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Inhibiting Janus Kinases (JAK) is a crucial therapeutic strategy in rheumatoid arthritis (RA). However, the use of JAK inhibitors has recently raised serious safety concerns. The study aims to evaluate the safety profile of JAKi in patients with RA and identify potential risk factors (RFs) for adverse events (AEs). Data of RA patients treated with JAKi in three Italian centers from January 2017 to December 2022 were retrospectively analyzed. 182 subjects (F:117, 64.3%) underwent 193 treatment courses. 78.6% had at least one RF, including age ≥ 65 years, obesity, smoking habit, hypertension, dyslipidemia, hyperuricemia, diabetes, previous VTE or cancer, and severe mobility impairment. We identified 70 AEs (28/100 patients/year), among which 15 were serious (6/100 patients/year). A high disease activity was associated with AEs occurrence (p = 0.03 for CDAI at T0 and T6; p = 0.04 for SDAI at T0 and T6; p = 0.01 and p = 0.04 for DAS28ESR at T6 and T12, respectively). No significant differences in AEs occurrence were observed after stratification by JAKi molecules (p = 0.44), age groups (p = 0.08) nor presence of RFs (p > 0.05 for all of them). Neither the presence of any RFs, nor the cumulative number of RFs shown by the patient, nor age ≥ 65 did predict AEs occurrence. Although limited by the small sample size and the limited number of cardiovascular events, our data do not support the correlation between cardiovascular RFs-including age-and a higher incidence of AEs during JAKi therapy. The role of uncontrolled disease activity in AEs occurrence should by emphasized., (© 2024. The Author(s).)

Introduction: The use of Janus Kinase Inhibitors (JAK-Is) in rheumatoid arthritis (RA) has entered in daily practice. In consideration of ORAL-Surveillance trial and the new EULAR recommendations, real-world data are needed to assess Jak-Is safety and effectiveness. The multicenter study presented here aimed to evaluate effectiveness and safety of tofacitinib in a real-life cohort., Methods: A retrospective analysis was performed from September 2021 to December 2022. Data were collected when tofacitinib was started (T0) and after 3 (T3), 6 (T6) and 12 (T12) months of treatment. The primary objective was to analyze the efficacy and safety of tofacitinib. Safety was assessed by recording adverse events (AEs) with and without discontinuation. The secondary objective was to assess the difference between Patient-Reported Outcomes (PROs) and Physician's Global Assessment of disease activity (PhGA)., Results: 122 patients were included in the study from the following rheumatology Centers: Pisa, Ancona, Florence (two Centers), Siena, and Sardinia. A statistically significant improvement in DAS-28-CRP, CDAI and SDAI score was observed at T3, T6, compared to baseline (p < 0.001). Improvement was confirmed in patients who reach T12. Patients naïve to bDMARDs showed a shorter remission time and higher remission rates. There was also a statistically significant improvement in PROs compared to baseline (p < 0.001). The improvement was rapid and was consistent with PhGA. The 12-month retention rate for tofacitinib was 89.35%. Reasons to stop tofacitinib were: insufficient response (7), gastrointestinal symptoms (2), infection (1), malignancy (1), Zoster (1), pruritus sine materia (1)., Conclusions: Tofacitinib is safe and effective in our RA cohort. It induces higher remission rates in patients naive to bDMARDs, suggesting that there may be a benefit using it as first-line therapy. Additionally, improvement in PROs was consistent with PhGA scores, demonstrating how tofacitinib affects both the objective and subjective components of disease activity. Key Points 1. JAK inhibitors are considered at a similar level as biologic agents in terms of effectiveness. 2. After ORAL-Surveillance results, real-world data are needed to assess the benefit/risk profile of Jaki. 3. Disagreement between patients and physicians has been previously reported with biologic therapy among patients with rheumatoid arthritis, with patients rating disease activity higher than physicians. 4. Jak inhibitors could reduce this discrepancy, due to their mechanism of action., (© 2023. The Author(s).)

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.

