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Predictors of poor response to methotrexate in polyarticular-course juvenile idiopathic arthritis: analysis of the PRINTO methotrexate trial
  1. Iris Vilca1,
  2. Pablo Garcia Munitis1,
  3. Angela Pistorio2,
  4. Angelo Ravelli3,
  5. Antonella Buoncompagni1,
  6. Blanca Bica4,
  7. Lucia Campos5,
  8. Renate Häfner6,
  9. Michael Hofer7,
  10. Seza Ozen8,
  11. Christian Huemer9,
  12. Sang Cheol Bae10,
  13. Flavio Sztajnbok11,
  14. Olga Arguedas1,
  15. Ivan Foeldvari12,
  16. Hans Iko Huppertz13,
  17. Maria Luz Gamir14,
  18. Bo Magnusson15,
  19. Frank Dressler16,
  20. Yosef Uziel17,
  21. Marion A J van Rossum18,
  22. Peter Hollingworth19,
  23. Gail Cawkwell20,
  24. Alberto Martini3,
  25. Nicolino Ruperto1,
  26. for the Pediatric Rheumatology International Trials Organisation (PRINTO)
  1. 1IRCCS G Gaslini, Pediatria II, Reumatologia, PRINTO, Genova, Italy
  2. 2IRCCS G Gaslini, Servizio di Epidemiologia e Biostatistica, Genova, Italy
  3. 3IRCCS G Gaslini, Pediatria II, Reumatologia and Dipartimento di Pediatria, Università degli Studi, Genova, Italy
  4. 4Hospital Universitário Clementino Fraga Filho – UFRJ, Reumatologia, Rio De Janeiro, Brasil
  5. 5Instituto Da Criança – Hospital Das Clinicas, Sao Paulo, Brasil
  6. 6Deutsches Zentrum für Kinder- und Jugendrheumatologie, Garmisch-Partenkirchen, Germany
  7. 7Centre Multisite Romand de Rhumatologie Pediatrique/Centre Hospitalier Universitaire Vaudois (CHUV), Hôpitaux Universitaires (HUG), Genève, Lausanne, Switzerland
  8. 8Hacettepe University Department of Pediatrics, Ankara, Turkey
  9. 9Landeskrankenhaus Bregenz, Bregenz, Austria
  10. 10Department of Rheumatology, Hospital for Rheumatic Diseases, Hanyang University, Seoul, South Korea
  11. 11Hospital Universitário Pedro Ernesto, Núcleo de Estudos da Saúde do Adolescente, Rio de Janeiro, Brasil
  12. 12Hamburger Zentrum für Kinder- und Jugendrheumatologie, Hamburg, Germany
  13. 13Professor Hess-Kinderklinik, Bremen, Germany
  14. 14Hospital Ramon y Cajal, Madrid, Spain
  15. 15Karolinska University Hospital, Stockholm, Sweden
  16. 16Medizinische Hochschule Hannover, Hannover, Germany
  17. 17Haemek Hospital, Afula, Israel
  18. 18Emma Childrens Hospital AMC and Department of Rheumatology Jan van Breemen Instituut, Amsterdam, The Netherlands
  19. 19North Bristol NHS Trust, Bristol, UK
  20. 20New York, NY, USA
  1. Correspondence to Nicolino Ruperto, IRCCS G Gaslini, Università di Genova, Pediatria II – Reumatologia, Largo Gaslini, 5, 16147 Genova, Italy; nicolaruperto{at}


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 ≤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.

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  • IV and PGM contributed equally to this work.

  • Competing interests GC is currently a full-time employee of Pfizer.

  • Ethics approval This study was conducted with the approval of the ethics committees of all participating institutions.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Patient consent Not obtained.

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