Long-term safety of mepolizumab for up to ∼10 years in patients with severe asthma: open-label extension study

Long-term safety monitoring of mepolizumab is necessary to support real-world use for the treatment of severe asthma. This Long-Term Access Program assessed the safety and benefit:risk of mepolizumab in pediatric, adolescent, and adult patients with severe asthma. This was a multicenter, Phase IIIb safety, open-label extension study of multiple prior studies assessing mepolizumab in addition to standard of care (Aug 2015 − Aug 2022). Adults/adolescents (≥12 years of age) received mepolizumab 100 mg subcutaneously (SC) every 4 weeks until mepolizumab was commercialized. Pediatric patients (6–11 years of age) received mepolizumab 40 mg or 100 mg SC (bodyweight <40 or ≥40 kg, respectively) every 4 weeks. Safety was assessed every 4 weeks and benefit:risk every 12 weeks. Of the 514 patients enrolled, 57% were female and the mean age was 51.1 (standard deviation: 14.9) years; 24 (5%) patients were 6–17 years of age. Total cumulative mepolizumab exposure across all mepolizumab studies included in this analysis was 1500.59 patient-years; median exposure was 2.03 (range, 0.08 to 9.97) years. Overall, 37 (7%) patients experienced on-treatment serious adverse events (SAEs): 34/502 (7%) in the 100 mg SC group and 3/7 (43%) in the 40 mg SC pediatric group. Two patients experienced SAEs considered to be treatment-related by the investigator. Infections were the most common SAEs of special interest (9 [2%] patients). Physician-assessed benefit:risk of mepolizumab supported continued treatment over the study period. This long-term safety analysis of mepolizumab was consistent with previous reports, with no emerging safety concerns; most patients had a favorable benefit:risk up to ∼10 years. NCT00244686 (GSK ID 201956)

为支持美泊利珠单抗（mepolizumab）治疗重度哮喘的真实世界应用，开展其长期安全性监测十分必要。本长期准入项目（Long-Term Access Program）评估了美泊利珠单抗用于重度哮喘儿童、青少年及成年患者的安全性与获益-风险比。本研究为一项多中心、IIIb期开放性延伸研究，基于多项既往评估美泊利珠单抗联合标准治疗的研究开展，研究周期为2015年8月至2022年8月。成人及青少年（≥12岁）患者每4周皮下注射100mg美泊利珠单抗，直至该药商业化上市；儿科患者（6~11岁）则根据体重调整给药剂量：体重<40kg者予40mg、≥40kg者予100mg，同样每4周皮下注射1次。安全性每4周评估一次，获益-风险比每12周评估一次。本研究共纳入514例患者，其中57%为女性，平均年龄为51.1岁（标准差：14.9）；24例（5%）患者年龄为6~17岁。本次分析纳入的所有美泊利珠单抗研究中，总累计暴露量达1500.59患者-年，中位暴露时间为2.03年（范围：0.08~9.97年）。总体而言，37例（7%）患者出现治疗期间严重不良事件（SAEs）：其中100mg皮下注射组为34/502例（7%），40mg皮下注射儿科亚组为3/7例（43%）。2例患者被研究者判定为治疗相关严重不良事件。感染为最常见的特殊关注严重不良事件，共9例（2%）患者出现此类不良事件。经医师评估的美泊利珠单抗获益-风险比支持患者在研究期间持续接受治疗。本次美泊利珠单抗长期安全性分析与既往报道结果一致，未出现新的安全性担忧；多数患者在长达约10年的随访中获益-风险比表现良好。本研究注册号为NCT00244686（GSK编号：201956）