINTING TECHNOLOGY FOR THE CONSTRUCTION OF DEVICES AS INTEGRATION OF OCCUPATIONAL THERAPY INTERVENTION WITH RHEUMATOID ARTHRITIS PATIENTS (RA)
[Abstract in Rivista]
Sandri, Gilda; Bottini, Angelo; Franchi, F.; Mascia, Maria Teresa
abstract
Background: RA is a chronic inflammatory disease that can interfere with the ability to perform activities of daily living. The adoption of aid devices allows to maintain and/or improve employment performance, reducing the pain preventing further joint damage. However, it is known that the abandonment rate of such devices is quite high, resulting in failure of the rehabilitation project, and waste of resources. The reasons people give for abandoning support technology are that they have not been involved in the process of provision, and that the devices do not have the intended effect (1).
Objectives: technology may allow customization of 3D printing devices agreed together with patients, utilizing materials which are cheap, fast and easily adjustable.
Methods: The study was organized into the following phases: recruitment of RA patients for the “joint protection laboratories”; sessions of the “joint protection laboratories”; recruitment of patients for the identification of needs for customized aid devices; co-design of customized aid devices; printing of customized aid devices; delivery of customized aid devices; detection using customized aid devices.
We have collected a list of needs to be able to develop such customized aid devices at the end of a course to educate on joint protection covering: ergonomic gestures, management of fatigue and pain, environmental adaptations and aid devices.
18 patients (17 women and 1 man), age between 30 and 75 years old, were organized into small groups for the “joint protection laboratories”. 9 patients expressed their specific needs regarding the aid devices and therefore subsequent meetings were organized that have allowed us to produce and deliver customized objects.
Autodesk® Fusion360 for object modeling; Ultimaker Care for slicing; 3D printing DeltaWASP 20 40. For the collection of the design features we used the PA board (product analysis) of the USERfit tool. For the psycho-social impact assessment of the assistance, the PIADS (Psychosocial Impact of Assistive Devices Scale – scale -3+3) was used, and for the evaluation of the patient's satisfaction with respect to the aid device, QUEST (Quebec User Evaluation of Satisfaction with Technical Aids, scale 1–5) was used.
Results: 6 aid devices were customized: hand grip holder for chalk, toothbrush, ignition key, tablespoon, iron, as well as a handle to open the moka coffee machine.
The psychosocial assessment of 6 delivered aid devices, collected through PIADS, showed an overall positive outcome (mean competence +1.488; adaptability: +1.690; self-esteem: +1.375). The assessment of patient satisfaction through QUEST, was good overall (scale 1–5: satisfaction aid: 4.75; service satisfaction: 4.68).
Conclusions: This work also demonstrated, over a range of small numbers, that the path of co-design and production of customized aid devices via rapid manufacturing with 3D printing technology is feasible and fulfilling
2017
- Interstitial lung disease is associated to infections of lower respiratory tract in immunocompromised rheumatoid arthritis patients
[Articolo su rivista]
Sebastiani, Marco; Manfredi, Andreina Teresa; Cassone, Giulia; Sandri, Gilda; Cerri, Stefania; Ferri, Clodoveo
abstract
Immunosuppressive treatment increase the risk of lower respiratory tract infections particularly in RA-ILD
patients, suggesting a more careful surveillance in this subgroup of patients
2017
- La legislazione del dolore e la sua applicazione in Italia: pregi e difetti
[Relazione in Atti di Convegno]
Sandri, Gilda
abstract
Nella storia molti sono stati gli studiosi, i filosofi, gli scienziati e i medici che hanno contribuito alla conoscenza del dolore da vari punti di vista, etico, fisiopatologico e terapeutico; tuttavia, ancora oggi la corretta terapia del dolore resta una delle più importanti controversie della società in generale e della comunità scientifica e sanitaria in particolare. Combattere la sofferenza e dare sollievo alla persona malata significa migliorare la qualità della vita per la persona assistita, ma anche la qualità dell’assistenza. La cura del dolore, oltre che un dovere etico, è infatti una buona pratica clinica, il dolore infatti è un fenomeno patologico, che condiziona pesantemente la vita delle persone, con conseguenze sulla sfera psicologica, emotiva, relazionale. In Italia l’attenzione al problema “dolore” ha cominciato a svilupparsi soprattutto nel campo delle cure palliative, volte a garantire una dignità di fine vita, trattando le sofferenze fisiche e psicologiche dei malati terminali. Palliativo deriva dal termine latino pallium, che significava mantello, per sottolineare l’avvolgente presa in carico, proprio come un mantello, del dolore del malato con terapie mediche e psicologiche. L’inutilità del dolore da cancro, considerato una sofferenza fine a se stessa perché priva del ruolo di campanello d’allarme, e la sua insopportabilità, unite all’elevata incidenza e mortalità della malattia neoplastica in quegli anni, hanno spinto tanti clinici tra cui l’oncologo Umberto Veronesi, a quel tempo direttore generale dell’Istituto Nazionale dei Tumori dal 1975, e l’anestesiologo professor Vittorio Ventafridda, responsabile del Servizio di Terapia del Dolore e di Cure Palliative e direttore scientifico della Fondazione Floriani, a intraprendere una personale battaglia contro il dolore neoplastico. Dall’impegno di questi due clinici e con l’aiuto di altri colleghi, venne istituita anche la European Association for Palliative Care volta a diffondere le cure palliative in Europa. Le cure palliative, che racchiudevano in sé il concetto di terapia del dolore, hanno cominciato a organizzarsi negli anni ’80 con il preciso scopo di diffonderle e applicarle ai pazienti in fase terminale. Dal punto di vista legislativo le cure palliative e la terapia del dolore, a causa di non poche resistenze politiche e culturali, sono state recepite dal Governo e prese in considerazione dalle istituzioni solo negli anni ’90, grazie alla volontà delle organizzazioni non profit e agli stimoli provenienti dalle realtà internazionali più all’avanguardia in materia di assistenza. Da allora, l’opinione pubblica ha cominciato a far entrare nel proprio vocabolario le parole “cure palliative” e “terapia del dolore”. L’idea di indire una vera e propria lotta al dolore è nata, dunque, circa 50 anni fa dalla consapevolezza di alcuni medici illuminati di trovarsi di fronte a una duplice realtà: da un lato essi constatavano una globale arretratezza di pensiero nel considerare il dolore e dall’altro una mancata occasione di poterlo alleviare con farmaci oppiacei idonei a combatterlo. La maggior parte dei malati e dei loro familiari aveva infatti un atteggiamento di passiva accettazione della sofferenza, interpretata il più delle volte come una punizione o un fenomeno ineluttabile contro cui non bisognava ribellarsi, mentre i medici vivevano la sua insorgenza come una sconfitta professionale oltre che umana.
2017
- NEW PERSPECTIVES IN DIAGNOSIS OF INTERSTITIAL LUNG DISEASE RELATED TO RHEUMATOID ARTHRITIS. VALIDATION STUDY OF AN ELECTRONIC STETHOSCOPE AND AD HOC SOFTWARE FOR DETECTION OF PULMONARY CRACKLES
[Abstract in Rivista]
Manfredi, Andreina Teresa; Sebastiani, Marco; Cassone, Giulia; Fedele, A. L.; Venerito, V.; Trevisani, M.; Furini, F.; Addimanda, O.; Gremese, E.; Iannone, F.; DELLA CASA, Giovanni; Cerri, Stefania; Sandri, Gilda; Pancaldi, Fabrizio; Luppi, Fabrizio; Ferri, Clodoveo
abstract
Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial joint swelling and tenderness, secondary to the immune-system dysfunction, often complicated by extra-articular manifestations. Among them, lung involvement is very frequent and interstitial lung disease (ILD) represents one of the deleterious complications of RA with impact on both therapeutic approach and overall prognosis. Nevertheless, diagnosis of ILD often remains missing or delayed.
Objectives: To preliminarily evaluate the predictive value of pulmonary sound recorded by an electronic stethoscope (ES) and elaborated by an ad hoc software in identification of RA-ILD diagnosed by mean of high resolution computed tomography (HRCT) in a multicenter study.
Methods: RA patients who underwent HRCT in the last 12 months were enrolled. They were all auscultated with the ES (Littmann 3200TM 3M, USA), bilaterally, at dorsal level, in at least 3 pulmonary fields (medium and basal). All tracks recorded were analyzed by a suitably developed software capable of recognizing pathological crackles in lung sounds. Results were compared with radiologic findings detected in a blind manner by an expert radiologist.
Results: One hundred and six RA patients were enrolled (M/F: 1/2.5, mean age 68.7±10.3); among them 45 (42.5%) showed ILD at HRCT. Three patients were excluded because of a low quality of the sound recorded. The algorithm showed a sensitivity and specificity of 72.1% and 84.4%, respectively and a positive/negative predictive value of 69.1% and 86.3%, respectively.
Conclusions: Despite preliminary, these data suggest an important role of ES in clinical practice for an early diagnosis of ILD in RA patients and a significant reduction of inappropriate prescription of HRCT. Since very different types of ILD can occur in course of RA, with different radiologic features and localization, proper development of the measurement setup (ES and ad hoc software for the detection of PC) could further increase its predictive value, in particular to avoid incorrect records and misdiagnosis. The routinely employment of ES and proper software, combined to clinical findings (cough, dyspnea) and respiratory lung function, could increase our ability to early identify ILD in RA patients.
