Methotrexate in juvenile idiopathic arthritis: towards tailor-made treatment

Abstract

Methotrexate (MTX) is the key treatment in juvenile idiopathic arthritis (JIA). Nevertheless, MTX is not always sufficiently efficacious and can lead to adverse effects, which compromises complete disease control. In such cases, combination therapies with biologicals are given, even at MTX start, before knowing the patients’ MTX response. Ideally, clinicians should be able to practice precision medicine by knowing before or early after MTX start, which patients will benefit from MTX only and which patients will not, thus requiring addition of biologicals. To make such tailor-made treatment decisions, clinicians require tools to optimize MTX treatment. In this review, we focus on tools for tailor-made MTX treatment in JIA.

Keywords::

• intolerance
• juvenile idiopathic arthritis
• methotrexate
• Pavlovian conditioning
• polyglutamates
• prediction
• response
• single nucleotide polymorphisms

Financial & competing interest disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Prediction model for methotrexate (MTX) non-response should be used to offer biologicals to MTX non-responders and to spare MTX responders costly biologicals with poorly elucidated long-term adverse effects.

• MTX polyglutamates should be used as a therapeutic drug monitoring tool to escalate MTX dose in patients with low polyglutamation rate and to give biologicals to patients with adequate polyglutamation, but insufficient MTX response.

• Patients should be monitored with the Methotrexate Intolerance Severity Score to allow for early MTX intolerance detection and timely MTX intolerance treatment.

• Treatment strategies for MTX intolerance should be tailored to individual patients, based on their motivation and expectations.

• Prediction model for MTX intolerance should be used to identify patients at risk of developing MTX intolerance.

• Tailor-made MTX treatment is possible and should be applied in order to offer optimal treatment to all JIA patients.

Notes