Colon to Rectum
Clin Gastroenterol Hepatol. 2022;20(11):2577–87.e6
Immunomodulator withdrawal from anti-TNF therapy is not associated with loss of response in inflammatory bowel disease
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. The authors compared outcomes after immunomodulator withdrawal versus continuation of combination therapy.
Methods: This was a retrospective cohort study in a general hospital and a tertiary referral center. They 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 end points were loss of response (LOR) (i.e., anti-TNF discontinuation because of disease activity) and anti-drug antibodies (ADAs). Adjusted hazard ratios (aHRs) were calculated by mixed-effects Cox regression analysis.
Results: The authors included 614 treatment episodes of combination therapy in 543 individuals, yielding 1664 patient-years of follow-up. The immunomodulator was withdrawn in 296 episodes (48.2%) after 0.9 (interquartile range, 0.6–2.1) years, which was not associated with a higher risk of LOR (aHR = 1.08; 95% confidence interval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 ADAs 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 ADAs (HR per year = 0.56; 95% CI: 0.32–0.91). Higher prewithdrawal infliximab trough levels reduced the subsequent risks of ADAs and LOR. Infliximab trough levels were lower after immunomodulator withdrawal (p = 0.01).
Conclusions: Patients who withdrew the immunomodulator in this retrospective cohort were not at increased risk of loss of response within the following 1–2 years, but an increase in anti-drug antibodies was observed. These findings require prospective validation, preferably in adequately powered randomized controlled trials.