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Objectives: We aimed to investigate the effectiveness of tumour necrosis factor inhibitors (TNFi), anti-interleukin-17 or interleukin-12/23 monoclonal antibodies (anti-IL) on comorbidities in a cohort of patients with spondyloarthritis (SpA), using an average treatment effect (ATE) analysis., Methods: SpA patients from the multicentre Italian GISEA Registry were divided into groups according to pharmacological exposure: no treatment (G0), TNFi (G1) and non-responders to TNFi switched to anti-IL (G2). In each group, we recorded the prevalence and incidence of infectious, cardiopulmonary, endocrinological, gastrointestinal, oncologic, renal and neurologic comorbidities. Each comorbidity was then fitted for ATE and baseline features were evaluated for importance., Results: The main findings of this study comprising 4458 SpA patients relate to cancer, other gastrointestinal diseases (OGID) and fibromyalgia. ATE showed no increased risk of solid cancer in G1 (0.42 95% CI 0.20-0.85) and G2 (0.26 95% CI 0.08-0.71) vs. G0, with significantly higher incidence in G0 (14.07/1000 patient-years, p=0.0001). Conversely, a significantly higher risk of OGID and fibromyalgia was found in G1 (1.56 95% CI 1.06-2.33; 1.69 95% CI 1.05-2.68, respectively) and G2 (1.91 95% CI 1.05-3.24; 2.13 95% CI 1.14-3.41, respectively) vs. G0. No treatment risk reduction was observed in haematological malignancies, cardiovascular events and endocrinological comorbidities., Conclusions: Overall, our study confirms the safety of TNFi and anti-IL in SpA patients, albeit with some caveats pertaining to solid cancers, OGID and fibromyalgia. Furthermore, taking into consideration causality with observational data may yield more reliable and relevant clinical information.

Objectives: To examine the effectiveness of Janus-kinase inhibitors (JAKis) or abatacept (ABA) in patients with rheumatoid arthritis-interstitial lung disease (RA-ILD)., Methods: Patients with RA-ILD receiving JAKis or ABA were retrospectively evaluated at baseline and after 18 months of treatment. A computer-aided method (CaM) was used to assess the extent of high-resolution computed tomography (HRCT) fibrosis percentage. According to HRCT fibrosis changes, patients were classified as "worsened" (progression of 15% or more), "stable" (changes within 15%) or "improved" (reduction of 15% or more). Correlations between RA characteristics and JAKis or ABA responses were studied using a multivariate regression model., Results: Seventy-five patients (69.3% women) were evaluated, 31 received a JAKi while 44 received ABA. In the JAKis group, five patients (16.1%) showed RA-ILD progression, 20 patients (64.5%) were considered stable, and six patients (19.4%) demonstrated RA-ILD improvement. In the ABA group, five patients (11.3%) showed RA-ILD progression, 32 patients (72.7%) were stable, and seven patients (16.0%) demonstrated RA-ILD improvement. In both groups, the percentage of current smokers was different between those classified as "worsened" and those classified as "improved/stable" (p = 0.01). In multivariate regression analysis, current smoking habit (p = 0.0051) and concomitant methotrexate treatment (p = 0.0078) were the two variables related to RA-ILD progression in ABA-treated patients, whereas in JAKis-treated patients, the only RA-ILD progression-related variable was disease duration of RA (p < 0.001)., Conclusions: Treatment with JAKis or ABA was related to stability or improvement of RA-ILD in 83.9% and 88.6% of patients, respectively. RA duration is the only variable associated with worsening RA-ILD in JAKis-treated patients., (© 2022. The Author(s).)

Introduction: Interstitial lung disease in rheumatoid arthritis (RA-ILD) is an extra-articular involvement that impairs the prognosis and for which there is still no well-coded treatment. The aim of this study was to evaluate abatacept (ABA) effectiveness and safety in patients with RA-ILD., Methods: RA-ILD patients who started ABA treatment were consecutively enrolled. Chest high-resolution computed tomography (HRCT), clinical, laboratory and respiratory function variables were collected at baseline and after 18 months of ABA treatment. HRCT abnormalities were evaluated using a computer-aided method (CaM). ABA response was established based on the change in the percentage of fibrosis evaluated at HRCT-CaM, dividing patients into "worsened" (progression ≥ 15%), "improved" (reduction ≥ 15%), and "stable" (changes within the 15% range). The multivariate regression model was used to assess the associations between RA characteristics and ABA response., Results: Forty-four patients (81% women, mean age 59.1 ± 8.0, mean disease duration of 7.5 ± 3.1 years) were studied. Five patients (11.4%) showed RA-ILD progression, 32 patients (72.6%) were considered stable, and 7 patients (16.0%) showed an RA-ILD improvement. The proportion of current smokers was significantly different between "worsened" patients, respect to those defined as "improved/stable" (p = 0.01). Current smoking habit (p = 0.005) and concomitant methotrexate treatment (p = 0.0078) were the two variables related to RA-ILD progression in multivariate regression analysis., Conclusion: Treatment with ABA is associated with a RA-ILD stability or improvement in the 88.6% of patients. Current smoking habit and concomitant treatment with methotrexate are the modifiable factors associated with RA-ILD worsening. Key Points • Abatacept plays a favourable role in the control of RA-ILD, with a significant worsening in only 11.4% of patients during a 18-month follow-up period. • The predictive variables related to RA-ILD progression during abatacept therapy are the concomitant treatment with methotrexate and current smoking habit., (© 2021. The Author(s).)

Objectives: To evaluate the health-related quality of life (HRQoL), disease activity, treatment adherence, and work ability in the real-world setting in patients with axial spondyloarthritis (axSpA)., Methods: QUASAR was a prospective 12-month, observational study involving 23 rheumatology centres across Italy, including adult patients with axSpA according to the Assessment of SpondyloArthritis International Society (ASAS) criteria. Patients were followed at baseline, 3, 6, and 12 months for disease activity and health-related QoL (HRQoL), treatment adherence and work ability. Regression analysis was used to assess the association between treatment and outcome variables., Results: 413 (80.7%) out of axSpA 512 patients were diagnosed with ankylosing spondylitis (AS) and 99 (19.3%) with non-radiographic axSpA (nr-axSpA). Nr-axSpA and AS patients had similar baseline disease activity and HRQoL. Biologic disease-modifying anti-rheumatic drugs (bDMARDs) were the most frequent medication (n=426, 83.2%). Over the 1-year follow-up, disease activity measures (joint pain and swelling, CRP, global assessment, BASDAI, ASDAS), HRQoL and work ability significantly improved, while few differences emerged between nr-axSpA and AS patients. Treatment satisfaction and adherence questionnaires improved over the 12 months. Patients treated with bDMARDs showed improved outcomes for disease activity measures and HRQoL variables, greater benefit observed in patients with AS., Conclusions: We found clinical and HRQoL improvement over 1 year in a large, real-world population of nr-axSpA and AS patients treated with bDMARDs or conventional synthetic DMARDs.

