Background/Purpose: Canakinumab (CAN), a human anti-interleukin-1 monoclonal antibody, has shown to be efficacious and safe in the treatment of all phenotypes of cryopyrin-associated periodic syndrome (CAPS).¹ However, no real-life data are available on the effect of different doses of CAN in CAPS patients (pts) of different age groups. Here, we analyze the safety of different doses of CAN (<2, 2−<4 and 4−<8 mg/kg) in pts of different age groups (<4–≥65 years; yrs) with CAPS and other autoinflammatory syndromes from a real-life study (β-CONFIDENT Registry; NCT01213641).

Methods: The β-CONFIDENT Registry was a multicenter, long-term, prospective, observational study conducted at 38 sites across 13 countries. Pts with CAPS and those with other autoinflammatory diseases receiving CAN at physician’s discretion were enrolled in the registry. Cumulative safety data were reported as exposure-adjusted incidence rate per 100 pt–yrs (IR/pyr) from enrollment of the first pt (November 2009) until the end of study (December 2015). Pts were followed up for at least 1 yr. The protocol did not mandate any visits or procedures. All observed and reported adverse events (AEs) and serious AEs (SAEs) were recorded for the following age groups: <4, 4−<12, 12−<18, 18−<65, and ≥65 yrs.

Results: Of the 285 pts enrolled, 21% (n=60) discontinued the study mainly due to loss to follow-up (35%, n=21), followed by AEs (10%, n=6), poor efficacy (8%, n=5), and pt preference (3%, n=2). In total, 1114 AEs and 155 SAEs were reported in 223 pts (110.7 IR/100 pyr) and 83 pts (15.4 IR/100 pyr), respectively. Incidence rates of AEs (IR/100 pyr) among pts in the <4 and 4–<12 yrs age group were lowest in pts who received <2 mg/kg (130.3 and 59.7, respectively) compared with pts who received 2–<4 mg/kg (450.8 and 169.6, respectively) and 4–<8 mg/kg (121.5 and 90.0, respectively) CAN. In pts aged 12–<18 yrs, IR/100 pyr were lowest in pts who received 2–<4 mg/kg doses (118.2) compared with pts who received <2 mg/kg (169.6) and 4–<8 mg/kg (139.4) CAN. Similarly, in the 18–<65 yrs age group, IR/100 pyr were lowest in pts who received <2 mg/kg (93.1) compared with pts who received 2–<4 mg/kg (100.7) and 4–<8 mg/kg (154.4) CAN. In the ≥65 yrs age group, IR/100 pyr decreased with increasing dose (<2 mg/kg: 26, 2−<4 mg/kg: 17). Overall, 5, 13, 19, 84, and 7 SAEs were reported in the <4, 4−<12, 12−<8, 18−<65, and ≥65 yrs age groups, respectively. One death (metastatic rectal adenocarcinoma in a 76-yr-old Muckle-Wells syndrome pt) was reported.

Conclusion: These results from the β-Confident Registry demonstrated that in general the incidence of adverse events in each dose group of canakinumab increased with age (<4−<65 years). However, an increase in canakinumab dose from 2–<4 mg/kg to 4–<8 mg/kg in each age group was not associated with an increased rate of AEs, which corroborate the need of treat-to-target strategies for different age groups. Canakinumab demonstrated a safety profile consistent with previous reports^2,3, and is well tolerated in CAPS patients aged <4−≥65 years.

References: 1. Kuemmerle-Deschner JB, et al. Ann Rheum Dis. 2015; 74 (S2): 850. 2. Hoffman HM, et al. Arthritis Rheumatol. 2016;68(suppl 10). 3. Kuemmerle-Deschner JB, et al. Ann Rheum Dis. 2016;75:617.