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

Abigale Jagger¹, Mara Becker², Susan Thompson³, Mekibib Altaye⁴, John Bohnsack⁵, Hermine Brunner⁶, Margaret Chang⁷, Ashley Cooper⁸, Stefanie Davidson⁹, Alexandra Duell⁶, Bharti Gangwani⁷, Carl Langefeld¹⁰, Melissa Lerman¹¹, Mindy Lo⁷, Serena Pastore¹², Mariia Pavlenko¹³, Sampath Prahalad¹⁴, Megan Quinlan-Waters¹⁵, Laura Ramsey¹⁶, Grant Schulert⁶, Gabriele Simonini¹⁷, Erin Stahl⁸, Gabriele Stocco¹⁸, Marc Sudman¹⁹, Andrea Taddio¹⁸, Virginia Miraldi Utz⁶, Rae Yeung²⁰ and Sheila Angeles-Han¹, ¹Cincinnati Children's Hospital, Cincinnati, OH, ²Duke University Medical Center/Duke Clinical Research Institute, Chapel Hill, NC, ³Cincinnati Children's Hospital Medical Center/Univ of Cincinnati College of Medicine, BLUE ASH, OH, ⁴Cincinnati Children's Hospital, Cincinnati, ⁵University of Utah, Salt Lake City, UT, ⁶Cincinnati Children's Hospital Medical Center, Cincinnati, OH, ⁷Boston Children's Hospital, Boston, MA, ⁸Children's Mercy Kansas City, Kansas City, MO, ⁹University of Pennsylvania/CHOP, Philadelphia, PA, ¹⁰Wake Forest University School of Medicine, Winston Salem, NC, ¹¹Children's Hospital of Philadelphia, Philadelphia, PA, ¹²Institute of Child and Maternal Health - IRCCS "Burlo Garofolo", Trieste, Italy, ¹³Cincinnati Children`s Hospital Medical Center, Cincinnati, OH, ¹⁴Emory + Children's Pediatric Institute, Atlanta, GA, ¹⁵Cincinnati Children's Hospital Medical Center, CCHMC, ¹⁶Children's Mercy, Kansas City, MO, ¹⁷Rheumatology Unit, ERN-ReCONNET center, Meyer Children's Hospital IRCCS, Firenze, Firenze, Italy, ¹⁸Insitute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy, ¹⁹Cincinnati Children's Hospital Medical Center, Cincinnati, ²⁰The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

Meeting: ACR Convergence 2025

Keywords: Disease-Modifying Antirheumatic Drugs (Dmards), Juvenile idiopathic arthritis, race/ethnicity, risk factors

Session Information

Date: Sunday, October 26, 2025

Title: (0387–0429) Pediatric Rheumatology – Clinical Poster I

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

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.

Disclosures: A. Jagger: None; M. Becker: None; S. Thompson: None; M. Altaye: None; J. Bohnsack: Bristol-Myers Squibb(BMS), 5, Janssen, 5, Pfizer, 5; H. Brunner: AbbVie, 2, AstraZeneca-Medimmune, 2, Biogen, 2, Boehringer-Ingelheim, 2, Bristol-Myers Squibb(BMS), 2, Eli Lilly, 2, EMD Serono, 2, F. Hoffmann-La Roche, 2, Genentech, 5, GlaxoSmithKline, 2, Merck, 2, Novartis, 2, Pfizer, 2, 5, Sanofi, 2, UCB, 2; M. Chang: None; A. Cooper: None; S. Davidson: None; A. Duell: None; B. Gangwani: None; C. Langefeld: None; M. Lerman: None; M. Lo: None; S. Pastore: None; M. Pavlenko: None; S. Prahalad: None; M. Quinlan-Waters: None; L. Ramsey: BTG Specialty Pharmaceuticals, 2, 5; G. Schulert: IpiNovoyx, 5, Novartis, 2, SOBI, 2; G. Simonini: None; E. Stahl: Sydnexis, 2; G. Stocco: None; M. Sudman: None; A. Taddio: None; V. Miraldi Utz: None; R. Yeung: AstraZeneca, 5, SOBI, 6; S. Angeles-Han: None.

To cite this abstract in AMA style:

Jagger A, Becker M, Thompson S, Altaye M, Bohnsack J, Brunner H, Chang M, Cooper A, Davidson S, Duell A, Gangwani B, Langefeld C, Lerman M, Lo M, Pastore S, Pavlenko M, Prahalad S, Quinlan-Waters M, Ramsey L, Schulert G, Simonini G, Stahl E, Stocco G, Sudman M, Taddio A, Miraldi Utz V, Yeung R, Angeles-Han S. Clinical Indicators of Methotrexate Response in Juvenile Idiopathic Arthritis (JIA) and JIA with Uveitis (JIA-U) [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/clinical-indicators-of-methotrexate-response-in-juvenile-idiopathic-arthritis-jia-and-jia-with-uveitis-jia-u/. Accessed .

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