Methotrexate Therapy in Juvenile Idiopathic Arthritis: No Clinically Relevant Pulmonary Impairment but Frequent Transient Liver Enzyme Elevations in a Longitudinal Single-Center Pediatric Cohort of 274 Children Over 30 Years.

OBJECTIVE

Methotrexate (MTX) is a cornerstone in treating juvenile idiopathic arthritis (JIA). The long-term impact of MTX, particularly on pulmonary and liver function, remains a concern. We longitudinally examined the effects of MTX on pulmonary and hepatic function in the largest reported cohort to date.

METHODS

In this retrospective, single-center study, patients with JIA receiving MTX (10-15 mg/m2) between 1993 and 2023 were analyzed. Pulmonary function tests (PFTs), including body plethysmography and diffusing capacity for carbon monoxide (DLCO), were performed annually (±3 months) starting at age 5-6 years by professional lung function technicians according to international guidelines. Hepatic enzymes (glutamate pyruvate transaminase [GPT]/alanine aminotransferase) were assessed quarterly with annual abdominal ultrasounds. Data points were compared using paired t-tests against baseline and prior values.

RESULTS

A total of 274 patients with JIA (189 female patients and 85 male patients) with a mean age at disease onset of 7.8 years were treated with MTX for a mean duration of 42.7 months (maximum 14.3 years), corresponding to 918 treatment-years. No clinically relevant MTX-associated lung disease occurred, and spirometric, lung volume, and diffusion parameters remained stable over time. One-third of the 274 pt hat RANSIENT liver enzyme elevations in liver enzyme levels that resolved after dose adjustment or temporary interruption; only 17 of 63 affected patients required permanent discontinuation due to recurrent transaminase elevations. No structural hepatic pathology was detected. Overall, MTX was discontinued in 59% of patients, most commonly due to sustained remission (53%). Other reasons included GPT elevation, nausea, cytopenia, inefficacy, and noncompliance and accounted for only a small minority of patients.

CONCLUSION

In children with JIA, long-term treatment with MTX appears to be safe regarding the pulmonary outcome. Hepatic involvement was frequent but transient, occasionally requiring dose adjustment or discontinuation without long-term complications.