Anti-TNF alpha therapies for rheumatoid arthritis

The cytokine tumour necrosis factor alpha is found at increased levels in the joint tissues of patients with rheumatoid arthritis. It is an important mediator of inflammation and tissue destruction. Two therapies are currently available: Etanercept and Infliximab. It is believed that they represent a significant advance in the treatment of rheumatoid arthritis.

A systematic review has examined the risk of serious infections and malignancies in patients on anti-TNF antibody therapy (1):

• estimated effects for high and low doses separately
• pooled odds ratio for malignancy was 3.3 (95% confidence interval [CI], 1.2-9.1) and for serious infection was 2.0 (95% CI, 1.3-3.1). Malignancies were significantly more common in patients treated with higher doses compared with patients who received lower doses of anti-TNF antibodies
• for patients treated with anti-TNF antibodies in the included trials, the number needed to harm was 154 (95% CI, 91-500) for 1 additional malignancy within a treatment period of 6 to 12 months. For serious infections, the number needed to harm was 59 (95% CI, 39-125) within a treatment period of 3 to 12 months
• the study authors concluded that there is evidence of an increased risk of serious infections and a dose-dependent increased risk of malignancies in patients with rheumatoid arthritis treated with anti-TNF antibody therapy. The formal meta-analysis with pooled sparse adverse events data from randomized controlled trials serves as a tool to assess harmful drug effects

Reference:

1. Bongartz T et al. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006 May 17;295(19):2275-85. Review. Erratum in: JAMA. 2006 Jun 7;295(21):2482.