Long-term safety and effectiveness of canakinumab therapy in patients with cryopyrin-associated periodic syndrome: results from the β-Confident Registry

Abstract

Objective: To report the long-term safety and effectiveness of canakinumab, a fully human anti-interleukin 1β monoclonal antibody, in patients with cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID), in a real-world setting.

Methods: From December 2009 to December 2015, the β-Confident Registry prospectively enrolled patients with CAPS and non-CAPS conditions who received canakinumab per routine care and were prospectively followed for up to 6 years. The registry protocol did not mandate specific visits or procedures; however, all observed adverse events (AEs) and serious adverse events (SAEs) had to be recorded. Canakinumab effectiveness was evaluated by Physician's Global Assessment (PGA).

Results: Of 288 patients enrolled, 3 were excluded due to missing informed consent. Among the remaining 285 patients, 243 (85.3%) were patients with CAPS and 42 (14.7%) had atypical CAPS (6.3%) or other conditions (8.4%). The median age was 26.6 years. Based on PGA, 58 of 123 (47.2%) patients with CAPS had no disease activity at 48 months, and 65 of 123 (52.8%) experienced mild/moderate disease activity at 48 months. Among CAPS phenotypes, AE incidence rates per 100 patient-years were lowest for FCAS (73.1; 95% CI 60.3 to 87.8) compared with those with MWS (105.0; 95% CI 97.2 to 113.2) or NOMID (104.6; 95% CI 86.6 to 125.2). One hundred twenty-eight SAEs were reported in 68 patients with CAPS (incidence rate/100 patient-years, 14.0; 95% CI 11.6 to 16.6). One death (metastatic rectal adenocarcinoma in a patient with MWS) was reported.

Conclusions: The response to canakinumab was sustained for up to 6 years. Canakinumab demonstrated a favourable safety profile over long-term treatment in patients with CAPS.

Trial registration number: NCT01213641.

Keywords: biological therapy; cryopyrin-associated periodic syndromes; inflammation.

Conflict of interest statement

Competing interests: UAW reports personal fees from Novartis, during the conduct of the study. HHT reports honorarium and travel expenses from Novartis, during the conduct of the study; serving on Scientific Advisory Boards for Pharmacoepidemiology Studies for GSK, Novartis, Seqirus, Jazz and Allergan. For all of these HHT receives only honoraria and expenses. PNH, TvdP and EV have nothing to declare. SN is an employee and shareholder of Novartis; shareholder of Bristol-Myers Squibb, Merck and Johnson & Johnson. JL reports personal fees from Novartis, during the conduct of the study; personal fees from Novartis, outside the submitted work. HH reports personal fees from IFM, Novartis, Regeneron and Sobi; grants from Jecure, Takeda and Zomagen, outside the submitted work. JBK-D reports grant support and speaker fees from Novartis and Sobi, during the conduct of the study.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1

Physician’s Global Assessment of autoinflammatory disease activity in patients with CAPS over time. Note that the number of patients decreased after 48 months. Percentages are based on the number of available patients at the respective time point. BL, baseline; CAPS, cryopyrin-associated periodic syndrome; M, months; N, number of patients in the group; n, number of evaluable patients.