Introduction: Since the 1990s thebiological disease-modifying anti-rheumatic drugs (bDMARDs) have revolutionized the treatment of chronic dysimmune inflammatory arthropathies such as Rheumatoid Arthritis, Psoriatic Arthritis and Axial Spondylarthritis. Nevertheless, despite a full treatment regimen, mono- and oligoarticular persistence of the synovitis is sometimes observed. The intra-articular (IA) use of bDMARD drugs could resolve the persistent joint inflammation and result in a reduction in the degree of immunosuppression of individuals; moreover, the use of these drugs intra-articularly could be associated with a reduction in the treatment-related costs., Methods: We extensively searched via PubMed and Google Scholar articles using as keywords "etanercept", "infliximab", "adalimumab", "certolizumab", "golimumab", "tocilizumab", "ixekizumab", "secukinumab", "rituximab" each combined with "intra-articular injection"., Results: We found and evaluated 161 papers, and then we selected 24 that were highly related to the topic of the present work. The articles examined a total of 349 patients, 85 males (M), and 168 females (F), mean age of 44.75±12.09 years old and considered 556 treated joints. Three hundred and forty-one patients were affected by Rheumatoid Arthritis, 198 by Psoriatic Arthritis, 56 by Axial Spondylarthritis, 26 by Juvenile Idiopathic Arthritis, 19 by Undifferentiated Arthritis, 1 by arthritis associated with inflammatory bowel disease and 9 patients by an unspecified inflammatory articular disorder. All patients were treated intra-articularly with a TNFα inhibitor among Adalimumab, Etanercept or Infliximab. Side effects were documented in 9 out of 349 (2.57%) treated patients and all were mild or moderate. In some cases the effectiveness of IA bDMARDs treatment was maintained for several months, however in the few published randomized controlled trials(RCTs) the corticosteroids (GCs) appeared to act better when administered intra-articularly compared to bDMARDs., Conclusions: The IA use of bDMARDs seems to be weakly effective in the management of resistant synovitis and not superior to GCs injections. The treatment's main limit appears to be the poor persistence of the compound in the joint., (Copyright © 2023 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: To describe clinical characteristics of patients with Still's disease treated with methotrexate (MTX) and to assess drug effectiveness evaluating change in disease activity, reduction of inflammatory markers, and glucocorticoid (GC)-sparing effect., Methods: Patients with Still's disease treated with MTX were assessed among those included in AIDA Network Still Disease Registry., Results: In this registry, 171 patients with Still's disease were treated with MTX (males 43.3%, age 37.1 ± 16.0 years). They were mainly characterised by joint features and fever without a prominent multiorgan involvement. MTX was administered with GCs in 68.4% of patients, with other conventional synthetic DMARDs in 6.4%, and with biologic DMARDs in 25.1%. A significant reduction of the modified systemic score was observed, and 38.6% patients were codified as being in clinical remission at the end of follow-up. The concomitant administration of a biologic DMARD resulted a predictor of the clinical remission. Furthermore, a reduction of inflammatory markers and ferritin levels was observed following the administration of MTX. Additionally, a marked reduction of the dosage of concomitant GCs was identified, while 36.7% discontinued such drugs. Male gender appeared as a predictor of GC discontinuation. MTX was discontinued in 12.3% of patients because of adverse effects, and in 12.3% for lack of efficacy., Conclusions: Clinical characteristics of patients with Still's disease treated with MTX were described, mainly joint features and fever without a prominent multiorgan involvement. The clinical usefulness of MTX was reported in reducing the disease activity, decreasing the inflammatory markers, and as GC-sparing agent., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest for this work., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: To evaluate the impact of obesity in patients with adult-onset Still's disease (AOSD) and to assess their clinical characteristics and disease outcomes., Methods: The clinical features of AOSD patients with a body mass index (BMI)≥30 were assessed among those included in the multicentre Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort., Results: Out of 139 AOSD patients, who had BMI registered in our database, 26 (18.7%) had a BMI≥30. A lower rate of sore throat (P<0.05), pericarditis (P<0.05), and pleuritis (P<0.05) was shown in obese patients. Additionally, obese patients showed higher values of C-reactive protein (CRP) (P<0.05) and ferritin (P<0.05) than others. Furthermore, obese patients were characterised by biologic disease-modifying antirheumatic drug (bDMARD) failure in subsequent follow-up (P<0.05). They also presented higher rate of comorbidity than non-obese patients (P<0.05). Finally, obesity predicted the presence of a chronic disease course in both univariate (HR: 1.72, 95%CI: 1.03-2.51, P<0.05) and multivariate analyses (HR: 1.85, 95%CI: 1.45-2.89, P<0.05). Obesity was also a significant predictor of bDMARD failure in AOSD patients in both univariate (HR: 3.03, 95%CI: 1.42-6.45, P<0.01) and multivariate analyses (HR: 3.59, 95%CI: 1.55-8.27, P<0.01)., Conclusion: Obese patients at the time of diagnosis of the disease were characterised by a lower prevalence of sore throat, serositis, as well as by higher values of CRP and ferritin. Obesity was also a predictive factor for a chronic disease course and bDMARD failure, thus highlighting a subset of patients with AOSD to be carefully managed., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To compare clinical features and treatments of patients with systemic JIA (sIJA) and adult-onset Still's disease (AOSD)., Methods: The clinical charts of consecutive patients with sJIA by International League of Association of Rheumatology criteria or AOSD by Yamaguchi criteria were reviewed. Patients were seen at a large paediatric rheumatology referral centre or at 10 adult rheumatology academic centres. Data collected included clinical manifestations, inflammation biomarkers, systemic score, macrophage activation syndrome (MAS), parenchymal lung disease, disease course, disability, death and medications administered., Results: A total of 166 patients (median age at diagnosis 5 years) with sJIA and 194 patients with AOSD (median age at diagnosis 41 years) were included. The frequency of fever, rash, arthralgia, abdominal pain, MAS, parenchymal lung disease and increased acute phase reactants and ferritin were comparable between the two cohorts. Patients with sJIA had a higher prevalence of arthritis, whereas patients with AOSD had experienced leucocytosis and extra-articular organ involvement more frequently. Patients with AOSD were given more commonly low-dose corticosteroids, whereas biologic DMARDs were administered first-line more frequently in patients with sJIA., Conclusion: We found remarkable disparities in the prevalence of clinical manifestations between the two illnesses, which may partly depend on their classification by different criteria., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: EULAR recommendations do not suggest which biologic disease-modifying anti-rheumatic drug (bDMARD) should be preferred after failure of a first bDMARD in the treatment of rheumatoid arthritis (RA). In particular, few data are available regarding the effectiveness of a second-line bDMARD after failure of abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX). The aim of this study was to analyze the retention rate of a second line with tumor necrosis factor inhibitors (TNFi) or other mechanisms of action (MoAs), after the failure of either RTX, TCZ, or ABA., Methods: Two hundred and seventy-eight RA patients from the Italian GISEA registry were included in the study. RTX was the first bDMARD in 18% of patients, ABA in 45.7%, and TCZ in 36.3%, while the second bDMARD was a TNFi (group 1) in 129 patients and an agent with a different MoA (group 2) in 149., Results: During a median follow-up of 22 months (IQR 68), 129 patients discontinued their treatment; patients of group 1 discontinued the treatment more frequently than patients of group 2 (p<0.001) with retention rates of 33.6±5.7% and 63.6±4.6% after 104 weeks for group 1 and group 2, respectively (p<0.001). At multivariate analysis, the mechanism of action was the only predictor for the maintenance in therapy., Conclusions: According to our data, ABA, RTX, and TCZ seem to maintain a good retention rate also when used as a second-line therapy, suggesting their use after the failure of a non-TNFi as first-line therapy. However, specifically designed studies are needed to evaluate the more appropriate therapeutic strategies in RA, according to the first-line drug, including new targeted synthetic DMARDs. Key Points • A large proportion of rheumatoid arthritis patients fail the first biologic DMARD. • Few data are available about the efficacy of biologic DMARD after the failure of a non-TNF inhibitor. • Abatacept, rituximab, or tocilizumab seem to maintain a good retention rate after the failure of a first-course therapy with a non-TNF inhibitor., (© 2021. International League of Associations for Rheumatology (ILAR).)