Objective: The COVID-19 pandemic has raised questions about the management of systemic immunosuppressive treatments for rheumatic conditions. It is well known that rheumatic patients are at risk of developing infections because of their immunocompromised state. Moreover, drugs such as hydroxychloroquine or tocilizumab that are widely used to treat rheumatic diseases are now being used to treat COVID-19. The aim of this multicentre retrospective study of rheumatic patients in the Italian regions of Lombardy and Marche was to determine whether patients receiving biological or small molecules treatment are more susceptible to the development of COVID-19 than the general population., Methods: The local registry data of 10,260 rheumatic patients being treated with bDMARDs or small molecules were evaluated from 15 March to 23 April 2020. The final analysis was based on the registry data relating to 7.204, telephone contacts and/or outpatient visits., Results: Forty-seven of the 7.204 patients were diagnosed with COVID-19, seven of whom died; the patients who had symptoms resembling those of COVID-19 but had negative swabs were considered negative for the disease. The overall infection rate was 0.65, and the crude case fatality risk (CFR) in the patients with COVID-19 was 14.9%. There was no difference in the mortality rate among the patients receiving the different individual biological drugs or small molecules., Conclusions: Our findings suggest that the susceptibility of rheumatic patients to COVID-19 is the same as that of the general population, but confirm that age, disease duration, and the number of co-morbidities are associated with an increased risk of a severe form of the disease. It seems that immunosuppressants drugs do not effectively represent a risk factor for COVID- 19., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the clinical effectiveness of golimumab in biologic inadequate responder (IR) patients with Rheumatoid arthritis (RA), Spondyloarthritis (SpA), and Psoriatic arthritis (PsA)., Methods: We analyzed 1424 patients on golimumab from the GISEA registry. Drug survival was estimated by Kaplan-Meier analysis in biologic-naïve, 1-biologic IR, ≥2-biologics IR patients. Hazard ratios (HRs) of discontinuing golimumab at 2 years were assessed by multivariate Cox regression. Patients achieving CDAI based low disease activity (LDA) or BASDAI<4 were calculated at 6 and 12 months., Results: In RA (n.370), the 2-years survival on golimumab was 61.4% in 1-biologic IR, 51.9% in≥2-biologics IR, and 73.1% in biologic-naive patients (P=0.002 vs≥2-biologics IR). In SpA (n.502), the survival was similar among 1-biologic IR (80%), ≥2-biologics IR (76.5%), and biologic-naive (74.6%) patients (P>0.05). In PsA (n.552) the survival was 72% in 1-biologic IR, 72.5% in≥2-biologics IR, and 71.8% in naïve-biologic (P>0.05). Predictors of golimumab discontinuation were monotherapy (HR 1.65) for RA, female gender for SpA (HR 2.48) and PsA (HR 1.57). In RA, patients on CDAI-LDA were lower in 1-biologic IR (40%) or≥2 biologics IR (40%) than in biologic-naïve (60%) group at 6 months (P=0.02), but no difference was observed at 12 months. In PsA and SpA, the percentage of patients on CDAI-LDA or BASDAI<4 at 6 months was almost identical across the subgroups., Conclusions: Golimumab had similar effectiveness in biologic-failure and biologic-naïve SpA and PsA, but seems to be less effective in multi-failure RA patients, especially as monotherapy. The best outcomes were seen in male patients., (Copyright © 2020 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Background: Adherence is a key factor for therapeutic success in patients with rheumatoid arthritis (RA). The aim of this study was to determine whether results from the 5-item Compliance Questionnaire for Rheumatology (CQR5) can predict future poor adherence to biological disease-modifying anti-rheumatic drugs (bDMARDs) in patients with RA, using medication possession ratio (MPR) as the gold standard comparator., Methods: RA patients starting a bDMARD were prospectively followed for 12 months. At baseline, CQR5 was collected in relation to the prescribed bDMARD. Patients were dichotomised into good adherers and poor adherers, categories that were then used as the variable in a predictive function analysis of the CQR5 in order to determine the accuracy of the classification at the end of the study period in comparison with the MPR. The sensitivity, specificity, and likelihood ratio of detecting poor adherers were also determined because this is the clinically important purpose of the questionnaire. Satisfactory adherence was defined as > 80% compliance with the prescribed dose regimen., Results: Of the 210 RA patients enrolled (147 women and 63 men; mean age 58.6 ± 12.8 years; mean disease duration 7.4 ± 2.5 years), at the end of the 12-month follow-up, 152 patients (72.4%) were good adherers and 58 (27.6%) were poor adherers according to MPR. Predictive analyses showed that the sensitivity and specificity of the CQR5 in detecting poor adherence were respectively 89.9% (95% CI 84.07-94.10%) and 80.8% (95% CI 67.46-90.37%). The accuracy of the CQR5 was 83.04% (95% CI 77.27-87.85%), the positive likelihood ratio (i.e. detecting ≤ 80% adherence) 4.67 (95% CI 2.58-8.18), and the area under curve 0.85 (95% CI 0.79-0.89)., Conclusion: Higher baseline CQR5 scores significantly predict the treatment adherence of RA patients. This suggests that this instrument could be used for screening purposes in order to identify patients who are poorly adherent to bDMARDs.

Objectives: Recently, research has been focused on the identification of predictors of response to treatment in patients with active psoriatic arthritis (PsA). The objective of this study was to develop a model to predict the clinical response at 6 months in patients with PsA starting the anti-tumour necrosis factor-α golimumab., Methods: This prospective observational study explored a range of factors, including demographic data and baseline characteristics of the disease, measures of disease activity and functional disability, and potential laboratory biomarkers in the prediction of response, defined as the achievement of modified-minimal disease activity (mMDA), to golimumab in PsA patients., Results: We studied 151 PsA patients starting golimumab because of their active disease. After 6 months, the rate of drug persistence on golimumab was 80%, and mMDA was achieved in 44.3% of patients. Using univariate and multivariate logistic regression models, lower disease activity in PsA score (DAPSA) at baseline (odds ratio [OR] 0.92; 95% confidence interval [CI] 0.89-0.96, p<0.001) was independent predictor of mMDA at 6 months. High sensitivity C-reactive protein value (OR 1.06; 95% CI 1.00-1.13, p=0.026) at baseline also was a predictive factor of mMDA achievement at 6 months in the laboratory-enhanced prediction model. Golimumab was safe and well tolerated., Conclusions: The identification of factors predictive of response to treatment may help in better understanding the response to golimumab and in identifying PsA patients that are most likely to achieve mMDA following therapy with golimumab.

