Predictors of poor response to methotrexate in polyarticular-course juvenile idiopathic arthritis: analysis of the PRINTO methotrexate trial

Abstract

OBJECTIVES: To determine whether baseline demographic, clinical, articular and laboratory variables predict methotrexate (MTX) poor response in polyarticular-course juvenile idiopathic arthritis. METHODS: Patients newly treated for 6 months with MTX enrolled in the Paediatric Rheumatology International Trials Organization (PRINTO) MTX trial. Bivariate and logistic regression analyses were used to identify baseline predictors of poor response according to the American College of Rheumatology pediatric (ACR-ped) 30 and 70 criteria. RESULTS: In all, 405/563 (71.9%) of patients were women; median age at onset and disease duration were 4.3 and 1.4 years, respectively, with anti-nuclear antibody (ANA) detected in 259/537 (48.2%) patients. With multivariate logistic regression analysis, the most important determinants of ACR-ped 70 non-responders were: disease duration > 1.3 years (OR 1.93), ANA negativity (OR 1.77), Childhood Health Assessment Questionnaire (CHAQ) disability index > 1.125 (OR 1.65) and the presence of right and left wrist activity (OR 1.55). Predictors of ACR-ped 30 non-responders were: ANA negativity (OR 1.92), CHAQ disability index > 1.14 (OR 2.18) and a parent's evaluation of child's overall well-being < or = 4.69 (OR 2.2). CONCLUSION: The subgroup of patients with longer disease duration, ANA negativity, higher disability and presence of wrist activity were significantly associated with a poorer response to a 6-month MTX course. Results In all, 405/563 (71.9%) of patients were women; median age at onset and disease duration were 4.3 and 1.4 years, respectively, with anti-nuclear antibody (ANA) detected in 259/537 (48.2%) patients.

Prediction of clinical non-response to methotrexate treatment in juvenile idiopathic arthritis

“…Several studies did report associations of MTX non-response in JIA with polyarticular disease, longer disease duration, ANA negativity and a higher level of disability 24 25. In our study, longer disease duration and ANA negativity were univariately associated with MTX non-response, although not significantly.…”

Defining Juvenile Idiopathic Arthritis Remission and Optimum Time for Disease-Modifying Anti-Rheumatic Drug Withdrawal

“…Some children experience extended periods of remission whilst others have continuing or recurrent disease activity into adulthood. [10][11][12][13] options for treatment are rapidly changing, these need revision. This body (now the British Society for Paediatric and Adolescent Rheumatology) recently published standards of care for JIA [15] emphasizing the need for 'tight control' and a multidisciplinary team approach, but without specific guidelines on treatment.…”

Role of methotrexate in juvenile idiopathic arthritis: where we have been and where we are going

“…Post hoc analysis of the Ruperto et al study [20] revealed that longer disease duration (>1.3 years), negative ANA, high Childhood Health Assessment Questionnaire disability index and bilateral wrist involvement were associated with poor response to MTX, defined as being an ACR Pedi 70 nonresponder by 6 months [36]. Additionally, in a retrospective study by Albers et al investigating clinical and genetic predictors to MTX response in a cohort of 128 JIA patients, responders started MTX earlier, had higher disease activity at baseline on the physician's global assessment (PGA) and received a lower starting dose of MTX than nonresponders [37].…”

“…MTHFR is a well-studied enzyme in the folate pathway and has been variably associated with MTX response in RA [52] and JIA [73], and MTR is integral in the one carbon donation from 5-CH 3 -THF for conversion of homocysteine to methionine (Figure 2). Although most studies investigating the role of genetic variation in cellular folate concentrations [26,36] or homocysteine concentrations [37] have focused on MTHFR, these data imply that genetic control may be exerted at many additional levels.…”