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Bone loss is a typical consequence of Rheumatoid Arthritis (RA). It occurs not only locally, affecting the inflamed joints (erosions), but also systemically, leading to osteopenia and/or overt osteoporosis, with increased risk of fragility fractures. This complication, often underestimated, can worsen the burden of disability in RA patients. Moreover, systemic and local bone loss are closely intertwined as osteoporosis per se can facilitate the development of erosions. A fundamental role in this process is played by the osteoimmunologic dysregulation typical of RA and other chronic inflammatory conditions. The poor response to the DMARDs, in terms of progression of bone erosions, might depend on the concomitant osteoporosis and on other determinants of bone loss. Thus, we need a deeper investigation in RA patients of bone health and effects of DMARDs on it and, eventually, a specific anti-osteoporotic treatment, other than DMARDs, for the prevention of both fragility fractures and bone erosions. The present review summarizes the most relevant evidence on systemic bone loss of biological and targeted synthetic DMARDs., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice., Methods: We performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab., Results: 254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47-5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55-1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56-3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83-9.62]; p=0.019 as compared with controls vs 3 [0.66-5.35]; p=0.012)., Conclusion: Rituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial., Competing Interests: Competing interests: OD has consultancy relationship with Actelion, Bayer, BiogenIdec, Boehringer Ingelheim, ChemomAb, espeRare foundation, Genentech/Roche, GSK, Inventiva, Italfarmaco, Lilly, medac, MedImmune, Mitsubishi Tanabe Pharma, Pharmacyclics, Novartis, Pfizer, Sanofi, Sinoxa and UCB in the area of potential treatments of scleroderma and its complications. OD has received research funding from Actelion, Bayer, Boehringer Ingelheim, Mitsubishi Tanabe Pharma and Roche in the area of potential treatments of scleroderma and its complications. In addition, OD has a patent mir-29 for the treatment of systemic sclerosis licensed. M-ET has received consulting fees, speaking fees or honoraria from Abbvie, BMS, Lilly, Medac, MSD, Pfizer, Roche and UCB. PA has received travel expenses from Roche (<2500€). SV received speaking fees by Pfizer, Abbvie, Bristol-Myers Squibb, consultant fee from Thermofischer and Boehringer-Ingelheim Italia and Educational support from Pfizer, Roche, BMS. EH has received speaker fees and/or honoraria for consultations from Roche, less than 10 000€. NH received lecture fees from Actelion Pharmaceuticals, Pfizer, Roche and grant support from Actelion and Bayer Pharmaceuticals. CM has/had consultancy relationship and/or has received honoraria from Actelion, Abbvie, Roche and Geneva Romfarm in the area of systemic sclerosis and its complications. CC has received travel grants from Roche. YA has/had consultancy relationship and/or has received grants from Actelion, Bayer, BMS, Boehringer-Ingelheim, Inventiva, Roche, Sanofi-Aventis in the area of systemic sclerosis., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

The prognosis for patients with rheumatoid arthritis or spondyloarthritides has improved dramatically due to earlier diagnosis, recognition of the need to treat early with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), alone or in combinations, the establishment of treatment targets, and the development of biological DMARDs (bDMARDs). Many patients are now able to achieve clinical remission or low disease activity with therapy, and reduce or eliminate systemic corticosteroid use. Guidelines recommend methotrexate as a first-line agent for the initial treatment of rheumatoid arthritis; however, a majority of patients will require a change of csDMARD or step up to combination therapy with the addition of another csDMARD or a bDMARD. However, treatment failure is common and switching to a different therapy may be required. The large number of available treatment options, combined with a lack of comparative data, makes the choice of a new therapy complex and often not evidence based. We summarize and discuss evidence to inform treatment decisions in patients who require a change in therapy, including baseline factors that may predict response to therapy.