Infliximab - A review of its use in the management of rheumatoid arthritis

Infliximab is a chimaeric monoclonal antibody to human tumour necrosis fact or-alpha (TNF alpha). It binds to both soluble and transmembrane forms of T NF alpha at picomolar concentrations in vitro. Secondary to inhibition of T NF alpha, infliximab reduces serum levels of inflammatory mediators and vas cular endothelial growth factor, decreases the expression of chemokines in the synovial tissue and reduces lymphocyte migration into the joints of pat ients with rheumatoid arthritis. In 2 multicentre randomised double-blind trials conducted over 26 and 30 we eks, infliximab plus methotrexate was significantly more effective than pla cebo plus methotrexate according to American College of Rheumatology respon se criteria in patients with active rheumatoid arthritis. A substantial res ponse to infliximab-containing regimens was evident within 2 weeks. Extensi on phases of these studies indicate sustained clinical efficacy for up to 5 4 weeks. Of considerable importance are preliminary 1-year radiographic fin dings that show zero median progression of joint damage in infliximab plus methotrexate recipients compared with a 7 to 8% deterioration in placebo pl us methotrexate recipients. Headache, nausea, upper respiratory tract infection and infusion-related re actions are the most commonly reported adverse events with infliximab. Seri ous events occurred in 4.4% of infliximab versus 1.8% of placebo recipients . In the largest clinical trial, 2 patients died from disseminated infectio n and 3 developed new or recurrent malignancies, although the exact relatio nship between infliximab and these events is unknown. To date, 2 patients w ith rheumatoid arthritis have developed drug-induced lupus. About 10% of pa tients may develop antibodies to infliximab, although the clinical signific ance of these is presently unknown. Conclusion: Infliximab represents an important advance in the treatment of rheumatoid arthritis, with tolerability concerns raised by early studies ha ving been eased somewhat by mon recent data in larger patient numbers. If p reliminary results indicating that infliximab is able to arrest joint destr uction in patients with rheumatoid arthritis are corroborated, the drug wil l likely become an integral component of future management strategies for t his difficult-to-treat condition.