清晨好,您是今天最早来到科研通的研友!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您科研之路漫漫前行!

Rare Cases of Infusion-Related Reactions (IRRs) Presenting As Pain Events during or after Crizanlizumab Infusion in Patients (Pts) with Sickle Cell Disease (SCD): A Systematic Evaluation of Post-Marketing (PM) Reports

医学 肌痛 不利影响 血管闭塞危象 关节痛 急性胸部综合征 胸痛 疾病 内科学 镰状细胞性贫血
作者
Julie Kanter,Amit Shah,Vikas Joshi,Harshit Mehta,Michael P. Levine,Uma Arunagiri,Jincy Paulose,Breanne Donohue,Alissa Scalera,Deepa Manwani
出处
期刊:Blood [Elsevier BV]
卷期号:138 (Supplement 1): 3112-3112 被引量:7
标识
DOI:10.1182/blood-2021-152362
摘要

Abstract Background: Vaso-occlusive crises (VOCs) are the hallmark of SCD. VOCs and silent vaso-occlusion can lead to complications (eg acute chest syndrome, hepatic/renal dysfunction, chronic pain, multi-organ failure) and premature death. Crizanlizumab, an anti-P-selectin monoclonal antibody (mAb), is authorized in >40 countries to prevent/reduce VOCs in SCD pts aged ≥16 yrs. IRRs are defined as any signs/symptoms (S/S) experienced by pts during/within 24 hrs of infusion of a pharmacologic/biologic agent. IRRs are quite common with mAbs (frequency 1.6‒99%; Rombouts et al Anticancer Res 2020). S/S of IRRs vary; pain events, such as headache, back pain, myalgia, chest pain and joint pain, have been described as S/S of IRRs. Although pain events are known adverse drug reactions in the crizanlizumab label (eg arthralgia, myalgia, pain at various locations), due to data limitations and confounding manifestations of SCD, pain events occurring during/within 24 hrs of crizanlizumab infusion in SUSTAIN were not identified as potential IRRs (Ataga et al N Engl J Med 2017). For pts receiving crizanlizumab, IRR-related pain events may differ in location, severity and/or nature from a pt's usual SCD/VOC pain. Aim: To review data on IRRs presenting as pain events in SCD pts treated with crizanlizumab via reports received by Novartis since approval in Nov 2019. Methods: Data sources included PM reports from providers (spontaneous) and reports from the managed access/pt orientation program. To obtain the reports (which could include ≥1 event), a cumulative custom search of the Novartis safety database was performed up to Jun 2021, using ~111 MedDRA terms associated with potential S/S of IRRs presenting as pain events. IRRs must have occurred during/within 24 hrs of the most recent crizanlizumab infusion, and pain could differ from a pt's usual SCD/VOC, with/without other S/S. IRR incidence was measured by the reporting rate (RR). Reports were not gathered via a uniform data collection system, so there are limitations, including potential underreporting, incompletely documented cases, or bias towards reporting severe events. Results: IRRs presenting as pain events were experienced by 28 pts (Table 1); the most common S/S were back pain, pain in extremity, arthralgia, musculoskeletal chest pain and headache. RR was 1.67 cases per 100 pt-yrs (95% CI 1.11‒2.42). Most pts (n=24) initially experienced IRR at the 1st or 2nd infusion, and the majority recovered within 3 days. IRR recurred on subsequent infusion(s) in 6 pts. Of the 28 pts, 20 (71%) were hospitalized for further treatment, including analgesics, antihistamines, IV fluids and/or steroids. Nine pts (32%) reported SCD complications after IRR (Table 2). Crizanlizumab was discontinued in 23 pts (82%) after their most recent IRR occurrence, including all pts who experienced secondary SCD complications. Discussion: Comprehensive investigation identified 28 pts with reported IRRs presenting as pain events that had a potential causal relationship with