Klein Allan L, Lin David, Cremer Paul C, Nasir Saifullah, Luis Sushil Allen, Abbate Antonio, Ertel Andrew, LeWinter Martin, Beutler Anna, Fang Fang, Paolini John F
Center for the Diagnosis and Treatment of Pericardial Diseases, Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA
The Minneapolis HeartInstitute, Abbott Northwestern Hospital, Minneapolis, Minnesota, USA.
Heart. 2020 Nov 23;107(6):488-96. doi: 10.1136/heartjnl-2020-317928.
Recurrent pericarditis (RP) incurs significant morbidity. Rilonacept inhibits both interleukin-1 alpha (IL-1α) and IL-1β; these cytokines are thought to play a major role in RP. This phase II study evaluated rilonacept efficacy and safety in RP.
This multicentre, open-label study enrolled adult patients with idiopathic or postpericardiotomy RP, symptomatic (≥2 pericarditis recurrences) or corticosteroid (CS) dependent (≥2 recurrences prior).Patients received rilonacept 320 mg SC load/160 mg SC weekly maintenance in a 6-week base treatment period (TP) followed by an optional 18-week on-treatment extension period (EP) (option to wean background therapy).
Outcomes: pericarditis pain (numeric rating scale (NRS)) and inflammation (C reactive protein (CRP)) for symptomatic patients; disease activity after CS taper for CS-dependent patients.
health-related quality of life (HRQOL), pericarditis manifestations and additional medications. 25 unique patients enrolled, while 23 completed the EP (seven colchicine failures and five CS failures). In symptomatic patients, NRS and CRP decreased; response was observed after first rilonacept dose. NRS decreased from 4.5 at baseline to 0.7, and CRP decreased from 4.62 mg/dL at baseline to 0.38 mg/dL at end of TP. Median time to CRP normalisation: 9 days. Pericarditis manifestations resolved. 13 patients on CS at baseline completed the EP; 11 (84.6%) discontinued CS, and 2 tapered; CRP and NRS remained low without recurrence. Mean HRQOL scores improved in symptomatic patients. One serious adverse event (SAE) resulted in discontinuation of rilonacept.
Rilonacept led to rapid and sustained improvement in pain, inflammation (CRP and pericarditis manifestations) and HRQOL. CSs were successfully tapered or discontinued; safety was consistent with known rilonacept safety profile.
NCT03980522.
复发性心包炎（RP）会导致严重的发病率。利罗那肽可抑制白细胞介素-1α（IL-1α）和白细胞介素-1β（IL-1β）；这些细胞因子被认为在RP中起主要作用。这项II期研究评估了利罗那肽在RP中的疗效和安全性。
这项多中心、开放标签研究纳入了患有特发性或心包切开术后RP的成年患者，有症状（≥2次心包炎复发）或依赖皮质类固醇（CS）（之前≥2次复发）。患者在为期6周的基础治疗期（TP）接受320mg皮下注射负荷剂量/每周160mg皮下注射维持剂量的利罗那肽治疗，随后是一个可选的为期18周的治疗延长期（EP）（可选择逐渐减少背景治疗）。
观察指标：有症状患者的心包炎疼痛（数字评分量表（NRS））和炎症（C反应蛋白（CRP））；依赖CS患者在CS减量后的疾病活动度。
健康相关生活质量（HRQOL）、心包炎表现和额外用药情况。共纳入25例不同患者，23例完成了EP（7例秋水仙碱治疗失败，5例CS治疗失败）。在有症状的患者中，NRS和CRP下降；在首次注射利罗那肽后即观察到反应。NRS从基线时的4.5降至0.7，CRP从基线时的4.62mg/dL降至TP结束时的0.38mg/dL。CRP恢复正常的中位时间为9天。心包炎表现得到缓解。13例基线时使用CS的患者完成了EP；11例（84.6%）停用了CS，2例逐渐减量；CRP和NRS保持在低水平且无复发。有症状患者的平均HRQOL评分有所改善。1例严重不良事件（SAE）导致利罗那肽停药。
利罗那肽使疼痛、炎症（CRP和心包炎表现）和HRQOL迅速且持续改善。CS成功减量或停用；安全性与已知的利罗那肽安全性特征一致。
NCT03980522。
