Objectives Patients with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS) respond to the janus kinase inhibitor 1/2 inhibition with baricitinib at exposures higher than in rheumatoid arthritis. Baricitinib dose reductions to minimise exposure triggered disease flares which we used to develop ‘flare criteria’. Methods Of 10 patients with CANDLE/PRAAS treated with baricitinib in an open-label expanded-access programme, baricitinib doses were reduced 14 times in 9 patients between April 2014 and December 2019. Retrospective data analysis of daily diary scores and laboratory markers collected before and after the dose reductions were used to develop ‘clinical’ and ‘subclinical’ flare criteria. Disease flare rates were compared among patients with <25% and >25% dose reductions and during study visits when patients received recommended ‘optimized’ baricitinib doses (high-dose visits) versus lower than recommended baricitinib doses (low-dose visits) using two-sided χ2 tests. Results In the 9/10 patients with CANDLE with dose reduction, 7/14 (50%) times the dose was reduced resulted in a disease flare. All four dose reductions of >25% triggered a disease flare (p <0.05). Assessment of clinical and laboratory changes during disease flares allowed the development of disease flare criteria that were assessed during visits when patients received high or low doses of baricitinib. Disease flare criteria were reached during 43.14% of low-dose visits compared with 12.75% of high-dose visits (p <0.0001). Addition of an interferon score as an additional flare criterion increased the sensitivity to detect disease flares. Conclusion We observed disease flares and rebound inflammation with baricitinib dose reductions and proposed flare criteria that can assist in monitoring disease activity and in designing clinical studies in CANDLE/PRAAS. Data are available upon reasonable request. Protocol ([NCT01724580][1]) and data can be made available upon request to the main author. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01724580&atom=%2Fannrheumdis%2Fearly%2F2024%2F04%2F29%2Fard-2023-225463.atom

中文翻译：

---

CANDLE/PRAAS 患者因巴瑞替尼剂量减少而疾病发作并制定发作标准

目的 患有脂肪营养不良和高温/蛋白酶体相关自身炎症综合征 (CANDLE/PRAAS) 的慢性非典型中性粒细胞皮肤病患者对巴瑞克替尼 janus 激酶抑制剂 1/2 抑制有反应，其暴露量高于类风湿性关节炎。减少巴瑞替尼剂量以最大程度地减少暴露引发的疾病发作，我们用它来制定“发作标准”。方法 2014 年 4 月至 2019 年 12 月期间，在开放标签扩大访问计划中接受巴瑞替尼治疗的 10 名 CANDLE/PRAAS 患者中，9 名患者的巴瑞替尼剂量减少了 14 倍。对治疗前后收集的每日日记评分和实验室标志物进行回顾性数据分析剂量减少后用于制定“临床”和“亚临床”耀斑标准。使用两种方法比较剂量减少<25%和>25%的患者以及研究访视期间患者接受推荐的“优化”巴瑞替尼剂量（高剂量访视）与低于推荐的巴瑞替尼剂量（低剂量访视）的疾病发作率。单侧 χ2 检验。结果 在 9/10 剂量减少的 CANDLE 患者中，7/14 (50%) 剂量减少导致疾病发作。所有四次剂量减少 >25% 都会引发疾病发作 (p <0.05)。对疾病发作期间临床和实验室变化的评估允许制定疾病发作标准，该标准在患者接受高剂量或低剂量巴瑞克替尼时就诊期间进行评估。低剂量就诊期间达到疾病突发标准的比例为 43.14%，而高剂量就诊的比例为 12.75% (p <0.0001)。添加干扰素评分作为额外的突发标准增加了检测疾病突发的敏感性。结论 我们观察到巴瑞克替尼剂量减少后疾病发作和炎症反弹，并提出了发作标准，可帮助监测疾病活动性和设计 CANDLE/PRAAS 临床研究。数据可根据合理要求提供。协议（[NCT01724580][1]）和数据可根据主要作者的要求提供。 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01724580&atom=%2Fannrheumdis%2Fearly%2F2024%2F04%2F29%2Fard-2023-225463.atom