Background Cryopyrin-associated periodic syndrome (CAPS), is a rare autoinflammatory disease encompassing a spectrum of 3 phenotypes with an estimated population frequency ranging from 1–3 per million.1,2 The β -confident Registry (NCT01213641) is a multicenter, long-term, prospective, observational study with an enrollment period of 5 years (yrs) to monitor the long-term safety and efficacy of canakinumab (CAN) for CAPS. Here we report the overall final results.
Objectives The primary objective of the Registry was to monitor the safety of CAN, focusing on SAEs including serious infections, vertigo, malignancies and hypersensitivity reactions.
Methods Cumulative safety data were reported as incidence rate per 100 patient-yr (IR/100 pyr) from the enrollment of the first patient (November 2009) until end of study (December 2015). The registry protocol did not mandate any visits or procedures; however, all observed and reported AEs and SAEs or AEs potentially related to CAN were recorded. Efficacy was measured using physician global assessments (PGA).
Results Overall, 288 patients were enrolled at 39 sites across 13 countries with mean patient exposure duration of 3.6 yrs. Of these, 22 (8%) discontinued CAN: 5 due to AEs, 10 due to poor efficacy and patient preference; and 7 due to unknown reasons. The IR/100 pyr for overall AEs was 100.0. Among the phenotypes of CAPS, patients with familial cold autoinflammatory syndrome (FCAS) had the lowest IR/100 pyr (78.0) compared to patients with Muckle–Wells syndrome (MWS) (IR/100 pyr 113.4) and neonatal onset multisystem inflammatory disease (NOMID) (IR/100 pyr 119.0). The most common AEs were infections and infestations (IR/100 pyr, 39.1). Overall, 161 SAEs were reported by 86 patients (IR/100 pyr, 16.3), most commonly, infections (IR/100 pyr, 5.0). One death (metastatic rectal adenocarcinoma in 76-yr-old MWS patient) was reported. Of 23 patients that received pneumococcal vaccination (PPV), 15 (65%) reported local post-PPV injection site reactions, of which 5 were considered as serious. Based on PGA, 50% of patients had no disease activity, whereas most of the others experienced mild/moderate disease activity up to Month 48. Similarly, disease activity was absent or mild/moderate in patients with NLRP3 mutation negative CAPS (n=13) treated with CAN.
Conclusions The β-confident Registry is the largest CAPS cohort documented in a registry. This registry demonstrated that safety profile of canakinumab was consistent with previous findings and efficacy was sustained for more than 5 years. Canakinumab therapy was also effective in patients with NLRP3 mutation negative CAPS.
Kuemmerle-Deschner JB, et al. Arthritis Res Ther. 2011;13(1):R34.
Cuisset L, et al. Ann Rheum Dis. 2011;70(3):495–9.
Disclosure of Interest J. Kuemmerle-Deschner Grant/research support from: Novartis, Consultant for: Novartis, SOBI, Baxalta, H. Hoffman Grant/research support from: BMS, Consultant for: Novartis, SOBI, Regeneron, Speakers bureau: Novartis, P. Hawkins Grant/research support from: Novartis, T. van der Poll: None declared, U. Walker Consultant for: Novartis, A. Speziale Employee of: Novartis, H. Tilson Consultant for: Novartis, Y. Joubert Employee of: Novartis