Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Canakinumab (ILARIS) Provides Rapid Response and Sustained Remission in Cryopyrin-Associated Periodic Syndrome (CAPS) Patients across All Severity Phenotypes.
Lachmann12, H. J., Kuemmerle-Deschner6, J. B., Hachulla3, E., Cartwright1, R., Kone-Paut4, I., Hoyer2, J., Quartier11, P.
Allergy Center at Brookstone, Columbus, GA
UCSF School of Medicine, San Francisco, CA
Unit'e d'Immunologie, Hematologie et Rhumatologie Pediatrique, Hopital Necker-Enfants Malades, Paris, France
University College London Medical School, London, United Kingdom
University College London Medical School, London, United Kingdom
University of Wisconsin Hospital and Clinics, Madison, WI
Department of Internal Medicine and Nephrology, Universitaetsklinikum Giessen und Marburg GmbH, Marburg, Germany
Hôpital Claude Huriez CHRU, Lille Cedex, France
Hôpital Kremlin Bicetre, CEREMAI, Le Kremlin Bicetre, France
Istituto Giannina Gaslini, Genova, Italy
Klinik fuer Kinder-und Jugendmedizin, Universitaetsklinikum, Tuebingen, Germany
Novartis Pharma AG, Basel, Switzerland
Novartis Pharmaceuticals Corporation, East Hanover, NJ
Rheumazentrum Ruhrgebiet, Herne, Germany
Background:
CAPS (a disease spectrum consisting of familial cold auto-inflammatory syndrome [FCAS], Muckle-Wells syndrome [MWS], neonatal-onset multisystem inflammatory disease [NOMID]) is a rare systemic inflammatory disease associated with mutations in NLRP3 causing excessive production of interleukin-1b (IL-1b). The fully human monoclonal antibody canakinumab provides prolonged selective blockade of IL-1b. This study evaluated the long-term efficacy and safety of canakinumab subcutaneous (sc) injections every 8 weeks in a large cohort of CAPS patients.
Methods:
Patients enrolled in this open-label, multi-center study were canakinumab-naive or rolled-over from earlier studies. Patients received canakinumab 150 mg sc or 2 mg/kg sc (body weight <=40 kg) every 8 weeks. The primary objective was to assess the long-term safety and tolerability of canakinumab in CAPS patients. Secondary objectives included assessment of response (for naive patients), maintenance of response for those patients who had achieved a complete response, percentage of patients requiring dose adjustment. Complete response was defined as: physician's global assessment of disease activity and skin assessment score <=minimal and normal CRP and/or SAA values (<10 mg/L). Relapse was defined as: serum levels of CRP and/or SAA >30 mg/L and physician's global assessment of disease activity >minimal or physician's global assessment of disease activity minimal along with the assessment of skin disease >minimal.
Results:
166 (47 pediatric) patients aged 3–91 years were enrolled (30 FCAS; 103 MWS; 32 MWS/NOMID [14 NOMID]; 1 child did not have CAPS and was discontinued [protocol violator]). 109 patients were canakinumab-naive, while 57 had been pre-treated with canakinumab. 151 (91%) patients completed the study and 15 patients discontinued (4 due to adverse events [AEs]). Median duration of exposure to canakinumab was 414 days (range 29–687 days) and the mean number of injections per patient was 7.2. A complete response (CR) was achieved in 85/109 (78%) canakinumab-naive patients (80 patients achieved CR within 8 days, the others achieved CR within 21 days). Of the 141 patients who were included in the relapse assessment, 127 (90%) had no relapse, while 14 (10%) experienced a relapse. Dose adjustments were required in 36 (22%) patients (17% adults vs 34% children). In canakinumab-naive patients median CRP and SAA levels rapidly decreased within 7 days (2.5 and 4.9 mg/L [baseline levels were 19.6 and 35.6 mg/L, respectively]) and these levels were maintained within normal levels (<10 mg/L) during the study in the entire patient cohort. Predominant AEs were infections (65%), mostly mild to moderate in severity. Most frequent AEs were nasopharyngitis, headache and rhinitis. Serious AEs were reported in 18 patients. Majority of patients (92%) had no injection site reactions, 8% reported reactions which were all mild or moderate.
Conclusions:
Canakinumab 150 mg sc every 8 weeks provided rapid improvement of symptoms and sustained remission in a large cohort of CAPS patients across different severity phenotypes. Long-term safety profile was comparable to that established in earlier trials of shorter duration.
To cite this abstract, please use the following information:
Lachmann, H. J., Kuemmerle-Deschner, J. B., Hachulla, E., Cartwright, R., Kone-Paut, I., Hoyer, J., et al; Canakinumab (ILARIS) Provides Rapid Response and Sustained Remission in Cryopyrin-Associated Periodic Syndrome (CAPS) Patients across All Severity Phenotypes. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :895
DOI: 10.1002/art.28663
