Background/Purpose: to identify the optimal regimen for the treatment with Canakinumab in CAPS patients and, in patients receiving both Anakinra and Canakinumab during their disease course, to compare the two drugs in term of the efficacy and impact on the quality of life.

Methods: 13 CAPS patients (10 paediatric, 3 adults) treated with Canakinumab were followed for 12 months; 12 patients were previously treated with Anakinra. Clinical and laboratory parameters were collected at each visit and health-related quality of life (HRQoL) was recorded at month 12.

Disease activity, doses of IL-1 inhibitors and HRQoL were analyzed at the time of the last administration of Anakinra and after 12 months of treatment with Canakinumab.

Results:

7 patients were classified as CINCA, 4 patients as Muckle-Wells syndrome (MWS) while 2 patients displayed an overlapping MWS/CINCA phenotype.

Nine modifications of the schedule were necessary in 6/7 CINCA patients, while a single modification was performed in two MWS and MWS/CINCA patients only.

At the last follow-up during Canakinumab treatment 4 patients (2 MWS, 1 MWS/CINCA and 1 CINCA patients) were treated with a stable dose of 2 mg/kg (or 150 mg if weight was higher than 40 Kg) every 8 weeks, all of them displaying a complete response. Two CINCA and one MWS patients were treated with the dose of 2 mg/kg (or 150 mg) every 7, 6 and 6 weeks respectively, with a complete response. Four patients (3 CINCA and 1 MWS/CINCA patients) were treated with the dosage of 300 mg with a frequency of 7, 6, 5 and 4 weeks. All of them displayed a partial response. One MWS patient, in light of the persistent good control of the disease, discontinued the treatment with the aim to use the drug on demand, with a subsequent complete wellbeing for the following 6 months. One CINCA patients withdrew Canakinumab due to incomplete response and poor compliance.

At the last administration of Anakinra the patients were treated with a mean dose of 1,38 mg/kg/day (range 0,66-2). Seven patients (3 CINCA, 1 MWS/CINCA and 2 MWS) displayed a complete response while a partial response was observed in 5 patients (4 CINCA, 1 MWS/CINCA patients), due to a slight increase of acute phase reactants.

The number of complete responders at the last follow up in Canakinumab (8/13) was comparable to that registered at the moment of Anakinra discontinuation (6/12). The evaluation of the quality of life with the CHQ-PF50 questionnaire did not reveal a significant difference of the impact of the two drugs on physical concepts (Phs 51.88 during Anakinra, 51.55 during Canakinumab), while Canakinumab determined a significant amelioration of psychosocial concepts (p < 0.03, Wilcoxon Pairs Test)

Conclusion: the long-term use of Canakinumab is associated with a satisfactory control of disease activity but needs a progressive dose adjustments in more severe patients. CAPS phenotype, rather than the age, represents the main variable able to determine the need of more frequent administrations of the drug at higher dosage. We propose that pediatric MWS patients should  be treated with the proposed schedule of 2 mg/kg every 8 weeks. Conversely, patients with a severe CINCA phenotype should be more aggressively treated since the beginning with a monthly administration of 4 mg/kg as the starting dose.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-schedule-of-administration-of-canakinumab-in-cryopyrin-associated-periodic-syndrome-is-driven-by-the-phenotype-severity-rather-than-the-age/