Withdrawing IMM Not Associated With Loss of Response to TNFi

Patients with inflammatory bowel disease (IBD) treated with antitumor necrosis factor (anti-TNF) maintenance therapy and concomitant immunomodulators (IMM) such as thiopurines and methotrexate were not at higher risk of losing response to anti-TNF therapy over the subsequent 1 to 2 years, according to results of a new study.

However, these patients did show higher levels of antidrug antibodies (ADABs) and reduced trough levels of anti-TNFs following withdrawal of IMMs.

This retrospective cohort study identified adult patients with IBD treated at a general hospital and a tertiary referral center who received anti-TNF therapy for more than 4 months and an immunomodulator at baseline during the period January 1, 2011, and January 1, 2019.  The primary endpoints were loss of response (LOR) to the anti-TNF—defined as discontinuation of the therapy due to heightened disease activity—and the development of ADABs. The investigators calculated adjusted hazard rates (aHR) by mixed-effects Cox regression analysis.

“We included 614 treatment episodes of combination therapy in 543 individuals, yielding 1664 patient-years of follow-up. The immunomodulator was withdrawn in 296 (48.2%) episodes after 0.9 (IQR 0.6 – 2.1) years, which was not associated with a higher risk of LOR (aHR 1.08, 95%CI 0.72 – 1.61), although anti-drug antibodies were detected more frequently (aHR 2.14, 95%CI: 1.17 – 3.94), compared with continuation.”

The researchers found that patients who were in clinical remission when IMMs were withdrawn had a reduced risk of LOR (aHR 0.48, 95%CI: 0.25 – 0.93), while the risk of developing antidrug antibodies was lower among patients with a longer duration of combination therapy before withdrawal (HR 0.56 per year, 95%CI: 0.32 – 0.91). Higher trough levels of infliximab prior to withdrawal of IMMs also reduced subsequent risks of antidrug antibodies and LOR, the authors noted, even though trough levels of the drug were lower after withdrawing the IMM (p=0.01).

“Patients who withdrew the immunomodulator in this retrospective cohort were not at increased risk of LOR within the following 1-2 years, but an increase in antidrug antibodies was observed,” the authors concluded. “Our findings require prospective validation, preferably in adequately powered randomized-controlled trials.”

—Rebecca Mashaw

Reference:
Mahmoud R, Schultheiss JPD, Louwers JM. Immunomodulator withdrawal from anti-TNF therapy is not associated with loss of response in inflammatory bowel disease. Clin Gastroenterol Hepatol. Published online January 28, 2022. DOI:10.1016/j.cgh.2022.01.019