2017
- PREVALENCE OF ULTRASOUND ABNORMALITIES IN PATIENTS WITH PSORIATIC ARTHRITIS IN A CLINICAL PHASE OF MINIMAL DISEASE ACTIVITY UNDER ANTI-TNF TREATMENT
[Abstract in Rivista]
Macchioni, .; Ciancio, G.; Sandri, Gilda; Zabotti, A.; Vukatana, G.; Montaguti, L.; Focherini, M.; Verduci, E.; Chessa, D.; Govoni, M.; Spinella, Amelia; Malavolta, N.; Zuliani, F.; Bruschi, M.; Mascella, F.
abstract
Background: Few studies have analized the persistence of ultrasound (US) abnormalities in patients (pts) with Psoriatic Artritis (PA) during the phase of minimal disease activity (MDA)
Objectives: To investigate the prevalence of US alterations at enthesis, joint and tendon levels in pts with psoriatic arthritis (PA) during a phase of MDA.
Methods: Pts treated with anti-tumor necrosis factor (TNF) for at least 12 months and with at least 6 months duration of MDA were consecutively recruited at 6 Italian centers. In every center, the local rheumatologists provided PA pts to be examined by US. Personal history, demographic and clinical data were recorded. Each patient underwent the following US examinations: metacarpophalangeal (MCP), knee and tibio-tarsal (TT) joint, flexor and extensor tendon of hand digit, flexor and extensor tendon at carpal area, flexor and extensor tendon of foot, and enthesis of common extensor tendon insertion on the lateral epicondyle of the humerus, quadriceps tendon, patellar tendon, Achilles tendon and plantar fascia insertions on the calcaneus. Each examination were performed by rheumatologists expert in US, to assess synovitis (joint effusion, synovial proliferation, and power Doppler (PD) signal), and bone erosions, flexor tendon tenosynovitis, hand finger extensor tendon tenonitis, and enthesel involvement using an Esaote MyLabClass with a 5–13 or 6–18 MHz linear probe. The following elementary lesions were assessed at each enthesis: morphologic abnormalities (hypoechogenicity and/or thickening), entheseal calcific deposits, cortical abnormalities (bone erosion and/or proliferation), adjacent bursitis and intraenthesis and perienthesis (tendon body and/or bursa) PD signal. All US findings were scored using a 4 degree semiquantitative scoring system. US acute enthesitis was defined by the presence of entheseal edema or PD signal. US chronic entheseal alterations by the presence of calcifications, erosions, or enthesophytes. US peripheral active synovitis if synovial hypertrophy was associated with the presence of PD signal. US examinator were blind of clinical data of the pts.
Results: Sixty-three pts were recruited (mean age 53±13y, mean PA duration 13±8y, mean MDA duration 21±11m). At US examination 66.7% of pts had at least one peripheral joint involved (17.5% had peripheral active synovitis), 47.6% had acute enthesitis and 95.2% chronic enthesopathy. US bursitis was present in 22.2% of pts, 3.7% had hand extensor finger tendon involvement.
Table 1 shows clinical and demographical data of the pts and table 2 the US results
Nail involvement
Previous dactylitis
FamHyst
IBP
Patients with abnormality (%)
28.3
42.9
23.9
19.7
Table 2. US abnormalities in 63 pts in MDA
Perypheral active sinovitis
Joint peripheral involvement
Chronic entheseal alterations
Acute entheseal alterations
Tenosynovitis
Patients with abnormality (%)
17.5
66.7
95.2
47.6
29.6
Conclusions: Joint, entheseal and tendon abnormalities have a high prevalence in PA patients treated with anti-TNF during MDA.
2016
- INTERSTITIAL LUNG DISEASE IS ASSOCIATED TO INFECTIONS OF LOWER RESPIRATORY TRACT IN IMMUNOCOMPROMISED RHEUMATOID ARTHRITIS PATIENTS
[Abstract in Rivista]
Cassone, Giulia; Sebastiani, Marco; Manfredi, Andreina Teresa; Campomori, Federica; Spinella, Amelia; Sandri, Gilda; Luppi, Fabrizio; Cerri, Stefania; Ferri, Clodoveo
abstract
Objectives. To investigate the possible association between demographic, serological and clinical features of rheumatoid arthritis (RA) and the lower respiratory tract (LRT) infections.
We further analyzed the possible relationships between demographic, serological and clinical features and LRT infections in a sub-group of patients with RA-associated interstitial lung disease (ILD).
Materials and Methods. Demographic, serological, clinical and therapeutic features of 563 RA patients were retrospectively analyzed (female/male ratio 3.43, mean age 64.8±13.6SD years, mean disease duration 11.5±9.4SD years).
Results. During a mean follow-up of 138.9±131.3SD months, we observed 47 patients with at least one episode of LRT infection.The presence of RA-associated ILD, therapy with steroids, and b-DMARDs were significantly associated to LRT infections (p=0.016, p=0.000, and p=0.01 for ILD, steroids and b-DMARDs, respectively).
All variables remained independently associated to infections of LRT also at logistic regression analysis; while no differences were observed with regard to the kind of the b-DMARDs, namely anti-tumor necrosis factors alpha inhibitors, rituximab, abatacept, tocilizumab. Moreover, the presence of ILD was associated to more severe LRT infectious
complications, requiring hospitalization in 55.6% of patients, compared to 27.8% of patients without ILD (p=0.042). Since patients with ILD showed a risk to develop an infection of LRT 4.5 times higher of patients without ILD, we further analyzed this peculiar sub-group of patients. Among 33/563 (5.9%) patients with ILD (female/male ratio 2/1, mean age 71.8±10.6 years, mean disease duration 16.1±13.0 years), only b-DMARDs were associated to infections of LRT (p=0.002). Of interest, a combination therapy with b-DMARDs, methotrexate, and corticosteroids was significantly more
frequently recorded in RA-ILD patients compared to those without LRT infections (81.8% vs 13.6% of patients; p=0.001).
Conclusions. ILD is an important extra-articular complication of RA, involving about 5-10% of patients, and its current therapeutic approach is still under debate, because the lack of evidences that immunosuppressants are effective both on joint and lung involvement. Idiopathic pulmonary fibrosis (IPF) is usually compared to RA-ILD for their similarity in radiological and histological features. In IPF patients, the PANTHER-IPF study showed an excess mortality due to pulmonary infection in azathioprine and prednisone treatment arm, and corticosteroids increase the risk of serious infection fourfold. Our data confirm, with the limit of a low number of patients analyzed, that immunosuppressive treatment increase the risk of LRT infections particularly in RA-ILD patients, suggesting a more careful surveillance in this sub-group of patients.
In conclusion, in patients with RA-ILD, it is necessary to balance the control of joint inflammation with the risk of drug-related LRT infections; this latter could be significantly reduced by tailoring both drug combination and doses (corticosteroids, traditional, and b-DMARDs) on individual patients.
2015
- Evoluzione dello CSURI (Capillaroscopic Skin Ulcer Risk Index) in pazienti affetti da sclerosi sistemica in terapia con antiendotelina-1 e prostanoidi
[Abstract in Rivista]
Cestelli, V; Sebastiani, Marco; Manfredi, Andreina Teresa; Praino, E; Cannarile, F; Giuggioli, Dilia; Colaci, Michele; Sandri, Gilda; Iannone, F; Gerli, R; Ferri, Clodoveo
abstract
Il ruolo della capillaroscopia nei pazienti affetti da sclerosi sistemica (SSc) è progressivamente cresciuto nel corso degli ultimi anni. I farmaci vasoattivi utilizzati nel trattamento e nella prevenzione delle ulcere digitali, in particolare iloprost e bosentan, sembrano in grado di migliorare la microangiopatia sclerodermica, anche se i dati a favore di tale ipotesi sono piuttosto limitati. Lo CSURI (Capillaroscopic Skin Ulcer Risk Index), dimostratosi efficace nell’individuare i pazienti a rischio di sviluppare ulcere digitali, potrebbe rappresentare un ottimo indicatore dell’effetto di questi farmaci sul microcircolo.
Scopo dello studio. Valutare l’evoluzione della microangiopatia in pazienti affetti da SSc con storia di ulcere digitali in terapia con iloprost (ILO) o con bosentan e iloprost (BOS+ILO).
Materiali e Metodi. 95 pazienti sclerodermici consecutivi secondo i criteri ACR/EULAR 2013 (M/F 3,3/1; età media 52,7±14,3 anni) venivano sottoposti a videocapillaroscopia periungueale al basale e dopo 12 mesi. Tutti i pazienti erano in trattamento infusionale mensile con ILO, mentre 33 assumevano terapia di combinazione con BOS+ILO. Di ogni paziente venivano valutati i principali parametri capillaroscopici (megacapillari, microemorragie, neoangiogenesi, disorganizzazione del letto capillare) e calcolato lo CSURI, registrando: numero minimo di capillari, numero massimo di megacapillari e diametro massimo capillare.
Risultati. I dati capillaroscopici ottenuti al basale ed al termine del follow-up sono riportati in tabella I. All’inizio del follow-up il 30% dei pazienti del gruppo ILO e il 54,5% dei pazienti in terapia di associazione BOS+ILO presentava uno CSURI positivo. Tutti i pazienti in terapia con BOS avevano presentato almeno un’ulcera digitale nella propria storia clinica, evento presentatosi nel 73,4% dei pazienti in monoterapia con ILO. Al termine del follow-up la percentuale dei pazienti del gruppo BOS+ILO con CSURI positivo si riduceva al 45,5% (p non significativo), mentre aumentava al 45,2% nei pazienti in terapia con ILO (p<0,001). In entrambi i gruppi si osservava inoltre una significativa riduzione dei megacapillari, mentre nel gruppo BOS+ILO si associava un significativo incremento delle neoangiogenesi (p=0,020).
