Methotrexate in juvenile idiopathic arthritis: advice and recommendations from the MARAJIA expert consensus meeting

Abstract

BackgroundConventional pharmacological therapies for the treatment of juvenile idiopathic arthritis (JIA) consist of non-biological, disease-modifying antirheumatic drugs, among which methotrexate (MTX) is the most commonly prescribed. However, there is a lack of consensus-based clinical and therapeutic recommendations for the use of MTX in the management of patients with JIA. Therefore, the Methotrexate Advice and RecommendAtions on Juvenile Idiopathic Arthritis (MARAJIA) Expert Meeting was convened to develop evidence-based recommendations for the use of MTX in the treatment of JIA.MethodsThe preliminary executive committee identified a total of 9 key clinical issues according to the population, intervention, comparator, outcome (PICO) approach, and performed an evidence-based, systematic, literature review. During the subsequent Expert Meeting, the relevant evidence was assessed and graded, and 10 recommendations were made.ResultsRecommendations relating to the efficacy, optimal dosing and route of administration and duration of treatment with MTX in JIA, and to the issue of folic acid supplementation to prevent MTX side effects, use of MTX in the treatment of chronic JIA-associated uveitis, combination treatment with biologic agents, and the use of vaccinations in patients with JIA were developed. The selected topics were considered to represent clinically important issues facing clinicians caring for patients with JIA. Evidence was insufficient to formulate recommendations for the use of biomarkers predictive of treatment response.ConclusionsThese consensus recommendations provide balanced and evidence-based recommendations designed to have broad value for physicians and healthcare clinicians involved in the clinical management of patients with JIA.

Pediatric Collagenous Gastroenterocolitis Successfully Treated with Methotrexate

“…Methotrexate has proven useful in the management of adults with refractory collagenous colitis, and we now report the first case of a child with extensive collagenous mucosal involvement successfully treated with methotrexate [15]. Methotrexate was chosen due to existing data demonstrating its favorable risk/benefit profile for use in the treatment of children with inflammatory and rheumatologic diseases [16,17].…”

The Patient and Parent Perspective on Methotrexate in Recent Juvenile Idiopathic Arthritis Guidelines: Comment on the Article by Ringold et al

“…MTX is the most commonly used maintenance treatment in JIA. Effectiveness and safety of this classic disease‐modifying antirheumatic drug (DMARD) are well documented . However, from the perspective of a patient or parent, MTX is notorious for its gastrointestinal side effects, e.g., nausea, abdominal pain, vomiting, or diarrhea .…”

Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach inactive disease state and remission. Results of a double-blind placebo-controlled trial.

“…At all phases, the frequency of AEs in the ETA + MTX group was 17% (6 AEs) / 11% (5 AEs) / 26% (3 AEs) during phases 1, 2, and 3, respectively ( (21,22). Given the time lag between MTX treatment initiation and the patient response (about 3 months), it would be particularly useful to determine a priori the probability of beneficial therapeutic response (19). According to the results of this study, ETA + MTX combination therapy allows patients to achieve remission sooner.…”

“…Furthermore, the investigators believe that reaching an inactive disease state in the early stage of arthritis (up to 2 years after the onset) may prevent the development of irreversible osteoarticular changes and reduce the future risk of disability. In fact, the delay in identifying the optimal treatment at an early stage of disease can influence long-term joint damage(19). When preparing the novel clinical guidelines, the experts should take into account a number of questions related to identification of optimal administration of biologic (monotherapy versus combination with non-biologic DMARD).…”