BACKGROUND: Most data for treatment of dermatomyositis and juvenile dermatomyositis are from anecdotal, non-randomised case series. We aimed to compare, in a randomised trial, the efficacy and safety of prednisone alone with that of prednisone plus either methotrexate or ciclosporin in children with new-onset juvenile dermatomyositis. METHODS: We did a randomised trial at 54 centres in 22 countries. We enrolled patients aged 18 years or younger with new-onset juvenile dermatomyositis who had received no previous treatment and did not have cutaneous or gastrointestinal ulceration. We randomly allocated 139 patients via a computer-based system to prednisone alone or in combination with either ciclosporin or methotrexate. We did not mask patients or investigators to treatment assignments. Our primary outcomes were the proportion of patients achieving a juvenile dermatomyositis PRINTO 20 level of improvement (20% improvement in three of six core set variables at 6 months), time to clinical remission, and time to treatment failure. We compared the three treatment groups with the Kruskal-Wallis test and Friedman's test, and we analysed survival with Kaplan-Meier curves and the log-rank test. Analysis was by intention to treat. Here, we present results after at least 2 years of treatment (induction and maintenance phases). This trial is registered with ClinicalTrials.gov, number NCT00323960. FINDINGS: Between May 31, 2006, and Nov 12, 2010, 47 patients were randomly assigned prednisone alone, 46 were allocated prednisone plus ciclosporin, and 46 were randomised prednisone plus methotrexate. Median duration of follow-up was 35.5 months. At month 6, 24 (51%) of 47 patients assigned prednisone, 32 (70%) of 46 allocated prednisone plus ciclosporin, and 33 (72%) of 46 administered prednisone plus methotrexate achieved a juvenile dermatomyositis PRINTO 20 improvement (p=0.0228). Median time to clinical remission was 41.9 months in patients assigned prednisone plus methotrexate but was not observable in the other two treatment groups (2.45 fold [95% CI 1.2-5.0] increase with prednisone plus methotrexate; p=0.012). Median time to treatment failure was 16.7 months in patients allocated prednisone, 53.3 months in those assigned prednisone plus ciclosporin, but was not observable in patients randomised to prednisone plus methotrexate (1.95 fold [95% CI 1.20-3.15] increase with prednisone; p=0.009). Median time to prednisone discontinuation was 35.8 months with prednisone alone compared with 29.4-29.7 months in the combination groups (p=0.002). A significantly greater proportion of patients assigned prednisone plus ciclosporin had adverse events, affecting the skin and subcutaneous tissues, gastrointestinal system, and general disorders. Infections and infestations were significantly increased in patients assigned prednisone plus ciclosporin and prednisone plus methotrexate. No patients died during the study. INTERPRETATION: Combined treatment with prednisone and either ciclosporin or methotrexate was more effective than prednisone alone. The safety profile and steroid-sparing effect favoured the combination of prednisone plus methotrexate. FUNDING: Italian Agency of Drug Evaluation, Istituto Giannina Gaslini (Genoa, Italy), Myositis Association (USA).

Aristotle University of Thessaloniki Ippokration General Hospital 1st Department of Pediatrics Ippokration Hospital Thessaloniki Greece

Assistance Publique Hôpitaux de Paris Hôpitaux Universitaires Paris Sud and Université Paris Sud Paris France

Azienda Ospedaliero Universitaria Meyer Florence Italy

Centro Medico Nacional La Raza Reumatologia Pediatrica Mexico City Mexico

CHU Clinique Médicale Pédiatrique Nantes France

Clinica Pediatrica 1 Unità di Reumatologia Pediatrica Padua Italy

Clinica Pediatrica dell'Università di Brescia Spedali Civili Unità di Immunologia e Reumatologia Pediatrica Brescia Italy

Clínica Universitaria Privada Reina Fabiola Universidad Católica de Córdoba Rheumatology Cordoba Argentina

Department of Pediatric Immunology and Rheumatology Wilhelmina Kinderziekenhuis Utrecht Netherlands

Detska Fakultna Nemocnica 1st Pediatric Department Kosice Slovakia

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Clinica Pediatrica 2 De Marchi Milan Italy

Great Ormond Street Hospital for Sick Children Centre of Paediatric and Adolescent Rheumatology University College London London UK

Hopital d'Enfants Dijon France

Hôpital Universitaire Hautepierre Pédiatrie 1 Strasbourg France

Hospital Civil de Guadalajara Fray Antonio Alcalde Servicio de Reumatología Guadalajara Jalisco Mexico

Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo Department of Pediatrics Division of Immunology Allergy and Rheumatology Ribeirao Preto Brazil

Hospital de Clinicas Caracas Caracas Venezuela

Hospital de Pediatria Juan P Garrahan Servicio de Inmunología Reumatología Buenos Aires Argentina

Hospital General de Ninos Pedro de Elizalde Rheumatology Section Buenos Aires Argentina

Hospital Universitário Clementino Fraga Filho UFRJ Clinica Medica Reumatologia Rio de Janeiro Brazil

Instituto de Puericultura e Pediatria Martagao Gesteira Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil

Istituto Gaetano Pini Divisione di Reumatologia Milan Italy

Istituto Giannina Gaslini Epidemiologia Biostatistica e Comitati Genoa Italy

Istituto Giannina Gaslini Pediatria 2 Reumatologia PRINTO Coordinating Centre Genoa Italy

Istituto Giannina Gaslini Pediatria 2 Reumatologia PRINTO Coordinating Centre Genoa Italy; Università di Genova Dipartimento di Pediatria Genoa Italy

Medizinische Hochschule Hannover Kinderklinik Hannover Germany

Oslo University Hospital Rikshospitalet Department of Rheumatology Oslo Norway

Ospedale Pediatrico Bambino Gesù Reumatologia Rome Italy

Paediatric Nephrology and Internist Medicine Hôpital des Enfants Toulouse France

Pediatric Rheumatology Unit Charles University and General University Hospital Department of Pediatrics and Adolescent Medicine Prague Czech Republic

Pediatric Rheumatology Unit Karolinska University Hospital Stockholm Sweden

Skejby Sygehus Aarhus University Hospital Department of Pediatrics Aarhus Denmark

Unité d'Immunologie Hématologie et Rhumatologie Pediatrique Université Paris Descartes IMAGINE Institute Hôpital Necker Enfants Malades Paris France

Universitair Ziekenhuis Gent Centrum Voor Kinderreumatologie Gent Belgium

University Children's Hospital University Medical Centre Ljubljana Department of Allergology Rheumatology and Clinical Immunology Ljubljana Slovenia

University Hospital Gasthuisberg Department of Pediatrics Division of Pediatric Rheumatology Leuven Belgium

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ClinicalTrials.gov
NCT00323960