University of Ottawa, Ottawa, Ontario, Canada.
SUNY Upstate Medical University, Syracuse, New York, USA.
Headache. 2022 Mar;62(3):329-362. doi: 10.1111/head.14284.
Cluster headache is the most common primary headache disorder of the trigeminal autonomic cephalalgias, and it is highly disabling.
We undertake a scoping review to characterize therapies to prevent and acutely treat cluster headache, characterize trial methodology utilized in studies, and recommend future trial "good practices." We also assess homogeneity of studies and feasibility for future network meta-analyses (NMAs) to compare acute and preventive treatments for cluster headache.
A priori protocol for this scoping review was registered and available on Open Science Forum. We sought studies that enrolled adult patients with cluster headache as identified by accepted diagnostic criteria. Both randomized controlled trials (RCTs) and observational studies (with a control group) were included. The interventions of interest were medications, procedures, devices, surgeries, and behavioral/psychological interventions, whereas comparators of interest were placebo, sham, or other active treatments. Outcomes were predefined; however, we did not exclude studies lacking these outcomes. A systemic search was conducted in Ovid Medline, Embase, and Cochrane. We performed a targeted search for conference abstracts from journals prominent in the field.
We identified 56 studies: 45 RCTs, four studies only available in clinical trial registries, and seven observational studies. Of the 45 RCTs, 20 focused on acute therapies and 25 on preventive therapies. Overall, we determined that it is feasible to pursue a NMA for acute therapy focusing on 15 or 30-min headache reduction for acute trials, as we identified 11 trials in the combined population of patients with either episodic or chronic cluster headache (2 trials in populations with chronic cluster headache were also found). For preventive therapy of cluster headache, we identified trials with common outcomes that may be considered for NMA, however, as these trials had differences in treatment effect modifiers that could not be corrected, NMAs appear infeasible for this indication. We identified new studies looking at noninvasive vagal nerve stimulation, sphenopalatine ganglion stimulation, prednisone, and oxygen published since the most recent systematic review in the field, although these acute treatments were previously identified as effective. However, for calcitonin gene-related peptide (CGRP) monoclonal antibodies, galcanezumab demonstrated effectiveness in episodic cluster headache, but a lack of effectiveness in chronic cluster headache, and fremanezumab was not effective for episodic nor chronic cluster headache. This finding highlights that CGRP monoclonal antibodies may not show a class effect in cluster headache prevention and need to be considered individually.
We describe the treatment landscape of cluster headache for both acute and preventive treatments. Last, we present the NMAs we will undertake in acute therapies of cluster headache.
丛集性头痛是三叉自主神经性头痛中最常见的原发性头痛疾病，其致残性极高。
我们进行了范围界定审查，以描述预防和急性治疗丛集性头痛的疗法，描述研究中使用的试验方法，并建议未来试验的“良好实践”。我们还评估了研究的同质性和未来用于比较丛集性头痛急性和预防性治疗的网络荟萃分析 (NMA) 的可行性。
本范围界定审查的预先注册方案可在开放科学论坛上获得。我们纳入了符合公认诊断标准的成年丛集性头痛患者的研究。包括随机对照试验 (RCT) 和观察性研究 (对照组)。我们感兴趣的干预措施是药物、程序、设备、手术和行为/心理干预，而我们感兴趣的对照措施是安慰剂、假对照或其他活性治疗。结果是预先确定的；但是，我们不排除缺乏这些结果的研究。我们在 Ovid Medline、Embase 和 Cochrane 中进行了系统搜索。我们还针对该领域重要期刊的会议摘要进行了有针对性的搜索。
我们确定了 56 项研究：45 项 RCT、4 项仅在临床试验注册处可用的研究和 7 项观察性研究。在 45 项 RCT 中，20 项侧重于急性治疗，25 项侧重于预防治疗。总体而言，我们确定对于聚焦于急性试验中 15 或 30 分钟头痛缓解的急性治疗，可以进行 NMA，因为我们在合并的有或无慢性丛集性头痛的患者人群中发现了 11 项试验（在有慢性丛集性头痛的患者人群中还发现了 2 项试验）。对于丛集性头痛的预防性治疗，我们发现了具有常见结局的试验，这些试验可能适合进行 NMA，然而，由于这些试验在治疗效果修饰因子方面存在差异，无法纠正，因此对于该适应症，NMA 似乎不可行。我们发现了新的研究，着眼于非侵入性迷走神经刺激、蝶腭神经节刺激、泼尼松龙和氧气，这些研究发表于该领域最近的系统评价之后，尽管这些急性治疗之前已被确定为有效。然而，对于降钙素基因相关肽 (CGRP) 单克隆抗体，加兰他敏在发作性丛集性头痛中显示出有效性，但在慢性丛集性头痛中无效，而佛来美尼布在发作性和慢性丛集性头痛中均无效。这一发现表明，CGRP 单克隆抗体在丛集性头痛预防中可能不会表现出类效应，需要单独考虑。
我们描述了丛集性头痛的急性和预防性治疗方法。最后，我们介绍了我们将在丛集性头痛急性治疗中进行的 NMA。