Purpose: Body mass index (BMI) demonstrated to influence the clinical response to different drugs in rheumatoid arthritis (RA). The aim of this study was to investigate the role of BMI in the achievement of remission in active RA patients starting the treatment with abatacept., Methods: Data regarding 130 RA patients enrolled in the UltraSound-CLinical ARthritis Activity (US-CLARA) study were retrospectively analyzed. Patients were assessed at baseline (when starting abatacept treatment) and at 3- and 6-months. An extensive clinimetric evaluation, including a new ultrasound (US)/clinical composite disease activity index, termed US-CLARA, was performed at every timepoints. Outcome of interest of the study was the impact of BMI on the achievement of the Disease Activity Score 28-joints erythrocyte sedimentation rate (DAS28-ESR) or the ACR/EULAR Boolean remission criteria at 6 month., Results: At 6-month 26 out of 130 patients were defined as responders to abatacept. Comparing the baseline characteristics of responders to non-responders, US-CLARA showed a statistically significant difference between the two groups. The logistic regression analysis showed that the two indipendent variables, predictive of treatment response (keeping the DAS28-ESR and/or Boolean remission criteria as dependent variable), were the self-tender joint count assessment (p = 0.0412) and the ultrasound score (p = 0.0211). No other baseline variable, notably BMI, was associated to 6-month abatacept response., Conclusions: BMI does not influence the abatacept response in RA patients with active disease. During abatacept treatment, the clinical response can be achieved despite a condition of overweight or obesity., (Copyright © 2019 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objectives: To determine the incidence of serious infections (SIs) among the spondyloarthropathy (SpA) patients from the "Gruppo Italiano per lo Studio delle Early Arthritis" (GISEA) registry and treated with tumour necrosis factor (TNF) inhibitors (TNFIs), and to identify the factors associated with the development of the infections., Methods: This observational study on 3321 GISEA-registered SpA patients collected real-world demographic and clinical data relating to their biological drug treatments. The overall incidence of infections was analysed by type of SpA., Results: A total of 3321 SpA patients (1731 males, 52.2%; mean age 47±13 years; median disease duration 3 years, interquartile range [IQR] 0-8) were eligible for inclusion in the analysis. Two hundred and fifty-nine patients experienced at least one of 391 microbiologically diagnosed SIs, 32% of which were recorded during the first 12 months of treatment. The overall incidence of SIs was 43.9/1000 patient-years of follow-up (95% confidence interval [CI] 39.6-48.4): 29.9/1000 (95% CI 23.1-38.1) among those treated with adalimumab (ADA); 36.1/1000 (95% CI 30.0-43.1) among those treated with etanercept (ETN); and 61.4/1000 (95% CI 53.3-70.5) among those treated with infliximab (INF). The highest incidence was observed among the patients with psoriatic arthritis (PsA), but the difference was statistically significant only in comparison with the patients with undifferentiated SpA (p=0.002), whose incidence of SIs was also lower than in the patients with ankylosing spondylitis (AS) (p=0.034). Multivariate models showed that the number of comorbidities (hazard ratio [HR] 1.29, 95%CI 1.2-1.4; p<0.001), age at the start of TNFi treatment (HR 0.99, 95%CI 0.97-0.99; p=0.030), steroid use (HR 1.40, 95%CI 1.1-1.8; p=0.012) and male sex (HR 0.72, 95%CI 0.5-0.9; p=0.012) were all statistically significant predictors of infection. The factors independently associated with a lower risk of SIs were the use of ETN (HR 0.52, 95%CI 0.4-0.7; p<0.001) or ADA (HR 0.59, 95%CI 0.4-0.8; p=0.002) rather than INF., Conclusions: The incidence of SIs was higher among patients with PsA or AS than among those with undifferentiated SpA, and among patients treated with INF than among those treated with ADA or ETN. Male sex, steroid use and the number of comorbidities were all factors predictive of SIs.

Background: The presence of neuropatic pain (NeP) is common in subjects with established Rheumatoid Arthritis (RA), and it can influence the disease remission. These aspects have not been investigated in patients with Early Rheumatoid Arthritis (ERA)., Objective: To investigate the effect of NeP on the achievement of remission in patients with ERA., Method: The study involved consecutive ERA patients with moderate or high disease activity. The painDETECT Questionnaire (PDQ), the 36-item Short Form Health Survey (SF-36), and the Euro- QoL-5 Dimensions (EQ-5D) were administered to all the patients, and their co-morbidity data were used to calculate their modified Rheumatic Disease Comorbidity Index (mRDCI). After six months' follow-up, the presence or otherwise of NeP in each individual patient was calculated, and whether or not the Boolean remission criteria were satisfied., Results: The study was completed by 115 patients (76% females) whose PDQ scores indicated that 13% had probable NeP. At the end of the follow-up period, 25 patients (21.7%) met the Boolean remission criteria. Logistic regression analysis showed that baseline PDQ scores (p=0.0023) and the mRDCI (p=0.0054) were the strongest predictors of not being in Boolean remission. Only one of the 15 patients with concomitant NeP achieved Boolean remission., Conclusion: The presence of NeP may affect the achievement of remission in ERA patients. The PDQ can be a useful tool to measure central pain sensitisation in such patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: To assess the impact of baseline modified Rheumatic Disease Comorbidity Index (mRDCI) a simple comorbidity count, on overall survival of treatments with biological drugs in patients affected with Rheumatoid Arthritis (RA), Spondyloarthritis (SpA) and Psoriatic Arthritis (PsA) in real-world settings., Methods: Patients (nr. 635) with RA (nr. 214), SpA (nr. 213) and PsA (nr. 208) starting a first biological drug were retrospectively analysed. mRDCI was scored at baseline, and disease characteristics were recorded at entry and at last observation. Drug retention was analysed using Kaplan-Meier curves. Cox regression models were used to estimate the association of baseline mRDCI with drug discontinuation and clinical outcomes, the achievement of clinical remission based on 28 joint-Disease Activity Score (DAS28) <2.6 for RA and PsA, and on Ankylosing Spondylitis-C-reactive protein Disease Activity Score (ASDAS-CRP) <1.3 for SpA., Results: Baseline mRDCI significantly correlated with the number of biological drug switches (rho 0.26). Persistence on biologic therapy was significantly higher in patients with mRDCI=0 (96.4%), than in those with mRDCI ≥2 (83.9%). Patients without comorbidities showed significantly higher drug survival rate in PsA (P = 0.0001) or SpA (P = 0.02), but not in RA. mRDCI was also found to be a predictor of definitive drug discontinuation (HR: 1.53) and of failure to achieve remission in RA (HR: 0.66) or PsA (HR: 0.77), and in SpA (HR: 0.43)., Conclusions: This study provided evidence that baseline mRDCI negatively impacts the persistence on biologic treatments and clinical outcomes in patients with RA, SpA and PsA in real-life settings., (© 2018 Stichting European Society for Clinical Investigation Journal Foundation.)

