Rate and Clinical Presentation of Macrophage Activation Syndrome in Patients With Systemic Juvenile Idiopathic Arthritis Treated With Canakinumab. Issue 1 (January 2016)

• Record Type: Journal Article
• Authors: Grom, Alexei A.; Ilowite, Norman T.; Pascual, Virginia; Brunner, Hermine I.; Martini, Alberto; Lovell, Daniel; Ruperto, Nicolino; Leon, Karolynn; Lheritier, Karine; Abrams, Ken
• Other Names: Cuttica Ruben investigator.; Emminger Wolfgang investigator.; Goffin Laurence investigator.; Joos Rik investigator.; Lauwerys Bernard investigator.; Wouters Carine investigator.; Hilário Maria Odete Esteves investigator.; de Oliveira Sheila Knupp Feitosa investigator.; Len Claudio investigator.; Radominski Sebastiao investigator.; Sztajnbok Flavio Roberto investigator.; Haddad Elie investigator.; Hofer Michael investigator.; Houghton Kristin investigator.; Huber Adam investigator.; Saurenmann Traudel investigator.; Schneider Rayfel investigator.; Tucker Lori investigator.; Bader‐Meunier Brigitte investigator.; Desjonqueres Marine investigator.; Fischbach Michel investigator.; Kone‐Paut Isabelle investigator.; Marie Isabelle investigator.; Mogenet Agnes investigator.; Mouy Richard investigator.; Quartier Pierre investigator.; Berner Reinhard investigator.; Foeldvari Ivan investigator.; Foell Dirk investigator.; Frosch Michael investigator.; Haas Johannes‐Peter investigator.; Horneff Gerd investigator.; Hufnagel Markus investigator.; Kallinich Tilmann investigator.; Kuemmerle‐Deschner Jasmin investigator.; Lehmann Hartwig investigator.; Lutz Thomas investigator.; Thon Angelika investigator.; Trauzeddel Ralf investigator.; Tzaribachev Nikolay investigator.; Weibarth‐Riedel Elisabeth investigator.; Chrousos Georgios investigator.; Trachana Maria investigator.; Vougiouka Olga investigator.; Constantin Tamas investigator.; Barash Judith investigator.; Berkun Yackov investigator.; Brik Riva investigator.; Harel Liora investigator.; Nahum Amit investigator.; Pade Shay investigator.; Uziel Yosef investigator.; Alessio Maria investigator.; Cimaz Rolando investigator.; Corona Fabrizia investigator.; Gerloni Valeria investigator.; Wulffraat N. M. investigator.; Ferrandiz Manuel investigator.; Rutkowska‐Sak Lidia investigator.; Alekseeva Ekaterina investigator.; Chasnyk Vyacheslav investigator.; Nasonov Evgeny investigator.; Stanislav Marina investigator.; Anton Jordi investigator.; Calvo Inmaculada investigator.; Gamir Mari Luz investigator.; Robledillos Juan Carlos investigator.; Magnusson Bo investigator.; Erguven Muferet investigator.; Kasapcopur Ozgur investigator.; Ozdogan Huri investigator.; Ozen Seza investigator.; Unsal Erbil investigator.; Chieng Alice investigator.; Foster Helen investigator.; McCann Liza investigator.; Ramanan Athimalaip investigator.; Southwood Taunton investigator.; Wilkinson Nicholas investigator.; Woo Patricia investigator.; Higgins Gloria Christine investigator.; Kingsbury Daniel investigator.; Lopez‐Benitez Jorge investigator.; Marzan Katherine investigator.; Morris Paula investigator.; Natter Marc investigator.; Schikler Kenneth Noel investigator.;
• Is Part Of: Arthritis & rheumatology. Volume 68:Issue 1(2016)
• Page Start: 218
• Page End: 228
• Publication Date: 2016-01
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.39407
• Languages: English
• ISSNs: 2326-5191

Abstract

Abstract : Objective: In pivotal trials, canakinumab has been shown to be effective in the treatment of systemic juvenile idiopathic arthritis (JIA), but reported adverse events have included macrophage activation syndrome (MAS). This study was undertaken to assess the impact of canakinumab on MAS incidence. Methods: An independent MAS Adjudication Committee (MASAC), consisting of 3 of the authors, was convened, and a search of databases from clinical studies of canakinumab treatment in systemic JIA was performed using MASAC‐specified adverse event terms to identify potential MAS events. These were then adjudicated as "probable MAS, " "possible MAS, " or "MAS unlikely, " using criteria developed by the MASAC. MAS rates were expressed as numbers of cases per 100 patient‐years. Results: Of 72 potential MAS cases identified, 21 events (19 with canakinumab treatment; 2 with placebo treatment) in 19 patients were adjudicated as being probable MAS and 10 events in 9 patients as being possible MAS. Systemic JIA was well controlled in the majority of canakinumab‐treated patients at the time of MAS. The time period between initiation of canakinumab treatment and onset of MAS ranged from 3 to 1, 358 days (median 292 days). When the rates of probable MAS events were compared between canakinumab‐treated patients (2.8 per 100 patient‐years) and placebo‐treated patients (7.7 per 100 patient‐years), the difference was not significant (−4.9 [95% confidence interval −15.6, 5.9]). There were 3 deaths due to MAS‐related complications (2 in patients receiving canakinumab; 1 in a patient receiving placebo); full recovery was reported in all other patients. Infections were the most common trigger of MAS, and the clinical features of MAS were not modified by canakinumab. Conclusion: Canakinumab does not have a significant effect on MAS risk or its clinical features in patients with systemic JIA. Infections are the most common trigger, and MAS occurs even in patients whose systemic JIA is well controlled with this treatment.