Finckh A et al. (2006) Evidence for differential acquired drug resistance to anti-tumour necrosis factor agents in rheumatoid arthritis. Ann Rheum Dis 65: 746–752

Loss of effectiveness of traditional disease-modifying antirheumatic drugs (DMARDs) is a common problem for patients with rheumatoid arthritis (RA), and the development of resistance to anti-tumor necrosis factor (TNF) therapy is starting to be recognized. A study by Finckh et al. has now shown that acquired resistance to anti-TNF therapies differs between agents.

The study included 1,198 patients with RA, treated with infliximab, etanercept or adalimumab, identified from The Swiss Clinical Quality Management of RA System. Data were collected between January 1998 and September 2004. Several outcomes indicated resistance to anti-TNF therapy: an increase in concomitant DMARD treatment, dose escalation of anti-TNF treatment, and anti-TNF discontinuation.

The results showed that infliximab was associated with a higher risk of requiring intensification of co-therapy with traditional DMARDs compared with etanercept or adalimumab, and that dose escalation often occurred in infliximab-treated patients, but not in patients treated with etanercept or adalimumab. Discontinuation rates were similar for all three anti-TNF agents, with a median duration of therapy of 3.21 years.

The authors comment that the dose escalation associated with infliximab could have resulted from initial dose adjustments, rather than from acquired infliximab resistance; however, both phenomena are likely to be involved. This study had some limitations, including a short follow-up of patients treated with adalimumab, because of its recent launch. The authors conclude that further research into the mechanisms of anti-TNF resistance is required.