Conclusioni. Le ulcere digitali rappresentano una delle principali complicanze in corso di SSc ed un numero crescente di pazienti viene trattato con farmaci vasoattivi, fra cui iloprost e bosentan sono i più utilizzati, da soli o in associazione. Entrambi hanno dimostrato di essere in grado di influenzare la microangiopatia sclerodermica riducendo il numero dei megacapillari, anche se l’associazione con il bosentan sembrerebbe determinare anche uno stimolo rigenerativo, come evidenziato dall’incremento delle neoangiogenesi. Le variazioni dello CSURI confermano l’effetto di iloprost+bosentan sulla microangiopatia e la maggiore stabilizzazione del quadro capillaroscopico rispetto alla monoterapia con iloprost.
Questi dati confermano inoltre la sensibilità della capillaroscopia e suggeriscono per lo CSURI un ruolo nel monitoraggio della microangiopatia sclerodermica in corso di terapie vasoattive.
2015
- UTILITY OF A SELF ADMINISTERED QUESTIONNAIRE AS A TOOL FOR SCREENING JOINT INVOLVEMENT UNDERWAY PSORIASIS
[Abstract in Rivista]
Sandri, Gilda; Cestelli, V.; Mascia, Maria Teresa; Lasagni, C.; Pellacani, Giovanni
abstract
Background: The psoriatic arthropathy (AP) is a chronic inflammatory disease of skeletal muscle associated with psoriasis that can involve the synovium, cartilage, bone, tendons and entheses. The identification of individuals with AP can be difficult due to both the wide variability of the clinical manifestations, and the lack of bio-specific markers of the disease.
The dermatologist is not always able to recognize the clinical manifestations of this disease and therefore a multidisciplinary approach between the dermatologist and rheumatologist in this context is of considerable importance in order to make an early diagnosis and target treatment.
Methods: We have developed a questionnaire that can be self-administered to psoriasis patients to identify those who are more likely to be affected by rheumatology. There are 11 questions with the answers:, “no”, “I don't know”, “I don't understand”, that patients can compile themselves in the waiting room before their visit.
Results: 106 questionnaires were collected as part of the surgery “psoriasis” of the Dermatology Clinic of the Hospital. All patients who reported joint symptoms and who did not have a diagnosis of psoriatic arthritis (49) were subsequently evaluated by the rheumatologist. The survey showed a diagnosis of AP in 7 cases and suspected AP in another 5 cases. Among the 7 patients with ascertained AP: 86% reported back pain, 71% reported the presence of ”sausage fingers” and another 71% reported waking up with joint or muscle pain which resolved after at least half an hour of movement.Conclusions: Having identified in a simple way arthropathic complications in a group of patients who were already followed for only psoriasis, the self-administered questionnaire is, therefore, a simple and economical tool to help identify patients affected by psoriasis to be sent to the rheumatologist to confirm the diagnosis of psoriatic arthritis.
2014
- Efficacy and safety of rituximab with and without methotrexate in the treatment of rheumatoid arthritis patients: results from the GISEA register
[Articolo su rivista]
Sebastiani, Marco; Anelli, Maria Grazia; Atzeni, Fabiola; Bazzani, Chiara; Farina, Ilaria; Fedele, Anna Laura; Favalli, Ennio Giulio; Fineschi, Irene; Cino, Nicolò; Dal Forno, Ilaria; Gasparini, Stefania; Cassarà, Emanuele; Giardina, Rita; Bruschi, Eleonora; Addimanda, Olga; Cassone, Giulia; Lopriore, Simona; Sarzi Puttini, Piercarlo; Filippini, Matteo; Pignatti, Federica; Gremese, Elisa; Biggioggero, Martina; Manganelli, Stefania; Amato, Giorgio; Caimmi, Cristian; Salaffi, Fausto; Iannone, Florenzo; Ferri, Clodoveo; Sandri, Gilda; Lapadula, Giovanni; Gorla, Roberto; Govoni, Marcello; Ferraccioli, Gianfranco; Marchesoni, Antonio; Galeazzi, Mauro; Foti, Rosario; Carletto, Antonio; Cantini, Fabrizio; Triolo, Giovanni; Epis, Oscar Massimiliano; Salvarani, Carlo
abstract
Introduction
Rituximab (RTX) is a monoclonal anti-CD20 antibody approved for the treatment of rheumatoid arthritis (RA) in association with methotrexate (MTX).
Objectives
To evaluate the efficacy and safety of RTX–MTX combination therapy compared with RTX alone in the treatment of RA.
Methods
We analyzed data from a prospective cohort study, the Italian biologic register GISEA, to investigate the efficacy and safety of rituximab. Moreover, the adverse events (AE) and the causes of discontinuation therapy were analyzed.
Results
We identified 338 RA patients, 162 treated with RTX and 176 with RTX–MTX. After 52 and 104 weeks of therapy the disease activity score in 28 joints and the Health Assessment Questionnaire Score were available in 168 patients (78 with RTX–MTX and 60 with RTX alone), showing significant reduction without differences among the two groups. AE were reported in 142 patients (42%), for a total of 368 recorded side effects. The majority (90.5%) of AE were mild to moderate in severity. Comparable percentages of severe AE were reported in the 2 groups (9.9% for RTX alone and 9.3% for RTX + MTX). A poor disease control was observed in 14.2% and 13.5% of patients treated with RTX + MTX and RTX, respectively; while 12 patients (4.5% in RTX + MTX, and 2.5% in RTX group) suspended therapy for AE.
Conclusions
RTX showed a good efficacy and safety profile in the real-life management of RA patients regardless of the association with MTX.
2014
- Large Vessel Vasculitis Occurring in Rheumatoid Arthritis Patient under Anti-TNF Therapy
[Articolo su rivista]
Cestelli, Valentina; Spinella, Amelia; Campomori, Federica; Esposito, Carmela; Ciaffi, Sara; Sandri, Gilda; Ferri, Clodoveo
abstract
Vasculitis is a heterogeneous group of disorders characterized by the presence of necrotic inflammatory phenomena and destruction of blood vessels. Vasculitis is classified as primary (idiopathic) or secondary to infections, connective tissue diseases and drugs but can also be considered as a paraneoplastic phenomenon. Evidence shows that the increasing use of biological agents results in a growing number of reports of autoimmune diseases induced by these therapies. An inflammatory articular chronic disease such as rheumatoid arthritis may be complicated by extra-articular manifestations, such as cutaneous or systemic vasculitis. Herewith, we describe the case of a great vessels arteritis in a patient affected by rheumatoid arthritis in therapy with an anti-TNF agent (etanercept).
2014
- Ultrasonography in the diagnosis and management of patients with inflammatory arthritides
[Articolo su rivista]
Epis, Oscar; Paoletti, Franco; D'Errico, Tito; Favalli, Ennio; Garau, Pietro; Mancarella, Luana; Pomponio, Giovanni; Sandri, Gilda; Scioscia, Crescenzio; Selvi, Enrico; Tirri, Enrico
abstract
In primary care and internal medicine settings clinicians are often reluctant to take advantage of the resources that ultrasonography (US) offers as a diagnostic tool in the initial management of patients with inflammatory arthritis, despite the recognised importance of an accurate and timely diagnosis of rheumatoid arthritis (RA) and of early referral to ensure optimal patient management. Both grey-scale (GS) and power Doppler (PD) imaging have been extensively used in early detection of synovitis and bone erosions in patients with inflammatory arthritides. We reviewed the main data on the clinical use of US in the initial management of patients with inflammatory arthritis, focusing on RA diagnosis in patients with undifferentiated arthritis, prediction of disease severity, differential diagnoses and assessment of synovitis in children with juvenile idiopathic arthritis (JIA). The role of US in assessing treatment response and monitoring disease activity in clinical remission was also briefly evaluated. The reliability of US as a diagnostic tool in rheumatological diseases has greatly advanced in the last years and the use of this imaging technique, in association with conventional assessments such as physical examination and serological tests, should be considered more often also in primary care settings
2013
- Biological Therapy and Risk of Malignancies: A Literature Review
[Articolo su rivista]
Sandri, Gilda; Cestelli, Valentina; Mascia, Maria Teresa
abstract
Data from literature show that the overall risk of cancer does not as a result from treatment with these drugs. The only cancer for which various authors have reported an increased risk, in some cases, are skin cancers, different from melanoma and melanoma. Recent results of large observational studies and meta-analyzes indicate the absence of an increased risk of lymphoma related to therapy with anti-TNF-α. It has been reported, by some authors, that there is a possible increased risk of lung cancer, especially in patients with chronic obstructive pulmonary disease. There is limited information in literature about the effects of biologics in patients with a history of cancer. Most of the guidelines indicate that treatment with biologics can be considered with caution and only in patients free of cancer since at least 5 years. Some studies report a lower oncological risk with etanercept compared to monoclonal antibodies, especially in the case of lymphoma. However, this data has not been confirmed in other studies, and has been associated with a limited period of time after starting therapy. Information about the latest biological therapies is still poor. Therefore, there is not sufficient evidence for a preferential use of certain drugs rather than others.
