Rheumatoid arthritis: biological drugs and risk of infection

The first phase 3 trial of a biological drug for the treatment of rheumatoid arthritis was reported in 1999. 1 Maini R St Clair EW Breedveld F et al. for the ATTRACT study groupInfliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. Lancet. 1999; 354: 1932-1939 Summary Full Text Full Text PDF PubMed Scopus (2311) Google Scholar Infliximab, a monoclonal antibody that targets tumour necrosis factor (TNF), was shown to reduce disease severity. Nine biological drugs are now on the market for treatment of rheumatoid arthritis, which target various points in the inflammatory pathway, including TNF, interleukin 1, interleukin 6, CD28, and B cells. Biological treatments are undoubtedly effective; however, concerns about their safety have persisted, especially for the risk of infection. Although the results of the first trial of infliximab did not show an increased number of serious infections, 1 Maini R St Clair EW Breedveld F et al. for the ATTRACT study groupInfliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. Lancet. 1999; 354: 1932-1939 Summary Full Text Full Text PDF PubMed Scopus (2311) Google Scholar one case of tuberculosis and one of coccidioidomycosis were recorded during the second 6 months of follow-up. 2 Lipsky PE van der Heijde DM St Clair EW et al. for the Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study GroupInfliximab and methotrexate in the treatment of rheumatoid arthritis. N Engl J Med. 2000; 343: 1594-1602 Crossref PubMed Scopus (3005) Google Scholar Were these infections chance occurrences or an indication of a genuine risk? The possibility that biological drugs could increase the rate of infection has led to much attention over the past 15 years. Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysisStandard-dose and high-dose biological drugs (with or without traditional DMARDs) are associated with an increase in serious infections in rheumatoid arthritis compared with traditional DMARDs, although low-dose biological drugs are not. Clinicians should discuss the balance between benefit and harm with the individual patient before starting biological treatment for rheumatoid arthritis. Full-Text PDF