Background/Purpose: CAPS is a rare, heterogenous inflammasomopathy associated with gain-of-function mutations in NLRP3 that encodes cryopyrin. Mutations in NLRP3 result in excessive IL-1ß production that may underlie wide range of symptoms. IL-1 blockade demonstrated complete responses to treatment which has been life-changing in this monogenic inflammasomopathy.

Methods: Patients followed-up in GOSH and NAC specialist CAPS clinics from 2005 to 2021 were identified. Data on following parameters collected: disease subtype, presenting symptoms, CAPS disease activity scores, serum amyloid A (SAA) and CRP levels, MRI brain; and treatment. Descriptive statistical analysis was performed by GraphPad Prism version 9.1.1.

Results: A total of 48 patients [female (n=20, 42 %), male (n=28, 58 %)] with CAPS diagnosis in childhood/adolescence were identified. Median age at disease presentation was 3.50 years (range: 0.20 – 16.23). Disease subtypes were: CINCA (n=4), MWS (n=37), FCAS (n=6), CAPS-like disease (n=1). Two of 6 patients with FCAS harboured NLRP3 variants of unknown significance (VUS) and were discharged since they ultimately proved asymptomatic after review. Clinical symptoms were recorded, and CAPS disease activity score was calculated in each clinic visit. There was a significant drop in the mean CAPS activity scores between first and last visits (8.66/20 (±2.59), 1.12/20 (±1.29), respectively). Median treatment duration was 5.83 years (range:0.17–15.83). Mutations could not be detected by sanger in 6/48 (12,5 %) patients, although clinical characteristics of CAPS were identified. Two/6 patients had NGS that showed no evidence of mosaicism. The commonest mutation was p.A439V in NLRP3 gene (19/48), followed by p.V198M (3/48), p.T348M (3/48) and p.R488K (3/48) mutations. CRP and SAA levels were checked prior to treatment and at each clinic visit. 45 of 48 patients (94 %) were on anti-IL1 treatment: 42/45 (93 %) canakinumab, 27 of whom were switched from anakinra; and 3/45 (7 %) on anakinra. Two FCAS patients were discharged from clinic without any treatment, 1 patient with compound heterozygous IRAK4 mutations in addition to NLRP3 p.E457D was switched from canakinumab to tocilizumab, with complete clinical and serological response. Median CRP before and after treatment were 5.0 mg/L (range:1.0-83.0) and 5.0 mg/L (range:1.0–51.0). Median SAA before and after treatment were 8.5 mg/L (range:2.4–680.0) and 3.50 mg/L (range:2.0–222.0). Thirteen of 48 (27 %) patients underwent MRI brain due to neurological involvement, mainly due to recurrent headaches, with no abnormalities identified in 9/13 (70 %); whereas 4 patients (3 with CINCA) had changes on their MRI brain. None of the patients experienced deterioration neither in their clinical symptoms nor in their MRI brain scans after starting treatment with anti-IL1.

Conclusion: Anti-IL1 treatment has had a major impact in paediatric patients for the prevention and treatment of CAPS symptoms. Treatment efficacy was observed by improved CAPS clinical disease activity scores; and normalised inflammatory markers. In our cohort, neurological symptoms including sensorineural hearing loss have improved and MRI brain scans have remained stable with anti-IL1 therapies.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cryopyrin-associated-periodic-syndromes-gosh-and-national-amyloidosis-centre-experience/