2013
- COMPLEMENT DEPLETION IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH TOCILIZUMAB: A MARKER OF CLINICAL EFFICACY?
[Abstract in Rivista]
Sandri, Gilda; Lumetti, Federica; Ferri, Clodoveo; Mascia, Maria Teresa
abstract
Objectives: Tocilizumab (TCZ) is a humanized monoclonal antibody against the α-chain of the IL6 receptor. In clinical trials TCZ had been shown to lower complement levels in Rheumatoid Arthritis (RA) patients independently of disease activity. We therefore evaluated complement factors in our series of patients treated with anti IL6 to show whether there was any correlation.
Methods: 16 patients with active RA (14 F/2 M; mean age 56.3±11.2SD) were treated with TCZ (13 after anti-TNF failure and 3 naives). The patients were monitored for therapy response (DAS 28), HAQ, including clinical and laboratory parameters. All patients received DMARDs treatment and prednisolone ≤ 7.5 mg/day.
Results: Prior to the treatment, therapy complement levels were normal: C3 124.65±14.52 and C4 23.88±7.23 (normal values: C3 90-180 mg/dl, C4 10-40 mg/dl).
Revaluation of these parameters revealed a decrease already after the first 3-month treatment. The complement depletion increased at the 6th month and persisted during the ongoing therapy. After the 12th month mean values were C3 89.35±10.21 and C4 11.64±6.39.
In four patients the treatment was stopped for the clinical remission with normalization of C3/C4 factors in the follow-up.
Concerning the RA disease activity, 14/16 patients showed a good EULAR response (initial DAS28: 5.79±0.86, ESR 41.94±18.81, CRP 3.62±3.14, HAQ 1.39±0.71; after 3 months DAS 28 2.23±0.52, ESR 6.13±3.10, CRP 0.27±0.24, HAQ 0.79±0.73).
After 24 weeks, for 2/16 patients (1F/1M) the therapy was stopped for inefficacy; in both patients the levels of complement factors did not decrease during TCZ treatment.
In all patients no signs for the development of autoimmunity or infection could be observed.
Conclusions: In the Tocilizumab OPTION study, mean levels of complement proteins C3 and C4 decreased but the data were not shown. It can be hypothesized that complement factors are consumed during the elimination process of immune complexes (IL6-anti-IL6Ab); moreover, in a case report of six RA patients the authors commented that this phenomenon requires further observation with respect to the clinical relevance. In an open label, dose-escalating, Phase I study Tocilizumab in Systemic Lupus Erythematosus complement C3 and C4 showed clear dose-related decreases. The Authors of such trial provided the first evidence that the TCZ-associated hypocomplementemia represents decreased production rather than increased activation. Also Olokizumab, a novel IL6 inhibitor in trials showed in RA patients the same dose-related reductions in complement C3 and C4. Reduction in complement levels is therefore believed to be consecutive to the inhibition by TCZ of IL6 stimulation of hepatocyte acute phase protein synthesis and of significant C3 upregulation.
In our patients there is a good correlation between C3 and C4 decrease and clinical response, while we have not observed any decrease in patients unresponsive to TCZ. The levels of C3 and C4 are more related to the efficacy than PCR or ESR values, which in 1 patient decreased in absence of clear clinical improvement. The number of patients is too small to reach a conclusion but we hypothesize that the dosage of the C3 and C4 can be a rapid and sensitive marker of the response to anti-IL6 treatment. Therefore, a close follow-up of these parameters at 2-3 months from the start of the therapy can guide the therapeutic strategy.
2013
- Does early arthritis clinic organisation improve outcomes? What evidence is there? A systematic review
[Articolo su rivista]
Govoni, Marcello; Sciré, Carlo Alberto; Manara, Maria; Malavolta, Nazzarena; Mancarella, Luana; Sandri, Gilda; Mascella, Fabio; Macchioni, Pier Luigi; Delsante, Giovanni; Padovan, Melissa
abstract
To perform a systematic review aimed to identify studies addressing the effect of the establishment of a structured organisation programme, named early arthritis clinic (EAC), finalized to manage patients with early arthritis (EA) or suspected early rheumatoid arthritis (ERA).
2013
- Non-Hodgkin Lymphoma in Psoriatic Arthritis Treated with Sequential, Multiple Anti-TNF-α Agents: A Case Report
[Articolo su rivista]
Sandri, Gilda; Cestelli, Valentina; Liardo, ELIANA VALENTINA; Sacchi, Stefano; Mascia, Maria Teresa
abstract
Data obtained by large observational studies and meta-analysis indicate the absence of an increased risk of lymphoma related to therapy with anti-TNF-α, but there is limited information in literature about the safety of sequential, multiple biological agents therapy for a time longer than three years. We hereby present a case of psoriatic arthritis developing non-Hodgkin lymphoma after a six-year history of poorly effective therapy with different anti-TNF-α.
2012
- Beyond cat scratch disease: a case report of bartonella infection mimicking vasculitic disorder
[Articolo su rivista]
Spinella, Amelia; Lumetti, Federica; Sandri, Gilda; Cestelli, Valentina; Mascia, Maria Teresa
abstract
Cat scratch disease (CSD) is a bacterial disease caused by Bartonella henselae and it is mainly characterized by self-limiting lymphadenopathy in the draining site of a cat scratch or bite. We report a patient with history of fever, swelling lymph nodes, vasculitic-like skin lesions, and positivity of Bartonella serology initially considered as expression of a disimmune disease.
2012
- Efficacia e sicurezza delle vaccinazioni anti-influenza e anti-pneumococco nei pazienti con artrite reumatoide trattati con farmaci biologici
[Articolo su rivista]
Pomponio, G.; Rovinelli, M.; Scioscia, C.; Selvi, E.; Tirri, E.; D’Errico, T.; Epis, O.; Favalli, E. G.; Garau, P.; Mancarella, L.; Paoletti, F.; Sandri, Gilda
abstract
È noto da tempo come i pazienti con artrite reumatoide (AR) abbiano un alto
rischio di morbilità e mortalità legato a polmonite e sepsi e come queste infezioni contribuiscano in modo significativo alla riduzione delle aspettative di vita 1-3. Le ragioni per l’aumentata prevalenza di infezioni in questi pazienti non sono completamente chiare, e l’uso di farmaci immunosoppressivi (soprattutto corticosteroidi) sembra contribuire solo in parte all’aumentato rischio. Inoltre, la possibilità che i normali segni clinici di infezione siano meno evidenti nei pazienti in trattamento con farmaci antiinfiammatori o immunomodulanti può comportare un ritardo nell’inizio della terapia 1.
L’adozione di strategie che comprendano la vaccinazione anti-influenza (V-inf) e antipneumococco (V-pn) sembrano promettenti nel ridurre fino a 4 volte il rischio di ospedalizzazione e di fatalità legato alle infezioni polmonari nei pazienti con AR e pertanto le autorità sanitarie di molti paesi hanno formulato raccomandazioni specifiche sull’impiego dei vaccini nei soggetti in terapia immunosoppressiva 4. Tuttavia numerosi audit concordano nel registrare un utilizzo subottimale della V-inf e V-pn nei pazienti con AR, nei quali tali strategie di profilassi vengono impiegate in non più del 20-43% dei casi
2012
- Farmaci biologici e infezione tubercolare
[Articolo su rivista]
Scioscia, C.; Anelli, M. G.; Epis, O.; Favalli, E. G.; Garau, P.; Mancarella, L.; Paoletti, F.; Pomponio, G.; Sandri, Gilda; Selvi, E.; Tirri, E.; D’Errico, T.
abstract
Gli antagonisti del fattore di necrosi tumorale alfa (anti-TNF-α) interferiscono con importanti azioni immunitarie esercitate da questa citochina nell’infezione tubercolare (TBC).Il TNF agisce, infatti, su numerose cellule del sistema immunitario: è il principale fattore di attivazione dei macrofagi e partecipa alla co-stimolazione dei linfociti T, cellule fondamentali per la formazione e il mantenimento del granuloma; insieme alle chemochine e all’interferone-gamma (IFN-γ), il TNF-α richiama quindi cellule infiammatorie da un lato a formare il granuloma, dall’altro a promuoverne l’eliminazione. Gli anti-TNF-α bloccano la maturazione dei fagolisosomi, stimolano l’apoptosi di cellule chiave contro la TBC e potenziano la popolazione delle cellule Treg, sbilanciando l’equilibrio tra la risposta infiammatoria dei macrofagi e la soppressione dell’infiammazione da parte delle Treg, fondamentale per il mantenimento del granuloma, contenitore “safe” di micobatteri. La loro somministrazione può pertanto portare a una rottura del granuloma con disseminazione dei micobatteri.
Il rischio tubercolare risulta aumentato con tutti gli anti-TNF-α, ma esistono differenze tra una molecola e l’altra (Tabella I): etanercept si lega a una molecola di TNF-α trimerico, per lo più solubile, mentre gli anticorpi monoclonali (MAb) legano molecole di TNF-α mono e trimerico, sia solubile sia transmembrana, portando a una maggiore riduzione di TNF-α rispetto a etanercept.
