Leflunomide as Methotrexate Alternative in Juvenile Idiopathic Arthritis

Leflunomide may be used as an alternative treatment for juvenile idiopathic arthritis (JIA) in cases of methotrexate intolerance or toxicity, according to study results published in Rheumatology International.

Disease-modifying antirheumatic drugs (DMARDs) are the first-line treatment for JIA, with methotrexate being the most commonly prescribed DMARD. For the current study, researchers reviewed the medical files of 38 patients (age range, 0-18 years) with JIA who received leflunomide to determine its value as an alternative in cases of methotrexate toxicity or intolerance.

The study was a retrospective chart review of 38 patients diagnosed with JIA between January 2016 and January 2019. Of the total cohort, 1 patient had psoriatic arthritis, 2 had enthesitis-related arthritis (ERA), 11 had polyarticular JIA, and 24 had persistent oligoarticular JIA. A total of 36 patients were initially prescribed subcutaneous methotrexate at 15 mg/m²/week, but ceased the medication after a median of 5 months because of gastrointestinal intolerance. The 2 patients who had ERA were prescribed sulfasalazine and were switched to leflunomide after 3 months as a result of an inadequate response.

Thirteen of the 36 patients who ceased methotrexate due to gastrointestinal intolerance had low disease activity and 6 were in remission; leflunomide treatment was initiated among patients with low disease activity. A median of 2 months (range, 1-5 months) after methotrexate cessation, the 6 patients in remission relapsed and were also started on leflunomide treatment. Of the remaining 17 patients, 10 had moderate disease activity and 7 had high disease activity, therefore they were started on biologic agents. Leflunomide treatment was added to biologic therapy because their response to biologic therapy alone was inadequate.

Patients were checked every 2 weeks through the initial month of leflunomide treatment, and then every month through a median follow-up period of 11 months (range, 6-36 months). At the time of the last visit, all patients were clinically inactive, and only 2 adverse events were reported (1 case of lymphopenia and 1 case of elevated liver enzymes), both of which resolved within 2 weeks of ceasing leflunomide.

The researchers concluded that despite the confounding factors associated with a retrospective study with a small sample size, “our findings support that [leflunomide] may be an effective treatment alternative in patients with [methotrexate] intolerance and in presence of low disease activity may diminish the requirement for biologic agents. Even though, we did not observe any adverse effect among our patients, prospective trials with larger series are needed to show the safety of adding [leflunomide] to biologic agents in case of inadequate response to biological drugs.”

Reference

Ayaz NA, Karadağ ŞG, Çakmak F, Çakan M, Tanatar A, Sönmez HE. Leflunomide treatment in juvenile idiopathic arthritis. Rheumatol Int. 2019;39:1615-1619.