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

Remi Mahmoud; Hans-Paul Schultheiss; Jonas Louwers; Michiel van der Kaaij; Boris van Hellemondt; Nofel Mahmmod; Petra van Boeckel; Bindia Jharap; Herma Fidder; Bas Oldenburg

doi:10.1016/j.cgh.2022.01.019

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

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

Affiliations

¹ Division of Internal Medicine and Dermatology, Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands.
² Division of Internal Medicine, Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands.
³ Division of Internal Medicine, Department of Gastroenterology and Hepatology, Meander Medical Center, Amersfoort, the Netherlands.
⁴ Division of Internal Medicine and Dermatology, Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands. Electronic address: boldenbu@umcutrecht.nl.

PMID: 35101632
DOI: 10.1016/j.cgh.2022.01.019

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 The immunomodulator was withdrawn in 296 (48.2%) episodes after 0.9 (interquartile range, 0.6-2.1) years, which was not associated with a higher risk of LOR (aHR, 1.08; 95% confidence interval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

MeSH terms

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*

Substances

Adalimumab
Antibodies
Immunologic Factors
Infliximab
Tumor Necrosis Factor Inhibitors