2012
- Farmaci biologici e rischio oncologico
[Articolo su rivista]
Sandri, Gilda; Paoletti, F.; Pomponio, G.; Scioscia, C.; Selvi, E.; Tirri, E.; D’Errico, T.; Epis, O.; Favalli, E. G.; Garau, P.; Mancarella, L.
abstract
N
elle malattie infiammatorie che richiedono trattamenti prolungati con terapie immunosoppressive, vi è sempre stata la preoccupazione che tali trattamenti potessero aumentare il rischio dello sviluppo di tumori. I farmaci biologici agiscono tramite complessi meccanismi di immunomodulazione e, alcune citochine inibite da queste terapie (quali il TNF-α) esercitano importanti effetti biologici, sia pure non completamente chiariti, sui processi di carcinogenesi e di progressione tumorale. Per quanto i dati complessivi finora emersi sul rischio oncologico nei pazienti trattati con farmaci biologici siano confortanti, è opportuno tener presente che la valutazione di tale rischio è resa complicata da una serie di fattori, inclusi i seguenti: 1) l’artrite reumatoide (AR) comporta di per sé un rischio differenziale per vari tipi di tumori (aumentato o, in alcuni casi, diminuito), rispetto alla popolazione generale; 2) i tempi di sviluppo di una neoplasia sono spesso lunghi, e possono superare il periodo di osservazione di molti studi; 3) i tumori rappresentano eventi avversi relativamente rari, quindi l’analisi della loro incidenza richiede dati su popolazioni molto vaste per raggiungere un potere statistico sufficiente; 4) negli studi clinici è solitamente escluso l’arruolamento di pazienti con pregresse neoplasie o comunque ad alto rischio oncologico; 5) nella pratica clinica vi può essere un bias di selezione nella scelta dei pazienti da sottoporre a terapia con biologici (per es. a favore di soggetti ritenuti a minor rischio per lo sviluppo di tumori). Queste problematiche devono essere tenute presenti nell’interpretazione dei dati forniti sia dagli studi clinici sia da quelli osservazionali. Pertanto, anche quando non vengono indicate controindicazioni specifiche per l’uso di farmaci biologici in relazione al rischio di tumori, linee guida e documenti di consenso concordano sulla necessità di mantenere alto il livello di vigilanza, per l’eventuale rischio della comparsa di neoplasie nei pazienti sottoposti a terapie biologiche.
2012
- Farmaci biologici e tematiche relative alla cardiopatia ischemica e all’insufficienza cardiaca
[Articolo su rivista]
Garau, P.; D’Errico, T.; Epis, O.; Favalli, E. G.; Mancarella, L.; Paoletti, F.; Pomponio, G.; Sandri, Gilda; Scioscia, C.; Selvi, E.; Tirri, E.
abstract
L
a letteratura relativa al rischio cardiovascolare (CV) in corso di malattie reumatiche sistemiche è estremamente ricca e, negli ultimi anni, molto si è scritto sull’impatto esercitato dalla terapia con farmaci biologici, in particolare gli anti-TNF-alfa.
Nel rapporto esistente tra malattie reumatiche e rischio CV, alcuni aspetti appaiono di particolare rilevanza e meritevoli di approfondimento. Tra questi:
— valutazione del legame tra la flogosi nelle malattie reumatiche e le malattie cardiovascolari (MCV), nonché del potenziale predittivo di rischio CV, dei marcatori dell’infiammazione;
— valutazione del legame tra un alto grado – come si osserva nei reumatismi infiammatori cronici in fase attiva – piuttosto che un basso grado di flogosi e la cardiopatia ischemica;
— sulla base delle raccomandazioni riportate nelle linee guida EULAR 2009, l’opportunità di implementare un programma di screening del rischio CV, nei pazienti con artrite reumatoide (AR) ed altri reumatismi infiammatori, e la sua valutazione attraverso strumenti come il Systematic Coronary Risk Evaluation (SCORE);
— valutazione dell’effetto della terapia con farmaci biologici sulle MCV e sul livello di rischio CV.
2012
- Farmaci biologici ed epatiti da virus B e C
[Articolo su rivista]
D’Errico, T.; Tirri, E.; Favalli, E. G.; Garau, P.; Mancarella, L.; Paoletti, F.; Pomponio, G.; Sandri, Gilda; Scioscia, C.; Selvi, E.; Epis, O.
abstract
T
ra i virus epatitici definiti maggiori e minori, soltanto tre sono correlati all’insorgenza di infezioni croniche: il virus dell’epatite B (HBV, un virus a DNA trasmesso per via percutanea, sessuale, perinatale e parenterale inapparente), il virus dell’epatite C (HCV, un virus a ssRNA trasmesso prevalentemente per via percutanea) e il virus dell’epatite D (HDV, un virus difettivo a ssRNA che richiede la funzione helper di HBV ed è trasmesso per via percutanea, sessuale e perinatale). La terapia con farmaci biologici (in particolare con inibitori del TNF-α) è stata associata, in alcuni soggetti, alla riattivazione dell’infezione da HVB, con esiti potenzialmente fatali. Nel caso dell’infezione da HCV, non sono state segnalate alterazioni significative della funzionalità epatica correlate al trattamento con anti-TNF-α, ma la sicurezza a lungo termine dei farmaci biologici in questi pazienti non è ancora completamente nota. È quindi necessario adottare misure precauzionali nei confronti dell’infezione da HBV o HCV (con test di screening e, ove indicato, profilassi antivirale) prima di intraprendere un trattamento con farmaci biologici nei pazienti con AR.
2012
- L’infezione da papilloma virus umano (HPV) nei pazienti con artrite reumatoide trattati con farmaci biologici
[Articolo su rivista]
Selvi, E.; Mancarella, L.; Paoletti, F.; Pomponio, G.; Sandri, Gilda; Scioscia, C.; Tirri, E.; D’Errico, T.; Epis, O.; Garau, P.; Favalli, E. G.
abstract
L
’infezione da HPV, la più frequente infezione a trasmissione sessuale, è comune nella popolazione sia maschile sia femminile. Il virus è presente in molte varianti genotipiche (oltre un centinaio), con diversa patogenicità. Alcuni tipi di HPV possono causare lesioni benigne a carico degli epiteli squamosi, come verruche e condilomi, mentre altri hanno potenzialità oncogene e sono associati a tumori dell’apparato genitale. Il carcinoma della cervice uterina è il primo tumore umano riconosciuto dalla OMS come riconducibile totalmente ad un agente infettivo, con il DNA del virus HPV isolato nel 90-100% dei casi 1. Prima di raggiungere lo stadio di invasività, questo tumore a lenta evoluzione è preceduto da lesioni displastiche precancerose che possono essere identificate con Pap-test o altre metodiche (su cui si basano i programmi di screening). La maggior parte delle infezioni da HPV si risolve spontaneamente grazie alla risposta immunitaria di tipo cellulare. Nell’evoluzione tumorale, oltre alla presenza di genotipi ad alto rischio, pare assumano un ruolo importante fattori legati all’ospite, quali età, stato ormonale e familiarità
2012
- L’uso dei farmaci biologici durante la gravidanza e l’allattamento
[Articolo su rivista]
Favalli, E. G.; Mancarella, L.; Paoletti, F.; Pomponio, G.; Sandri, Gilda; Scioscia, C.; Selvi, E.; Tirri, E.; D’Errico, T.; Epis, O.; Garau, P.
abstract
M
olte malattie autoimmuni, tra le quali l’artrite reumatoide (AR), sono presenti con maggior frequenza nella popolazione femminile e colpiscono quindi molte donne in età fertile che contemplano la maternità. Per quanto vi sia spesso una tendenza al miglioramento dei segni e sintomi della malattia durante la gravidanza, non sempre è possibile la sospensione completa dei trattamenti. Il potenziale rischio di tossicità per il feto legato alla terapia va rapportato con la necessità di controllare l’attività della malattia nella madre, che può costituire essa stessa un fattore di rischio indipendente per esiti sfavorevoli della gravidanza 1. Il tema della gestione terapeutica ottimale della paziente in preparazione della, o durante, la gravidanza e il periodo post-partum è complesso e destinato ad assumere importanza sempre maggiore con il numero crescente di pazienti reumatologiche che, grazie ai miglioramenti nello stato di salute resi possibili dalle nuove terapie (con particolare riferimento ai cosiddetti farmaci biologici), sono più propense a pianificare una famiglia. In generale, vi sono 5 categorie di rischio per l’utilizzo di farmaci in gravidanza secondo la classificazione della Food and Drug Administration (FDA), riassunte nella Tabella I. Essenzialmente, vi è una carenza di dati sulla sicurezza delle terapie biologiche durante la gravidanza e l’allattamento. Queste due condizioni costituiscono un criterio di esclusione costante negli studi clinici randomizzati controllati registrativi, e le informazioni disponibili sugli effetti della somministrazione di terapie durante la gravidanza o l’allattamento sullo sviluppo fetale e sul neonato provengono esclusivamente da case report e registri. Inoltre, l’introduzione dei farmaci biologici è relativamente recente, per cui l’esperienza clinica accumulata in questo ambito è ancora scarsa. Nessun farmaco biologico, quindi, rientra nella categoria di rischio A, per quanto i dati finora disponibili siano complessivamente favorevoli.
