TOPLINE:

Among children with juvenile idiopathic arthritis (JIA), long-term methotrexate therapy was well tolerated; no clinically relevant lung disease was seen, and pulmonary function remained stable. Elevations in hepatic enzyme levels occurred frequently but remained transient and manageable, resolving through dose adjustment or temporary interruption.

METHODOLOGY:

• Researchers conducted a retrospective study in Germany involving 274 children with JIA (mean age at disease onset, 7.8 years; 189 girls; 47.4% with oligoarthritis) who received methotrexate treatment for 1 year or longer at doses of 10-15 mg/m² body surface area per week between 1993 and 2023.
• Pulmonary function tests, such as body plethysmography and diffusing capacity for carbon monoxide (DLCO), were performed annually beginning at age 5-6 years.
• Data on parameters such as forced expiratory volume in the first second, forced vital capacity, maximal mid-expiratory flow, total lung capacity, residual volume, and DLCO were extracted.
• Hepatic monitoring included quarterly measurements of levels of liver enzymes such as glutamate pyruvate transaminase or alanine aminotransferase (ALT).
• Annual abdominal ultrasounds were performed to evaluate potential hepatic damage attributable to methotrexate therapy.

TAKEAWAY:

• Among patients receiving methotrexate therapy, no significant longitudinal alterations were observed in pulmonary function test parameters over a follow-up duration of up to 14 years. Both residual volume and DLCO were within the physiologic range at baseline and throughout treatment, and no patients had clinical evidence of pulmonary disease at the last assessment.
• Within each JIA category, stable trends across all lung function parameters were observed, with no methotrexate-associated longitudinal decline; however, a small subset of 12 patients showed notable deviations from predicted pulmonary function test values.
• ALT level elevations exceeding twice the upper limit of normal occurred in 30.6% of patients; despite this, no patient had irreversible liver injury or clinically significant hepatic fibrosis. Annual abdominal ultrasonography showed no structural hepatic pathology. The increases in liver enzyme level were generally mild, reversible, and manageable without long-term liver complications.
• Among 161 patients (58.8%) who discontinued methotrexate during the observation period, stable clinical remission was the reason for discontinuation in 82 patients, whereas recurrent transaminase elevations led to permanent discontinuation in only 17 patients (10.9%); other causes were nausea, cytopenias, and inefficacy.

IN PRACTICE:

“[The study] findings support the continued use of [methotrexate] with appropriate liver function monitoring in line with current pediatric practice,” the authors of the study wrote.

SOURCE:

The study was led by Janosch Wessling, Hannover Medical School, Hannover, Germany. It was published online on March 23, 2026, in ACR Open Rheumatology.

LIMITATIONS:

The study was retrospective in nature and had variable follow-up durations. Documentation on dosing in the early years was incomplete, and missing pulmonary tests in younger children could bias the results.

DISCLOSURES:

Open-access funding was enabled and organized by Projekt DEAL. One author reported receiving honoraria for lectures, manuscript fees, and payment for advisory board membership from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.