Objectives: Baricitinib, an oral Janus kinase (JAK) 1-2 inhibitor, is currently used along biologic DMARDs (bDMARDs) after the failure of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated the efficacy and safety of baricitinib in real life., Methods: We prospectively enrolled 446 RA patients treated with baricitinib from 11 Italian centres. Patients were evaluated at baseline and after 3, 6, and 12 months. They were arrayed based on previous treatments as bDMARD-naïve and bDMARD-insufficient responders (IR) after the failure or intolerance to bDMARDs. A sub-analysis differentiated the effects of methotrexate (MTX) and the use of oral glucocorticoids (OGC)., Results: Our cohort included 150 (34%) bDMARD-naïve and 296 (66%) bDMARD-IR patients, with 217 (49%) using baricitinib as monotherapy. Considering DAS-28-CRP as the primary outcome, at 3 and 6 months, 114/314 (36%) and 149/289 (51.6%) patients achieved remission, while those in low disease activity (LDA) were 62/314 (20%) and 46/289 (15.9%), respectively; finally at 12 months 81/126 (64%) were in remission and 21/126 (17%) in LDA. At all-timepoints up to 12 months, bDMARDs-naïve patients demonstrated a better clinical response, independently of MTX. A significant reduction in the OGC dose was observed at 3 and 12 months in all groups. The serum positivity for both rheumatoid factors (RF) and anti-citrullinated protein antibodies (ACPA) conferred a lower risk of stopping baricitinib due to inefficacy. Fifty-eight (13%) patients discontinued baricitinib due to adverse events, including thrombotic events and herpes zoster reactivation., Conclusions: Real-life data confirm the efficacy and safety profiles of baricitinib in patients with RA and provide evidence that drug survival is higher in bDMARDs-naïve and seropositive patients.

Objectives: The efficacy and safety of certolizumab pegol (CZP), an Fc-free, PEGylated anti-TNF, in axial spondyloarthritis (axSpA) has been established in clinical trial settings. We report CZP effectiveness and safety in European clinical practice in patients with axSpA, including radiographic (r-) and non-radiographic (nr-) axSpA., Methods: CIMAX (NCT02354105), a European non-interventional multicentre prospective study, observed CZP treatment response and safety over 12 months in a real-world axSpA cohort. The primary outcome was change from baseline in BASDAI to week 52, with additional outcomes pertaining to effectiveness and safety. Patients who received ≥1 dose CZP were followed up for adverse events, and those with baseline and ≥1 post-baseline BASDAI assessment were included in effectiveness analyses., Results: A total of 672 patients (r-axSpA: 469; nr-axSpA: 201; unconfirmed diagnosis: 2) from 101 sites received ≥1 dose of CZP, of whom 564 (r-axSpA: 384; nr-axSpA: 179; unconfirmed: 1) were included in the effectiveness analyses. The mean baseline BASDAI was 6.1 in the overall axSpA population and r-axSpA and nr-axSpA subpopulations. At week 52, the mean (s.d.) change in BASDAI was -2.9 (2.3; n = 439); for r-axSpA and nr-axSpA, it was -2.9 (2.2; n = 301) and -2.8 (2.4; n = 137), respectively (P <0.0001 for all). Similar improvements were seen across other axSpA disease measures. In total, 37.9% (255/672) patients experienced adverse events, and 1.8% (12/672) experienced ≥1 serious adverse events., Conclusion: Improvements observed in signs and symptoms of axSpA following one year of CZP treatment in real-world clinical practice were similar to those from previous randomized clinical trials, with no new safety concerns., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

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: Interleukin-1 inhibition has revealed to be a successful treatment approach for patients with adult-onset Still's disease (AOSD). However, real-life experience is focused on the use of anakinra, while data about canakinumab (CAN) are mainly based on case reports and small case series. Patients and Methods . Patients classified with AOSD according to Yamaguchi criteria and treated with CAN were consecutively enrolled. Their clinical and therapeutic data were retrospectively collected and statistically analysed to assess the role of CAN as a therapeutic opportunity in AOSD patients in terms of clinical and laboratory disease control along with corticosteroid-sparing effect., Results: Nine AOSD patients (8 females and 1 male) treated with CAN for 15.00 ± 12.3 months were enrolled. Resolution of clinical manifestations was reported in 8/9 cases at the 3-month assessment; a significant decrease in the number of tender joints ( p = 0.009), swollen joints ( p = 0.027), and disease activity score on 28 joints-C-reactive protein (DAS28-CRP) ( p = 0.044) was observed during the study period. The systemic score of disease activity significantly decreased at the 3-month and 6-month assessments and at the last visit compared to the start of treatment ( p = 0.028, p = 0.028, and p = 0.018, respectively). The daily corticosteroid dosage was significantly reduced at the 3-month and at the last follow-up visits ( p = 0.017 and p = 0.018, respectively). None of the patients experienced adverse events or severe adverse events during the follow-up., Conclusions: CAN has shown prompt and remarkable effectiveness in controlling AOSD activity in a real-life contest, with a significant glucocorticoid-sparing effect and an excellent safety profile., Competing Interests: The authors declare that the research was carried out in the absence of any personal, professional, or financial relationships that could potentially be construed as a conflict of interest., (Copyright © 2020 Antonio Vitale et al.)

