CeRéMAIA, AP-HP, Bicêtre Hospital, University of Paris Sud Saclay, Paris, France.
University of Toulouse, Toulouse, France.
Arthritis Rheumatol. 2021 Jan;73(1):151-161. doi: 10.1002/art.41481. Epub 2020 Nov 17.
Anakinra has been shown to be successful in preventing and treating cardiovascular lesions both in experimental murine models of Kawasaki disease (KD) and in several studies on intravenous immunoglobulin (IVIG)- and steroid-resistant patients with KD. This study was undertaken to determine the safety of blocking interleukin-1 in patients with IVIG-resistant KD.
Sixteen patients were included in the present study. Patients with KD who were not responsive to 1 or more courses of 2 mg/kg of IVIG received anakinra by subcutaneous daily injections. Starting doses were 2 mg/kg of IVIG (4 mg/kg in patients who were age <8 months and who weighed ≥5 kilograms), and the dose was increased up to 6 mg/kg every 24 hours if the patient's body temperature remained >38°C, indicative of a fever. Treatment duration was 14 days. The last visit was on day 45. Primary outcome was abatement of fever. Secondary measures included disease activity, coronary artery Z score, and C-reactive protein (CRP) levels.
Seventy-five percent of patients in the intention-to-treat group and 87.5% in the per-protocol group became afebrile within 48 hours of the last escalation dose of anakinra. Reduction of disease activity by 50% was indicated on 93.3% (95% confidence interval [95% CI] 68.1-99.8%) of physician evaluations and on 100% (95% CI 73.5-100%) of parent evaluations. CRP values normalized by day 30. At the initial screening, 12 of 16 patients had a maximum coronary artery Z score of >2, and 10 of 16 patients had a maximum Z score of >2.5. At day 45, 5 of 10 patients (50% [95% CI 18.7-81.3%]) and 6 of 12 patients (50% [95% CI 21.1-78.9%]) had achieved coronary artery Z scores of <2.5 and <2, respectively. Five serious adverse events were observed in 3 patients, but no serious infections or deaths occurred.
Anakinra was well tolerated in the study patients and may have some efficacy in reducing fever, markers of systemic inflammation, and coronary artery dilatation in individuals with IVIG-refractory KD.
白介素-1 拮抗剂阿那白滞素已被证实可成功预防和治疗川崎病（KD）实验性小鼠模型和数项静脉注射免疫球蛋白（IVIG）及皮质类固醇治疗抵抗型 KD 患者的心血管损伤。本研究旨在评估 IVIG 抵抗型 KD 患者应用阿那白滞素的安全性。
本研究共纳入 16 例患者。对 1 或多疗程 2mg/kg IVIG 治疗无反应的 KD 患者接受每日皮下注射阿那白滞素治疗。起始剂量为 2mg/kg IVIG（体重≥5kg 且年龄<8 个月的患者为 4mg/kg），如果患者体温仍持续>38°C（发热），则每 24 小时增加剂量至 6mg/kg。治疗持续 14 天。末次随访时间为第 45 天。主要结局为退热。次要评估指标包括疾病活动度、冠状动脉 Z 评分和 C 反应蛋白（CRP）水平。
意向治疗组 75%的患者和方案治疗组 87.5%的患者在接受阿那白滞素最后一次剂量升级后 48 小时内退热。93.3%（95%可信区间[95%CI]68.1-99.8%）的医生评估和 100%（95%CI 73.5-100%）的家长评估显示疾病活动度降低 50%。CRP 值在 30 天内恢复正常。在初始筛选时，16 例患者中有 12 例最大冠状动脉 Z 评分>2，16 例患者中有 10 例最大 Z 评分>2.5。在第 45 天，10 例患者中有 5 例（50%[95%CI 18.7-81.3%]）和 12 例患者中有 6 例（50%[95%CI 21.1-78.9%]）的冠状动脉 Z 评分分别降至<2.5 和<2。3 例患者出现 5 例严重不良事件，但无严重感染或死亡发生。
阿那白滞素在研究患者中耐受良好，可能对降低 IVIG 抵抗型 KD 患者的发热、全身炎症标志物和冠状动脉扩张有一定疗效。
