Abstract：
OBJECTIVE: Cryopyrin-Associated Periodic Syndromes (CAPS) encompasses a spectrum of Interleukin-1 (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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
目的：Cryopyrin相关的周期性综合征（CAPS）包括一系列白细胞介素-1（IL-1）驱动的全身性疾病，具有巨大的个人和社会负担。该研究旨在确定参数和工具，以完善现实生活中的目标治疗（T2T）策略并控制CAPS疾病活动。
方法：单中心，我们对连续诊断为CAPS并接受抗IL-1治疗的儿童和成人进行了纵向研究.人口统计,除了一系列炎症标志物和医师和患者/父母全球评估(PGA/PPGA)外,还捕获了临床表型和NLRP3基因变异.确定了抗IL-1T2T策略的有效性和与治疗升级相关的因素。
结果：共纳入54例CAPS患者，随访759次；31/54(57%)为儿童；中位随访时间为108个月(12-620)。中度CAPS表型存在于89%;总体上59%具有致病性/可能致病性NLRP3变体。在50/759次访问中记录了治疗调整，包括35次治疗升级和15次减少；74％的治疗升级访问是儿童。在访问时,63%显示中等，37%严重临床疾病活动性。炎症标志物基本保持正常。在整个研究中,PGA/PPGA均观察到显著改善(p<0.01)。在最后一次随访中，96%的患者获得缓解。
结论：关于在CAPS队列中完善现实生活中的T2T策略的指南可以从可靠地反映疾病活动性变化的PGA和PPGA的系列评估中得出。包括年龄和NLRP3基因变异在内的个体参数是重要的预测因子，而由于混杂的抗IL-1治疗，炎症标志物的敏感性受到限制。
方法：单中心，我们对连续诊断为CAPS并接受抗IL-1治疗的儿童和成人进行了纵向研究.人口统计,除了一系列炎症标志物和医师和患者/父母全球评估(PGA/PPGA)外,还捕获了临床表型和NLRP3基因变异.确定了抗IL-1T2T策略的有效性和与治疗升级相关的因素。
结果：共纳入54例CAPS患者，随访759次；31/54(57%)为儿童；中位随访时间为108个月(12-620)。中度CAPS表型存在于89%;总体上59%具有致病性/可能致病性NLRP3变体。在50/759次访问中记录了治疗调整，包括35次治疗升级和15次减少；74％的治疗升级访问是儿童。在访问时,63%显示中等，37%严重临床疾病活动性。炎症标志物基本保持正常。在整个研究中,PGA/PPGA均观察到显著改善(p<0.01)。在最后一次随访中，96%的患者获得缓解。
结论：关于在CAPS队列中完善现实生活中的T2T策略的指南可以从可靠地反映疾病活动性变化的PGA和PPGA的系列评估中得出。包括年龄和NLRP3基因变异在内的个体参数是重要的预测因子，而由于混杂的抗IL-1治疗，炎症标志物的敏感性受到限制。