Background: The inflammatory contribution to type 2 diabetes (T2D) has suggested new therapeutic targets using biologic drugs designed for rheumatoid arthritis (RA). On this basis, we aimed at investigating whether interleukin-1 (IL-1) inhibition with anakinra, a recombinant human IL-1 receptor antagonist, could improve both glycaemic and inflammatory parameters in participants with RA and T2D compared with tumour necrosis factor (TNF) inhibitors (TNFis)., Methods and Findings: This study, designed as a multicentre, open-label, randomised controlled trial, enrolled participants, followed up for 6 months, with RA and T2D in 12 Italian rheumatologic units between 2013 and 2016. Participants were randomised to anakinra or to a TNFi (i.e., adalimumab, certolizumab pegol, etanercept, infliximab, or golimumab), and the primary end point was the change in percentage of glycated haemoglobin (HbA1c%) (EudraCT: 2012-005370-62 ClinicalTrial.gov: NCT02236481). In total, 41 participants with RA and T2D were randomised, and 39 eligible participants were treated (age 62.72 ± 9.97 years, 74.4% female sex). The majority of participants had seropositive RA disease (rheumatoid factor and/or anticyclic citrullinated peptide antibody [ACPA] 70.2%) with active disease (Disease Activity Score-28 [DAS28]: 5.54 ± 1.03; C-reactive protein 11.84 ± 9.67 mg/L, respectively). All participants had T2D (HbA1c%: 7.77 ± 0.70, fasting plasma glucose: 139.13 ± 42.17 mg). When all the enrolled participants reached 6 months of follow-up, the important crude difference in the main end point, confirmed by an unplanned ad interim analysis showing the significant effects of anakinra, which were not observed in the other group, led to the study being stopped for early benefit. Participants in the anakinra group had a significant reduction of HbA1c%, in an unadjusted linear mixed model, after 3 months (β: -0.85, p < 0.001, 95% CI -1.28 to -0.42) and 6 months (β: -1.05, p < 0.001, 95% CI -1.50 to -0.59). Similar results were observed adjusting the model for relevant RA and T2D clinical confounders (male sex, age, ACPA positivity, use of corticosteroids, RA duration, T2D duration, use of oral antidiabetic drug, body mass index [BMI]) after 3 months (β: -1.04, p < 0.001, 95% CI -1.52 to -0.55) and 6 months (β: -1.24, p < 0.001, 95% CI -1.75 to -0.72). Participants in the TNFi group had a nonsignificant slight decrease of HbA1c%. Assuming the success threshold to be HbA1c% ≤ 7, we considered an absolute risk reduction (ARR) = 0.42 (experimental event rate = 0.54, control event rate = 0.12); thus, we estimated, rounding up, a number needed to treat (NNT) = 3. Concerning RA, a progressive reduction of disease activity was observed in both groups. No severe adverse events, hypoglycaemic episodes, or deaths were observed. Urticarial lesions at the injection site led to discontinuation in 4 (18%) anakinra-treated participants. Additionally, we observed nonsevere infections, including influenza, nasopharyngitis, upper respiratory tract infection, urinary tract infection, and diarrhoea in both groups. Our study has some limitations, including open-label design and previously unplanned ad interim analysis, small size, lack of some laboratory evaluations, and ongoing use of other drugs., Conclusions: In this study, we observed an apparent benefit of IL-1 inhibition in participants with RA and T2D, reaching the therapeutic targets of both diseases. Our results suggest the concept that IL-1 inhibition may be considered a targeted treatment for RA and T2D., Trial Registration: The trial is registered with EU Clinical Trials Register, EudraCT Number: 2012-005370-62 and with ClinicalTrial.gov, number NCT02236481., Competing Interests: The authors have declared that no competing interests exist for this work.

Objectives: To assess the efficacy of monoclonal anti-tumour necrosis factor (TNF)-α agents in patients with anterior uveitis (AU) in terms of decrease of recurrences, variation of visual acuity and steroid sparing effect and to identify any demographic, clinical or therapeutic variables associated with a sustained response to monoclonal TNF-α inhibitors., Methods: Data from patients suffering from AU treated with adalimumab, infliximab, golimumab or certolizumab pegol were retrospectively collected and statistically analysed., Results: Sixty-nine patients (22 males, 47 females), corresponding to 101 eyes, were enrolled. The mean follow-up period was 29.25±23.51 months. The rate of ocular flares decreased from 42.03 events/100 patients/year recorded during the 12 months preceding the start of TNF-α inhibitors to 2.9 flares/100 patients/year after the start of treatment (p<0.0001). The overall decrease in ocular flares was 93.1%. No statistically significant changes were identified in the best corrected visual acuity during the follow-up period (p>0.99). The number of patients treated with corticosteroids at baseline was significantly higher compared with that referred to the 12-month evaluation (p<0.001) and to the last follow-up visit (p=0.006). Concomitant treatment with conventional disease-modifying anti-rheumatic drugs (cDMARDs) represented the sole clinical, demographic or therapeutic variable associated with long-term treatment duration (p=0.045, R2=0.87)., Conclusions: Monoclonal TNF-α inhibitors induce a remarkable decrease in the recurrence of AU during a long-term follow-up period and lead to a significant steroid sparing effect along with stabilisation of visual acuity. Concomitant treatment with cDMARDs represented the sole variable associated with treatment duration in the long-term.

The aim of the present study was to compare long-term adalimumab (ADA) and infliximab (IFX) retention rates in patients with intermediate, posterior, or panuveitis. Additional aims are as follows: (i) to identify any difference in the causes of treatment discontinuation between patients treated with ADA and IFX; (ii) to assess any impact of demographic features, concomitant treatments, and different lines of biologic therapy on ADA and IFX retention rates; and (iii) to identify any correlation between ADA and IFX treatment duration and the age at uveitis onset, the age at onset of the associated systemic diseases, and the age at the start of treatment. Clinical, therapeutic, and demographic data from patients with non-infectious intermediate, posterior, or panuveitis treated with ADA or IFX were retrospectively collected. Kaplan-Meier plot and log-rank (Mantel-Cox) test were used to assess survival curves. One hundred eight patients (188 eyes) were enrolled; in 87 (80.6%) patients, uveitis was associated with a systemic disease. ADA and IFX were administered in 62 and 46 patients, respectively. No statistically significant differences were identified between ADA and IFX retention rates (p value = 0.22). Similarly, no differences were identified between ADA and IFX retention rates in relation to gender (p value = 0.61 for males, p value = 0.09 for females), monotherapy (p value = 0.08), combination therapy with conventional disease-modifying antirheumatic drugs (log-rank p value = 0.63), and different lines of biologic therapy (p value = 0.79 for biologic-naïve patients; p value = 0.81 for subjects previously treated with other biologics). In conclusion, ADA and IFX have similar long-term retention rates in patients with non-infectious intermediate, posterior, and panuveitis. Demographic, clinical, and therapeutic features do not affect their long-term effectiveness.

