Safety and efficacy of additional courses of rituximab in patients with active rheumatoid arthritis: An open‐label extension analysis

Keystone, Edward; Fleischmann, Roy; Emery, Paul; Fürst, Daniel E.; Vollenhoven, Ronald van; Bathon, Joan M.; Dougados, Maxime; Baldassare, Andrew R.; Ferraccioli, Gianfranco; Chubick, Andrew; Udell, James; Cravets, Matthew; Agarwal, Sunil; Cooper, Simon; Magrini, Fabio

doi:10.1002/art.23059

Cited by 306 publications

(268 citation statements)

References 39 publications

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“…Rates of serious infection were not increased with prolonged followup or after successive courses of rituximab. Similar decreases in IgM levels have been reported with multidose rituximab regimens in RA (33), and this may complicate long-term therapy in some patients. Multiple courses of rituximab in this cohort appeared to be safe, although it is important to emphasize that patients who received multiple courses tended to be in remission, receiving little or no concomitant immunosuppressive therapy, and taking low doses of corticosteroids and were therefore generally at a lower risk of infection than other vasculitis cohorts.…”

Section: Discussionsupporting

confidence: 64%

“…Pharmacokinetic modeling in RA suggested that a body surface area-calculated dose would not improve the predictability of drug exposure (32), and clinical trials in RA have found that 2 infusions of 1 gm given 2 weeks apart is both effective (5,6) and safe with repeated use (33). The more extensive organ involvement that usually occurs in vasculitis as compared with RA raises the question of whether 2 infusions of 1 gm given 2 weeks apart would allow sufficient tissue penetration for B cell depletion from lesional tissue, perhaps allowing sustained remissions.…”

Section: Discussionmentioning

confidence: 99%

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A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody–associated vasculitis

Jones¹,

Ferraro²,

Chaudhry³

et al. 2009

Arthritis & Rheumatism

325

214

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Objective. B cell depletion with rituximab has allowed remissions in relapsing or refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in small studies. The aim of this study was to determine the efficacy and safety of rituximab for ANCA-associated vasculitis in a larger multicenter cohort. This permitted comparison of rituximab dosing regimens, the value of continuing immunosuppression, and investigation of ANCA and B cell levels as retreatment biomarkers.Methods. Retrospective, standardized data collection from 65 sequential patients receiving rituximab for refractory ANCA-associated vasculitis at 4 centers in the UK was used.Results. All patients achieved B cell depletion. Complete remission occurred in 49 of the 65 patients (75%), partial remission in 15 (23%), and no response in 1 (2%). The prednisolone dosage was reduced from 12.5 mg/day (median) to 9.0 mg/day at 6 months (P ‫؍‬ 0.0006). Immunosuppressive therapy was withdrawn in 37 of 60 patients (62%). Twenty-eight of 49 patients who achieved full remission (57%) experienced relapse (median 11.5 months). B cell return preceded relapse in 14 of 27 patients (52%). Although ANCA levels fell after rituximab therapy, relapse was not associated with ANCA positivity or a rise in ANCA levels. Neither the initial rituximab regimen (4 infusions of 375 mg/m 2 each given 1 week apart or 2 infusions of 1 gm each given 2 weeks apart) nor withdrawal of immunosuppressive therapy (37 of 60 patients [62%]) influenced the timing of relapse. Thirty-eight patients received >2 courses of rituximab, and complete remission was induced or maintained in 32 of them (84%). IgM levels fell, although IgG levels remained stable. Forty-six serious adverse events occurred, including 2 episodes of lateonset neutropenia, which were attributed to rituximab.Conclusion. Rituximab was effective remission induction therapy for refractory ANCA-associated vasculitis in this study. There was no difference in efficacy between the 2 main treatment regimens. Continuing immunosuppression did not reduce relapses. Relapses occurred, but re-treatment was effective and safe. There was no clear influence of rituximab on the frequency of serious adverse events. ANCA and B cell levels lacked sufficient sensitivity to guide the timing of re-treatment.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody–associated vasculitis

Jones¹,

Ferraro²,

Chaudhry³

et al. 2009

Arthritis & Rheumatism

325

214

View full text Add to dashboard Cite

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“…Longterm followup of patients treated with RTX in clinical trials has demonstrated good tolerability over multiple courses, with a safety profile similar to that of the placebo population 15 . Moreover, sustained clinical efficacy has also been documented over repeated courses 16,17 .…”