crizanlizumab infusion based on temporality. All pts recovered or are recovering, except 1 who had SCD complications and refused blood transfusions for personal reasons. Most pts had initial IRR at the 1st or 2nd infusion and discontinued crizanlizumab after initial IRR; 6 experienced recurrent IRRs on subsequent infusion(s). Resolution time was prolonged for pts who reported known SCD complications following IRR. Causal association of complications following IRR was confounded by the underlying disease and use of steroids to treat IRRs. Systemic corticosteroid exposure in SCD pts has been associated with pain and other complications, from severe VOCs to hemorrhagic stroke and death. No data are available regarding whether the 28 pts had an active VOC or other SCD complications prior to receiving crizanlizumab. Conclusions: Although rare, based on review of PM data, healthcare professionals should be aware of the possibility of IRRs presenting as pain events during or after any crizanlizumab infusion. Crizanlizumab labels have been/are being updated by Novartis to provide information on monitoring for S/S of IRRs presenting as pain events, and guidance on management/prevention of subsequent IRRs, including a statement recommending caution when using corticosteroids in SCD pts. Given the limited data regarding IRRs and predictability of complications, Novartis is committed to further understanding these events. Figure 1 Figure 1. Disclosures Kanter: Fulcrum Therapeutics, Inc.: Consultancy; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Forma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beam: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Graphite Bio: Consultancy; GuidePoint Global: Honoraria; Fulcrum Tx: Consultancy. Shah: Johnson & Johnson: Current equity holder in publicly-traded company; Novartis Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Joshi: Novartis Healthcare Private Limited: Current Employment. Mehta: Novartis Healthcare Pvt. Ltd.: Current Employment. Levine: Biontech: Current equity holder in publicly-traded company; Novartis: Current Employment, Current equity holder in publicly-traded company. Arunagiri: Novartis Pharmaceuticals: Current Employment, Current holder of stock options in a privately-held company. Paulose: Novartis Pharmaceuticals Corporation: Current Employment. Donohue: Novartis Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Scalera: Novartis Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Manwani: Novartis: Consultancy.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
木南完成签到 ,获得积分10
6秒前
wang完成签到,获得积分10
19秒前
望向天空的鱼完成签到 ,获得积分10
28秒前
健康的大船完成签到 ,获得积分10
35秒前
armpit完成签到,获得积分10
36秒前
52秒前
12A完成签到,获得积分10
53秒前
k001boyxw完成签到,获得积分10
1分钟前
你才是小哭包完成签到 ,获得积分10
1分钟前
酱豆豆完成签到 ,获得积分10
2分钟前
小二郎应助科研通管家采纳,获得10
2分钟前
深情安青应助科研通管家采纳,获得10
2分钟前
2分钟前
忘忧Aquarius完成签到,获得积分10
3分钟前
共享精神应助科研通管家采纳,获得10
4分钟前
充电宝应助科研通管家采纳,获得10
4分钟前
火之高兴完成签到 ,获得积分10
4分钟前
平常的三问完成签到 ,获得积分10
4分钟前
河豚不擦鞋完成签到 ,获得积分10
4分钟前
可夫司机完成签到 ,获得积分10
4分钟前
4分钟前
彩色亿先完成签到 ,获得积分10
4分钟前
kean1943完成签到,获得积分10
4分钟前
万晓博发布了新的文献求助30
4分钟前
芒果完成签到 ,获得积分10
4分钟前
万晓博完成签到,获得积分20
5分钟前
5分钟前
6分钟前
6分钟前
小二郎应助科研通管家采纳,获得10
6分钟前
科研通AI2S应助科研通管家采纳,获得10
6分钟前
情怀应助科研通管家采纳,获得10
6分钟前
小白发布了新的文献求助10
6分钟前
搜集达人应助lty采纳,获得10
6分钟前
6分钟前
lty完成签到,获得积分10
6分钟前
lty发布了新的文献求助10
6分钟前
6分钟前
王翎力完成签到,获得积分10
6分钟前
elisa828发布了新的文献求助10
7分钟前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
Immigrant Incorporation in East Asian Democracies 600
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3968521
求助须知:如何正确求助?哪些是违规求助? 3513341
关于积分的说明 11167298
捐赠科研通 3248700
什么是DOI,文献DOI怎么找? 1794417
邀请新用户注册赠送积分活动 875030
科研通“疑难数据库(出版商)”最低求助积分说明 804664