Adalimumab and Methotrexate Beneficial for Pediatric Crohn Disease suggests a new study published in the Gastroenterology
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