Safety of Biologic Therapy in Rheumatoid Arthritis and Other Autoimmune Diseases: Focus on Rituximab

doi:10.1016/j.semarthrit.2008.01.001

Seminars in Arthritis and Rheumatism

Volume 38, Issue 4, February 2009, Pages 265-280

https://doi.org/10.1016/j.semarthrit.2008.01.001 Get rights and content

Objectives

To review the safety of biologic agents used to treat rheumatoid arthritis (RA) and other autoimmune diseases, with a focus on rituximab.

Methods

Information was gathered from a search of the PubMed database and from major congress abstract listings through June 2007.

Results

Rituximab is approved for treating RA in patients with an inadequate response to TNF inhibitors and is under study in other indications for RA and other autoimmune disorders. The current safety profile of rituximab in RA is known from Phase II and III studies conducted preapproval, treating approximately 750 patients, as well as from long-term extension studies with repeated therapy. Clinical trials have established that the most common adverse events are infusion-associated reactions, seen in 29 to 40% of patients, most of which are mild to moderate and occur following the first rituximab infusion, with incidence and severity decreasing with subsequent infusions. Rates of infections and serious infections to date are within the range expected for RA patients treated with other biologic agents, but the longer term effects of B-cell depletion and the effects of repeated treatment on the risk of infections are uncertain. Information is limited for rituximab safety in other autoimmune disorders but current data do not suggest that there is a significant difference in adverse events from that previously reported.

Conclusions

Rituximab is an important addition to the rheumatologist's armamentarium for the treatment of difficult RA and ongoing trials will determine its utility in other indications for RA and other autoimmune conditions. The true safety profile of rituximab will emerge as larger numbers of patients are treated in routine clinical practice.

Section snippets

Methods

The information included in this review was gathered from a search of the PubMed database (the initial search used the strategy: [Safety] AND [rituximab OR adalimumab OR infliximab OR etanercept OR abatacept OR anakinra NOT lymphoma]) limited to articles on humans in English published between January 1997 and June 2007. The 543 retrieved articles were hand searched to identify relevant information and secondary citations. The PubMed search was complemented by a search of major congress abstract

Traditional Disease-Modifying Antirheumatic Drugs

The use of disease-modifying antirheumatic drugs (DMARDs) early in the course of the disease is the recommended option for patients newly diagnosed with RA. Traditional DMARDs, such as methotrexate (MTX), leflunomide, sulfasalazine, and hydroxychloroquine, either as monotherapy or in combination, are currently the first medications usually prescribed in patients with newly diagnosed RA, although this approach may change as data about the first-line use of biologics, especially the TNF

Discussion

Rituximab was effective in the 2 Phase II trials involving patients with severe RA as well as in a Phase III trial in patients who had an inadequate response or were intolerant to at least 1 TNF inhibitor. In the Phase III study, clinical benefit was observed not only with regard to clinical signs and symptoms and improvement in patient function at 6 months but also with a statistically significant slowing of radiographic progression at 1 year. The current safety profile of rituximab indicates

Acknowledgment

Writing assistance for this article was provided by Genentech, Inc.

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Rheumatoid arthritisSafety of Biologic Therapy in Rheumatoid Arthritis and Other Autoimmune Diseases: Focus on Rituximab

Objectives

Methods

Results

Conclusions

Section snippets

Methods

Traditional Disease-Modifying Antirheumatic Drugs

Discussion

Acknowledgment

Eur J Radiol

Rheum Dis Clin North Am

Ann Oncol

J Emerg Med

Transpl Immunol

Blood

Blood

J Am Acad Dermatol

Epidemiology and burden of illness of rheumatoid arthritis

Pharmacoeconomics

B-cell depletion for rheumatic diseases: where are we?

MedGenMed

Guidelines for the management of rheumatoid arthritis: 2002 Update

Arthritis Rheum

A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis

Rheumatology (Oxford)

Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexateLeflunomide Rheumatoid Arthritis Investigators Group

Arch Intern Med

Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: results of a two-year, randomized, double-blind, placebo-controlled trial

Arthritis Rheum

B cell-directed therapy in rheumatoid arthritis—clinical experience

J Rheumatol Suppl

Safety of rituximab in the treatment of B cell malignancies: implications for rheumatoid arthritis

Arthritis Res Ther

Vaccine responses in patients with rheumatoid arthritis

Curr Rheumatol Rep

Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial

Ann Intern Med

Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition

N Engl J Med

Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs: A one-year randomized, placebo-controlled study

Arthritis Rheum

Selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving etanercept: a randomised clinical trial

Ann Rheum Dis

Humira® [adalimumab] prescribing information

Adalimumab, a fully human anti tumor necrosis factor-α monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: results of STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis)

J Rheumatol

Long-term efficacy and safety of adalimumab plus methotrexate in patients with rheumatoid arthritis: ARMADA 4-year extended study

Ann Rheum Dis

Safety and efficacy of disease-modifying antirheumatic agents in rheumatoid arthritis and juvenile rheumatoid arthritis

Exp Opin Drug Saf

Infliximab and methotrexate in the treatment of rheumatoid arthritisAnti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group

N Engl J Med

Safety analyses of adalimumab (HUMIRA®) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis

Ann Rheum Dis

Kineret® [anakinra] prescribing information

Addressing the safety of anakinra in patients with rheumatoid arthritis

Rheumatology (Oxford)

Safety of extended treatment with anakinra in patients with rheumatoid arthritis

Ann Rheum Dis

Effectiveness of anakinra in rheumatic disease in patients naive to biological drugs or previously on TNF blocking drugs: an observational study

Clin Rheumatol

Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate

Arthritis Rheum

Enbrel® [etanercept] prescribing information

Long-term safety, efficacy, and radiographic outcome with etanercept treatment in patients with early rheumatoid arthritis

J Rheumatol

A long-term, open-label trial of the safety and efficacy of etanercept (Enbrel) in patients with rheumatoid arthritis not treated with other disease-modifying antirheumatic drugs

Ann Rheum Dis

Efficacy and safety of combination etanercept and methotrexate versus etanercept alone in patients with rheumatoid arthritis with an inadequate response to methotrexate: the ADORE study

Ann Rheum Dis

Etanercept treatment in adults with established rheumatoid arthritis: 7 years of clinical experience

J Rheumatol

Remicade® [infliximab] prescribing information

The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities: a large, randomized, placebo-controlled trial

Arthritis Rheum

The clinical and cost-effectiveness of anakinra for the treatment of rheumatoid arthritis in adults: a systematic review and economic analysis

Health Technol Assess

A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness

Health Technol Assess

Rheumatoid arthritis
Safety of Biologic Therapy in Rheumatoid Arthritis and Other Autoimmune Diseases: Focus on Rituximab

Humira^® [adalimumab] prescribing information

Safety analyses of adalimumab (HUMIRA^®) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis

Kineret^® [anakinra] prescribing information

Enbrel^® [etanercept] prescribing information

Remicade^® [infliximab] prescribing information

Orencia^® [abatacept] prescribing information