The American journal of gastroenterology · 2024
HLA DQA1*05 and Risk of Antitumor Necrosis Factor Treatment Failure and Anti-Drug Antibody Development in Children With Crohn's Disease.
СтатьяРандомизированное исследованиеМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Adler Jeremy, Galanko Joseph A, Ammoury Rana, Benkov Keith J, Bousvaros Athos, Boyle Brendan, Cabrera José M, Chun Kelly Y, Dorsey Jill, Ebach Dawn R, Firestine Ann M, Gulati Ajay S, Herfarth Hans H, Jester Traci W, Kaplan Jess L, Leibowitz Ian, Linville Tiffany M, Margolis Peter A, Minar Phillip, Molle-Rios Zarela, Moses Jonathan, Olano Kelly, Pashankar Dinesh S, Pitch Lisa, Saeed Shehzad A, Samson Charles M, Sandberg Kelly, Steiner Steven J, Strople Jennifer A, Sullivan Jillian S, Wali Prateek D, Kappelman Michael D
Аннотация
INTRODUCTION: Human leukocyte antigen (HLA) DQA1*05 has been associated with the development of anti-drug antibodies (ADA) to tumor necrosis factor antagonists (anti-TNFα) and treatment failure among adults with Crohn's disease (CD). However, findings from other studies have been inconsistent with limited pediatric data.
METHODS: We analyzed banked serum from patients with CD aged <21 years enrolled in clinical outcomes of Methotrexate Binary Therapy in practice, a multicenter, prospective randomized trial of anti-TNFα monotherapy vs combination with methotrexate. The primary outcome was a composite of factors indicative of treatment failure. The secondary outcome was ADA development.
RESULTS: A trend toward increased treatment failure among HLA DQA1*05-positive participants was not significant (hazard ratio 1.58, 95% confidence interval [CI] 0.95-2.62; P = 0.08). After stratification by HLA DQA1*05 and by methotrexate vs placebo, patients who were HLA DQA1*05 negative and assigned to methotrexate experienced less treatment failures than HLA DQA1*05-positive patients on placebo (hazard ratio 0.31, 95% CI 0.13-0.70; P = 0.005). A trend toward increased ADA development among HLA DQA1*05-positive participants was not significant (odds ratio 1.96, 95% CI 0.90-4.31, P = 0.09). After further stratification, HLA DQA1*05-negative participants assigned to methotrexate were less likely to develop ADA relative to HLA DQA1*05-positive patients on placebo (odds ratio 0.12, 95% CI 0.03-0.55; P = 0.008).
DISCUSSION: In a randomized trial of children with CD initiating anti-TNFα, 40% were HLA DQ-A1*05 positive, which was associated with a trend toward increased risk of both treatment failure and ADA. These risks were mitigated, but not eliminated, by adding oral methotrexate. HLA DQ-A1*05 is an important biomarker for prognosis and risk stratification.
METHODS: We analyzed banked serum from patients with CD aged <21 years enrolled in clinical outcomes of Methotrexate Binary Therapy in practice, a multicenter, prospective randomized trial of anti-TNFα monotherapy vs combination with methotrexate. The primary outcome was a composite of factors indicative of treatment failure. The secondary outcome was ADA development.
RESULTS: A trend toward increased treatment failure among HLA DQA1*05-positive participants was not significant (hazard ratio 1.58, 95% confidence interval [CI] 0.95-2.62; P = 0.08). After stratification by HLA DQA1*05 and by methotrexate vs placebo, patients who were HLA DQA1*05 negative and assigned to methotrexate experienced less treatment failures than HLA DQA1*05-positive patients on placebo (hazard ratio 0.31, 95% CI 0.13-0.70; P = 0.005). A trend toward increased ADA development among HLA DQA1*05-positive participants was not significant (odds ratio 1.96, 95% CI 0.90-4.31, P = 0.09). After further stratification, HLA DQA1*05-negative participants assigned to methotrexate were less likely to develop ADA relative to HLA DQA1*05-positive patients on placebo (odds ratio 0.12, 95% CI 0.03-0.55; P = 0.008).
DISCUSSION: In a randomized trial of children with CD initiating anti-TNFα, 40% were HLA DQ-A1*05 positive, which was associated with a trend toward increased risk of both treatment failure and ADA. These risks were mitigated, but not eliminated, by adding oral methotrexate. HLA DQ-A1*05 is an important biomarker for prognosis and risk stratification.