Sustained benefit with anti-TNFα less likely to lead to subsequent loss of response in IBD

Inflammatory bowel disease (IBD) patients receiving treatment with antitumour necrosis factor alpha (anti-TNFα) for more than 2 years represent a distinct group who obtain prolonged clinical benefit and tolerate maintenance treatment, according to a study.

In IBD, the use of anti-TNFα therapy is common but comes with high annual rates of loss of response (13–21 percent per patient-year). To determine whether this incidence of loss of response declined with longer treatment duration, researchers looked at 844 anti-TNFα treatment episodes (duration ≥4 months) in 708 patients with ulcerative colitis (UC) or Crohn's disease (CD).

The median treatment duration per episode was 2.4 years, and the duration was >4 years in 247 (29.3 percent) episodes. Anti-TNFα trough levels and/or antidrug antibodies were measured at least once in 681 (80.7 percent) treatment episodes.

Loss of response occurred in 211 (25 percent) treatment episodes, with antidrug antibodies found in 66 (31.3 percent). The incidence of loss of response was threefold lower after the fourth year of treatment than in the first year (4.8 percent vs 17.2 percent per patient-year; p<0.001).

From the first year to after the fourth year, there were parallel reductions in the incidence of anti-TNFα discontinuation (28.6 percent vs 14.0 percent per patient-year; p<0.001) and dose escalations (38.0 percent vs 6.8 percent per patient-year; p<0.001).

Several predictors of loss of response emerged. These included UC (adjusted hazard ratio [aHR], 1.53, 95 percent confidence interval [CI], 1.10–2.15) and, among patients with CD, stricturing or penetrating disease (aHR, 1.68, 95 percent CI, 1.15–2.46) and male sex (aHR, 0.55, 95 percent CI, 0.38–0.78). Conversely, use of immunomodulators was protective against loss of response with antidrug antibodies (aHR, 0.42, 95 percent CI, 0.24–0.74).