2012
- Reazioni cutanee e terapia con anti-TNF-α
[Articolo su rivista]
Mancarella, L.; Meliconi, R.; Sandri, Gilda; Scioscia, C.; Selvi, E.; Tirri, E.; D’Errico, T.; Epis, O.; Favalli, E. G.; Garau, P.; Paoletti, F.; Pomponio, G.
abstract
I dati sulle reazioni avverse di tipo cutaneo durante il trattamento con inibitori del TNF-α sono piuttosto limitati, e provengono soprattutto da case report o casistiche spesso esigue. Questo argomento è stato approfondito in una review di Moustou et al., in cui sono stati valutati 91 studi di varia natura in cui venivano analizzate le manifestazioni dermatologiche sviluppatesi in corso di terapia con anti-TNF-α 1. In questa analisi si è anche tentato di stabilire la forza dell’associazione tra evento descritto e uso del farmaco (definita, forte, moderata o debole) in base a criteri quali: il tipo di studio, il numero di farmaci inibitori del TNF-α descritti in associazione ad uno specifico evento, il numero delle malattie infiammatorie trattate con i farmaci durante la cui assunzione è comparso l’effetto avverso e l’eventuale risoluzione della lesione con sospensione del farmaco o ricomparsa del fenomeno alla ripresa della stessa terapia.
2012
- Tempi di sospensione dei farmaci biologici nello switch terapeutico e nella programmazione degli interventi chirurgici
[Articolo su rivista]
Selvi, E.; Pomponio, G.; Sandri, Gilda; Scioscia, C.; Tirri, E.; D’Errico, T.; Epis, O.; Favalli, E. G.; Garau, P.; Mancarella, L.; Paoletti, F.
abstract
N
onostante l’efficacia dimostrata in questi anni dalle terapie biologiche nel ri-
durre i sintomi e nel ritardare o prevenire il danno articolare nei pazienti con artrite reumatoide (AR), è emerso da subito come non tutti gli agenti biologici abbiano lo stesso tipo di efficacia o tollerabilità in tutti i pazienti. Si è osservato che circa il 30% dei pazienti trattati con anti-TNF-α non raggiunge un miglioramento del 20% secondo i criteri dell’American College of Rheumatology (ACR20) per mancanza di efficacia primaria, mentre un’ulteriore percentuale di pazienti ottiene una risposta solo parziale o perde la risposta inizialmente raggiunta, oppure manifesta problemi di tossicità tali da richiedere l’interruzione del trattamento 1. Lo switch tra farmaci biologici è considerato da tempo una delle strategie terapeutiche più utilizzate per superare questi problemi, facilitato dalla disponibilità di un numero sempre crescente di agenti biologici. Agli inibitori del TNF-α in uso da più tempo (etanercept, infliximab e adalimumab) si sono affiancati nuovi anti-TNF-α (golimumab e certolizumab) e agenti mirati all’inibizione di altre componenti del processo infiammatorio, quali rituximab, abatacept e tocilizumab. Nonostante il ricorso massiccio in ambito clinico alla pratica dello switch terapeutico, la maggior parte dei dati relativi a questo aspetto proviene da studi non controllati e retrospettivi, e non è ancora chiaro quali siano le strategie ottimali riguardo sia alle sequenze preferenziali, sia alle modalità di passaggio da una terapia all’altra.
2011
- Epstein-barr virus reactivation after infliximab in rheumatoid arthritis: a case report.
[Articolo su rivista]
Colaci, Michele; Sebastiani, Marco; Sandri, Gilda; Meacci, M; Ferri, Clodoveo
abstract
TNF-alpha blockers represent one of the most important therapeutic strategies for rheumatoid arthritis, but their use has raised the question about their safety profile, particularly in respect to viral infections/reactivations. We describe the case of a patient who developed a symptomatic EBV reactivation 11 days after the first infusion of infliximab.
2011
- The discrepancy between clinical and ultrasonographic remission in rheumatoid arthritis is not related to therapy or autoantibody status.
[Articolo su rivista]
Sandri, Gilda; Mascia, Maria Teresa; Spinella, Amelia; G., Carpenito:
abstract
To evaluate the clinical remission by means of power Doppler ultrasonographic (PDUS) monitoring in a group of patients with rheumatoid arthritis (RA) in clinical remission (DAS28 < 2.6). The study included 54 patients with RA in therapy with DMARDS, anti-TNF, or no therapy in clinical remission according to ACR criteria and DAS 28 < 2.6 for at least 6 months. All patients had active wrist or hand inflammation in the past. US examination evaluated the presence of active synovitis, power Doppler signal, and synovial hypertrophy on the following bilateral joints: metacarpophalangeal-proximal interphalangeal joints-flexor tendons (on 2°-3° fingers) and wrist (radiocarpal and midcarpal joints). In 19 patients, there was an agreement between clinical and US parameters. However, 35 patients with clinical remission showed a positive ultrasonographic assessment and at least an active parameter. No statistic correlation was found between US examination and antibody assessment (anti-CCP and/or RF). Patients in therapy with anti-TNF or other therapies showed similar US assessment without significant statistical differences. Among eleven patients that presented swollen and tender joints at the latest physical examination, which preceded US exam, just 5 patients had an US confirmation too. In the other patients, the PDUS did not confirm the presence of inflammation in the corresponding swollen and tender joints or showed a positive ultrasonographic assessment in other locations. The remission state is a great therapy target and not only through the biological therapy. Synovial inflammation could persist independently from type of therapy or autoantibody status
2010
- IS THERE A DISSOCIATION BETWEEN CLINICAL REMISSION AND ULTRASONOGRAPHIC ASSESSMENT IN RHEUMATOID ARTHRITIS?
[Abstract in Rivista]
Sandri, Gilda; Mascia, Maria Teresa; Spinella, Amelia; G., Carpenito
abstract
Background: Achieving remission is the aim of treatment in RA. Modern joint imaging improves the accuracy of remission measurement in RA; In particular Power Doppler Ultrasonographic (PDUS) findings may have a predictive value in disease activity and radiologic outcome.Objectives: To Evaluate and to confirm the clinical remission and the absence of synovial inflammation by means PDUS monitoring.Rheumatology Unit of Modena was the promoter of the URAR study (Ultrasound evaluation in RA patients with clinical remission) national group that aims to this target.Methods: The patients were recruited in the Rheumatology Unit of Modena and they were chosen sequentially in the rheumatologic out-patient's department dedicated to arthritis.The study included 54 patients (10 men, 44 women) with RA in therapy with DMARDS, anti-TNF or no therapy in clinical remission according to ACR criteria and DAS 28 < 2.6. All patients had active wrist or hand inflammation in the past. US examination evaluated the presence of active Synovitis (ACD), Power Doppler (PD) signal and Sinovial Hypertrophy (SH) on the following bilateral joints: Metacarpophalangeal – Proximal Interphalangeal joints – Flexor tendons (on 2°-3° fingers) and Wrist (radiocarpal and midcarpal joints). Scores and scales have been chosen according to the literature (1)Results: 19 patients (35.2%) displayed a negative US evaluation in the meaning of an agreement between clinical and US parameters. However 35 patients (64,1%) with clinical remission showed a positive ultrasonographic assessment and at least an active parameter (ACD, PD, SH). No correlation was found between US examination and antibody assessment (anti-CCP and RF): according to the statistic function "Half-Normal Plot" parameters are completely independent. Small differences were also found between patients in therapy with anti-TNF or other therapies (DMARDS, corticosteroids): they showed similar US assessment so that there is no statistical significance in the comparison between the two groups. Among eleven patients that presented swollen and tender joints at the latest physical examination which preceded US exam just 5 patients had a correspondence at the US: positive joints at the clinical evaluation showed a US confirmation too. Otherwise the other patients had a mismatch between clinical assessment and the PDUS: it did not confirm the presence of inflammation in the corresponding swollen – tender joints or showed a positive ultrasonographic assessment in other locations.Conclusion: The remission state is a great therapy target and its attainment seems to be possible and not only through the biological therapy.Clinical remission is not always confirmed by US evaluation, therefore it is not possible to exclude a complete absence of synovial inflammation just on the base of DAS 28 value. It seems particularly interesting the mismatch between clinical assessment and PDUS: according to this finding an integration between clinical and US results seems to be useful to guide clinical procedure and disease monitoring.
2009
- ANTI - TUMOR NECROSIS FACTOR ALPHA (ANTI-TNF) DRUGS IN RHEUMATOID ARTHRITIS: COMPARISON ON DISEASE MANAGEMENT BEFORE AND AFTER THE INTRODUCTION OF THESE BIOLOGICAL DRUGS IN MODENA, ITALY
[Abstract in Rivista]
Sandri, Gilda; Ferri, Clodoveo; L., Belletti; M., Giunti; A., Caruso; S., Venturi; Mascia, Maria Teresa
abstract
Background: Anti-Tumor Necrosis Factor alpha (anti-TNF) drugs markedly improved the therapeutic approach to Rheumatoid Arthritis (RA) and consequently the quality of life of these patients.Objectives: Aim of the present study was to compare the disease progression in RA patients treated before and after 2000, when anti-TNF drugs were introduced in our Rheumatology Unit.Methods: We currently follow a standardized protocol; namely, at our RA clinic all patients were carefully monitored with clinico-serological evaluation every 3 months; only patients with DAS-28 > 5.1, unresponsive to standard treatments, are treated with anti-TNF drugs. A study was performed in 2000 on 100 consecutive patients (F 81/M 19) with RA that came to the attention of our Department and was repeated in 2007 (F 82/M 18). All patients were evaluated by Disease Activity Score (DAS-28) and by Health Assessment Questionnaire (HAQ), both tests internationally accepted.Results: Patients in the first group (year 2000) had an average age of 63.5, disease presence for 14.3 years on average, DAS-28 of 4.47±0.98, HAQ of 1.5±0.7. Only 2 patients showed a DAS-28 lower than 2.6 whereas 25 patients had a DAS-28 higher than 5.1. These data are substantially similar to those emerging from a similar study published by Pincus (1), based on American population in the same years (paper published in 2007 but referred to a comparison between patients with RA followed in the United States in 1985 and in 2000). Patients in the second group (year 2006) had an average age of 60, disease presence for 13.1 years on average, DAS-28 of 3.45±1.1, HAQ of 1.09±0.7 DAS-28 was lower than 2.6 in 27 patients (9 of them on treatment with anti-TNF) DAS-28 was higher than 5.1 in 11 patients (2 of them on treatment with anti-TNF).No statistical differences, with regard to DAS-28 or HAQ, was uncovered among patients of the second group treated with standard treatments or on therapy with anti-TNFdrugs.Conversely first and second group showed a statistically significant difference for both DAS-28 index and HAQ index (p <0,001).Conclusion: These data clearly show that in 2000 disease progression was significantly worse than in 2007. A close and careful follow-up of the disease and the inclusion in a biological-drug therapy protocol with anti-TNF drugs only when necessary (DAS-28 > 5.1) improves disease activity and quality of life; this approach has enabled a better management of RA, bringing from 2% of 2000 to 27% of 2007 the cases in which the disease can be considered in remission (DAS-28 < 2.6).
