Study Identifies 4 Factors Predicting Response to Infliximab in CD

Infliximab is effective in treating moderate to severe Crohn disease (CD), but even in patients who achieve remission, loss of response (LOR) linked with antibody development has been reported. A recent study sought to clarify factors that could predict therapeutic response to infliximab in Japanese patients with CD, and found 4 key indicators that may predict response in clinical practice.

From 2014 to 2015, researchers enrolled 121 adult Japanese patients with CD at a single center and prospectively followed these patients for 1 year. In addition to being monitored for disease activity, the patients also consented to genetic analysis.

In total, 71 patients achieved remission, and 50 did not. Those who achieved remission had a mean disease duration of 12.1 (±7.5)years, and those who did not achieve remission had a mean disease duration of 17.3 (±7.4) years. Among those achieving remission, 14.1% experienced treatment escalation by doubling the infliximab dose to 10 mg/kg, while 52% of those who did not achieve remission experienced double-dosing. A total of 70.4% of those who achieved remission used concomitant immunomodulators, while only 62.0% of those who did not achieve remission used combination therapy.

Finally, multivariate logistic analysis adjusted by patient characteristics showed that the therapeutic response to infliximab was decreased in patients with the mutant allele oftumor necrosis factor (TNF)-α -857 C>T versus with those patients with the wild-type allele (odds ratio, 0.33; 95% CI, 0.12-0.95).

The authors concluded that longer disease duration, double-dosing with infliximab, no concomitant use of an immunomodulator, and the presence of the TNF-α -857 C>T polymorphism were all linked to nonremission during maintenance therapy with infliximab.

According to the authors, longer disease duration may be linked with development of bowel complications—such as strictures—that make controlling CD more challenging.

Furthermore, therapeutic response to infliximab was decreased in patients receiving infliximab at a double dose, suggesting that patients may have become nonresponsive to the TNF blockade due to antibody production. Those who received immunomodulators had a better response to infliximab, consistent with reports that combination therapy is preferable to monotherapy in inflammatory diseases.

These results, conclude the authors, could potentially be utilized to establish an individualized treatment strategy for patients with CD who are given infliximab therapy.

Reference

Matsuoka K, Hamada S, Shimizu M, et al. Factors predicting the therapeutic response to infliximab during maintenance therapy in Japanese patients with Crohn’s disease [published online October 4, 2018.] Plos One. doi: 10.1371/journal.pone.0204632.