Background

Trigeminal neuralgia is a severe facial pain disorder that is difficult to treat. Erenumab, a monoclonal antibody against the calcitonin gene-related peptide (CGRP) receptor, has proven efficacy in migraine. Erenumab modulates sensory processing in peripheral trigeminal pain pathways in mice and was reported to be effective for patients with trigeminal neuralgia in open-label studies. We aimed to evaluate the efficacy of erenumab in patients with trigeminal neuralgia.

Methods

We did a randomised, double-blind, placebo-controlled trial in adults (aged 18–85 years) with idiopathic or classic trigeminal neuralgia as defined by the 3rd edition of the International Classification of Headache Disorders. The trial was based at the Danish Headache Center, Copenhagen University Hospital. Eligible participants had no clinically significant cerebrovascular or cardiovascular disease, had self-reported pain intensity of at least 4 on the 11-point Numeric Rating Scale (0=no pain, 10=worst pain imaginable), and had at least three daily pain paroxysms. After a 1-week pre-screening period, patients entered a 4-week baseline period. Participants who met pain inclusion criteria at the end of the baseline period were randomly assigned (1:1) to receive subcutaneous injections of either erenumab 140 mg or placebo and entered the 4-week follow-up period. Randomisation was done in blocks of 10 using a computer-generated schedule by a third-party company. Participants and assessors were masked to treatment allocation, and erenumab and placebo were packed in identical prefilled syringes. The primary outcome was the number of responders, defined as patients who had a reduction of at least 30% in mean average daily pain intensity during the follow-up period compared with during the baseline period, analysed in the intention-to-treat population. This trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database, EudraCT number 2019–000848–95.

Findings

We assessed 860 patients for suitability and excluded 741 between Oct 28, 2019, and Sept 13, 2021. 119 participants entered a 1-week pre-screening period and 26 were excluded, 93 participants entered a 4-week baseline period with 13 excluded before randomisation, and 80 participants were randomly assigned to erenumab 140 mg (n=40) or placebo (n=40). There was no difference between groups in the number of responders at 4 weeks in the intention-to-treat population (14 [35%] of 40 with erenumab vs 18 [45%] of 40 with placebo; estimated effect size –10% [95% CI –31 to 11]; p=0·36). 20 (50%) of 40 participants reported adverse events in each group. The most common adverse events were constipation (28%) and headache (10%) in the erenumab group, and headache (13%), constipation (10%), and abdominal pain (10%) in the placebo group.

Interpretation

Erenumab did not reduce pain intensity compared with placebo in patients with trigeminal neuralgia and CGRP probably does not have an important role in paroxysmal pain. Well tolerated, effective treatments in trigeminal neuralgia are still needed.

Funding

Novartis.

中文翻译：

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erenumab 在丹麦治疗三叉神经痛患者的安全性和有效性：一项双盲、随机、安慰剂对照、概念验证研究

背景

三叉神经痛是一种难以治疗的严重面部疼痛疾病。Erenumab 是一种抗降钙素基因相关肽 (CGRP) 受体的单克隆抗体，已证明对偏头痛有效。Erenumab 调节小鼠外周三叉神经痛通路的感觉处理，据报道在开放标签研究中对三叉神经痛患者有效。我们旨在评估 erenumab 在三叉神经痛患者中的疗效。

方法

我们在患有特发性或经典三叉神经痛的成人（18-85 岁）中进行了一项随机、双盲、安慰剂对照试验，该试验定义为国际头痛疾病分类第 3 版。该试验在哥本哈根大学医院的丹麦头痛中心进行。符合条件的参与者没有临床上显着的脑血管或心血管疾病，在 11 点数字评定量表上自我报告的疼痛强度至少为 4（0 = 无疼痛，10 = 可以想象的最严重的疼痛），并且每天至少有 3 次疼痛发作. 经过 1 周的预筛选期后，患者进入 4 周的基线期。在基线期结束时符合疼痛纳入标准的参与者被随机分配（1：1) 接受皮下注射 erenumab 140 mg 或安慰剂并进入 4 周随访期。由第三方公司使用计算机生成的时间表以 10 个为一组进行随机化。参与者和评估者对治疗分配设盲，erenumab 和安慰剂包装在相同的预装注射器中。主要结局是在意向治疗人群中分析的缓解者人数，缓解者定义为在随访期间与基线期间相比平均每日疼痛强度至少降低 30% 的患者。该试验已在欧盟药品监管机构临床试验数据库中注册，EudraCT 编号为 2019-000848-95。参与者和评估者对治疗分配设盲，erenumab 和安慰剂包装在相同的预装注射器中。主要结局是在意向治疗人群中分析的缓解者人数，缓解者定义为在随访期间与基线期间相比平均每日疼痛强度至少降低 30% 的患者。该试验已在欧盟药品监管机构临床试验数据库中注册，EudraCT 编号为 2019-000848-95。参与者和评估者对治疗分配设盲，erenumab 和安慰剂包装在相同的预装注射器中。主要结局是在意向治疗人群中分析的缓解者人数，缓解者定义为在随访期间与基线期间相比平均每日疼痛强度至少降低 30% 的患者。该试验已在欧盟药品监管机构临床试验数据库中注册，EudraCT 编号为 2019-000848-95。定义为在随访期间与基线期间相比平均每日疼痛强度至少降低 30% 的患者，在意向治疗人群中进行分析。该试验已在欧盟药品监管机构临床试验数据库中注册，EudraCT 编号为 2019-000848-95。定义为在随访期间与基线期间相比平均每日疼痛强度至少降低 30% 的患者，在意向治疗人群中进行分析。该试验已在欧盟药品监管机构临床试验数据库中注册，EudraCT 编号为 2019-000848-95。

发现

我们评估了 860 名患者的适用性，并在 2019 年 10 月 28 日至 2021 年 9 月 13 日期间排除了 741 名患者。119 名参与者进入了 1 周的预筛选期，26 名被排除在外，93 名参与者进入了 4 周的基线期，之前有 13 名被排除在外随机化，80 名参与者被随机分配到 erenumab 140 mg (n=40) 或安慰剂组 (n=40)。意向治疗人群中 4 周时的应答者人数在组间没有差异（erenumab 组 40 人中有 14 人 [35%] vs40 人中有 18 人 [45%] 使用安慰剂；估计效应量 –10% [95% CI –31 至 11]；p=0·36）。40 名参与者中有 20 名 (50%) 报告了每组的不良事件。erenumab 组最常见的不良事件是便秘 (28%) 和头痛 (10%)，安慰剂组是头痛 (13%)、便秘 (10%) 和腹痛 (10%)。

解释

与安慰剂相比，erenumab 并未减轻三叉神经痛患者的疼痛强度，并且 CGRP 可能在阵发性疼痛中没有重要作用。仍然需要耐受性良好的三叉神经痛有效治疗方法。

资金

诺华。