Background/Purpose:

Canakinumab (CAN) is approved in over 60 countries for the treatment of CAPS. This meta-analysis evaluated the efficacy and safety of CAN and assessed potential differences across age and the 3 CAPS phenotypes (FCAS, MWS and NOMID).

Methods:

This meta-analysis pooled data from 5 studies (1 phase II and 4 phase III). Data from 2 of the 4 phase III, open-label, uncontrolled studies with similar efficacy endpoints (n=185, including 128 CAN-naïve patients) were pooled for efficacy analysis (the other studies were of a different design and not included). Patients previously treated with CAN could “roll over” into one of these phase III studies. Step-wise dose escalations from 150 mg or 2 mg/kg (if weight 15–40 kg) every 8 weeks (q8w) up to 600 mg or 8 mg/kg q8w were allowed in patients who did not achieve/remain in complete response (CR; defined as physician global assessment [PGA] ≤ minimal, assessment of skin disease ≤ minimal, serum C-reactive protein and/or serum amyloid A protein < 10 mg/L) in the 2 studies pooled for efficacy. The primary efficacy endpoint, CR was assessed in CAN-naïve patients (n=128). Percentage of patients with relapse assessment and PGA were evaluated in CAN-naïve plus roll-over patients [n=185]). For safety analysis, data from all 5 studies were pooled (n=194).

Results:

85.2% (109/128) of CAN-naïve patients achieved CR; 65.6% (84/128) with 150 mg or 2 mg/kg. 42 patients (32.8%) required dose escalation to 300 or 600 mg (4-8mg/kg) q8w of whom 25 achieved CR at a higher dose, including 7 patients at the highest dose. Of 159 patients assessed for relapse, 142 (89.3%) did not relapse at any dose. CR and relapse data by phenotype and age are shown in Table.

Patients treated with 150mg or 2mg/kg q8w had greater reduction in disease activity (PGA; absent/minimal symptoms) than patients who required dose escalation (91.4% vs 60% to 77.8%) at the End of Study (EOS) (or Week 48). FCAS patients (92%) showed lowest disease activity score at EOS compared to MWS (85.1%) and NOMID (81.8%). Patients as young as 2–<4 yrs had a reduction in disease activity score by Day 8 and EOS (57.1% and 71.4%, respectively, with absent/minimal symptoms). 94.3% (183/194) patients had at least 1 adverse event (AE). Most frequently reported AEs were nasopharyngitis (36.1%), headache (23.7%), rhinitis (17.5%) and upper respiratory tract infection (17.0%). Serious AEs (SAEs) occurred in 13.4% (26/194) patients (infections and infestations; 13 [6.7%]), and no deaths were reported. Incidence of AEs and SAEs was comparable between NOMID and MWS with lower incidence in FCAS (AEs: 98.1% and 96.4% vs 80.6%; SAEs: 13.5% and 16.4% vs 3.2%).

Conclusion:

This meta-analysis confirms the efficacy of CAN in CAPS across all phenotypes and also for the youngest patients (2–<4 yrs). Dose escalation was most frequent in younger and NOMID patients who did not respond to initial dose. It did not appear that there was an increase in AEs and SAEs with an increase in dose or decrease in age.