背景:常规,由于疗效或耐受性差,非特异性预防性偏头痛治疗通常表现出较低的治疗持续性.有效,需要耐受性良好的预防性治疗来减轻偏头痛症状,改善功能,提高生活质量。Atogepant是一种偏头痛特异性口服降钙素基因相关肽受体拮抗剂,适用于成人偏头痛的预防性治疗。该分析评估了用于偏头痛预防性治疗的atogepant的安全性和耐受性。包括感兴趣的不良事件(AE),比如便秘,恶心,肝安全性,体重变化,和心脏疾病。
方法:这项事后分析是使用2(12周)随机分组的数据进行的,双盲,安慰剂对照试验(RCTs)和2项(40周和52周)开放标签长期安全性(LTS)口服抗偏头痛(EM)试验。
结果:安全性人群包括来自合并RCT的1550名参与者(atogepant,n=1142;安慰剂,n=408)和1424名来自汇总LTS试验的参与者(atogepant,n=1228;标准护理[SC],n=196)。总的来说,643/1142(56.3%)名安慰剂参与者和218/408(53.4%)名安慰剂参与者在随机对照试验中经历了≥1次治疗紧急AE(TEAE)。在LTS试验中,792/1228(64.5%)的失能参与者和154/196(78.6%)的SC参与者经历了≥1个TEAE。每天一次服用atogepant的参与者中最常见的TEAE(≥5%)是上呼吸道感染(RCT中的5.3%,LTS试验中的7.7%),便秘(RCTs中的6.1%,在LTS试验中为5.0%),恶心(RCTs中的6.6%,LTS试验中的4.6%),和尿路感染(RCTs中3.4%,LTS试验中的5.2%)。此外,体重减轻似乎是剂量和持续时间依赖性的。大多数TEAE被认为与研究药物无关,很少导致停药。
结论:总体而言,在合并RCT和LTS试验中,atogepant用于成人EM的预防性治疗是安全且耐受性良好的。
背景:ClinicalTrials.gov标识符:NCT02848326(MD-01),NCT03777059(提前),NCT03700320(研究302),NCT03939312(研究309)。
BACKGROUND: Conventional, non-specific preventive migraine treatments often demonstrate low rates of treatment persistence due to poor efficacy or tolerability. Effective, well-tolerated preventive treatments are needed to reduce migraine symptoms, improve function, and enhance quality of life. Atogepant is a migraine-specific oral calcitonin gene-related peptide receptor antagonist that is indicated for the preventive treatment of migraine in adults. This analysis evaluated the safety and tolerability profile of atogepant for the preventive treatment of migraine, including adverse events (AEs) of interest, such as constipation, nausea, hepatic safety, weight changes, and cardiac disorders.
METHODS: This post hoc analysis was performed using data pooled from 2 (12-week) randomized, double-blind, placebo-controlled trials (RCTs) and 2 (40- and 52-week) open-label long-term safety (LTS) trials of oral atogepant for episodic migraine (EM).
RESULTS: The safety population included 1550 participants from the pooled RCTs (atogepant, n = 1142; placebo, n = 408) and 1424 participants from the pooled LTS trials (atogepant, n = 1228; standard care [SC], n = 196). In total, 643/1142 (56.3%) atogepant participants and 218/408 (53.4%) placebo participants experienced ≥ 1 treatment-emergent AEs (TEAEs) in the RCTs. In the LTS trials, 792/1228 (64.5%) of atogepant participants and 154/196 (78.6%) of SC participants experienced ≥ 1 TEAEs. The most commonly reported TEAEs (≥ 5%) in participants who received atogepant once daily were upper respiratory tract infection (5.3% in RCTs, 7.7% in LTS trials), constipation (6.1% in RCTs, 5.0% in LTS trials), nausea (6.6% in RCTs, 4.6% in LTS trials), and urinary tract infection (3.4% in RCTs, 5.2% in LTS trials). Additionally, weight loss appeared to be dose- and duration-dependent. Most TEAEs were considered unrelated to study drug and few led to discontinuation.
CONCLUSIONS: Overall, atogepant is safe and well tolerated in pooled RCTs and LTS trials for the preventive treatment of EM in adults.
BACKGROUND: ClinicalTrials.gov identifiers: NCT02848326 (MD-01), NCT03777059 (ADVANCE), NCT03700320 (study 302), NCT03939312 (study 309).