2009
- ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCA): THE RELATIONSHIP BETWEEN SEX, AGE AND ANTIGENIC SPECIFICITIES
[Abstract in Rivista]
F., Lumetti; Sandri, Gilda; A., Melegari; Ferri, Clodoveo; Mascia, Maria Teresa
abstract
Background: ANCA are specific and sensitive markers for different vasculitides, i.e.Wegener granulomatosis (WG), Churg Strauss syndrome, microscopic polyangiitis (MPA), for which the term ANCA-associated systemic vasculitis (AASV) is generally used. In patients with systemic vasculitis a significant prevalence of one major antigenic specificities of ANCA, namely proteinase 3 (PR3) or myeloperoxidase (MPO), is now well established. However, the relationships between sex, age and antigenic specificities of ANCA in seropositive patients have not been adequately investigated. Some authors did not find significant difference of gender in ANCA-positive patients, while a study in the Chinese population (1) reported that female patients were younger compared to males.Objectives: to assess possible differences of age and sex in patients with serum anti-Pr3 or anti-MPO antibodies.Methods: We retrospectively evaluated 10.671 serum samples, from a total of 6015 patients, consecutively examined at the laboratory of our hospital from 2003 to 2007 using antigen-specific direct ELISA (PR3- and MPO-ANCA, Hycor company, Great Britain). A cut-off >20 units for used for both autoantibodies.Results: a total of 57 seropositive patients (28M, 29F; mean age 60.7±21yrs) were identified. Among these, 39 patients showed a classical AASV (68%), while 18 affected by other autoimmune diseases (32%). Considering specific autoantibody seropositivity, we found 29 patients with serum anti-PR3 (M/F 17/12, mean age 54±22yrs) and 28 patients with anti-MPO (M/F 11/17,average age total 67±10yrs).There is no difference in gender and the average age of females and males is similar in ANCA-positive patients. There was no correlation between mean age of females and antigenic specificity (65±20yrs vs. 63±13yrs years; respectively), while anti-PR3-positive men were significantly younger compared to anti-MPO-positives (47±20yrs vs. 73±5.yrs) p=0. 001).Conclusion: In the literature, patients with WG are younger than those with MPA, but if we consider the ANCA specificity only males anti-PR3, but not females, are younger than those anti-MPO-positive. These findings, including the results of the present study, remain very difficult to explain. Molecular biology studies on larger patients' populations could better verify their correlations with clinico-epidemiological and demographic features of AASV patients.
2008
- Detection of autoimmunity in early primary Epstein-Barr virus infection by Western blot analysis
[Articolo su rivista]
Mascia, Maria Teresa; Sandri, Gilda; Guerzoni, C; Roncaglia, R; Mantovani, G; Ferri, Clodoveo
abstract
AbstractObjectivesThe Epstein-Barr virus (EBV) represents a potentially important factor in the pathogenesis of certain autoimmunedisorders such as systemic lupus erythematosus (SLE), and Sjögren’s syndrome, probably through a ’s molecular mimicrymechanism. Several studies have focused on the relationship between previous EBV infection and clinically overtconnective tissue diseases (CTDs), while the aim of this study was to investigate the immunological alterations during theearly phase of primary acute EBV infection by means of ENA Western blotting (WB) analysis. This technique is able todetect a wide spectrum of anti-ENA autoantibodies, potentially directed against diverse epitopes of the same antigen.MethodsSera from 54 subjects (F/M=24/30, mean age 17±6 SD years) with primary acute EBV infection were analysed usingindirect immunofl uorescence (IF) on Hep-2 cells for ANA, and both ELISA and WB for ENA.ResultsOnly 8 ANA+ and no ENA+ were found by means of IF and ELISA techniques, respectively; however, one or more ENAautoantibodies were detected in 24/54 (44%) sera using WB. The autoantibodies were no longer present at the secondevaluation. Subjects with immunological alterations had not developed any signifi cant clinical manifestations at a 5-yearfollow-up.ConclusionsThis study demonstrated the appearance of autoantibody production in a high proportion of individuals with primaryacute EBV infection; interestingly, the observed serological subsets are quite similar to clinical SLE clusters. Moreover,the absence of immunological disorders during the follow-up reinforces the role of multiple genetic and/or environmentalco-factors in the pathogenesis of CTDs.
2008
- EXPERIENCE OF MULTIDISCIPLINARY TEAM FOR COMPLEX HAND FUNCTION PROBLEMS AT THE RHEUMATOLOGY OUTPATIENT CLINIC OF MODENA
[Abstract in Rivista]
Mascia, Maria Teresa; Sandri, Gilda; A., Marcuzzi; S., Sartini
abstract
Orthopedic surgery (OS) is an integral part of the total management programme for patients with rheumatic disease (RD). Indication for synovectomies as well reconstructive surgery in RD should be based on a joint decision between the patient, the rheumatologist, the orthopaedic surgeon as well as other health professional. The proposed functional activities of the patients and their own personal goals should be taken into account. Consequently, the package of care should be individual and tailored to the persons identified needs.In 2006 in Academic Hospital of Modena, Italy, at the Rheumatology outpatient clinic a multidisciplinary team has been performed consisting of rheumatologists, hand surgeon, physiatrist, and hand physiotherapist, occupational therapist). Rheumatologists normally are responsible for referring the patients on to others specialists. The team works together to evaluate patients affected by chronic inflammatory diseases (rheumatoid arthritis - RA, spondyloarthropaties - Spa, microcristalline arthropathy) or connective tissue diseases with complex hand function problems.The discussion during the visit and the execution of the various tests have enabled patients to understand functional changes that the disease has caused and has made them more available to use splints or to undergo surgery.At the end of the diagnostic and functional study 19 patients were sent to the surgery (9 synovectomies, 10 reconstructive surgeries) while the others received physiotherapy/rehabilitation appropriate to their needsConclusion: These aspects support a team approach in the planning and performance procedures in patient with rheumatic diseases; ideally, orthopaedic surgeon, physiatrist, and rheumatologist as well as the multidisciplinary team should work together in a functional musculoskeletal unit with a multidisciplinary approach.Patients showed to appreciate this approach.
2008
- Patient characteristics of HCV-negative mixed cryoglobulinemia (MC) in Italy and Holland
[Abstract in Rivista]
Mascia, Maria Teresa; Ferri, Clodoveo; Sandri, Gilda; Willems, H; Tervaert, Jw
abstract
A striking association between Mixed Cryoglobulinemia (MC) and Hepatitis C Virus (HCV) infection has already been established by means of clinico-epidemiological and laboratory studies. The HCV-associated MC is more common in Southern Europe than in Northern Europe or Northern America; it is probably due to the endemic presence of HCV infection, as well as to unknown environmental and/or predisposing genetic co-factors. The etiopathogenesis and epidemiology of HCV-negative MC, an heterogeneous group of diseases consisting of a small number of 'essential' MC, various autoimmune-lymphoproliferative disorders and MC associated with infectious agents of scarce clinical relevance, remain still widely unknown. While HCV represents the major etiological agent of MC in the Mediterranean area, particularly in Italy, patients with HCV-negative MC are more frequent in areas where the overall prevalence of the disease is significantly low and less frequent its association with HCV.The purpose of this study is to compare patients with HCV-negative MC type II followed in Italy with Dutch patient's series with regard to their clinical characteristics and associated disorders.Overall clinical characteristics of HCV-negative MC are similar to that recorded in different patient's series of the HCV-positive MC except a lower percentage of purpura (52% vs 81%). No differences between Italian and Dutch patients were uncovered in this study except that nephropathy is significantly more frequent in Holland. The diagnosis of essential HCV-negative MC is more frequent in Holland than in Italy (42% versus 18%). These data suggest that one or more unknown infectious agent might be implicated in the etiopathogenesis of Dutch EMC patients. Finally, ‘essential’ MC represent a charming challenge for future etiopathogenetic studies.
