R. Mahmoud,J.P.D. Schultheiss,J.M. Louwers,M.T. van der Kaaij,B.P. van Hellemondt,N. Mahmmod,P.G. van Boeckel,B. Jharap,H.H. Fidder,B. Oldenburg Published in Clinical Gastroenterology and Hepatology.
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 The immunomodulator was withdrawn in 296 (48.2%) episodes after 0.9 (interquartile range, 0.6–2.1) years, which was not associated with a higher risk of LOR (aHR, 1.08; 95% confidence interval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.