Objectives: To assess the validity of the rheumatoid arthritis impact of disease (RAID) for measuring disease activity of rheumatoid arthritis (RA) and to determine cut-off values for defining the disease activity states., Methods: A total of 622 RA patients from an European database have been included. Cross-validation was based on assessment of convergent and discriminant validity. Optimal cut-offs were determined against external criteria by calculating the respective 25th and 75th percentiles mean values of RAID. External criteria included definitions for remission (REM), low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA), cut-offs of the 28-joint disease activity score-C-reactive protein (DAS28-CRP) score., Results: The RAID showed a moderate degree of correlation with respect to DAS28-CRP (rho=0.417; P<0.0001). The receiver operating characteristic (ROC) curves to discriminate the ability of RAID to distinguish patients with active and non-active disease was very good with an area under the curve (AUC) of 0.847 (95% confidence interval [CI]: 0.816 to 0.878; P<0.0001). Based on the distributions of RAID in the different disease activity groups, we propose the following cut-off values for REM: RAID ≤3; for LDA: RAID >3 and ≤4; for MDA: RAID >4 and ≤6; for HDA: RAID >6. Mean RAID differed significantly between patients classified as REM, LDA, MDA or HDA (P=0.001)., Conclusions: The cut-offs revealed good measurement characteristics in cross-validation analysis, had great discriminatory performance in distinguishing patients with different levels of disease activity and are suited for widespread use in everyday practice application and research., (Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objectives: Targeted drugs against key pathogenetic molecules such as TNF-alpha have significantly improved outcomes in rheumatoid arthritis (RA). They are widely used in clinical practice and drug registries give us information to support their use. Adalimumab (ADA) is able to induce a comprehensive disease control in RA by achieving clinical, functional and radiographic control., Methods: By interrogating 2 Italian registries, LORHEN and GISEA, we analysed the efficacy of ADA in first- or second-line in a total of 2262 RA patients., Results: Patients in 1st line were significantly older, with lower disease activity and HAQ scores compared to 2nd line. In 1st line, rates of DAS28-remission (DAS28rem) at 2 years were 34.4% while 26.5% in 2nd line (p=0.038). A normal HAQ score (HAQ≤0.5) was achieved in 53.5% after 2 years in 1st line versus 30.1% in 2nd (p<0.0001). DAS28rem+HAQ≤0.5, a combined parameter that we defined global clinical disease control, was reached in 20.7% in 1st line versus 13.3% in 2nd (p<0.01). Five-year-survival on therapy was higher for patients in 1st line (45.6% vs. 33.2%, p<0.0001). Discontinuation due to lack of efficacy was lower in 1st line (37.4 vs. 54.4%, p<0.0001). Rates of adverse events were similar., Conclusions: Responses in 1st line are generally significantly better than after a first anti-TNF-alpha failure but patients in 2nd line have a worse clinical and functional profile. A global disease control with clinical and functional remission is an achievable target in both lines.

The purpose of the study was to estimate the clinical profile of naïve biological patients with rheumatoid arthritis (RA) starting adalimumab through 3-year calendar periods and their clinical outcomes such as drug survival and global clinical disease control (GCDC). RA patients starting adalimumab as first biological drug between 2003 and 2012 were subdivided in 3-year calendar periods. Survival on therapy was estimated using the Kaplan-Meier analysis. One and 2-year clinical response was assessed by calculating percentage of patients attaining GCDC (28-joint Disease Activity Score (DAS28) ≤ 2.6 + Health Assessment Questionnaire (HAQ) ≤ 0.5), low disease activity (DAS28 ≤ 3.2), remission (DAS28 ≤ 2.6) and good European League Against Rheumatism (EULAR) response. Multivariate regression models were used to assess baseline predictors of drug discontinuation or achievement of clinical remission. We recruited 1695 RA patients. Overall drug persistence at 3 years was 40.6 %, while the global rate of nonswitching patients was 54.7 %. Compared to 2003-2005, initiators in more recent years had a significantly lower 3-year crude drug retention rate (log rank, p < 0.0001) and a significantly higher rate of switching to alternative biologics (log rank, p < 0.0001). No difference in adverse events or effectiveness rate among the calendar periods was found. A substantial proportion of patients (up to 27 %) achieved GCDC at 2 years, regardless of the calendar period. In real-life setting, RA patients starting adalimumab in more recent years had a higher rate of drug discontinuation not related to ineffectiveness or side effects but to switching, probably due to a wider availability of biologics. A meaningful proportion of patients attained GCDC without any difference across calendar periods.

Background: The advent of Internet and World Wide Web has created new perspectives toward interaction between patients and healthcare professionals. Telemonitoring patients with rheumatoid arthritis (RA) is an emerging concept to guide the collaborative management treatment and improve outcomes in patients. The objective of this study was to investigate whether an intensive treatment strategy, according to a telemonitoring protocol, is more effective than conventional management strategy in reaching remission and comprehensive disease control (CDC) after 1 year in early rheumatoid arthritis (ERA) patients., Methods: Forty-four ERA patients were randomly allocated into two groups: the telemonitoring intensive strategy (TIS) group (group 1) or the conventional strategy (CS) group (group 2). Three patients refused to participate. In group 1 (n = 21), a remote monitoring system of disease activity, in combination with protocolised treatment adjustments aiming for remission was applied. In group 2 (n = 20), patients were treated according to daily clinical practice, with regular evaluation of disease activity, but without protocolised treatment adjustments. A telemedical care called "REmote TElemonitoring for MAnaging Rheumatologic Condition and HEaltcare programmes" (RETE-MARCHE), was developed to perform the remote monitoring., Results: A higher percentage of patients in the TIS group achieved CDAI remission vs patients in the CS group (38.1 % vs 25 % at year 1, p <0.01). Time to achieve remission was significantly shorter in the group 1 than in the group 2, with a median of 20 weeks vs a median over 36-weeks (p <0.001). Concordantly, the patients in group 1 showed a greater improvement (p <0.001), compared with group 2 in terms of functional impairment (71.4 % vs 35 %) and radiological damage progression (23.8 % vs 10 %), resulting in a greater rate of CDC (19.4 % vs 5 %)., Conclusions: According to our results, an intensive treatment strategy by telemonitoring leads to more effective disease remission and more rapid CDC than treatment according to conventional management strategy in ERA., Trial Registration Number: ISRCTN13142685 Date of registration: March, 17(th) 2016.

Background: Adherence to biologic therapy is relatively poorly studied in rheumatoid arthritis (RA) because many of the studies have investigated the drug persistence, which represents only a surrogate of adherence., Objectives: The aims of this study were to determine the extent of adherence in RA patients with subcutaneously administered anti-tumor necrosis factor methotrexate agents and to identify the risk factors for nonadherence., Methods: A cohort of RA patients who started a subcutaneous anti-tumor necrosis factor treatment were enrolled. After 12 months of treatment, all patients completed the 4-item Morisky Medication Adherence Scale questionnaire. Associations between beliefs and nonadherence and the influence of demographic, clinical, and radiographic features were assessed using logistic regression model., Results: A total of 209 (80.4%) of the 260 patients were included in the analyses. Forty-three of 209 patients were considered nonadherent to their medication (20.6%) according to the 4-item Morisky Medication Adherence Scale. More than half (53.1%) of patients showed at least 1 form of nonadherent behavior.The logistic model showed that low disease activity (P = 0.003), higher patient-physician discordance ratings (P = 0.012), older age (P = 0.041), and a high number of comorbid conditions (P = 0.011) were significantly associated with increased likelihood of nonadherence., Conclusions: The overall nonadherence with subcutaneous biologic therapy is relatively high among RA patients and should be taken into account when a patient's response to treatment is unsatisfactory.

