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

Vilca, Iris; Munitis, Pablo Garcia; Pistorio, Angela; Ravelli, Angelo; Buoncompagni, Antonella; Bica, Blanca; Campos, Lucia; Häfner, Renate; Hofer, Michael; Ozen, Seza; Huemer, Christian; Bae, Sang Cheol; Sztajnbok, Flavio; Arguedas, Olga; Foeldvari, Ivan; Huppertz, Hans Iko; Gamir, Maria Luz; Magnusson, Bo; Dressler, Frank; Uziel, Yosef; van Rossum, Marion A J; Hollingworth, Peter; Cawkwell, Gail; Martini, Alberto; Ruperto, Nicolino

doi:10.1136/ard.2009.120840

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

Iris Vilca1,
Pablo Garcia Munitis1,
Angela Pistorio2,
Angelo Ravelli3,
Antonella Buoncompagni1,
Blanca Bica4,
Lucia Campos5,
Renate Häfner6,
Michael Hofer7,
Seza Ozen8,
Christian Huemer9,
Sang Cheol Bae10,
Flavio Sztajnbok11,
Olga Arguedas1,
Ivan Foeldvari12,
Hans Iko Huppertz13,
Maria Luz Gamir14,
Bo Magnusson15,
Frank Dressler16,
Yosef Uziel17,
Marion A J van Rossum18,
Peter Hollingworth19,
Gail Cawkwell20,
Alberto Martini3,
Nicolino Ruperto1,
for the Pediatric Rheumatology International Trials Organisation (PRINTO)

¹IRCCS G Gaslini, Pediatria II, Reumatologia, PRINTO, Genova, Italy
²IRCCS G Gaslini, Servizio di Epidemiologia e Biostatistica, Genova, Italy
³IRCCS G Gaslini, Pediatria II, Reumatologia and Dipartimento di Pediatria, Università degli Studi, Genova, Italy
⁴Hospital Universitário Clementino Fraga Filho – UFRJ, Reumatologia, Rio De Janeiro, Brasil
⁵Instituto Da Criança – Hospital Das Clinicas, Sao Paulo, Brasil
⁶Deutsches Zentrum für Kinder- und Jugendrheumatologie, Garmisch-Partenkirchen, Germany
⁷Centre Multisite Romand de Rhumatologie Pediatrique/Centre Hospitalier Universitaire Vaudois (CHUV), Hôpitaux Universitaires (HUG), Genève, Lausanne, Switzerland
⁸Hacettepe University Department of Pediatrics, Ankara, Turkey
⁹Landeskrankenhaus Bregenz, Bregenz, Austria
¹⁰Department of Rheumatology, Hospital for Rheumatic Diseases, Hanyang University, Seoul, South Korea
¹¹Hospital Universitário Pedro Ernesto, Núcleo de Estudos da Saúde do Adolescente, Rio de Janeiro, Brasil
¹²Hamburger Zentrum für Kinder- und Jugendrheumatologie, Hamburg, Germany
¹³Professor Hess-Kinderklinik, Bremen, Germany
¹⁴Hospital Ramon y Cajal, Madrid, Spain
¹⁵Karolinska University Hospital, Stockholm, Sweden
¹⁶Medizinische Hochschule Hannover, Hannover, Germany
¹⁷Haemek Hospital, Afula, Israel
¹⁸Emma Childrens Hospital AMC and Department of Rheumatology Jan van Breemen Instituut, Amsterdam, The Netherlands
¹⁹North Bristol NHS Trust, Bristol, UK
²⁰New York, NY, USA

Correspondence to Nicolino Ruperto, IRCCS G Gaslini, Università di Genova, Pediatria II – Reumatologia, Largo Gaslini, 5, 16147 Genova, Italy; nicolaruperto{at}ospedale-gaslini.ge.it

Accepted 26 January 2010
Published Online First 4 June 2010

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 ≤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.

Footnotes

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.