The primary aim of the study was to evaluate the efficacy of tumor necrosis factor (TNF)-α blockers adalimumab (ADA) and infliximab (IFX) in refractory sight-threatening retinal vasculitis (RV) during a 12-month follow-up period. Secondary aims were to evaluate (i) any impact of concomitant conventional disease-modifying anti-rheumatic drugs (cDMARDs) and different lines of biologic therapy; (ii) any difference in terms of efficacy between ADA and IFX; (iii) consequences of biotherapies on the best-corrected visual acuity (BCVA); (iv) corticosteroid-sparing effect; and (vi) ocular complications during anti-TNF-α treatment. Demographic, clinical, and therapeutic data were retrospectively collected from the medical records and statistically analyzed. Forty-eight patients (82 eyes) were recruited, 22 (45.8%) of which received IFX and 26 (54.2%) ADA. The percentages of patients achieving RV remission within 3 and 12 months were 54 and 86%, respectively. A significant decrease in RV detection was identified from baseline to 3-month (p < 0.0001) and 12-month (p < 0.0001) assessments and between 3-month and 12-month visits (p = 0.004). No differences were identified in terms of RV resolution between (i) patients undergoing monotherapy and those co-administered with cDMARDs at 3-month (p = 0.560) and 12-month (p = 0.611) follow-up; (ii) biologic-naïve patients and those already exposed to other biologics at 3-month (p = 0.497) and 12-month (p > 0.99) visits; and (iii) patients treated with ADA and those treated with IFX (p = 0.357). During the study period, a statistically significant corticosteroid-sparing effect was observed (p = 0.0002), while BCVA values did not significantly change (p = 0.950). Anti-TNF-α monoclonal antibodies have proved excellent results in patients with recalcitrant sight-threatening RV.

Objective: To establish clinical consensus for the optimal placement of TNF inhibitor (TNFi) in DMARDs-naïve RA patients., Methods: The steering group was composed of 15 Italian rheumatologists expert in the field of RA, who proposed and selected by consensus the clinically relevant questions on the role of TNFi treatment in DMARDs-naïve RA patients. The question was rephrased according to the population, intervention, comparison and outcome statement. The available scientific evidence on this topic were collected by updating the systematic literature reviews used for the EULAR 2013 recommendations up to January 2016. The aspects evaluated in the studies concerned clinical efficacy, radiographic structural damage and safety. After the systematic literature review the expert panel formulated a consensus statement, and a modified Delphi panel evaluated the level of agreement between panellists (strength of recommendation)., Results: From a total of 1080 records we have included 6 studies, 2 randomized clinical trials and 4 open-label extension trials. Evidence from publications generated three statements for the final consensus document. The systematic literature review and the consensus statements developed showed that, for patients with early RA and in the presence of a treat-to-target strategy, the immediate use of anti-TNFi compared with an early (within 12 weeks) step-up to anti-TNF therapy did not confer a significant advantage regarding clinical, functional and radiographic outcomes., Conclusion: The most appropriate placement of the TNFi therapy in the treatment algorithm of early RA still remains a challenging clinical question that needs to be further addressed.

To identify clinical variables capable of predicting long-term treatment duration of TNF-α inhibition in patients with Behçet's disease (BD)-related uveitis. Demographic, clinical, and therapeutic data were retrospectively collected from BD patients treated with the tumor necrosis factor (TNF)-α blockers infliximab and adalimumab. Patients still continuing TNF-α inhibitors at 48-month follow-up visits were classified as long-term responders and were statistically compared to patients discontinuing treatment before the 48-month visit. Forty-five patients (75 eyes) were enrolled. Thirty-two patients continued anti-TNF-α treatment for more than 48 months; 13 patients discontinued the treatment after a mean time of 12.3 ± 10.44 months due to lack (61.5%) or loss (38.5%) of efficacy. Baseline value of BD current activity form was the only variable discriminating long- and short-term responsive patients (p = 0.048, OR = 0.656, C.I. 95% 0.433-0.996). Disease activity levels at the start of treatment predict duration of response to monoclonal TNF antagonists in ocular BD.

Objectives: The purpose of the present study was to describe our experience with the recombinant Fab' antibody fragment against TNF-α Certolizumab Pegol (CZP) in patients with Behçet's disease (BD) refractory to standardized therapies and previous biologic agents., Methods: Retrieved data including demographic characteristics, clinical manifestations, and previous treatments were collected in three different specialized Rheumatologic Units in Italy. In order to evaluate disease activity, the BD current activity form (BDCAF) has been used before starting CZP therapy and at each visit during treatment., Results: Thirteen BD patients (mean age 42.6 ± 8.8 years) with a disease duration of 8.80 ± 6.9 years, underwent CZP treatment for 6.92 ± 3.52 months. Six patients (46.15%) experienced a worsening of symptoms after 4.16 ± 1.21 months, whereas a satisfactory response was achieved in seven patients (53.84%) who were still on CZP therapy at the last follow-up visit (after 9.28 ± 3.03 months of treatment). The mean decrease of BDCAF between the first and last visit was 0.308 ± 1.84 without reaching significant difference (mean 8.3 ± 1.3 and 8 ± 2.08, respectively; p= .51). During the whole study period, CZP was well tolerated in all patients except one who developed a generalized cutaneous reaction after the third administration., Conclusions: These results suggest that despite an improvement of clinical manifestations has been observed in more than half of the patients, it is not possible to draw firm conclusions about the effectiveness of CZP in BD and further studies with larger cohorts of patients are warranted. Whether the increase of CZP dosage may ensure a better clinical response remains an unsolved issue that needs to be considered.

