0392: Clinical Indicators of Methotrexate Response in Juvenile Idiopathic Arthritis (JIA) and JIA with Uveitis (JIA-U)

Background/Purpose: Patients with JIA are at high risk for development of chronic anterior uveitis (CAU), impacting 10-20% of this population. Although methotrexate (MTX) is the first-line systemic treatment for JIA-U patients, only 50% respond to therapy. Poor MTX response and delayed escalation of therapy can lead to sight-threatening complications. Non-white race, male sex, ANA positivity, and young age at JIA diagnosis have been associated with a lack of response. We aim to identify clinical risk factors associated with non-response to MTX in JIA-U patients.

Methods: This is a multicenter, prospective study – PEDIA-U and PROMOTE. Patients diagnosed with JIA or JIA-U who were prescribed MTX and who had 12 months follow-up were included. Patients were grouped as MTX non-responders (MTX-NR) vs responders (MTX-R). MTX-NR for CAU was defined as active or worse CAU by Standardization of Uveitis Nomenclature (SUN) criteria, presence of new or worsening complications, and/or need for > 2 drops/day of topical or oral steroids after 3 months. MTX-NR for arthritis was defined as no change in active joint count after 3 months. Clinical phenotypes were compared between MTX-NR and MTX-R using Chi-square and two sample tests. Odds ratios were calculated by multiple logistic regression.

Results: A total of 635 patients with JIA were identified, 187 (29.4%) of whom had JIA-U (Table 1). The overall cohort was predominately white (73.7%) and female (74.9%), with 298 (46.9%) being identified as MTX-NR. Average MTX oral and subcutaneous dose was similar at 16.5 mg/m² (SD 6.6) and 17.4 mg/m² (SD 5.7), respectively. White race was associated with MTX-NR on bivariate (X²=20.0, p=0.0012) and multivariate (OR 2.429, CI 1.512-3.904) analysis, with no other significant clinical variables identified. Of the 187 JIA-U patients, 91 (48.6%) were identified as being MTX-NR (Table 2). Of the 91 JIA-U MTX-NR, a majority were non-responders due to arthritis activity (61.5%), followed by both CAU and arthritis activity (26%) and isolated CAU activity (12%). In contrast to the overall cohort, MTX intolerance (MTX-IT) was associated with MTX-NR (X²=9.3, p=0.00023) in the JIA-U group. The most common reason for MTX-IT being GI symptoms (76.2%), followed by laboratory abnormalities (11.9%). The most initiated biological DMARD in MTX-NR patients was adalimumab (37.9%). No significant differences in predictors of response were found between JIA and JIA-U groups across clinical and demographic variables.

Conclusion: Patients of white race and those who experience MTX-IT were significantly more likely to be MTX-NR in the combined and JIA-U cohorts, respectively. Risk factors of MTX-NR from previously reported smaller cohorts were not significant in our population. Our study does not support evidence of using clinical criteria alone to identify at-risk populations for MTX-NR. Future investigation could include ocular findings on novel imaging modalities, biomarkers, and genetics as risk factors of MTX-NR, with the potential for developing individualized JIA-U therapy plans while minimizing ophthalmic morbidity.