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

• Published in: Clinical gastroenterology and hepatology Vol. 20; no. 11; pp. 2577 - 2587.e6
• Main Authors: Mahmoud, Remi, Schultheiss, Hans-Paul, Louwers, Jonas, van der Kaaij, Michiel, van Hellemondt, Boris, Mahmmod, Nofel, van Boeckel, Petra, Jharap, Bindia, Fidder, Herma, Oldenburg, Bas
• Format: Journal Article
• Language: English
• Published: United States 01-11-2022
• Subjects: Adalimumab - therapeutic use; Adult; Antibodies; Crohn Disease - drug therapy; Drug Therapy, Combination; Humans; Immunologic Factors - therapeutic use; Inflammatory Bowel Diseases - drug therapy; Infliximab - therapeutic use; Retrospective Studies; Treatment Outcome; Tumor Necrosis Factor Inhibitors; De-escalation; Remission; Azathioprine; Biologicals
• ISSN: 1542-3565; 1542-7714
• DOI: 10.1016/j.cgh.2022.01.019

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.
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.
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 The immunomodulator was withdrawn in 296 (48.2%) episodes after 0.9 (interquartile range, 0.6-2.1) years, which was not associated with a higher risk of LOR (aHR, 1.08; 95% confidence interval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).
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.