Research, Education, Evaluation and Engagement Activities Center for Headache, Headache Centers of Excellence, US Department of Veterans Affairs, Orange, Connecticut.
Yale Center for Analytic Sciences, Yale School of Public Health, New Haven, Connecticut.
JAMA Netw Open. 2023 Jul 3;6(7):e2326371. doi: 10.1001/jamanetworkopen.2023.26371.
Calcitonin gene-related peptide (CGRP), a neuropeptide involved in migraine pathophysiology, is also a key neuroimmune modulator. CGRP antagonists may help mitigate the hyperinflammatory response observed in patients with COVID-19; however, findings from the literature are contradictory, and to date, no study has investigated the safety and effectiveness of CGRP antagonists against COVID-19.
To evaluate the association between CGRP monoclonal antibody (mAb) treatment and risk of SARS-CoV-2 infection and sequela hospitalization, requiring supplemental oxygen, use of mechanical ventilation, or death.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study analyzed the electronic health records of US veterans aged 18 to 65 years who were diagnosed with migraine disorder and were at risk of COVID-19 between January 20, 2020, and May 19, 2022.
Initiation of CGRP mAbs.
The main outcome was cumulative incidence of SARS-CoV-2 infection. Odds of 30-day hospitalization, requiring supplemental oxygen, use of mechanical ventilation, or death were secondary outcomes.
Among 8 178 652 eligible person-trials (354 294 veterans), 9992 (mean [SD] age, 46.0 [9.5] years; 53.9% male) initiated CGRP mAbs and 8 168 660 (mean [SD] age, 46.6 [10.2] years; 65.7% male) did not initiate CGRP mAbs. Over a 28-month follow-up period, 1247 initiators (12.5%) and 780 575 noninitiators (9.6%) tested positive for SARS-CoV-2. After censoring persons who deviated from treatment, the incidence was 7.4 cases per 1000 person-months among initiators and 6.9 per 1000 person-months among noninitiators. The inverse probability-weighted observational analogs of intention-to-treat and per-protocol hazard ratios were 0.95 (95% CI, 0.89-1.01) and 0.93 (95% CI, 0.86-1.02), respectively. No significant differences in the likelihood of hospitalization (odds ratio [OR], 0.93; 95% CI, 0.62-1.41), requiring supplemental oxygen (OR, 0.77; 95% CI, 0.45-1.30), use of mechanical ventilation (OR, 0.85; 95% CI, 0.26-2.84), or death (OR, 0.67; 95% CI, 0.09-5.23) were observed between CGRP mAb initiators and noninitiators who tested positive for SARS-CoV-2.
In this cohort study, CGRP mAb treatment was not associated with positive SARS-CoV-2 test results or risk of severe COVID-19 outcomes, suggesting that CGRP mAbs may be used for migraine prevention during the COVID-19 pandemic. Given the few events of requiring supplemental oxygen, use of mechanical ventilation, and death, replication analysis in a larger sample of patients later in the course of disease is warranted.
降钙素基因相关肽 (CGRP) 是一种参与偏头痛病理生理学的神经肽，也是关键的神经免疫调节剂。CGRP 拮抗剂可能有助于减轻 COVID-19 患者中观察到的过度炎症反应；然而，文献中的发现存在矛盾，迄今为止，尚无研究调查 CGRP 拮抗剂对 COVID-19 的安全性和有效性。
评估 CGRP 单克隆抗体 (mAb) 治疗与 SARS-CoV-2 感染风险以及需要补充氧气、使用机械通气或死亡的 COVID-19 后遗症住院之间的关联。
设计、设置和参与者：这项回顾性队列研究分析了美国年龄在 18 至 65 岁之间、患有偏头痛且有 COVID-19 风险的退伍军人的电子健康记录，这些患者的诊断时间为 2020 年 1 月 20 日至 2022 年 5 月 19 日。
CGRP mAb 的启动。
主要结果是 SARS-CoV-2 感染的累积发生率。30 天住院、需要补充氧气、使用机械通气或死亡的几率是次要结果。
在 8178652 名合格的人-试验中（354294 名退伍军人），9992 人（平均[SD]年龄，46.0[9.5]岁；53.9%为男性）启动了 CGRP mAb，8168660 人（平均[SD]年龄，46.6[10.2]岁；65.7%为男性）未启动 CGRP mAb。在 28 个月的随访期间，1247 名启动者（12.5%）和 780575 名非启动者（9.6%）的 SARS-CoV-2 检测呈阳性。在对偏离治疗的人进行删失后，启动者的发病率为每 1000 人-月 7.4 例，而非启动者的发病率为每 1000 人-月 6.9 例。意向治疗和方案内的逆概率加权观察模拟风险比分别为 0.95（95%CI，0.89-1.01）和 0.93（95%CI，0.86-1.02）。在需要补充氧气（比值比[OR]，0.93；95%CI，0.62-1.41）、需要补充氧气（OR，0.77；95%CI，0.45-1.30）、使用机械通气（OR，0.85；95%CI，0.26-2.84）或死亡（OR，0.67；95%CI，0.09-5.23）方面，CGRP mAb 启动者和 SARS-CoV-2 检测呈阳性的非启动者之间没有显著差异。
在这项队列研究中，CGRP mAb 治疗与 SARS-CoV-2 检测结果呈阳性或严重 COVID-19 结局风险无关，这表明在 COVID-19 大流行期间，CGRP mAb 可用于偏头痛预防。鉴于需要补充氧气、使用机械通气和死亡的事件很少，需要在疾病后期的更大患者样本中进行复制分析。
