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Ann Rheum Dis. 2018 Dec;77(12):1710-1719. doi: 10.1136/annrheumdis-2018-213150. Epub 2018 Sep 29.

Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features: results from the 5-year long-term extension of the phase III pivotal trials.

Author information

Clinica Pediatrica e Reumatologia, PRINTO, IRCCS Istituto Giannina Gaslini, Genoa, Italy
Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Centre de référence national pour les maladies inflammatoires rhumatologiques et auto-immunes systémiques rares de l'enfant (RAISE), Unité d'Immunologie, Hématologie et Rhumatologie Pediatrique, Université Paris-Descartes, IMAGINE Institute, Hôpital Necker-Enfants Malades, Paris, France.
2nd Department of Pediatrics, Unit of Pediatric Rheumatology-Immunology, Semmelweis University, Budapest, Hungary.
Department of Pediatric Immunology and Rheumatology, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
Department of General Paediatrics, Asklepios Klinik Sankt Augustin, Sankt Augustin, Germany.
Department of Paediatric and Adolescents Medicine, Medical Faculty, University Hospital of Cologne, Cologne, Germany.
Department of Pediatric Rheumatology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
Pediatric Rheumatology, The University of Toronto and Hospital for Sick Children, Toronto, Ontario, Canada.
Pediatric Rheumatology, Unidad de Reumatología Pediátrica, Esplugues de Llobregat, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain.
Pediatrics, Kaplan Medical Center, Rehovot, Israel.
Klinik und Poliklinik für Kinder- und Jugendmedizin, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Clinica Pediatrica De Marchi, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milano, Italy.
Unidad de Reumatología, Hospital General de Niños Pedro de Elizalde, Buenos Aires, Argentina.
Service de néphrologie et rhumatologie pédiatrique, Hôpital Universitaire femme mère enfant, Groupement Hospitalier Est, Bron (Lyon), France.
Pédiatrie I, Hôpital Universitaire Hautepierre, Strasbourg, France.
Newcastle University and Newcastle Hospitals NHS Foundation Trust, Great North Children's Hospital, Newcastle Upon Tyne, UK.
Universitätsklinikum Münster, Klinik für Pädiatrische Rheumatologie und Immunologie, Münster, Germany.
Centro de estudos em terapias inovadoras, Hospital de Clínicas da UFPR, Curitiba, Brazil.
Department of Pediatric Rheumatology Berlin, Helios Kliniken Berlin-Buch, Children's Hospital, Berlin, Germany.
Department of Paediatric Rheumatology, Bristol Royal Hospital for Children & Royal National Hospital for Rheumatic Diseases, Bristol, UK.
Department of Pediatrics, Division of Pediatric Rheumatology, Dokuz Eylül University Medical Faculty, Balcova, Izmir, Turkey.
Biometrical Practice BIOP, Basel, Switzerland.
Global Clinical Development, Immunology and Dermatology, Novartis Pharma AG, Basel, Switzerland.
Direzione Scientifica, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Contributed equally



To evaluate the long-term efficacy and safety of canakinumab in patients with active systemic juvenile idiopathic arthritis (JIA).


Patients (2-19 years) entered two phase III studies and continued in the long-term extension (LTE) study. Efficacy assessments were performed every 3 months, including adapted JIA American College of Rheumatology (aJIA-ACR) criteria, Juvenile Arthritis Disease Activity Score (JADAS) and ACR clinical remission on medication criteria (CRACR). Efficacy analyses are reported as per the intent-to-treat population.


144 of the 177 patients (81%) enrolled in the core study entered the LTE. Overall, 75 patients (42%) completed and 102 (58%) discontinued mainly for inefficacy (63/102, 62%), with higher discontinuation rates noted in the late responders group (n=25/31, 81%) versus early responders (n=11/38, 29%). At 2 years, aJIA-ACR 50/70/90 response rates were 62%, 61% and 54%, respectively. CRACR was achieved by 20% of patients at month 6; 32% at 2 years. A JADAS low disease activity score was achieved by 49% of patients at 2 years. Efficacy results were maintained up to 5 years. Of the 128/177 (72.3%) patients on glucocorticoids, 20 (15.6%) discontinued and 28 (22%) tapered to 0.150 mg/kg/day. Seven patients discontinued canakinumab due to CR. There were 13 macrophage activation syndrome (three previously reported) and no additional deaths (three previously reported). No new safety findings were observed.


