Plasma SuPAR and therapeutic response to erenumab in migraine: a REFORM study.

IF 7.3 1区医学 Q1 CLINICAL NEUROLOGY

Journal of Headache and Pain Pub Date : 2025-04-24 DOI:10.1186/s10194-025-02037-9

William K Karlsson, Rune H Christensen, Haidar M Al-Khazali, Thomas Kallemose, Baker N Jawad, Ove Andersen, Messoud Ashina, Håkan Ashina

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引用次数: 0

Abstract

Background: Soluble urokinase-plasminogen activator receptor (suPAR) is a biomarker of systemic inflammation and elevated in plasma of individuals with migraine with aura. As inflammatory cytokines can upregulate calcitonin gene-related peptide (CGRP), suPAR levels might be linked to response to CGRP-targeting therapies. Therefore, we investigated whether plasma suPAR levels are associated with response to the CGRP-receptor antagonist erenumab.

Methods: In this single-center, prospective study, adults with ≥ 4 monthly migraine days received 140 mg erenumab subcutaneously every 4 weeks for 24 weeks. Blood samples were collected at baseline, Week 24 (end of treatment), and Week 48 (24 weeks post-treatment). Responders were defined as achieving a ≥ 50% reduction in monthly migraine days from baseline to weeks 13-24. Associations between baseline suPAR and treatment response were analyzed using logistic and linear regression. Longitudinal changes in suPAR were assessed using linear mixed models.

Results: The study included 623 participants with migraine (mean age 44.1 ± 12.3 years; 90.4% female) and 154 healthy controls. Among participants, 183 (29.4%) had migraine with aura, and 406 (65.2%) had chronic migraine. Baseline plasma suPAR levels were not associated with response to erenumab in the total migraine population (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.64 to 1.07; p = 0.14) or in the aura subgroup (OR 0.73, 95% CI 0.48 to 1.10; p = 0.14). Plasma suPAR levels were significantly higher in non-responders compared to responders at Week 48 (7.5% higher, 95% CI 3.3 to 11.5%; p = 0.005). Non-responders with aura had higher suPAR concentrations than controls at baseline (difference 10.1%; 95% CI 3.0 to 17.8%; p = 0.023) and Week 24 (8.7%; 95% CI 1.6 to 16.2%; p = 0.047). These differences persisted at Week 48 (12.4%; 95% CI 4.6 to 20.7%; p = 0.013). No longitudinal changes in suPAR concentrations were observed.

Conclusions: We did not find an association between baseline plasma suPAR levels and response to erenumab. Plasma suPAR concentrations remained stable, even among participants with aura. These findings suggest that systemic low-grade inflammation, as measured by suPAR, does not influence treatment efficacy.

Trial registration: Pre-registered on ClinicalTrials.gov (NCT04603976 and NCT04674020).

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血浆SuPAR和偏头痛患者对伊列那单抗的治疗反应：一项改革研究。

背景：可溶性尿激酶-纤溶酶原激活物受体（suPAR）是系统性炎症的生物标志物，在先兆偏头痛患者血浆中升高。由于炎症细胞因子可以上调降钙素基因相关肽（CGRP）， suPAR水平可能与CGRP靶向治疗的反应有关。因此，我们研究了血浆suPAR水平是否与对cgrp受体拮抗剂erenumab的反应有关。方法：在这项单中心前瞻性研究中，每月偏头痛天数≥4天的成年人每4周皮下注射140 mg erenumab，持续24周。在基线、第24周（治疗结束）和第48周（治疗后24周）采集血样。应答者被定义为从基线到第13-24周每月偏头痛天数减少≥50%。使用逻辑回归和线性回归分析基线suPAR与治疗反应之间的关系。采用线性混合模型评估suPAR的纵向变化。结果：研究纳入623名偏头痛患者(平均年龄44.1±12.3岁；90.4%女性)和154名健康对照者。在参与者中，183人（29.4%）患有先兆偏头痛，406人（65.2%）患有慢性偏头痛。在整个偏头痛人群中，基线血浆suPAR水平与对erenumab的反应无关(优势比[OR] 0.83, 95%可信区间[CI] 0.64至1.07；p = 0.14)或先兆亚组(or 0.73, 95% CI 0.48 ~ 1.10；p = 0.14)。在第48周，无应答者的血浆suPAR水平显著高于应答者(高7.5%,95% CI 3.3 - 11.5%；p = 0.005)。无反应的先兆患者在基线时的suPAR浓度高于对照组(差异10.1%；95% CI 3.0 ~ 17.8%；p = 0.023)和第24周(8.7%；95% CI 1.6 - 16.2%；p = 0.047)。这些差异在第48周继续存在(12.4%；95% CI 4.6 ~ 20.7%；p = 0.013)。未观察到suPAR浓度的纵向变化。结论：我们没有发现基线血浆suPAR水平与对erenumab的反应之间的关联。血浆suPAR浓度保持稳定，即使在有先兆的参与者中也是如此。这些发现表明，全身低度炎症，如suPAR测量，不影响治疗效果。试验注册：在ClinicalTrials.gov上预注册（NCT04603976和NCT04674020）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Headache and Pain 医学-临床神经学

CiteScore

11.80

自引率

13.50%

发文量

143

审稿时长

6-12 weeks

期刊介绍： The Journal of Headache and Pain, a peer-reviewed open-access journal published under the BMC brand, a part of Springer Nature, is dedicated to researchers engaged in all facets of headache and related pain syndromes. It encompasses epidemiology, public health, basic science, translational medicine, clinical trials, and real-world data. With a multidisciplinary approach, The Journal of Headache and Pain addresses headache medicine and related pain syndromes across all medical disciplines. It particularly encourages submissions in clinical, translational, and basic science fields, focusing on pain management, genetics, neurology, and internal medicine. The journal publishes research articles, reviews, letters to the Editor, as well as consensus articles and guidelines, aimed at promoting best practices in managing patients with headaches and related pain.