Treatment with a third anti-TNF (tumor necrosis factor) agent could be an effective therapeutic option for patients with Crohn's disease who have lost response, or developed intolerance, to two previous anti-TNF agents.

Failure of, or intolerance to, an anti-TNF agent can be a significant problem when treating Crohn's disease. Studies have demonstrated that switching to a second anti-TNF agent can be effective. However, treatment with a second agent can also sometimes fail.

Now, Allez and colleagues have carried out a retrospective study to analyze the safety and efficacy of treatment with a third anti-TNF agent after failure of two other anti-TNF agents.

A total of 67 patients with active disease who had received a third anti-TNF agent were included in the study. Only those patients who had received a third agent because of primary failure, loss of response or intolerance to two other anti-TNF agents were included.

Data were collected using a standardized questionnaire. The primary analysis included clinical response (defined as a decrease in the Harvey-Brashaw index of more than 3 points) at weeks 6 and 20 after the start of treatment with the third anti-TNF agent. The secondary analysis investigated the probability of continuing to receive treatment during follow-up.

41 patients (61%) had a clinical response at week 6. At week 20, a clinical response was observed in 34 patients (51%). The probability of continuing to receive treatment with the third anti-TNF agent at 3, 6 and 9 months was 68%, 60% and 45%, respectively.

Serious adverse events occurred in five patients (7%), including two deaths. Notably, a 37-year-old male patient died suddenly after successive treatment with certolizumab pegol and adalimumab—with a 3-day interval between treatments. The authors suggest that a 'wash-out' period between treatment with two different agents may be beneficial. Anti-TNF treatment also had to be stopped in 14 patients as a result of adverse events.

In conclusion, a third anti-TNF agent could be effective for treating patients with Crohn's disease in whom two previous anti-TNF agents have failed. However, owing to the safety concerns raised in this study, the authors recommend that “this strategy ... should only be considered after careful case-by-case discussion.”