Section: Rheumatologymentioning

confidence: 96%

Safety and Effectiveness of Rituximab in Patients with Rheumatoid Arthritis Following an Inadequate Response to 1 Prior Tumor Necrosis Factor Inhibitor: The RESET Trial

Haraoui

Bokarewa²,

Kallmeyer³

et al. 2011

J Rheumatol

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Objective.To evaluate the safety and effectiveness of rituximab (RTX) in combination with methotrexate in patients with active rheumatoid arthritis (RA) after failure of a single tumor necrosis factor-α (TNF-α) inhibitor. Changes in patient-reported outcomes after primary treatment or retreatment with RTX and factors determining retreatment in clinical practice were also evaluated.Methods.In this phase 3b open-label, multicenter trial, patients received 2 slow infusions of RTX 1000 mg 14 days apart after premedication (primary treatment). Patients with a clinically relevant response could receive retreatment between 24 and 48 weeks. The primary endpoint was evaluation of safety. Secondary outcomes were safety of retreatment, effectiveness of primary treatment and retreatment, and changes in patient-reported outcomes after primary treatment or retreatment.Results.Of 120 patients enrolled at 36 centers and receiving primary RTX treatment, 77 received retreatment, 112 completed the 24-week primary treatment period, and 25 completed the 48-week primary treatment and retreatment period following a single course of RTX. The most common adverse events were mild to moderate nausea, vomiting, nasopharyngitis, and headache. No infections or infusion reactions were considered life-threatening. At 24 weeks, 58%, 27%, and 7% of patients achieved American College of Rheumatology 20, 50, and 70 improvements, respectively, and similar improvements were seen after retreatment.Conclusion.RTX was well tolerated, with a low incidence of infusion reactions and infections. Efficacy results, including enhanced response in rheumatoid factor-positive patients, were comparable to those reported in the literature. Based on its efficacy and safety profile and retreatment schedule, RTX is an attractive treatment option for patients that have not responded to a single TNF-α inhibitor.

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“…The response was not associated with a reduction in rheumatoid factor antibodies, and the mean serum levels of IgM, IgG, and IgA generally stayed within normal limits through the trial period. A follow-up study demonstrated the safety of subsequent infusions following B cell repopulation, with no increase in the infection rate (Keystone et al, 2007). On the basis of these results, Rituximab was approved in 2006 for use in RA patients who do not respond to TNF-antagonists (Sabahi and Anolik, 2006).…”

Section: Therapeutic Depletion Of B Cells In Ms With Rituximabmentioning

confidence: 99%

Chapter 4 B Cells and Autoantibodies in the Pathogenesis of Multiple Sclerosis and Related Inflammatory Demyelinating Diseases

McLaughlin

Wucherpfennig

2008

Advances in Immunology

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Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). The mainstream view is that MS is caused by an autoimmune attack of the CNS myelin by myelin-specific CD4 T cells, and this perspective is supported by extensive work in the experimental autoimmune encephalomyelitis (EAE) model of MS as well as immunological and genetic studies in humans. However, it is important to keep in mind that other cell populations of the immune system are also essential in the complex series of events leading to MS, as exemplified by the profound clinical efficacy of B cell depletion with Rituximab. This review discusses the mechanisms by which B cells contribute to the pathogenesis of MS and dissects their role as antigen-presenting cells (APCs) to T cells with matching antigen specificity, the production of proinflammatory cytokines and chemokines, as well as the secretion of autoantibodies that target structures on the myelin sheath and the axon. Mechanistic dissection of the interplay between T cells and B cells in MS may permit the development of B cell based therapies that do not require depletion of this important cell population.

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Safety and efficacy of additional courses of rituximab in patients with active rheumatoid arthritis: An open‐label extension analysis

Cited by 306 publications

References 39 publications

A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody–associated vasculitis

A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody–associated vasculitis

Safety and Effectiveness of Rituximab in Patients with Rheumatoid Arthritis Following an Inadequate Response to 1 Prior Tumor Necrosis Factor Inhibitor: The RESET Trial

Chapter 4 B Cells and Autoantibodies in the Pathogenesis of Multiple Sclerosis and Related Inflammatory Demyelinating Diseases

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