Methotrexate persistence and adverse drug reactions in patients with juvenile idiopathic arthritis.

ABSTRACT

OBJECTIVES: This analysis aims to calculate MTX monotherapy persistence and describe the occurrence of and factors associated with the occurrence of adverse drug reactions (ADRs) with MTX. METHODS: Patients with JIA starting MTX monotherapy from two UK studies were included. Patient characteristics, treatment details and ADR occurrence were collected at treatment start, 6 months, 1 year and annually. The following groups of ADRs were included gastrointestinal, elevated liver enzymes, leukopenia, drug hypersensitivity, rash, needle phobia and any events leading to permanent MTX discontinuation. Treatment exposure was calculated from MTX start until MTX monotherapy cessation, last follow-up or 31 December 2017 (cut-off), whichever came first. Survival analysis assessed the time on MTX monotherapy and the time to the first ADR on MTX monotherapy within 2 years. Multivariable logistic regression assessed characteristics associated with any ADR and gastrointestinal ADRs. RESULTS: A total of 577 patients started MTX. At 2 years, 310 (54%) were no longer on MTX monotherapy. Reasons included ineffectiveness (60%; 161/185 started a biologic), adverse event (25%), remission (8%) and patient/family decision (3%). Over this time, 212 (37%) patients experienced one or more ADR; commonly gastrointestinal (68%) or elevated liver enzymes (26%). Lower physician global assessment and older age predicted any ADR and gastrointestinal ADR, respectively. Patients with polyarticular RF and JIA had reduced odds of both any ADR and a gastrointestinal ADR. CONCLUSION: After 2 years, more than half the patients were no longer on MTX monotherapy, while more than one-third experienced one or more ADR, most commonly gastrointestinal. Research focusing on identifying which children will respond and/or experience ADRs is crucial to inform treatment decisions and management planning.