Methotrexate Persistence, Adverse Drug Reactions in Juvenile Idiopathic Arthritis

Data show that more than half of patients with juvenile idiopathic arthritis were no longer on methotrexate therapy.

Data published in Rheumatology show that more than half of patients with juvenile idiopathic arthritis (JIA) were no longer receiving methotrexate therapy at 2 years, while one-third of patients experienced an adverse drug event.

Researchers analyzed 2 large, prospective observational studies, the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study and the Biologics for Children with Rheumatic Diseases study, to evaluate the effect of methotrexate treatment on patients with JIA in regard to treatment discontinuation and adverse drug reactions. These studies followed juvenile patients who started methotrexate at baseline and collected information on demographics, disease features, disease activity, antirheumatic therapies, and any adverse drug reactions at 6 months, 1 year, and 2 years into treatment.

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Of the 577 patients included in this study, 68% were women, the median age was 9 years, the median 71-joint juvenile arthritis disease activity score was 12, the median Childhood Health Assessment Questionnaire was 0.9, and the median dose of methotrexate was 15 mg/m2. The median methotrexate monotherapy time frame was 1.1 years, and by the 2-year follow-up, 54% of patients were no longer receiving methotrexate monotherapy. Methotrexate monotherapy was discontinued due to ineffectiveness (60%), adverse events (25%), and remission (8%). At least 1 adverse drug reaction was reported in the first year of treatment by 37% of the patients, and gastrointestinal problems were the most common (68%). Patients with polyarticular rheumatoid factor-positive JIA and higher physician global assessment of disease activity were less likely to develop an adverse drug reaction.

Limitations of this study include some missing data that could affect adverse drug reaction reporting, the lack of a specific liver enzyme cut-off level for adverse drug reactions, and the lack of data on the timing of methotrexate administration and adverse drug reactions.

Researchers concluded their study “supports the opinion that [methotrexate] is considered an effective and safe first-line [disease-modifying antirheumatic drug] treatment for patients with JIA.”


Kearsley-Fleet L, Vicente González L, Steinke D, et al. Methotrexate persistence and adverse drug reactions in patients with juvenile idiopathic arthritis [published online March 8, 2019]. Rheumatology. doi:10.1093/rheumatology/kez048