Adalimumab and Methotrexate Beneficial for Pediatric Crohn Disease

Tumor necrosis factor inhibitors, including infliximab and adalimumab, are a mainstay of pediatric Crohn’s disease therapy; however, nonresponse and loss of response are common. As combination therapy with methotrexate may improve response, we performed a multicenter, randomized, double-blind, placebo-controlled pragmatic trial to compare tumor necrosis factor inhibitors with oral methotrexate to tumor necrosis factor inhibitor monotherapy.

Patients with pediatric Crohn’s disease initiating infliximab or adalimumab were randomized in 1:1 allocation to methotrexate or placebo and followed for 12–36 months. The primary outcome was a composite indicator of treatment failure. Secondary outcomes included anti-drug antibodies and patient-reported outcomes of pain interference and fatigue. Adverse events (AEs) and serious AEs (SAEs) were collected.

Results

• Of 297 participants, 156 were assigned to methotrexate and 141 to placebo

• In the overall population, time to treatment failure did not differ by study arm

• Among infliximab initiators, there were no differences between combination and monotherapy

• Among adalimumab initiators, combination therapy was associated with longer time to treatment failure

• A trend toward lower anti-drug antibody development in the combination therapy arm was not significant

• No differences in patient-reported outcomes were observed.

• Combination therapy resulted in more AEs but fewer SAEs.

Among adalimumab but not infliximab initiators, patients with pediatric Crohn’s disease treated with methotrexate combination therapy experienced a 2-fold reduction in treatment failure with a tolerable safety profile. ClinicalTrials.gov, Number: NCT02772965

Reference:

Comparative Effectiveness of Anti–Tumor Necrosis Factor in Combination with Low-Dose Methotrexate vs Anti–Tumor Necrosis Factor Monotherapy in Pediatric Crohn’s Disease: A Pragmatic Randomized Trial. Michael D. Kappelman, David A. Wohl, Hans H. Herfarth, Morris Weinberger, Shehzad A. Saeed, Athos Bousvaros. Gastroenterology

Published:March 31, 2023DOI:https://doi.org/10.1053/j.gastro.2023.03.224

Keywords:

Comparative, Effectiveness, Anti–Tumor, Necrosis, Factor, Combination, Low-Dose Methotrexate, Anti–Tumor Necrosis, Factor, Monotherapy, Pediatric, Crohn’s Disease, Pragmatic, Randomized, Trial, Michael D. Kappelman, David A. Wohl, Hans H. Herfarth, Morris Weinberger, Shehzad A. Saeed, Athos Bousvaros, Gastroenterology