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Benefit-Risk Assessment of Infliximab in the Treatment of Rheumatoid Arthritis

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Abstract

In the last decade, there have been substantial advances in the treatment of rheumatoid arthritis with the addition of several new disease-modifying agents to the therapeutic armamentarium. Biological agents targeting tumour necrosis factor (TNF) represent one such important addition. Infliximab, a chimeric anti-TNF monoclonal antibody, has shown remarkable promise in alleviating the signs and symptoms of rheumatoid arthritis in addition to retarding radiographic disease progression when used in combination with methotrexate. In its pivotal phase III trial, the addition of infliximab to patients with methotrexate-refractory disease was associated with substantial clinical benefit. Using American College of Rheumatology criteria for improvement, one-half of patients receiving infliximab (3 mg/kg every 8 weeks) plus methotrexate showed at least 20% improvement compared with only 20% of those receiving placebo plus methotrexate (p < 0.001) with over one-half of eventual responders obtaining criteria for improvement by the second week of observation. Although its use has been met with much deserved enthusiasm, recent reports have highlighted several potential serious adverse effects associated with infliximab (and other TNF antagonists), including infusion reactions, congestive heart failure, drug-induced lupus, and CNS demyelination. In addition, recent reports have cited the potential for reactivation of mycobacterial and fungal infection in patients receiving infliximab, mandating appropriate tuberculosis screening prior to drug initiation. Although the frequency of serious drug-related toxicity (requiring discontinuation of the agent) appears to be quite low, these reports underscore the need for caution and close surveillance with the administration of TNF inhibitors, particularly given that strategies aimed at preventing toxicity remain unproven. Despite its potential for toxicity, infliximab remains a valuable alternative for patients with rheumatoid arthritis.

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Acknowledgements

Dr Mikuls has no conflicts of interest to report. Dr Moreland is the Director of a large academic Arthritis Clinical Intervention Programme. He has received grant support or served as a consultant for the biotechnology and/or pharmaceutical companies that develop and/or market tumour necrosis factor inhibitors. These include: Centocor, Immunex, Amgen, Wyeth, Pharmacia, Knoll, Abbott, and Johnson and Johnson. Dr Moreland also received grant support and has been a consultant for other companies that are developing antirheumatic medications.

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Authors and Affiliations

  1. Department of Medicine, Section of Rheumatology and Immunology, University of Nebraska Medical Center and VA Medical Center 983025, Omaha, Nebraska, NE 68198-3025, USA

    Ted R. Mikuls

  2. Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA

    Larry W. Moreland

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Correspondence to Ted R. Mikuls.

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Mikuls, T.R., Moreland, L.W. Benefit-Risk Assessment of Infliximab in the Treatment of Rheumatoid Arthritis. Drug-Safety 26, 23–32 (2003). https://doi.org/10.2165/00002018-200326010-00003

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