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., (Copyright © 2014 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objectives: An educational programme was conducted in Italy in order to favour the diffusion of the rheumatoid arthritis (RA) treat-to-target (T2T) recommendations among Italian rheumatologists. Our objective was to measure the level of acceptance and applicability of the 10 recommendations to treat RA to a target of remission/low disease activity in the Italian rheumatology community, before and after the educational programme., Methods: One hundred rheumatologists working throughout Italy were invited to participate in this two-stage web-based survey (S1-2). Three questions concerning agreement with, applicability of and possible barriers to the applicability of each of the ten T2T recommendations were administered before (S1) and after (S2) an educational event on the T2T strategy in RA. The agreement with each of the 10 recommendations was measured by a 10-point Likert scale. The applicability of each recommendation was assessed by a 5-point Likert scale (never, almost never, sometimes, almost always, always). Finally, three possible barriers to each recommendation applicability were identified., Results: Seventy-one rheumatologists participated in S1 and 61 in S2. Level of agreement was high (mean score: 8.9 in S1, 9.1 in S2), with each recommendation receiving a score ≥7.9. The highest agreement score was achieved by recommendation 7 in both surveys. Recommendation 8 received the lowest overall agreement in both surveys. Concerning applicability, the majority of responses was 'almost always'. Following the educational programme, the mean degree of agreement with the recommendations increased significantly for recommendations 3, 4, 6, and 10., Conclusions: The level of knowledge of and agreement with the T2T recommendations for RA among Italian rheumatologists is high and increased significantly for some recommendations following a specific educational event, indicating that a deeper knowledge of the T2T strategy may increase agreement and acceptance.

Objectives: To compare drug survival of different anti-TNF drugs (infliximab, INF, etanercept, ETA, and adalimumab, ADA) in rheumatoid arthritis (RA) and spondyloarthritis (SpA) by analysing data collected from an Italian multicenter observational cohort study., Methods: All patients with RA or SpA registered in the MonitorNet database who started their first course of anti-TNF therapy were included. Overall drug survival was measured, along with specific reasons of discontinuation (inefficacy or adverse events). A first set of analyses using RA as reference category assessed the relationship between diagnosis and drug survival. A second set of analyses stratified by diagnosis (RA and SpA) used INF as reference drug. Adjustment for confounders was performed. The results are presented as adjusted hazard ratios (adjHR) and 95% confidence intervals (95%CI)., Results: 2640 RA patients and 1220 SpA patients with a median follow-up of 17 months (IQR 7.2-33.4) were included in the analyses. Patients with a diagnosis of SpA showed a lower risk of drug discontinuation with an adjHR (95%CI) of 0.81 (0.73, 0.90). In SpA, the subset of patients with ankylosing spondylitis (AS) showed the best survival on treatment. In RA, both ETA and ADA showed a significantly lower probability of withdrawal when compared to INF [adjHR (95%CI) 0.46 (0.38, 0.56) and 0.68 (0.57, 0.81), respectively]. Similar results were found in SpA., Conclusions: Drug survival for SpA is longer than that in RA mainly due to the AS subgroup. In both RA and SpA, ETA and ADA showed a better retention on treatment when compared to INF.

Background: To assess whether, in the real world of three early arthritis clinics, early referral could allow the best outcome, ie, remission, to be reached, and whether reaching the outcome was more dependent on therapy than on disease duration or vice versa., Methods: 1795 patients with early arthritis (symptom duration≤12 months) were entered into a prospective follow-up study. 711 patients (39.6%) were diagnosed with rheumatoid arthritis (RA). Each RA patient was treated according to the local algorithm, in three tertiary referral centres (representing a small province, a medium sized province and a metropolitan area, respectively). Remission, defined using the disease activity score in 28 joints (DAS28<2.6) and American College of Rheumatology (ACR) criteria, was the major outcome evaluated at the 12-month follow-up., Results: DAS28 remission was achieved in 34.3% (range 19.5-49%) of RA patients and ACR remission in 15.2% (range 8.5-20.6%). At the multivariate logistic regression analysis only two variables emerged as predictors of the major outcome: being in very early rheumatoid arthritis (VERA; less than 12 weeks symptom duration at the time of first treatment) and being on disease-modifying antirheumatic drugs (DMARD) within 3 months from disease onset. Among RA patients in remission, only 10% of VERA subjects received an anti-TNF blocker compared with 32.2% of non-VERA patients (p=0.002, OR 0.23, 95% CI 0.09 to 0.64)., Conclusions: In a real-world setting, the 12 weeks disease duration and an early intervention with DMARD represent the most significant opportunities to reach the major outcome, ie, remission of RA. Moreover, VERA represents a window of opportunity in terms of cost saving.

Objectives: To provide a survey of disease activity in patients treated with standard care in Italian clinical practice., Methods: This was an observational prospective cohort study in patients with early, aggressive rheumatoid arthritis (RA; duration ≤2 years but ≥6 weeks; DAS28 >3.2) naïve to anti-tumour necrosis factor (TNF) therapy who were treated with disease-modifying anti-rheumatic drugs (DMARDs) and/or biologics according to standard practice at 15 Italian ARPA (Artrite Reumatoide Precoce Aggressiva) centres. Patients were evaluated at baseline and after 6, 12 and 24 months. The primary endpoint was the proportion of patients achieving remission, as defined by disease activity score in 28 joints (DAS28) <2.6, after 1 year., Results: Among the 152 patients enrolled, 92 were evaluable after 1 year and 77 after 2 years for DAS28. At baseline, patients had a mean DAS28 of 6.1±1.0. At 12 months, 62.6% of patients were treated with DMARDs (in monotherapy or in combination), and 37.4% with anti-TNFs (in monotherapy or in association with DMARDs). At 24 months, 35.1% were receiving anti-TNF therapy. The rate of DAS28 remission rates at 12 months and 24 months were 28.3% (95% confidence interval [CI] 19.1-37.5) and 41.6% (95% confidence interval [CI] 30.6-52.6), respectively., Conclusions: The remission rate was lower at 12 months compared with previous large randomised clinical trials for early, aggressive RA, but significantly improved at 24 months. These results suggest that patients in real-world clinical settings in Italy may experience a delay in receiving the best possible care.

