Background Methotrexate (MTX) is the agent of first choice for the treatment of children with Juvenile Idiopathic Arthritis (JIA). Leflunomide (LFN) has demonstrated to be an effective alternative to MTX. There is a lack of evidence regarding the advantages of combined treatment of MTX plus LFN in JIA.
Objectives To evaluate the safety and efficacy of the combined therapy with Methotrexate (MTX) and Leflunomide (LFN) in patients with Juvenile Idiopathic Arthritis (JIA) in clinical practice.
Methods We conducted a retrospective descriptive study of patients with JIA visited in a single Unit of Pediatric Rheumatology who had been treated with the combination of MTX plus LFN. All patients were classified according to the International League of Associations for Rheumatology (ILAR) criteria. Included data were: demographics, JIA subtype, reason for starting combined treatment, time on treatment, withdrawals, causes of discontinuation, efficacy and safety (both assessed at baseline and every 6 months). Safety was evaluated analyzing adverse events (AE), findings on physical examination and laboratory values. Efficacy was assessed grading uveitis according to the Standardization of Uveitis Nomenclature Working Group (SUN) recommendations and arthritis through the pediatric core set variables. Patients were classified as “responders” or “non responders”. Responders were those patients with articular improvement ≥ ACR pediatric 30 and/or ocular improvement according to the SUN definitions.
Results Nineteen patients (16 female, 3 male) were included: 12 oligoarthritis (63%), 4 polyarthritis (21%), 2 psoriatic arthritis (11%) and 1 undifferentiated arthritis (5%). The mean age at diagnosis was 57 months (4.75 years ± 3.65). The mean age at initiation of combined treatment was 112 months (9.37 years ± 4.12). The mean duration of MTX+LFN treatment was 28.6 months ± 31.6 (range 5-144). Overall, 26 AE were reported. There were no serious AE. The most frequently reported AE was upper respiratory tract infection. One of the two DMARD was stopped in 11 patients (58%) due to AE in 4 children, inefficacy or loss of efficacy in 3 and clinical remission in 4. Among patients who withdrew the combined treatment 4 switched to anti-TNF therapy and 7 continued monotherapy with MTX or LFN. Eight children are still on MTX plus LFN. Fifteen patients (79%) were responders. Twelve patients (63%) achieved articular clinical remission. All patients who had had uveitis were in clinical remission at last followup. The analysis of the response data (average results) is summarized in the table below:
Conclusions In our patients with JIA the combined therapy of MTX plus LFN was well-tolerated and proved to be effective. Most of the patients experienced a substantial improvement either articular or ocular. AE were generally mild. Gastrointestinal intolerance was the more common cause of discontinuation of one of the two DMARD. LFN plus MTX could be a safe and effective alternative for patients with JIA who do not respond to MTX or LFN in monotherapy.
Disclosure of Interest None Declared