Our aim was to retrospectively assess the role of golimumab as a treatment choice in patients with Behçet's disease (BD). Seventeen patients diagnosed with BD according to the international criteria were consecutively enrolled; the BD Current Activity Form (BDCAF) was used to evaluate disease activity. After having collected clinical data from patients, statistical analysis was performed to identify differences between the start of therapy and last visit; significance was defined as p < 0.05. The mean duration of golimumab treatment was 18.47 ± 20.8 months. At the time of data enrollment, 12/17 (70.6%) patients were still on golimumab therapy. The mean time required to obtained clinical response was 4.9 ± 5.7 weeks. At 3 months evaluation, golimumab was able to control BD-related manifestations in 16/17 (94.1%) cases; the BDCAF values were significantly decreased at the last follow-up compared to those assessed at the start of golimumab (p = 0.002). The BDCAF improvement was significantly higher among patients co-administered with DMARDs than those undergoing golimumab as monotherapy (p = 0.048). At the last follow-up visit, corticosteroids had been discontinued in 10 (58.8%) patients, while the corticosteroid dosage was significantly lower at the last follow-up visit compared to the start of therapy in those patients already on corticosteroids at the end of the study (p = 0.001). Golimumab is a promising and safe treatment opportunity in BD patients with different systemic involvement, inducing a prompt resolution of clinical manifestations, a meaningful improvement of BDCAF score, and a significant corticosteroid-sparing effect. However, golimumab co-administered with DMARDs has provided better results than in patients undergoing monotherapy.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS), caused by mutations in the TNFRSF1A gene, is the most frequent autosomal dominant autonflammatory disease displaying a relevant risk of reactive AA amyloidosis, if left untreated. Our report deals with one adult with TRAPS complicated by amyloidosis-related renal failure, treated with the recombinant human interleukin-1 receptor antagonist anakinra at a higher than conventional dosage. This treatment did not present any adverse event and led remarkably to the disappearance of all TRAPS-related manifestations and prompt decrease of laboratory abnormalities, including proteinuria. A review of the medical literature has been also considered to evaluate efficacy and safety of interleukin-1 inhibition in patients with TRAPS.

Our aim was to evaluate the effectiveness of adalimumab (ADA) during a 24-month study period in patients affected with Behçet's disease (BD). Clinical and therapeutic data from 100 consecutive BD patients treated with ADA were retrospectively collected and statistically analyzed. At 12-week follow-up, ADA induced clinical efficacy in 81 patients, with a mean time to response of 7.63 ± 3.43 weeks; 25 (30.9 %) patients underwent a disease relapse after 22.17 ± 1.57 months, but treatment adjustments allowed a recovery of efficacy in 11 cases. At 24-month follow-up, 67/100 patients were still on ADA therapy despite concomitant treatments. No differences were identified between ADA monotherapy and co-treatment with DMARDs about efficacy (p = 0.09), time to response (p = 0.61), relapses (p = 0.36), and ADA discontinuation (p = 0.40). No differences existed in patients switched from other tumor necrosis factor (TNF)-α inhibitors about efficacy at 12 weeks (p = 0.13) and rapidity of response (p = 0.93) while relapses (p = 0.01) and ADA discontinuation at 24 months (p = 0.001) were significantly more common. Adverse events occurred in 10 patients. ADA confirmed its effectiveness in BD. Combination therapy with DMARDs seems not significantly superior to monotherapy. Frequency and time to response for ADA was not conditioned by a previous lack or loss of efficacy to other TNF-α inhibitors, but long-term loss of efficacy seemed more likely in patients switched from other anti-TNF agents.

The study aim was to evaluate the efficacy of adalimumab (ADA) in a large series of Behçet's disease (BD)-related uveitis. We performed a multicenter retrospective observational study including 40 selected patients (66 eyes) receiving ADA. Clinical data were retrospectively analyzed at baseline, at 3 and 12 months of treatment. Primary end point was reduction of ocular inflammatory flares. Secondary end points were improvement of best corrected visual acuity (BCVA), reduction of macular thickness measured by optical coherence tomography (OCT), reduction in the occurrence of vasculitis assessed by fluorescein angiography (FA), and evaluation of statistically significant differences between patients treated with ADA monotherapy and those undergoing ADA plus DMARDs and in patients firstly treated with ADA compared to patients previously administered with other biologics; ADA steroid sparing effect was also evaluated. During the first 12 months of ADA therapy, the number of flares significantly decreased from 200 flares/100 patients/year to 8.5 flares/100 patients/year (p < 0.0001). Similarly, BCVA improved if compared to baseline (7.4 ± 2.9 versus 8.5 ± 2.1, p = 0.03). OCT findings significantly improved showing a mean reduction of central macular thickness (CMT) of 27.27 ± 42.8 μm at the end of follow-up (p < 0.006). FA identified retinal vasculitis in 22 cases at baseline (55%), 8 (20%) cases after 3 months, and in only one (2.5%) case at 12-month follow-up. FA improvement was highly significant at 3- and 12-month follow-up if compared to baseline (p < 0.0001 and p = 0.006, respectively). ADA is highly effective and safe for the treatment of BD-related uveitis, providing a long-term control of ocular inflammation.

Objectives: The aim of the study was to retrospectively evaluate the long-term safety profile of anti-tumour necrosis factor (TNF)-α agents on the liver of patients with spondyloarthritis (SpA) and a previously resolved hepatitis B virus (HBV) infection., Methods: Medical records from 992 consecutive outpatients receiving anti-TNF-α therapy between 2007 and 2015 were retrospectively reviewed. HBV infection was assessed evaluating HBV surface antigen (HBsAg), antibodies to HBsAg (anti-HBs), antibodies to hepatitis B core (anti-HBc), and HBV-DNA levels. In patients with a previously resolved HBV infection, serum levels of aminotransferase (AST/ALT) were also assessed every three months, while HBsAg and HBV-DNA every six months., Results: We identified 131 consecutive patients (70 males, 61 females) with SpA and resolved HBV infection. At baseline none of the patients were positive for HBV-DNA, and AST/ALT levels were within the normal range with no subsequent increase during the observational treatment period. None received antiviral therapy prior to or during anti-TNF drug administration. At the end of the follow-up period (75.50±33.37 months) no viral reactivation was observed in anti-HBc positive patients, regardless of anti-HBs positivity. During the whole follow-up, HBV-DNA was undetectable in all patients, HBsAg remained negative, and it was not necessary to discontinue biologic therapy because of liver damage., Conclusions: Our results confirm that pre-emptive antiviral prophylaxis may not be necessary routine, but strict monitoring for AST/ALT levels, as well as for changes in HBV serology and HBV-DNA remain necessary and seem a realistic and cost-effective approach to identify early viral reactivation.

