Methotrexate for Treating Juvenile Idiopathic Arthritis

A Cochrane review [Abstract] 1 included 5 studies with a total of 575 subjects. Methotrexate compared with placebo increased the number of patients achieving treatment response up to 6 months (RR 1.67, 95% CI 1.21 to 2.31; 3 studies, n=328) but had little or no effect on pain (MD −1.10 points, 95% CI −9.09 to 6.88), improvement in participant global assessment of well‐being (RR 1.23, 95% CI 0.88 to 1.72) and occurrence of serious adverse events (RR 0.63, 95% CI 0.04 to 8.97) up to 6 months.

Oral methotrexate plus intra-articular glucocorticoid (IAGC) injections compared to IAGC injections alone had little or no effect on the likelihood of sustained clinically inactive disease (RR 1.37 95% CI 0.91 to 2.06; 1 study, n=207).

Methotrexate compared with leflunomide had little or no effect on treatment response (RR 1.40, 95% CI 0.93 to 2.10; 1 study, n=94), function (MD 0.05 points worse, 95% CI 0.20 points better to 0.30 points worse), and participant global assessment of well-being (MD 6.10 mm better, 95% CI 14.28 better to 2.08 worse). Methotrexate compared to leflunomide had little or no difference in serious adverse events (RR 0.1495% CI 0.01 to 2.69).

The effect of methotrexate may be underestimated due to suboptimal dosing.

Tthe Methotrexate Advice and RecommendAtions on Juvenile Idiopathic Arthritis (MARAJIA) expert meeting developed evidence-based recommendations for the use of methotrexate in the treatment of juvenile idiopathic arthritis 2. A total of 9 key clinical issues were identified, and an evidence-based, systematic, literature review was performed. During the subsequent expert meeting, the relevant evidence was assessed and graded, and 10 recommendations were made. Methotrexate was recommended as the first-line treatment in oligoarthritis that persists despite nonsteroidal anti-inflammatory drugs (NSAIDs) and intraarticular steroid therapy, and in polyarticular disease.

Comment: The quality of evidence is downgraded by imprecise results (few patients and wide confidence intervals).

References

• Tan J, Renton WD, Whittle SL, et al. Methotrexate for juvenile idiopathic arthritis. Cochrane Database Syst Rev 2024;2(2):CD003129 [PubMed]
• Ferrara G, Mastrangelo G, Barone P et al. Methotrexate in juvenile idiopathic arthritis: advice and recommendations from the MARAJIA expert consensus meeting. Pediatr Rheumatol Online J 2018;16(1):46. [PubMed]