Refining treat-to-target strategies in cryopyrin-associated periodic syndromes: the role of inflammatory markers

Abstract

Abstract Objectives Cryopyrin-associated periodic syndromes (CAPS) encompasses a spectrum of IL-1 driven systemic diseases with dramatic individual and societal burden. The study aimed to identify parameters and instruments to refine real-life treat-to-target (T2T) strategies and control CAPS disease activity. Methods A single-centre, longitudinal study of consecutive children and adults diagnosed with CAPS and treated with anti-IL-1 therapy was performed. Demographics, clinical phenotype and NLRP3 gene variants in addition to serial inflammatory markers and physician and patient/parent global assessments (PGA/PPGA) were captured. Effectiveness of anti-IL-1 T2T strategies and factors associated with therapy escalation were determined. Results A total of 54 CAPS patients with 759 follow-up visits were included; 31/54 (57%) were children; the median follow-up was 108 months (12–620). The moderate CAPS phenotype was present in 89%; overall 59% had pathogenic/likely pathogenic NLRP3 variants. Therapy adjustments were documented in 50/759 visits including 35 therapy escalations and 15 reductions; 74% of the therapy escalation visits were for children. At time of visit, 63% showed moderate, 37% severe clinical disease activity. Inflammatory markers remained largely normal. Significant improvement was observed in both PGA/PPGA throughout the study (P < 0.01). At the last follow-up, 96% of patients achieved remission. Conclusion Guidance for refining real-life T2T strategies in CAPS cohorts can be drawn from serial assessments of PGA and PPGA, reliably reflecting changes in disease activity. Individual parameters including age and NLRP3 gene variants are important predictors, while the sensitivity of inflammatory markers is limited due to the confounding anti-IL-1 therapy.