The treatment of rheumatoid arthritis has been revolutionized by the use of anti tumor necrosis factor alpha (anti-TNF) drugs.  These are biologic medicines which act with great specificity on the cells and pathways responsible for rheumatoid arthritis.  But what if a patient fails one anti-TNF drug?  Will using another one be effective?

A new study has shown that if a patient with rheumatoid arthritis is unable to tolerate or fails to respond to one anti-TNF agent, he or she is likely to be able to continue treatment with a second anti-TNF agent. However, a significant number will again experience inefficacy or toxicity.

The findings come from a large prospective study that reviewed the British Society for Rheumatology Biologics Register and was published in the January 2007 issue of Arthritis and Rheumatism.

The analysis evaluated 6,739 patients who started new anti-TNF treatment: 876 on adalimumab (Humira), 2,826 on etanercept (Enbrel) and 3,037 on infliximab (Remicade). During a mean of 15 months of follow-up, 841 patients stopped taking the initial anti-TNF-alpha agent because of a lack of efficacy and 1,023 stopped because of toxicity.

Of the total number of patients who stopped taking the first drug, 503 switched to a second drug because of a lack of efficacy and 353 switched because of toxicity.

Of those patients who switched, 73% remained on the second drug for at least six months.

Those patients who switched because of inefficacy were 2.7 times more likely to stop taking the second drug for continued inefficacy. This was not accompanied by an increase in adverse events.

Those who switched because of toxicity were 2.3 times more likely to discontinue the second drug because of continued toxicity, but there was no associated change in efficacy. The types of adverse event associated with the second drug were often different from those caused by the first.

The authors noted that "based on treatment continuation rates, there is a strong case for switching patients to a second anti-TNF-alpha agent when failure to respond to the first agent occurs... However, our data also indicated that the reasons for anti-TNF-alpha failure were recurrent."

For patients who fail with two agents, it remains to be determined "whether there is a role for yet a third anti-TNF-alpha agents in these patients," the investigators conclude, "or whether it is better to move on to a different class of biologic agent."

(Hyrich KL, Lunt M, Watson KD, Symmons DPM, Silman AJ, et al. Outcomes after switching from one anti-tumor necrosis factor ± agent to a second anti-tumor necrosis ± agent in patients with rheumatoid arthritis: Results from a large UK National Cohort study. Arthritis Rheum 2007;56:13-20).

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