The purpose of the present review was to provide a comprehensive picture of the efficacy of the different tumor necrosis factor (TNF)-α inhibiting agents in the treatment of acute anterior uveitis (AAU), the most common extra-articular manifestation of ankylosing spondylitis (AS). AS related, AAU may lead to severe visual impairment, due to frequent flare recurrences, anterior, and posterior segment complications and traditional treatment side effects. Considerably higher levels of tumor necrosis factor (TNF) have been assessed in the aqueous humor and inflamed joints of patients with AS. Anti-TNF drugs have shown efficacy in preventing relapses of rheumatological manifestations of spondyloarthropathies. Several studies have underlined the sustained efficacy of the monoclonal anti-TNF antibodies also in reducing the recurrence of anterior chamber flares in patients with AS-related AAU. On the other hand, retrospective studies and observational reports have indicated lower effectiveness and some paradoxical occurrence of uveitis following treatment with the soluble receptor agent etanercept. Growing evidence suggests that a prophylactic strategy could be advocated in subjects with frequent and recalcitrant attacks of AS-AAU. In this regard, the administration of monoclonal anti-TNF antibodies such as adalimumab (ADA) has been shown to significantly reduce the rate of AAU recurrences. Indeed, during ADA treatment about 90 % of patients have shown to remain completely free of attacks for the entire follow-up period, in most studies. Further studies are needed to confirm the long-term efficacy of TNF inhibitors in AS related AAU and also their role in preventing ocular complications and visual impairment.

Rheumatoid arthritis (RA) is a chronic disease characterised by inflammation of the synovial tissue in joints, which can lead to joint destruction. The primary goal of the treatment is to control pain and inflammation, reduce joint damage and disability, and maintain or improve physical function and quality of life. The present review is aimed at providing a critical analysis of the recent literature on the novelties in the treatment of RA, with a particular focus on the most relevant studies published over the last year.

The study objective was to report treatment with an interleukin (IL)-1 receptor antagonist, anakinra, in patients with multiorgan Behcet's disease (BD). Comparison of clinical manifestations, previous treatments, markers of inflammation, concomitant medications, treatment regimen modifications, relapses, and adverse events before and during anakinra administration among patients with BD were evaluated. Nine BD patients (mean age 34.55 ± 16.30 years) refractory to tumor necrosis factor blockers and standardized therapies are reported in our survey. Their mean age at disease onset was 25 ± 13.88 years and their overall disease duration was 9.55 ± 5.33 years. All patients were positive for the HLA-B51 allele. Within 1 or 2 weeks following the initiation of anakinra, eight out of nine patients promptly responded, and most of them were maintained on 100 mg of daily anakinra with low doses of prednisone. However, most patients experienced a relapse in one or more clinical manifestations over time (mean time to relapse 29 ± 21.65 weeks), and only one patient remained completely under control on anakinra monotherapy. Despite a relapse in one or more disease manifestations, treatment was continued in most patients for a mean period of 13.75 ± 6.49 months. No serious adverse events occurred. Eight out of nine refractory BD patients showed a prompt improvement after starting anakinra, supporting the concept that IL-1 plays a pathological role in this disease. Nevertheless, after several months, most patients experienced a relapse. It remains unclear whether increasing the dose of anakinra would have prevented the reoccurrence of disease activity.

Rheumatoid arthritis (RA) is a chronic disease characterised by inflammation of the synovial tissue in joints, which can lead to joint destruction. The primary aim of the treatment is to control pain and inflammation, reduce joint damage and disability, and maintain or improve physical function and quality of life. In this article, we provide a critical analysis of the recent literature on the novelties in the treatment of RA, with a particular focus on the most relevant studies published over the last two years.

Rheumatoid arthritis is a complex multifactorial disease, whose pathogenesis has not been fully elucidated. Biologic agents have revolutionized RA treatment, but a significant percentage of patients does not obtain an adequate response to the therapy. Most of the biologic agents do better if combined with conventional immunosuppressive DMARDs and they show a similar efficacy profile: most of the responders achieve the minimum desirable level of response (ACR20) and only few patients obtain a worthwhile clinical improvement (ACR70 or better). We need to identify new strategies of treatment, able to comply the non satisfied needs of RA patients. Taking inspiration from other medical fields, we could hypothesize a combined regimen in which biologic agents are administered simultaneously at a low or ultra-low dosage, targeting several pathogenetic mechanisms but avoiding important side effects. Alternatively it should be useful to identify rapid succession regimens in which biologic drugs are taken according to an established sequence. Research in this field is obviously not encouraged by pharmaceutical industries, but our efforts should be driven in this direction. According to these observations, adequate clinical trials should be designed to search for appropriate drugs associations and dosages., (Copyright © 2013. Published by Elsevier Ltd.)

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: Filgotinib (FIL) is a selective JAK1 inhibitor with an affinity 30-fold higher than JAK2, approved to treat moderate to severe active rheumatoid arthritis (RA), in adults with inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). Methods: We conducted a retrospective, multicentric study in order to evaluate efficacy and safety of FIL 200 mg daily therapy, after 3 and 6 months, in 120 patients affected by RA, managed in Tuscany and Umbria rheumatological centers. The following clinical records were analyzed: demographical data, smoking status, previous presence of comorbidities (Herpes zoster -HZ- infection, venous thromboembolism -VTE-, major adverse cardiovascular events -MACE-, cancer, diabetes, and hypertension), disease duration, presence of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), number of biological failures, and prior csDMARDs utilized. At baseline, and after 3 (T3) and 6 (T6) months of FIL therapy, we evaluated mean steroid dosage, csDMARDs intake, clinimetric indexes (DAS28, CDAI, HAQ, patient and doctor PGA, VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and body mass index (BMI). Results: At baseline, the mean disease duration was 9.4 ± 7.5 years; the prevalence of previous HZ infection, VTE, MACE, and cancer was respectively 4.12%, 0%, 7.21%, and 0.83%, respectively. In total, 76.3% of patients failed one or more biologics (one biological failure, 20.6%; two biological failures, 27.8%; three biological failures, 16.5%; four biological failures, 10.3%; five biological failures, 1.1%). After 3 months of FIL therapy, all clinimetric index results significantly improved from baseline, as well as after 6 months. Also, ESR and CRP significatively decreased at T3 and T6. Two cases of HZ were recorded, while no new MACE, VTE, or cancer were recorded during the observation time. Conclusion: Despite the limitations of the retrospective study and of the observational period of only 6 months, real-life data on the treatment of RA patients with FIL demonstrate that this Jak inhibitor therapy is safe in terms of CV, VTE events, and occurrence of cancer, and is also effective in a population identified as "difficult to treat" due to failure of previous b-DMARD therapy. [ABSTRACT FROM AUTHOR]

