Background/Purpose: 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 is a multicenter, long-term, observational study
with an enrollment period of 5 years and a 1-year follow-up period to monitor
the long-term safety and efficacy of canakinumab (CAN) for CAPS. The primary
objective of the Registry is to monitor the overall safety of CAN, focusing on
SAEs including serious infections, vertigo, malignancies, and hypersensitivity
reactions. Here we report interim data of CAN in CAPS patients from the
enrollment period.

Methods: The registry protocol does not mandate
any visits or procedures; however, all observed and reported AEs and SAEs or
AEs potentially related to CAN are recorded. Cumulative safety data are
reported as incidence rate per 100 patient-years (IR/100 pyr) from the
enrollment of the first patient (Nov 19, 2009) until the current data cut-off
date (Dec 31, 2014). The enrollment is now complete and follow-up will continue
through Dec 2015. Although only partial data are available for 11 patients
owing to the cut-off date for the analysis, the data will be updated later.
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
2.8 years. Of these, 21 (7.3%) discontinued CAN: 5 each due to AEs, poor
efficacy, and patient preference; and 6 due to unknown reasons. The IR/100 pyr
for overall AEs was 100.0. Patients with familial cold autoinflammatory
syndrome (FCAS) had the lowest IR/100 pyr (60.9) compared to patients with
Muckle–Wells syndrome (MWS) (IR/100 pyr 107.2), and chronic infantile
neurologic cutaneous and articular (CINCA) syndrome/neonatal onset multisystem
inflammatory disease (NOMID) (IR/100 pyr 120.3). The most common AEs were
infections and infestations (IR/100 pyr, 36.7). Vertigo was reported by 19
patients (IR/100 pyr, 3.7). Overall, 117 SAEs were reported by 62 patients
(IR/100 pyr, 15.0), most commonly, infections (IR/100 pyr, 4.1). One death
(metastatic rectal adenocarcinoma in 76-year-old MWS patient) was reported. Of
18 patients that received pneumococcal vaccination (PPV), 13 (72%) reported
local post-PPV injection site reactions, of which 5 were considered as serious.
Based on PGA, nearly half the patients had no disease activity, whereas most of
the others experienced mild/moderate disease activity. Similarly, disease
activity was mostly absent in patients with NLRP3 mutation negative CAPS
(n=14) treated with CAN. No evidence of loss of effect was observed with time.
Further analyses of this cohort are ongoing.

Conclusion: The β
-confident Registry is the largest CAPS cohort documented in a registry. Canakinumab demonstrated a safety
profile consistent with that observed in the clinical trial program and
provided continued effectiveness in patients with CAPS for up to 5 years.
Canakinumab therapy was also effective in patients with NLRP3 mutation
negative CAPS.

References:

1.    Kuemmerle-Deschner
JB, et al. Arthritis
Res Ther.
2011;13(1):R34.

2.     Cuisset L, et
al. Ann Rheum Dis. 2011;70(3):495-9.