Low Dose Oral Methotrexate in Pediatric Crohn's Disease Patients Initiating Anti-Tumor Necrosis Factor (Anti-TNF) Therapy

Phase 3 Completed 306 enrolled University of North Carolina, Chapel Hill Children's Hospital Medical Center, Cincinnati · collab Grifols Diagnostics Solutions, Inc · collab ImproveCareNow (ICN) · collab National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) · collab National Institutes of Health (NIH) · collab Patient-Centered Outcomes Research Institute · collab The Leona M. and Harry B. Helmsley Charitable Trust · collab

RandomizedParallel-groupTriple-blindTreatment

Summary

The purpose of this study is to determine whether adding low dose methotrexate to anti -TNF therapy is more effective than treatment with anti-TNF therapy alone in inducing and maintaining steroid-free remission for children with Crohn's Disease.

Timeline

Start: 2016-10
Primary completion: 2022-04-07
Completion: 2022-04-07

Outcome

Missed primary endpoint

registry analysis (superiority test); Methotrexate vs Sugar Pill (Placebo); p = 0.08; Hazard Ratio (HR) 0.69 (95% CI 0.45 to 1.05); Log Rank NCT02772965 ↗

paper In the overall population, time to treatment failure did not differ by study arm (hazard ratio, 0.69; 95% CI, 0.45-1.05). PMID 37004887 ↗

Publications

Kappelman MD, Wohl DA, Herfarth HH, Firestine AM, Adler J, Ammoury RF, Aronow JE, Bass DM, Bass JA, Benkov K, Tobi CB, Boccieri ME, Boyle BM, Brinkman WB, Cabera JM, Chun K, Colletti RB, Dodds CM, Dorsey JM, Ebach DR, Entrena E, Forrest CB, Galanko JA, Grunow JE, Gulati AS, Ivanova A, Jester TW, Kaplan JL, Kugathasan S, Kusek ME, Leibowitz IH, Linville TM, Lipstein EA, Margolis PA, Minar P, Molle-Rios Z, Moses J, Olano KK, Osaba L, Palomo PJ, Pappa H, Park KT, Pashankar DS, Pitch L, Robinson M, Samson CM, Sandberg KC, Schuchard JR, Seid M, Shelly KA, Steiner SJ, Strople JA, Sullivan JS, Tung J, Wali P, Zikry M, Weinberger M, Saeed SA, Bousvaros A. Comparative Effectiveness of Anti-TNF in Combination With Low-Dose Methotrexate vs Anti-TNF Monotherapy in Pediatric Crohn's Disease: A Pragmatic Randomized Trial. Gastroenterology. 2023 Jul;165(1):149-161.e7. doi: 10.1053/j.gastro.2023.03.224. Epub 2023 Mar 31.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Methotrexate	Small molecule	10 mg	Oral
Subject	Methotrexate	Small molecule	12.5 mg	Oral
Subject	Methotrexate	Small molecule	15 mg	Oral