Center for Neurology, Tylna 12, 90-324 Łódź, Poland and Collegium Medicum, Department of Neurology, University of Warmia and Mazury, Warszawska 30, 11-082 Olsztyn, Poland.
Department of Neurology, Mellen Center for MS Treatment and Research, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio, 44195, USA.
Mult Scler Relat Disord. 2021 Jun;51:102844. doi: 10.1016/j.msard.2021.102844. Epub 2021 Feb 15.
Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for the treatment of relapsing multiple sclerosis (RMS). In phase 3 trials, ozanimod was well tolerated and superior to interferon beta-1a 30 µg once-weekly in reducing clinical and radiologic disease activity. The objective of this integrated safety analysis was to evaluate the safety of extended ozanimod exposure in participants with RMS from all clinical trials and compare it with phase 3 trial data.
We report pooled incidence and study duration‒adjusted incidence rates (IR) of treatment-emergent adverse events (TEAEs) from an interim data cut (January 31, 2019) of RMS participants treated with ozanimod. Data were pooled from a phase 1 pharmacokinetic/pharmacodynamic trial, a placebo-controlled phase 2 trial with dose-blinded extension, 2 large active-controlled phase 3 trials, and an open-label extension (OLE). Results were compared with pooled phase 3 trial data.
At the data cutoff, 2631 RMS participants had exposure to ozanimod 0.92 mg (mean 32.0 months) and 2787 had exposure to either ozanimod 0.46 or 0.92 mg (mean 37.1 months). The IRs per 1000 person-years (PY) for any TEAE (772.2) and serious TEAEs (33.2) in the overall population were similar to those in the phase 3 population (896.1 and 31.2, respectively). There were no serious opportunistic infections. There were no second-degree or higher atrioventricular blocks on electrocardiogram. Hepatic enzyme elevations declined over time. Malignancy rates remained low with longer exposure. Pulmonary function tests showed minimal reductions in lung function. Seven ozanimod-treated participants with comorbid risk factors had confirmed macular edema, including 3 in the ongoing OLE.
Safety results in this larger RMS population with greater ozanimod exposure demonstrated no new safety concerns and were consistent with phase 3 trial results.
奥扎尼莫德是一种鞘氨醇 1-磷酸受体 1 和 5 调节剂，已在多个国家获得批准，用于治疗复发型多发性硬化症（RMS）。在 3 期临床试验中，奥扎尼莫德的耐受性良好，且优于每周一次皮下注射 30μg 干扰素β-1a，可降低临床和影像学疾病活动度。本综合安全性分析的目的是评估 RMS 参与者延长奥扎尼莫德暴露的安全性，并与 3 期试验数据进行比较。
我们报告了截至 2019 年 1 月 31 日 RMS 参与者接受奥扎尼莫德治疗的中期数据截止时，治疗中出现的不良事件（TEAE）的发生率和研究持续时间调整发生率（IR）。数据来自 1 期药代动力学/药效学试验、剂量盲法扩展的安慰剂对照 2 期试验、2 项大型活性对照 3 期试验和开放标签扩展（OLE）。结果与 3 期试验数据进行了比较。
在数据截止时，2631 名 RMS 参与者接受了奥扎尼莫德 0.92mg 的暴露（平均 32.0 个月），2787 名参与者接受了奥扎尼莫德 0.46 或 0.92mg 的暴露（平均 37.1 个月）。全人群中任何 TEAE（772.2）和严重 TEAE（33.2）的每 1000 人年（PY）发生率与 3 期人群相似（分别为 896.1 和 31.2）。无严重机会性感染。心电图无二度或更高的房室传导阻滞。肝酶升高随时间下降。随着暴露时间的延长，恶性肿瘤发生率仍然较低。肺功能检查显示肺功能有轻微下降。7 名合并有潜在风险因素的奥扎尼莫德治疗参与者发生了确认的黄斑水肿，包括在正在进行的 OLE 中的 3 名。
在 RMS 人群中，具有更大的奥扎尼莫德暴露量的安全性结果没有新的安全性问题，与 3 期试验结果一致。
Zotero 插件