Sørensen Per Soelberg, Comi Giancarlo, Vollmer Timothy L, Montalban Xavier, Kappos Ludwig, Dadon Yuval, Gorfine Tali, Margalit Maya, Sasson Nissim, Rubinchick Svetlana, Knappertz Volker
Int J MS Care. 2017 Jan-Feb;19(1):16-24. doi: 10.7224/1537-2073.2015-024.
Laquinimod 0.6 mg is a once-daily, oral, disease-modifying therapy in development for the treatment of multiple sclerosis (MS) that was investigated in two double-blind, placebo-controlled, phase 3 trials: ALLEGRO and BRAVO.
Data from these studies were pooled to assess the safety profile of laquinimod versus placebo. Adverse events (AEs), laboratory value changes, and potential risks identified in preclinical studies were evaluated in participants in ALLEGRO and BRAVO treated with at least one dose of laquinimod or matching placebo (1:1 random assignment).
In total, 1988 patients received at least one dose of study drug (laquinimod: n = 983 [mean ± SD duration, 639 ± 190 days]; placebo: n = 1005 [mean ± SD duration, 627 ± 198 days]). Early terminations due to AEs were infrequent (laquinimod: 6.4%; placebo: 4.7%). Death was reported in four patients (laquinimod: n = 1; placebo: n = 3). Rates of serious AEs (including malignancies, infections, and cardiovascular AEs) were similar between groups. The most common AEs identified with laquinimod use were back and neck pain and appendicitis. Laquinimod was also associated with asymptomatic changes in liver enzyme levels, fibrinogen levels, and hematologic parameters that followed a consistent temporal pattern: mild, nonprogressive, and occurring within 90 days of treatment initiation, then stabilizing or reverting to baseline levels during continued treatment.
Data from these pivotal laquinimod studies demonstrate a safety profile comprising benign or manageable AEs and asymptomatic laboratory findings with a clear temporal pattern. Potential risks noted in preclinical studies were not observed.
0.6毫克拉喹莫德是一种每日一次的口服疾病改善疗法，正处于治疗多发性硬化症（MS）的研发阶段，已在两项双盲、安慰剂对照的3期试验（ALLEGRO和BRAVO）中进行了研究。
汇总这些研究的数据，以评估拉喹莫德与安慰剂的安全性。在接受至少一剂拉喹莫德或匹配安慰剂（1:1随机分配）治疗的ALLEGRO和BRAVO参与者中，评估不良事件（AE）、实验室值变化以及临床前研究中确定的潜在风险。
共有1988名患者接受了至少一剂研究药物（拉喹莫德：n = 983 [平均±标准差持续时间，639 ± 190天]；安慰剂：n = 1005 [平均±标准差持续时间，627 ± 198天]）。因AE导致的早期终止情况不常见（拉喹莫德：6.4%；安慰剂：4.7%）。有4名患者报告死亡（拉喹莫德：n = 1；安慰剂：n = 3）。两组之间严重AE（包括恶性肿瘤、感染和心血管AE）的发生率相似。使用拉喹莫德时最常见的AE是背痛、颈痛和阑尾炎。拉喹莫德还与肝酶水平、纤维蛋白原水平和血液学参数的无症状变化相关，这些变化呈现出一致的时间模式：轻度、非进行性，在治疗开始后90天内出现，然后在持续治疗期间稳定或恢复到基线水平。
这些关键的拉喹莫德研究数据表明，其安全性包括良性或可控制的AE以及具有明确时间模式的无症状实验室检查结果。未观察到临床前研究中指出的潜在风险。
