Two-year results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patients with cryopyrin-associated periodic syndrome across different severity phenotypes
- Jasmin B Kuemmerle-Deschner1,
- E Hachulla2,
- R Cartwright3,
- P N Hawkins4,
- T A Tran5,
- B Bader-Meunier6,
- J Hoyer7,
- M Gattorno8,
- A Gul9,
- J Smith10,
- K S Leslie11,
- S Jiménez12,
- S Morell-Dubois2,
- N Davis13,
- N Patel13,
- A Widmer14,
- R Preiss13,
- H J Lachmann4
- 1Division of Pediatric Rheumatology, Department of Pediatrics, University Hospital Tübingen, Tübingen, Germany
- 2Service Médecine Interne, Hopital Claude Huriet, Lille Cedex, France
- 3Center at Brookstone, Columbus, Georgia, USA
- 4Department of Medicine, University College London Medical School, London, UK
- 5Service de Pédiatrie Generale, Le Kremlin Bicêtre, France
- 6Department of Pediatric Immunology and Rheumatology, Université Paris-Descartes and Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France
- 7Innere Medizin und Nephrologie, Univ.-Klinikum Giessen und Marburg, Marburg, Germany
- 8D.I.P.E.-U.O.Pediatria II, Istituto Giannina Gaslini-I.R.C.C.S. Università degli Studi, Genova, Italy
- 9Department of Rheumatology, Istanbul University Istanbul Medical Faculty, Istanbul, Turkey
- 10Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
- 11Department of Dermatology, UCSF School of Medicine, San Francisco, California, USA
- 12Department of Pediatrics, Hospital Central De Asturias, Oviedo, Spain
- 13Clinical Development, Novartis Pharma Co., East Hanover, New Jersey, USA
- 14Development, Novartis Pharma AG, Basel, Switzerland
- Correspondence to Jasmin B Kuemmerle-Deschner, Division of Pediatric Rheumatology, Department of Pediatrics, University Children's Hospital Tuebingen, Hoppe‑Seyler-Strasse 1, 72076 Tübingen, Germany;
- Accepted 5 July 2011
- Published Online First 21 August 2011
Objective Longer-term effects of prolonged selective interleukin-1β blockade with canakinumab were evaluated in the largest cohort of cryopyrin-associated periodic syndrome (CAPS) patients studied to date.
Methods Adult and paediatric CAPS patients (n=166, including canakinumab-naive and pretreated patients from previous studies) received canakinumab subcutaneously 150 mg or 2 mg/kg (≤40 kg) every 8 weeks for up to 2 years. Response and relapse was assessed using scores for disease activity, skin rash and C-reactive protein (CRP) and/or serum amyloid A (SAA) levels.
Results Complete response was achieved in 85 of 109 canakinumab-naive patients (78%; 79/85 patients within 8 days, and five patients between days 10 and 21). Of 141 patients with an available relapse assessment, 90% did not relapse, their CRP/SAA levels normalised (<10 mg/l) by day 8, and remained in the normal range thereafter. Median treatment duration was 414 days (29–687 days). Upward adjustments of dose or frequency were needed in 24.1% patients; mostly children and those with severe CAPS. Predominant adverse events (AE) were infections (65.7%) of mostly mild-to-moderate severity. Serious AE reported in 18 patients (10.8%) were mainly infections and were responsive to standard treatment. The majority of patients (92%) reported having no injection-site reactions and only 8% patients reported mild-to-moderate reactions. Patients receiving vaccination (15%) showed normal immune response.
Conclusions Subcutaneous canakinumab 150 mg every 8 weeks was well tolerated and provided substantial disease control in children and adults across all CAPS phenotypes. Higher canakinumab doses in younger patients and more severe CAPS disease were efficacious in achieving complete responses without evidence of increased AE.
Trial registration number: NCT00685373 (clinicaltrials.gov)
Funding This work was supported by Novartis Pharma.
Competing interests JBK-D reports receiving grant support (to her institution) and consulting fees from Novartis Pharma; EH, PNH and BB-M report receiving consulting fees from Novartis Pharma; RC reports receiving consulting fees from Novartis Pharma, receiving payment as a member of speaker's bureau of Glaxo SmithKline, Sanofi-Aventis, Pfizer Inc. and UCB, Inc.; MG reports receiving payment as a member of speaker's bureau of Novartis Pharma; AG reports receiving consulting fees from Novartis Pharma, Pfizer Inc. and UCB, Inc.; ND, NP, AW and RP report being employees of Novartis Pharma and they hold stock in the company; HJL reports receiving consultancy fees (to her institution), honoraria and receiving payment as a member of speaker's bureau of Novartis Pharma. No other potential conflict of interest relevant to this paper was reported.
Patient consent Obtained.
Ethics approval The study was conducted with the approval of the ethics committees/institutional review boards at the participating centers.
Provenance and peer review Not commissioned; externally peer reviewed.