Objective: Since Behçet's syndrome (BS) is the prototype of inflammation‐induced thrombosis, immunosuppressants are recommended in place of anticoagulants. We undertook this study to assess the clinical efficacy and the corticosteroid‐sparing effect of adalimumab (ADA)–based treatment versus disease‐modifying antirheumatic drug (DMARD) therapy in a large retrospective cohort of patients with BS‐related venous thrombosis. Methods: We retrospectively collected data on 70 BS patients treated with DMARDs or ADA‐based regimens (ADA with or without DMARDs) because of venous complications. Clinical and imaging evaluations were performed to define vascular response. We explored differences in outcomes between ADA‐based regimens and DMARDs with respect to efficacy, corticosteroid‐sparing role, and time on treatment. We also evaluated the role of anticoagulants as concomitant treatment. Results: After a mean ± SD follow‐up period of 25.7 ± 23.2 months, ADA‐based regimens induced clinical and imaging improvement of venous thrombosis more frequently (P = 0.001) and rapidly (P < 0.0001) than did DMARDs. The mean dose of corticosteroids administered at the last follow‐up visit was significantly lower with ADA‐based regimens than with DMARDs (P < 0.0001). The time on treatment was significantly longer with ADA plus DMARDs than with DMARDs alone (P = 0.002). No differences were found in terms of efficacy and time on treatment between DMARDs or ADA‐based regimens among patients who received anticoagulants and those who did not. Conclusion: In this large retrospective study, we have shown that ADA‐based regimens are more effective and rapid than DMARDs in inducing resolution of venous thrombosis in BS patients, allowing reduction of steroid exposure. Moreover, our findings suggest that anticoagulation does not modify the efficacy of either ADA‐based regimens or DMARDs for venous complications. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the role of interleukin (IL)-1 inhibitors anakinra (ANA) and canakinumab (CAN) in the treatment of Behçet's disease (BD)-related uveitis. Multicenter retrospective observational study includes 19 consecutive BD patients (31 affected eyes) received treatment with anti-IL-1 agents. Data were analyzed at baseline and at 3 and 12 months. The primary endpoint is the reduction of ocular inflammatory flares (OIF). The secondary endpoints are improvement of best corrected visual acuity (BCVA); reduction of macular thickness defined by optical coherence tomography (OCT) and of vasculitis identified with fluorescein angiography (FA); evaluation of statistically significant differences between patients treated with IL-1 inhibitors as monotherapy, subjects also administered with disease modifying anti-rheumatic drugs (DMARDs) and/or corticosteroids as well as between patients administered with IL-1 inhibitors as first line biologic treatment and those previously treated with TNF-α inhibitors. At 12 months, OIF significantly decreased from 200 episodes/100 patients/year to 48.87 episodes/100 patients/year ( p < 0.0001). The frequency of retinal vasculitis identified by FA significantly decreased between baseline and 3- and 12-month follow-up visits ( p < 0.0001 and p = 0.001, respectively). OIF rate was significantly higher in patients co-administered with DMARDs (81.8 episodes/100 patients/year) than in patients undergoing IL-1 inhibitors as monotherapy (0.0 episodes/100 patients/year) ( p = 0.03). No differences were identified on the basis of corticosteroid use and between patients administered with IL-1 inhibitors as first line biologic approach or second line. Steroid dosage was significantly decreased at 12-month visit compared to baseline ( p = 0.02). Treatment with IL-1 inhibitors is effective in the management of BD-related uveitis and provides a long-term control of ocular inflammation in refractory and long-lasting cases. [ABSTRACT FROM AUTHOR]

Idiopathic inflammatory myopathies (IIM) are a group of different conditions typically affecting striate muscle, lung, joints, skin and gastrointestinal tract. Treatment typically relies on glucocorticoids and synthetic immunosuppressants, but the occurrence of refractory, difficult to treat, manifestations, may require more aggressive treatment, borrowed from other autoimmune diseases, including biologic disease modifying drugs (bDMARDs). In this regard, we conducted a systemic literature review in order to depict the current evidence about the use of bDMARDs in IIM. A total of 78 papers, published during the last 21 years, were retrieved. The majority of patients was treated with TNF-α inhibitors, whose effectiveness was assessed particularly in recalcitrant striate muscle, skin and joints involvement. Rituximab, whose evidence is supported by a large number of real-life studies and trials, seems to be an excellent option in case of ILD and anti-synthetase syndrome, while Tocilizumab, despite not meeting primary and secondary endpoints in a recently published clinical trial, proved its effectiveness in rapidly progressing ILD. Similarly, Abatacept, studied in a phase IIb clinical trial with conflicting evidence, was reported to be effective in some case reports of refractory dermatomyositis. Less data exist for anti-IL1 and anti-IL23 agents, which were employed particularly for inclusion body myositis and severe skin disease, respectively. This study provides an organ-focused assessment of bDMARDs in IIM, which display encouraging results in the treatment of refractory subsets of disease. • bDMARDs may play a role in the management of refractory IIM. • RTX should be preferred in case of ILD and its use is supported by the most robust evidence. • TCZ is effective in rapidly progressive ILD and recalcitrant joint involvement. • Anti-TNFα agents are the most employed, particularly in case of refractory myositis. [ABSTRACT FROM AUTHOR]