Long-term safety of rituximab in rheumatoid arthritis: 9.5-year follow-up of the global clinical trial programme with a focus on adverse events of interest in RA patients
Ronald F van Vollenhoven,Paul Emery,Clifton O. Bingham,Edward C. Keystone,Roy Fleischmann,Daniel E. Furst,Nicola Tyson,Neil Collinson,P.B. Lehane +8 more
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It is demonstrated that rituximab remains generally well tolerated over time and multiple courses, with a safety profile consistent with published data and clinical trial experience.Abstract:
Objectives Evaluation of long-term safety of rituximab in rheumatoid arthritis (RA). Methods Pooled observed case analysis of data from patients with moderate-to-severe, active RA treated with rituximab in a global clinical trial programme. Results As of September 2010, 3194 patients had received up to 17 rituximab courses over 9.5 years (11 962 patient-years). Of these, 627 had >5 years’ follow-up (4418 patient-years). A pooled placebo population (n=818) (placebo+methotrexate (MTX)) was also analysed. Serious adverse event and infection rates generally remained stable over time and multiple courses. The overall serious infection event (SIE) rate was 3.94/ 100 patient-years (3.26/100 patient-years in patients observed for >5 years) and was comparable with placebo+MTX (3.79/100 patient-years). Serious opportunistic infections were rare. Overall, 22.4% (n=717) of rituximab-treated patients developed low immunoglobulin (Ig)M and 3.5% (n=112) low IgG levels for ≥4 months after ≥1 course. SIE rates were similar before and during/after development of low Ig levels; however, in patients with low IgG, rates were higher than in patients who never developed low IgG. Rates of myocardial infarction and stroke were consistent with rates in the general RA population. No increased risk of malignancy over time was observed. Conclusions This analysis demonstrates that rituximab remains generally well tolerated over time and multiple courses, with a safety profile consistent with published data and clinical trial experience. Overall, the findings indicate that there was no evidence of an increased safety risk or increased reporting rates of any types of adverse events with prolonged exposure to rituximab during the 9.5 years of observation.read more
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References
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TL;DR: At 24 weeks, a single course of rituximab with concomitant MTX therapy provided significant and clinically meaningful improvements in disease activity in patients with active, longstanding RA who had an inadequate response to 1 or more anti-TNF therapies.
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The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial.
Paul Emery,Roy Fleischmann,Anna Filipowicz-Sosnowska,Joy Schechtman,Leszek Szczepanski,Arthur Kavanaugh,Artur Racewicz,Ronald F van Vollenhoven,Nicole F. Li,Sunil Agarwal,E. W. Hessey,T. Shaw +11 more
TL;DR: Both rituximab doses were effective and well tolerated when added to MTX therapy in patients with active rheumatoid arthritis, although intravenous glucocorticoid premedication improved tolerability during the first ritUXimab infusion.
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Eva Baecklund,Anastasia Iliadou,Johan Askling,Anders Ekbom,Anders Ekbom,Carin Backlin,Fredrik Granath,Anca I. Catrina,Richard Rosenquist,Nils Feltelius,Christer Sundström,Lars Klareskog +11 more
TL;DR: Risk of lymphoma is substantially increased in a subset of patients with RA, those with very severe disease, and high inflammatory activity, rather than its treatment, is a major risk determinant.
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