Objective: To evaluate the risk of serious infections (SIs) in RA patients receiving anti-TNF therapy on the basis of the data included in the GISEA register., Methods: The study involved 2769 adult patients with long-standing RA (mean age 53.2±13.4 years; mean disease duration 9.0±8.3 years) enrolled in the GISEA register, who had been treated for at least 6 months with TNF inhibitors or had discontinued therapy due to SI: 837 (30%) treated with infliximab (IFN), 802 (29%) with adalimumab (ADA), and 1130 (41%) with etanercept (ETN)., Results: 176 patients had experienced at least one of the 226 Sis during the 9 years of treatment with an anti-TNF agent, an overall incidence of 31.8/1000 patient-years (95% CI 25.2-38.3): 23.7/1000 patient-years (95% CI 13.1-34.2) on ADA; 12.8/1000 patient-years (95% CI 6.3-19.4) on ETN and 65.1/1000 patient-years (95% CI 48.4-81.8) on IFN. The risk was higher in the first than in the second year of treatment, but this difference was not statistically significant (p=0.08) (38.9% of the SIs were recorded in the first 12 months of treatment). The risk of SI was significantly different among the three treatment groups (p<0.0001). Multivariate models confirmed that the use of steroids (p<0.046), concomitant DMARD treatment during anti-TNF therapy (p=0.004), advanced age at the start of anti-TNF treatment (p<0.0001), and the use of IFN or ADA rather than ETN (respectively p<0.0001 and p=0.023) were strong and statistically significant predictors of infection., Conclusions: Anti-TNF therapy is associated with a small but significant risk of SI that is associated with the concomitant use of steroids, advanced age at the start of anti-TNF treatment, and the type of anti-TNF agent., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objectives: This paper aims to evaluate the internal and external responsiveness of the patient self-report questionnaires, comparatively to the traditional composite indices to assess the activity of rheumatoid arthritis (RA) in everyday practice., Methods: One hundred and ninety-one RA out-patients completed the clinical arthritis activity (PRO-CLARA) index, the rheumatoid arthritis disease activity index (RADAI), the routine assessment of patient index data (RAPID3), and the patient activity score (PAS). Simultaneously, the disease activity score-28 joints based on CRP (DAS28-CRP) and ESR (DAS28-ESR), the simplified disease activity index (SDAI), the clinical disease activity index (CDAI), and the mean overall index for RA (MOI-RA) were computed for each patient. Sensitivity to change was assessed after 6 months of treatment with disease-modifying anti-rheumatic drugs or biologics. Internal responsiveness was evaluated with the effect size (ES) and standardised response mean (SRM). External responsiveness was investigated by receiver operating characteristic (ROC), in categories of respondents, stratified according to the response on an item on change in overall health. In addition, change scores were compared by calculating correlation coefficients., Results: No significant differences in internal and external responsiveness were found between self-report questionnaires and composite indices. The internal responsiveness of the self-report questionnaires and composite measures was wide, with SRM and ES ranging from 1.03 (RADAI) to 1.80 (DAS28-ESR) and higher than that of the each individual measures. The responsiveness of the PRO-CLARA was equal to the DAS28-ESR, DAS28-CRP, SDAI or MOI-RA, but better than the CDAI. The RADAI and PAS were less responsive than the PRO-CLARA and RAPID3. The area under ROC curve of the PRO-CLARA gives identical results to those provided by other comparator composite indices. The score changes of all combinations were highly correlated (p<0.0001)., Conclusions: The self-report questionnaires showed comparable internal and external responsiveness to the composite activity scores and allow for the detection of rheumatoid disease activity. They appear suitable for clinical decision making, epidemiologic research and clinical trials. Further longitudinal studies are needed to validate these encouraging results.

Objective: To develop a preliminary power Doppler (PD) US composite score for global assessment of PsA patients., Methods: Sixteen PsA patients receiving anti-TNF-α therapy were enrolled. All patients were involved in multiple psoriatic targets, including joints, tendon, enthesis, skin and nail. The target with the highest PD signal, one for each target area, was selected to be scanned at baseline and at follow-up visit 8 weeks after. For each target, PD was graded according to semi-quantitative scoring systems. Inter- and intra-observer reliability and feasibility was also investigated. The new PD composite score for PsA was called Five Targets PD for Psoriatic Disease (5TPD)., Results: Sixty targets (16 joints, 9 tendons, 11 enthesis, 16 psoriatic plaques and 8 psoriatic onychopathies) were assessed. A significant improvement of the clinical scores was found at follow-up with respect to the baseline: HAQ modified for SpA (HAQ-S) (P = 0.0001); Psoriasis Area and Severity Index (P = 0.0001) and Nail Psoriasis Severity Index (P = 0.35). The 5TPD showed a significant change between baseline and follow-up (P = 0.0001). There was no significant correlation between HAQ-S and 5TPD findings. The inter- and intra-observer κ-values varied from good to excellent at baseline and follow-up. The time spent on baseline US examinations was mean (s.d.) 10.5 (2.0) min and no more than 7 min for follow-up assessment., Conclusion: The present study provides a new working hypothesis that the sonographic core set may be useful to construct a PDUS composite score for the assessment of PsA. The 5TPD formula provides a feasible and reliable approach for multi-target monitoring of psoriatic disease.

Objective: To evaluate 4-year retention rates of tumor necrosis factor-α (TNF-α) inhibitors adalimumab, etanercept, and infliximab among patients with longstanding rheumatoid arthritis (RA), as derived from an Italian national registry., Methods: The clinical records of 853 adult patients with RA in the GISEA (Gruppo Italiano Studio Early Arthritis) registry were prospectively analyzed to compare drug survival rates and the baseline factors that may predict adherence to therapy., Results: In 2003 and 2004, 324 patients started treatment with adalimumab, 311 with etanercept, and 218 with infliximab. After 4 years, the global retention rate of anti-TNF-α therapy was 42%. Etanercept survival (51.4%) was significantly better than that of infliximab (37.6%) or adalimumab (36.4%; p < 0.0001). Accordingly, the mean duration of therapy was significantly longer for etanercept (3.1 ± 2 yrs) than for adalimumab (2.6 ± 2 yrs) or infliximab (2.7 ± 2 yrs; p < 0.05). The use of concomitant disease-modifying antirheumatic drugs, mainly methotrexate, and the presence of comorbidities significantly predicted drug continuation (p < 0.01), whereas a high Disease Activity Score did not., Conclusion: The 4-year global drug survival of adalimumab, etanercept, and infliximab was lower than 50%, with etanercept having the best retention rate. The main positive predictor of adherence to anti-TNF-α therapy was the concomitant use of methotrexate. Our study provides further evidence that the real-life treatment of patients with RA may be different from that of randomized clinical trials.

Objectives: The objective of this study is to assess cost-effectiveness of different biologic strategies in patients with moderate-to-severe active RA after an insufficient response to anti-TNF agents within the context of the Italian healthcare system., Methods: Simulation models were developed allowing for potential biologic therapy switch at each 6-month time point in case of an insufficient response to the previous biologic agent. Biologic treatments included etanercept, abatacept, adalimumab, rituximab or infliximab. Effectiveness criteria for these models were defined as achieving a state of low disease activity (LDAS) [DAS28 ≤3.2] or remission (RS) [DAS28<2.6]. Monte-Carlo simulations were performed for each sequence to manage data variability., Results: The biologic treatment sequence using abatacept after an insufficient response to a first anti-TNF agent appeared significantly more efficacious over 2 years (102 days in LDAS) compared to rituximab (82 days in LDAS). The sequence using abatacept after 2 anti-TNF agents appeared significantly more efficacious (63 days in LDAS) compared to using a third anti-TNF agent (32 days in LDAS). Mean cost-effectiveness ratios showed significantly lower costs per day in LDAS with abatacept used after one anti-TNF agent (€376) compared to rituximab (€456). The sequence using abatacept after 2 anti-TNF agents was also more cost-effective (€642 per day in LDAS) versus a sequential use of anti-TNF therapies (€1164 per day in LDAS). All comparisons were confirmed when using the remission effectiveness criteria., Conclusions: The results of this health economics modelling study suggest that the biologic treatment sequence using abatacept after an insufficient response to a first anti-TNF agent appears significantly more effective and cost-effective versus a similar sequence using rituximab for achieving remission or LDAS. The results also indicate that in the case of an insufficient reponse to 2 anti-TNF agents, abatacept appears more effective and cost-effective than using a 3rd anti-TNF agent.

