Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Children's Hospital at Montefiore, Bronx, New York.
Arthritis Rheumatol. 2016 Jan;68(1):218-28. doi: 10.1002/art.39407.
In pivotal trials, canakinumab has been shown to be effective in the treatment of systemic juvenile idiopathic arthritis (JIA), but reported adverse events have included macrophage activation syndrome (MAS). This study was undertaken to assess the impact of canakinumab on MAS incidence.
An independent MAS Adjudication Committee (MASAC), consisting of 3 of the authors, was convened, and a search of databases from clinical studies of canakinumab treatment in systemic JIA was performed using MASAC-specified adverse event terms to identify potential MAS events. These were then adjudicated as "probable MAS," "possible MAS," or "MAS unlikely," using criteria developed by the MASAC. MAS rates were expressed as numbers of cases per 100 patient-years.
Of 72 potential MAS cases identified, 21 events (19 with canakinumab treatment; 2 with placebo treatment) in 19 patients were adjudicated as being probable MAS and 10 events in 9 patients as being possible MAS. Systemic JIA was well controlled in the majority of canakinumab-treated patients at the time of MAS. The time period between initiation of canakinumab treatment and onset of MAS ranged from 3 to 1,358 days (median 292 days). When the rates of probable MAS events were compared between canakinumab-treated patients (2.8 per 100 patient-years) and placebo-treated patients (7.7 per 100 patient-years), the difference was not significant (-4.9 [95% confidence interval -15.6, 5.9]). There were 3 deaths due to MAS-related complications (2 in patients receiving canakinumab; 1 in a patient receiving placebo); full recovery was reported in all other patients. Infections were the most common trigger of MAS, and the clinical features of MAS were not modified by canakinumab.
Canakinumab does not have a significant effect on MAS risk or its clinical features in patients with systemic JIA. Infections are the most common trigger, and MAS occurs even in patients whose systemic JIA is well controlled with this treatment.
在关键性试验中，卡那单抗已被证明对全身型幼年特发性关节炎（JIA）的治疗有效，但报告的不良事件包括巨噬细胞活化综合征（MAS）。本研究旨在评估卡那单抗对 MAS 发病率的影响。
成立了一个由 3 名作者组成的独立的 MAS 裁决委员会（MASAC），并使用 MASAC 规定的不良事件术语对卡那单抗治疗全身型 JIA 的临床试验数据库进行了检索，以识别潜在的 MAS 事件。然后，根据 MASAC 制定的标准，将这些事件裁决为“可能的 MAS”、“可能的 MAS”或“MAS 不太可能”。MAS 发生率以每 100 患者年的病例数表示。
在 72 例潜在 MAS 病例中，19 例患者中有 21 例（19 例接受卡那单抗治疗，2 例接受安慰剂治疗）被裁决为可能的 MAS，9 例患者中有 10 例被裁决为可能的 MAS。在大多数接受卡那单抗治疗的患者中，全身型 JIA 得到了很好的控制。卡那单抗治疗开始至 MAS 发病的时间间隔为 3 至 1358 天（中位数为 292 天）。当比较卡那单抗治疗患者（2.8/100 患者年）和安慰剂治疗患者（7.7/100 患者年）的可能 MAS 事件发生率时，差异无统计学意义（-4.9[95%置信区间-15.6，5.9]）。有 3 例死亡归因于 MAS 相关并发症（2 例接受卡那单抗治疗，1 例接受安慰剂治疗）；所有其他患者均报告完全康复。感染是 MAS 最常见的诱因，而卡那单抗并未改变 MAS 的临床特征。
卡那单抗对全身型 JIA 患者的 MAS 风险或其临床特征没有显著影响。感染是最常见的诱因，即使在全身型 JIA 得到很好控制的患者中也会发生 MAS。