2007
- Immunodeficiency and autoimmune phenomena in female hyper-IgM syndrome
[Articolo su rivista]
Melegari, A; Mascia, Maria Teresa; Sandri, Gilda; Carbonieri, A.
abstract
We report an unusual case that highlights the clinical problemsassociated with autoimmune phenomena. A female (born 1972) was referred to our hospital with systemic lupus erythematosus (SLE) diagnosis. During the follow-up (7 years),we observed the appearance and the disappearance of a lot of autoantibodies detected. The history of recurrent bacterial sinopulmonary infections since puberty and enlargement of lymphonodes, elevated IgM, very low IgA and normal IgG levels, and the variable autoantibody profile oriented toward a “defective Ig class switch recombination” disorder: the hyper-IgM syndrome. Immunodeficiency and autoimmune phenomena may occur concomitantly in the same individual and sometimes the differential diagnosis is difficult.
2007
- Indicazioni chirurgiche alla artrodesi totale di polso nei pazienti affetti da artrite reumatoide.
[Abstract in Rivista]
A., Marcuzzi; S., Sartini; Mascia, Maria Teresa; Sandri, Gilda; L., Chirila; Ferri, Clodoveo
abstract
Indicazioni chirurgiche alla artrodesi totale di polso nella sinovite reumatoide
2007
- Non HCV-related mixed cryoglobulinemia
[Articolo su rivista]
Mascia, Maria Teresa; Ferrari, D; Campioli, D; Sandri, Gilda; Mussini, C; Ferri, Clodoveo
abstract
A striking association (>90%) between mixed cryoglobulinemia (MC) and hepatitis C virus (HCV) infection has been established by means of clinico-epidemiological and laboratory studies. However, little information is available as regards the etiopathogenesis and the actual percentage of HCV-negative MC. This latter seems to be more frequent in the same geographical areas where the overall prevalence of MC is low. In 195 Italian patients with serum mixed cryoglobulins consecutively analyzed at the laboratory of our hospital, during one year, the prevalence of HCV-negative MC was 15,9%. Moreover, we evaluated the clinico-serological characteristics of our whole series of 65 HCV-negative MC patients: ‘essential’ MC was present in only 25%, while the majority of cases showed different connective tissue diseases or neoplastic disorders. Interestingly, patients with Sjögren’s syndrome or lymphoma had higher levels of cryocrit with cryoglobulinemic syndrome comparable to that found in HCV-positive MC patients.MC is a multifactorial disorder; considering possible etiological factors and clinical associations the disease may present different subsets: the prevalent group of HCV-positive MC; HCV-positive MC associated to different autoimmune-lymphoproliferative disorders; two MC subsets without any apparent causative agent: those with well-known autoimmune-lymphoproliferative disorders and the rare cases of ‘essential’ MC; and finally MC associated with other infectious agents.
2004
- HCV associated cryoglobulinemic vasculitis
[Abstract in Rivista]
Ferri, Clodoveo; Mascia, Maria Teresa; Ghinoi, A; Ferrari, D; Giuggioli, D; Sebastiani, Marco; Sandri, Gilda; Manzini, C; Zignego, A.
abstract
Definition: Cryoglobulinemic vasculitis (CV) is an immune-complex-mediated systemic vasculitis; its histopathological hallmark is the leukocytoclastic vasculitis involving small-sized vessels.Clinical features: Besides the typical clinical triad - purpura, weakness, arthralgias -, the most frequent manifestations of CV are peripheral neuropathy, hepatitis, glomerulonephritis, Raynaud's phenomenon, sicca syndrome, and skin ulcers (Table). Moreover, in a limited but significant percentage of individuals (10-15%) the disease can be complicated by a malignancy, i.e. B-cell lymphoma, and less frequently hepatocellular carcinoma or thyroid cancer.CV and HCV infection: A striking association between CV and hepatitis C virus (HCV) infection has been established by means of clinico-epidemiological and laboratory studies. Due to its multiform clinico-pathological features (Table), CV can be regarded as a crossing road between autoimmune disorders and malignancies (B-cell lymphomas, liver and thyroid cancer). On these bases, a pathogenetic link among HCV and other autoimmune-lymphoproliferative disorders has been also investigated; namely, Sjogren's syndrome, polyarthritis, glomerulonephritis, endocrine disorders, B-cell lymphomas, etc. There is a great geographical etherogeneity in the prevalence of different HCV-related diseases, suggesting a possible contribution of other unknown environmental and/or genetic co-factors.Pathogenesis: HCV is a lymphotropic virus; the presence of active or latent viral replication in the peripheral lymphocytes may explain the B-lymphocyte proliferation observed in HCV-related CV. Given the biological properties of HCV, viral genomic sequences cannot be integrated into the host genome. HCV could trigger the immunological alterations only indirectly by exerting a chronic stimulus to the immune system through viral proteins (E2, core, NS3, NS4, and NS5A), HCV-induced autoantigens and/or molecular mimicry phenomena. In particular, HCV envelop protein E2, able to bind CD81 molecule expressed on B-lymphocytes, might be involved in the first steps of HCV-driven autoimmune and lymphoproliferative phenomena. The interaction between HCV-E2 and CD81 may increase the frequency of VDJ rearrangement in antigen-reactive B-cell. In this context the T(14;18) translocation, demonstrated in a significantly high percentage of HCV-related CV patients, leads to the activation of anti-apoptotic Bcl-2 protoncogene responsible for extended B-cell survival. Consequently, B-lymphocyte expansion may produce a variety of autoantibodies and immune-complexes, including mixed cryoglobulins.Prognosis: Patients with CV show a relatively benign clinical course in over 50% of cases; however, the cumulative 10th year survival is significantly worse if compared to general population (56.3 vs 93.4%; p<.001). In addition, significantly lower survival rates are observed in males and in subjects with renal involvement.Treatment: For a correct therapeutic approach to HCV-related CV we must deal with conflicting conditions: HCV infection, autoimmune, and lymphoproliferative alterations. Therapeutic strategy of CV includes etiologic, pathogenetic, and/or symptomatic therapies, which should be tailored for the single patient according to the severity of clinical symptoms. Finally, a careful clinical monitoring of patients with CV is mandatory in all cases, with particular attention to neoplastic complications.References: 1. Gorevic PD, Frangione B. Mixed cryoglobulinemia cross-reactive idiotypes: implication for relationship of MC to rheumatic and lymphoproliferative diseases.
2001
- Le crioglobuline miste: epidemiologia, clinica ed eziopatogenesi. Contributo personale.
[Articolo su rivista]
Mussini, C.; Ghini, M.; Mascia, Maria Teresa; Zanni, G.; Sandri, Gilda; Campioli, D.; Bonacorsi, G.; Artrusi,
abstract
The study of cryoglobulinemic syndromes carried out over the years by our research group has been wide-ranging and includes:1 immunochemical characterisation of the cryoimmunoglobulin, 2) histological and immunoistochemical study of bone marrow, 3) role of HCV, 4) HCv, cryoglobuinaemia and monoclonal gammopathies, 5) HCV, mixed cryoglobulinemia and lymphoprolifaration, 6) natural history and epidemiology of type II mixed cryoglobulinaemia, 7) followup of patients with cryoglobulinemic syndrome.Our most important achievements have been in the demostration of the monoclonal nature of symptomatic tipeII mixed cryoglobulinemia (igMk-IgG) associated with medullary aspects of nodular clonal B expansion. The subsequent report ( at the beginning of the 90s) of anti-HCV antibodies in the course of essential mixed cryoglobulinemia (EMC) was confirmed by us on a target population of 180 patients enlisted with the help of various medical and specialist department of Modena Policlinic and of hospitals in the Modena area. Accordingly we postulated a possible aetiopathogenetic role of the virus with respect to the aspects of clonal expansion. At the same time our case studies of patients qith monoclonal gammopathies, without cryoglobulinemic activity failed to reveal any connenction with HCV infection. Our findings qhich were followed up over a period of time by clinical, laboratory and instrumental checks, enabled us to show that nodular clonal B expansion, present in 75% of the HCV -correlated MCII cases, remains unchanged over time and that clinical manifestations of lymphoma do not appear; death in these cases is due mainly to vasculitis and/or infectious process. In conclusion, therefore HCV-correlated MCII must be seen as an autoimmune systemic disease of infectious origin in which bone-marrow complications are an expression of chronic viral stimulation.
2001
- Sanitary costs of osteoarthritis
[Articolo su rivista]
Leardini, G; Mascia, Maria Teresa; Stisi, S; Sandri, Gilda; Franceschini, M.
abstract
Muscoloskeletal disorders are the first cause of disability and the second cause of permanent disablement in Italy. Osteoarthritis is the most frequent rheumatic disease and affects about 4 million Italians. In spite of that, data concerning social costs are lacking. On account of this lack we measured sanitary costs of 314 patients suffering from osteoarthritis. A retrospective, prevalence-based multicentric study was performed using a bottom-up approach. The study period was 12 months and referred to 1999. Eight percent of patients didn't take any drug for the treatment of osteoarthritis; NSAIDs were prescribed to 86.9% of patients, analgesics to 29.9%, chondroprotective drugs to 7.6%, and gastroprotective drugs to 36.9%. Total sanitary costs came to 455 euro / patient / year: 122 euro were spent on diagnostics, 293 euro on therapy and 40 euro on management of drug-related gastropathy. Since the costs of anti-inflammatory drugs came to 30 euro we calculated iatrogenic cost factor of 2.3. Moreover, the study supplied interesting informations about prescriptive habits, which differ in Italy from international guidelines for the medical treatment of OA, about patient management, because of hospitalization, which by itself absorbs 1/3 of resources, and about physiotherapy, which costs twice as much as pharmacological therapy. At last, data analysis gave the cue for suggestions on changing patients' management