Objective: To obtain the simplest definition of minimal disease activity (MDA) and to compare it with published proposed definitions of MDA in patients with RA., Methods: Two hundred and fourteen patients with long-standing RA (LSRA) were evaluated for clinical and laboratory parameters. Factor analysis was performed to remove redundant variables included in the core set measure for MDA definition stated by the OMERACT. Receiver operating characteristic (ROC) curves analysis allowed to obtain optimal cut-off predictors of a 28-joint disease activity score (DAS28) < or =2.85. These were tested in 112 LSRA and 95 early-onset RA (ERA) patients., Results: Factor and ROC curve analysis showed that the best predictors of a DAS28 < or = 2.85 in LSRA cohort were: (i) ESR <20 mm/h (sensitivity: 80%, specificity: 54%); (ii) swollen joint count (out of 28) < or =2 (sensitivity: 95%, specificity: 74%); (iii) patient global assessment (0-100) < or =15 (sensitivity: 78%, specificity: 78%); and (iv) HAQ (0-3) < or =0.5 (sensitivity: 91%, specificity: 61%). To each of these four criteria we assigned a value of 1 when it was satisfied (score ranging: 0-4). The cut-off with the highest overall accuracy for identifying RA patients with DAS28 < or = 2.85 was a score > or =3. We adopted these four parameters in order to define the residual MDA (RMDA). Comparing RMDA criteria, in distinct 112 LSRA and 95 ERA patients, with OMERACT, Simplified Disease Activity Index and Clinical Disease Activity Index definitions of MDA, we found a good agreement in the LSRA cohort and moderate agreement in the ERA cohort., Conclusions: HAQ, PaGA, SJC28 and ESR allow identification of RA patients with an RMDA. The RMDA criteria behaves similarly to OMERACT definitions, but appears more simple and feasible.

The research carried out by Censis Foundation, in collaboration with SIR (Italian Society of Rheumatology) and ANMAR (National Association of Rheumatic patients), with the sponsorship of Roche S.p.A., involved more than 600 patients, diagnosed with arthritis by a rheumatologist according to ACR criteria. The patients were recruited through a representative sample of 300 general practitioners. A number of different research and survey tools were used to collect data, helping to identify several of the problems that affect Italian patients: a survey form to be filled by the GPs, in order to verify the diagnosis and the comorbidity level; a questionnaire for the self-assessment of the disease activity, Rheumatoid Arthritis Disease Activity Index (RADAI), and a sociological questionnaire set up for the analysis of the main aspects of the patients' path. Among the most serious criticalities found, the difficulties and the time needed for the patients to get a clear AR diagnosis, the problems in interacting with health structures, and the differences in accessing pharmaceutical therapies (only a slight majority of patients use DMARDs drugs, a small amount takes biological drugs, while a large number of patients is treated exclusively with symptomatic drugs) stand out. The differences in patients' condition appear then to be exaggerated, regarding the chances to get an early diagnosis, the access path to specialised centres, and in receiving the most appropriate treatments. Moreover, these differences appear to be strongly dependent on both the social characteristics of the patients and the supply arrangement in their area.

MonitorNet is a database established by the Italian Society of Rheumatology (SIR) in January 2007 and funded by the Italian Medicines Agency (AIFA), for the active long-term follow-up of patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis treated with biologic agents. All hospital Rheumatology Units in Italy were invited to participate in a non-interventional, observational, epidemiological study. The study is conducted in a routine clinical setting (real-world practice) where biologics are prescribed on the basis of current recommendations. In this report we describe the design, methodology, and present preliminary data of the study. At the time of the analysis (April 2009) the database included 3510 patients: 2469 (70.3%) with established RA, 675 (19.2%) with PsA and 366 (10.4%) with AS. The cumulative follow up period was 8,787 patient-years (RA: 8,388, PsA: 157; AS: 242). There were 1,538 adverse events in 938 (26.7%) patients. Infections were recorded in 630 patients, skin-related adverse events in 142 and post-infusion reactions in 90. A total of 30 malignancies were reported. An interim analysis of efficacy was conducted on 2,148 RA patients. Seven hundred and thirty-one patients (35.8%) achieved EULAR remission (defined as DAS28<2.4). When assessed with the more restrictive CDAI and SDAI criteria, the frequency of remission was lower (17.9% and 14.7% respectively). Availability of funding for this study provided an opportunity to organize a collaborative national network of rheumatology clinics to develop a large multicentre observational study.

Objective: To assess the prevalence of good clinical response and remission in rheumatoid arthritis (RA) patients with longstanding disease treated with anti-tumor necrosis factor-alpha (TNF-alpha) drugs at outpatient clinics., Methods: Retrospective national study of 14 academic tertiary referral rheumatology medical centers. RA patients with a Disease Activity Score (DAS28) > 3.2 were defined as having active disease and could start TNF-alpha blockers. All patients received one TNF-alpha blocker plus methotrexate (10-20 mg/wk). At the third month the patients were categorized as responders or nonresponders, based on improvement of at least 0.25 of the Health Assessment Questionnaire (HAQ). Those who had improved by at least 0.25 HAQ were analyzed for possible predictors of DAS28 remission at the sixth month., Results: A total of 1257 patients started TNF-alpha blockers. Of these, 591 (46.7%) reached the sixth month with an improvement of HAQ of 0.25 at the third month. In the cohort of patients reaching HAQ of 0.25, DAS28 remission was seen in 24% of rheumatoid factor (RF)-positive and 36% of RF-negative patients (p = 0.03). Logistic regression analysis for predictors of remission identified age at baseline, HAQ < 1.63, and RF negativity as positive predictors of remission at 6 months along with sex (male)., Conclusion: We show that only a minority of patients with longstanding RA achieve a good clinical response or remission at the outpatient community level. Predictors of remission identify characteristics commonly observed in subsets with less severe RA.

Objective: To use power Doppler sonography (PDS) to evaluate changes in synovial perfusion induced by adalimumab in the wrist joints of patients with rheumatoid arthritis., Methods: 48 wrists of 24 patients (18 women and 6 men) were examined. Despite prior treatment with disease-modifying antirheumatic drugs, including methotrexate, patients with clinically active rheumatoid arthritis were recruited in two rheumatological centres to receive 40 mg adalimumab subcutaneously every other week. Clinical, laboratory and PDS assessments were carried out at 0, 2, 6 and 12 weeks. Clinical and laboratory measurements of disease activity included physician's global assessment of disease activity, erythrocyte sedimentation rate and serum levels of C reactive protein. The Disease Activity Score for 28 joints (DAS28) was calculated. PDS signal was scored from 0 to 3 according to the overall expression of PDS findings at the wrists., Results: A significant reduction in both clinical (p<0.001) and PDS findings (p<0.001) was found at all follow-up examinations. A tendency to positive correlation (Spearman's r = 0.382; p = 0.067) was shown between reduction in PDS score and improvement in DAS28 at week 2 examination., Conclusion: PDS detected a rapid and significant reduction in synovial perfusion at the wrist joints of patients with rheumatoid arthritis receiving adalimumab. Ongoing follow-up will provide further information regarding the persistence of considerable reduction in PDS signal score and its correlation with DAS28.

