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. 2022 Nov;20(11):2577-2587.e6.
doi: 10.1016/j.cgh.2022.01.019. Epub 2022 Jan 31.

Immunomodulator Withdrawal From Anti-TNF Therapy Is Not Associated With Loss of Response in Inflammatory Bowel Disease

Remi Mahmoud  1 , Hans-Paul Schultheiss  1 , Jonas Louwers  1 , Michiel van der Kaaij  1 , Boris van Hellemondt  1 , Nofel Mahmmod  2 , Petra van Boeckel  2 , Bindia Jharap  3 , Herma Fidder  1 , Bas Oldenburg  4
Affiliations

Immunomodulator Withdrawal From Anti-TNF Therapy Is Not Associated With Loss of Response in Inflammatory Bowel Disease

Remi Mahmoud et al. Clin Gastroenterol Hepatol. 2022 Nov.

Abstract

Background and aims: The benefit of concomitant immunomodulators (thiopurines or methotrexate) in patients with inflammatory bowel disease (IBD) on anti-tumor necrosis factor α (anti-TNF) (infliximab or adalimumab) maintenance therapy is debated. We compared outcomes after immunomodulator withdrawal vs continuation of combination therapy.

Methods: This was a retrospective cohort study in a general hospital and a tertiary referral center. We included adult IBD patients, receiving anti-TNF therapy for ≥4 months, plus an immunomodulator at baseline, between January 1, 2011, and January 1, 2019. The primary endpoints were loss of response (LOR) (ie, anti-TNF discontinuation because of disease activity) and anti-drug antibodies. Adjusted hazard ratios (aHRs) were calculated by mixed-effects Cox regression analysis.

Results: 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 The immunomodulator was withdrawn in 296 (48.2%) episodes after 0.9 (interquartile range, 0.6-2.1) years, which was not associated with a higher risk of LOR (aHR, 1.08; 95% confidence interval [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. Clinical remission at the time of withdrawal reduced the risk of LOR (aHR, 0.48; 95% CI, 0.25-0.93), while longer duration of combination therapy before withdrawal decreased the risk of anti-drug antibodies (HR per year, 0.56; 95% CI, 0.32-0.91). Higher prewithdrawal infliximab trough levels reduced the subsequent risks of anti-drug antibodies and LOR. Infliximab trough levels were lower after immunomodulator withdrawal (P = .01).

Conclusions: 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 anti-drug antibodies was observed. Our findings require prospective validation, preferably in adequately powered randomized controlled trials.

Keywords: Azathioprine; Biologicals; De-escalation; Remission.

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