Safety and Efficacy of Additional Courses of Rituximab in Patients With Active Rheumatoid Arthritis An Open-Label Extension Analysis
Edward C. Keystone,Roy Fleischmann,Paul Emery,Daniel E. Furst,Ronald F van Vollenhoven,Joan M. Bathon,Maxime Dougados,Andrew R. Baldassare,Gianfranco Ferraccioli,Andrew Chubick,James Udell,M. Cravets,Sunil Agarwal,Simon Cooper,Fabio Magrini +14 more
TLDR
Findings indicate that patients treated with repeated courses of rituximab have sustained clinical responses with no new adverse events.Abstract:
Objective
To determine the safety and efficacy of additional courses of rituximab in patients with rheumatoid arthritis (RA).
Methods
An open-label extension analysis of RA patients previously treated with rituximab was conducted. Patients who had participated in any of 3 double-blind trials were eligible for additional courses (2 infusions of 1,000 mg given 2 weeks apart) if they exhibited a swollen joint count and tender joint count of ≥8 with ≥16 weeks elapsing after the previous course. Safety was assessed in patients receiving all or a portion of a rituximab course. Efficacy was assessed 24 weeks after each course, using the American College of Rheumatology 20% criteria for improvement (ACR20), ACR50, ACR70, European League Against Rheumatism (EULAR) response criteria, Disease Activity Score in 28 joints, the disability index of the Health Assessment Questionnaire, and Short Form 36 scores, stratified according to prior tumor necrosis factor (TNF) inhibitor exposure.
Results
A total of 1,039 patients received ≥1 course of rituximab. Of these, 570 received 2 courses, 191 received 3 courses, and 40 received 4 courses, for a total of 1,669 patient-years. Irrespective of prior TNF inhibitor exposure, ACR20 responses were comparable at week 24 after course 1 and at week 24 after course 2 (65% versus 72%), as were ACR50 and ACR70 responses. EULAR moderate/good responses were also comparable in course 2 relative to course 1 (88% versus 79%), with EULAR remission occurring in a 2-fold higher proportion of patients after course 2 than after course 1 (13% versus 6%). The most common adverse events, which were mild-to-moderate acute infusion-related events, decreased with each course. The serious infection rate after course 1 (5.1 per 100 patient-years) remained stable through additional courses. The proportion of patients with circulating IgM and IgG levels below the lower limit of normal (LLN) increased with subsequent courses; however, serious infection rates in these patients (5.6 per 100 patient-years in patients with low IgM levels and 4.8 per 100 patient-years in patients with low IgG levels were comparable with those in patients with immunoglobulin levels above the LLN (4.7 per 100 patient-years). Patients with human antichimeric antibody (9.2%) did not exhibit decreasing efficacy or present additional safety concerns.
Conclusion
These findings indicate that patients treated with repeated courses of rituximab have sustained clinical responses with no new adverse events.read more
Citations
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Journal ArticleDOI
Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2010
Daniel E. Furst,E.C. Keystone,J. Braun,F. C. Breedveld,G.-R. Burmester,F De Benedetti,Thomas Dörner,Paul Emery,Roy Fleischmann,Allan Gibofsky,Joachim R. Kalden,A. Kavanaugh,Bruce Kirkham,Philip J. Mease,J. Sieper,Nora G. Singer,Josef S Smolen,P.L.C.M. van Riel,Michael H. Weisman,Kevin L. Winthrop +19 more
TL;DR: The consensus statement is annotated to document the credibility of the data supporting it as much as possible and the number of possible references has become so large that reviews are sometimes included; if they contain category A references, they will be referred to as category A evidence.
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Adverse effects of biologics: a network meta‐analysis and Cochrane overview
Jasvinder A. Singh,George A. Wells,Robin Christensen,Elizabeth Tanjong Ghogomu,Lara J Maxwell,John K MacDonald,Graziella Filippini,Nicole Skoetz,Damian K Francis,Luciane Cruz Lopes,Gordon Guyatt,Jochen Schmitt,Loredana La Mantia,Tobias Weberschock,Juliana F. Roos,Hendrik Siebert,Sarah. Hershan,Chris Cameron,Michael P. Lunn,Peter Tugwell,Peter Tugwell,Rachelle Buchbinder +21 more
TL;DR: The rate of serious adverse events, serious infections, lymphoma, and congestive heart failure were not statistically significantly different between biologics and control treatment, and direct comparisons revealed that abatacept and anakinra were associated with a significantly lower risk ofserious adverse events compared to most other biologicics.
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EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases
S. van Assen,Nancy Agmon-Levin,Ori Elkayam,Ricard Cervera,Michele F. Doran,Maxime Dougados,Paul Emery,Paul Emery,Pierre Geborek,John P. A. Ioannidis,David Jayne,Cees G. M. Kallenberg,Ulf Müller-Ladner,Yehuda Shoenfeld,Yehuda Shoenfeld,Ljudmila Stojanovich,Guido Valesini,NM Wulffraat,Marc Bijl +18 more
TL;DR: Recommendations for vaccination in patients with AIIRD based on the currently available evidence and expert opinion were formulated, and more research is needed, particularly regarding the incidence of vaccine-preventable infectious diseases and the safety of vaccination in Patients with A IIRD.
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Rituximab therapy leads to rapid decline of serum IgG4 levels and prompt clinical improvement in IgG4-related systemic disease.
TL;DR: Treatment with rituximab led to prompt clinical and serologic improvement in these patients with refractory IgG4-RSD, and is a viable treatment option for this condition, suggesting that ritUXimab achieves its effects in IgG 4- RSD by depleting the pool of B lymphocytes that replenish short-lived IgG3-secreting plasma cells.
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Rituximab for the treatment of IgG4-related disease: lessons from 10 consecutive patients.
Arezou Khosroshahi,Mollie N. Carruthers,Vikram Deshpande,Sebastian Unizony,Daniel Bloch,John H. Stone +5 more
TL;DR: Treatment with RTX led to prompt clinical and serologic improvement in refractory IgG4-RD in all patients with active inflammation, and Serial treatments with RTX may lead to progressive declines in serum IgG 4 concentrations and better disease control.
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