Response to canakinumab treatment was sustained and associated with substantial glucocorticoid dose reduction or discontinuation and a relatively low retention-on-treatment rate. No new safety findings were observed on long-term use of canakinumab.


NCT00886769, NCT00889863, NCT00426218 and NCT00891046.


canakinumab; clinical trial; interleukin-1β; long-term extension; systemic juvenile idiopathic arthritis.

Conflict of interest statement

Competing interests: NR: consultant and speaker’s bureaus from AbbVie, Ablynx, Amgen, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli-Lilly, EMD Serono, Gilead Sciences, Janssen, MedImmune, Novartis, Pfizer, R-Pharm, Roche, Sanofi, Servier, Takeda; NR works as a full-time public employee of the public hospital Istituto Giannina Gaslini, which has received contributions from Bristol-Myers Squibb, Hoffman-La Roche, Janssen, Novartis, Pfizer, Sobi for the coordination activity of the PRINTO network. HIB: consultant: AstraZeneca, Bristol-Myers Squibb, Genentech, Janssen, Novartis, Pfizer, Sanofi, Takeda; speaker’s bureaus: Genentech, Novartis Pierre Quartier; has received consultant fees from Novimmune, Novartis and SOBI; has received speaker’s bureaus from Abbvie, BMS, Chugai-Roche, Lilly, Novartis, Pfizer and Sobi; has acted as coordinator or investigator in clinical trials for Abbvie, BMS, Chugai-Roche, Novartis, Sanofi, Sobi; has acted as member of a data monitoring board committee for Sanofi. NMW has received grant/research support from AbbVie; has received consultant fees from AbbVie, Sobi and Novartis. GH has received speaker’s bureaus from AbbVie, Boehringer Ingelheim, Chugai, MSD, Novartis, Pfizer, Roche and Sobi; has received scientific grants from AbbVie, Chugai, MSD, Novartis, Pfizer and Roche. OK has received speaker’s bureaus from Novartis, Roche, Pfizer and Abbvie. RS has received consultant fees from Novartis, Sobi and Novimmune. JLA has received consultant fees and speaker’s bureaus from AbbVie, Gebro, Novartis, Pfizer, Roche, Sanofi and Sobi. RC has received consultant fees and speaker’s bureaus from Bristol-Myers Squibb, Janssen, Novartis, Pfizer, Sanofi, Roche, Lilly and GlaxoSmithKline. HEF has acted as member of advisory boards for AbbVie, Novartis, Pfizer, Sanofi and Sobi; has received unrestricted educational bursaries from Pfizer, Genzyme, BioMarin and Sobi to develop educational resources for healthcare professionals. DF has received grant/research support from Pfizer and Novartis; has received consultant fees from Novartis, Pfizer, Chugai-Roche and Sobi; has received speaker’s bureaus from Novartis. SCR has received grants for clinical research from Novartis. AVR has received honoraria and participated in Advisory Boards for Novartis. RT has received lecture fees from Pfizer and Bristol-Myers Squibb. JL received fees from Novartis for conducting the statistical analysis. EV is an employee of Novartis Pharma, Basel, Switzerland. AM has no conflicts of interest to declare since March 2016 when he became the Scientific Director of the Istituto Giannina Gaslini, because this role does not allow him to render private consultancy resulting in personal income; consultant on behalf of the Istituto Giannina Gaslini: AbbVie, Boehringer, Novartis, R-Pharm. Istituto Giannina Gaslini has received contributions from Bristol-Myers Squibb, Hoffman-La Roche, Janssen, Novartis, Pfizer, Sobi for the coordination activity of the PRINTO network. DJL has received grant/research support from AbbVie, Bristol-Myers Squibb, NIH, Pfizer, Roche; speaker’s bureaus from Genentech; consultant of AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Genentech, GlaxoSmithKline, Janssen, Johnson & Johnson, Novartis, Takeda, UCB. EU, FC, JB, MF, MF-d, RB and TC have nothing to disclose.

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