Objective: To compare the efficacy and tolerability of cyclosporine (CSA) with that of symptomatic therapy (ST) alone and sulfasalazine (SSZ) in the treatment of psoriatic arthritis (PsA)., Methods: Twelve rheumatology centers recruited 99 patients with active PsA in a 24 week, prospective, randomized, open, controlled study. The patients were treated with CSA (3 mg/kg/day) or SSZ (2,000 mg/day) plus ST, or ST alone (nonsteroidal antiinflammatory drugs, analgesics, and/or prednisone < or = 5 mg/day). The primary endpoint was the 6 month change in pain. Analyses were on the basis of the intention-to-treat principle., Results: In comparison with both SSZ and ST, there was a statistically significant difference in favor of CSA in terms of the mean changes in the pain score (p < 0.05), which was considered the primary response variable. A significant decrease in favor of CSA versus ST alone was also observed for swollen joint count (p = 0.05), tender joint count (p = 0.01), joint/pain tenderness score (p = 0.002), patient and physician global assessment by at least one point (p = 0.04 and 0.01, respectively), total Arthritis Impact Measurement Scale score (p = 0.002), and spondylitis functional index (p = 0.002). There was a statistically significant difference in the ACR 50% and ACR 70% response rates between the CSA and ST groups (p = 0.02, 0.05). Comparing the SSZ and ST alone groups, only the spondylitis functional index decreased significantly in the SSZ treated patients (p = 0.03). The Psoriasis Area and Severity Index was significantly lower in the CSA than in the ST and SSZ groups (p = 0.0001 and 0.01, respectively). Decrease in erythrocyte sedimentation rate was significant only in the SSZ versus the ST group (p = 0.02), whereas reduction in C-reactive protein was significant in the CSA treated patients compared with the ST group (p = 0.006). The most common adverse event in the CSA group was mild, reversible kidney dysfunction., Conclusion: The results of this open trial confirm that CSA is well tolerated by patients with PsA and suggest that it is more efficacious than ST or SSZ.

Accelerated nodulosis (AN) is a potential complication of methotrexate (MTX) therapy for rheumatoid arthritis (RA). We report on a 62-year old man affected by seropositive RA who developed AN after five months of MTX treatment. MTX-dose reduction was followed by rapid regression of the skin nodules. The Authors describe the typical features of AN and discuss on the pathogenetic mechanisms.

Pneumonitis is emerging as one of the most unpredictable and potentially serious, adverse effects of treatment with MTX. Its prevalence in rheumatoid arthritis (RA) has been estimated from several retrospective and prospective studies to range from 0.3% to 18%. On the other hand, MTX-induced pneumonitis seems to be very rare in psoriatic arthritis (PsA). Our review of 194 RA patients and 38 PsA patients receiving MTX has identified four RA patients and one PsA patient with MTX-induced pneumonitis, giving a prevalence of 2.1% and 0.03%, respectively. Diagnosis was suggested by clinical history and radiographic findings, but the bronchoalveolar lavage plays an important role both in excluding infectious agents and in providing information for understanding the pathogenesis of lung injury. The presence of a lymphocyte alveolitis with a predominance of CD4+ T cells in 3 RA patients and CD8+ T cells with a concomitant increase in neutrophils in another case suggests that immunologically mediated reactions may be one damage mechanism in MTX-induced pneumonitis. Although risk factors for MTX-induced pulmonary toxicity are poorly understood, the presence in 3 out of 5 of our patients of pre-existing lung disease, represented by diffuse interstitial changes on chest X-ray, and mild bronchial asthma in two RA patients and by pulmonary silicosis in the patient with PsA may account for a predisposition to the development of MTX pneumonitis.

Objective: The effect of recombinant interferon alpha-2 (IFN alpha 2) therapy in Sjögren's syndrome (SS) was studied., Methods: An open study was performed in which 20 SS patients were given IFN alpha 2 3.10(6) MU/3 times/week or OH-chloroquine (OH-C) 6 mg/kg/daily, for a mean period of 11 months., Results: Gland assessment showed that lacrimal and salivary function improved by 67% and 61% versus 15% and 18% respectively (p < 0.01) in the patients treated with IFN alpha 2 compared to those treated with OH-C. Immunological parameters did not change over time in either group. In 3 patients a decrease in the tissue score was observed in the IFN alpha 2 group, while no changes were seen in the control group. Tolerability was acceptable., Conclusion: This study shows that IFN can improve tear function and dry mouth in SS, without causing significant side effects.

Objective: Steroids are the only treatment of polymyalgia rheumatica (PMR). We report the effects of methotrexate (MTX) plus prednisone versus prednisone alone in PMR., Methods: Twenty-four patients with recent onset PMR were studied in a randomized prospective study lasting one year. Patients were given MTX (MTX arm) 10 mg intramuscularly plus prednisone every week, or prednisone alone (Pred arm). After 6 months an attempt was made to stop prednisone, and to use the lowest possible dose over the next 6 months., Results: At the 12th month, all patients were in clinical remission, acute phase reactants were in the normal range in both arms of the study, 6 patients were no longer taking steroids in the MTX arm versus 0/12 in the Pred arm, and the amount of prednisone in the 2 groups was statistically different (1.84 versus 3.2 g; p < 0.0001). In addition, bone mineral density was significantly decreased in the Pred arm, but not in the MTX arm., Conclusion: The MTX regimen allowed the use of much less prednisone over one year to obtain full control of PMR with no loss of efficacy. It also allowed sparing of bone in elderly patients at increased risk of osteoporotic fractures.

The aim of this study was to assess the correlations of the serum soluble interleukin 2 receptor (sIL-2R) concentrations with disease activity parameters and response to treatment with second line drugs in patients with rheumatoid arthritis (RA). Sixty-seven patients with active disease completed a 24-week, open, randomized study of methotrexate (MTX) versus sulphasalazine (SSZ) or hydroxychloroquine (HCQ). Serum sIL-2R levels were evaluated before entry and after 24 weeks by ELISA. Serum sIL-2R were significantly higher in RA patients than in controls (P = 0.0001) and correlated significantly only with erythrocyte sedimentation rate (P = 0.03) and with Chronic Arthritis Systemic Index (P = 0.01) at study entry. No correlation was found between serum sIL-2R and other laboratory and clinical indices of disease activity. After 24 weeks of treatment no differences in serum sIL-2R in comparison with basal levels were found in either responding or in non-responding patients, although the mean reduction of sIL-2R was more marked in the MTX-treated cohort than in the HCQ and SSZ-treated groups. These data suggest that in RA the measurement of sIL-2R should be used with caution as an isolated index of disease activity and that it is not a useful marker of response to treatment with second line drugs.