Buse Dawn C, Serrano Daniel, Reed Michael L, Kori Shashi H, Cunanan Cedric M, Adams Aubrey Manack, Lipton Richard B
Albert Einstein College of Medicine, Bronx, NY, USA.
Montefiore Headache Center, Bronx, NY, USA.
Headache. 2015 Jun;55(6):825-39. doi: 10.1111/head.12556. Epub 2015 Apr 17.
Though triptans are the most widely used acute treatments for migraine, response to treatment is sometimes suboptimal. Triptan therapy is often augmented by the addition of other acute treatments. The benefits of this practice have not been examined in large-scale, real-world observational studies.
To assess changes in headache-related disability associated with adding additional acute treatments to a triptan regimen by category of added treatment including: a second triptan, nonsteroidal anti-inflammatory drugs (NSAID), opioids or barbiturates.
Subjects were participants in the American Migraine Prevalence and Prevention study, a longitudinal, US population-based study of individuals with "severe" headache. Respondents who met International Classification of Headache Disorders 3 beta criteria for migraine were on triptan therapy per respondent self-report, used the same triptan, and provided headache-related disability data for at least 2 consecutive years. Subjects were divided based on headache days per month into 3 groups: low-frequency episodic migraine (LFEM, 0-4), moderate-frequency episodic migraine (MFEM, 5-9), and high-frequency episodic migraine/chronic migraine (HFEM/CM, ≥ 10 headache days per month). HFEM and CM were combined into a single group for analyses because of sample size limitations. Patterns of acute treatment for migraine were monitored from one year to the next over the following couplets of years (2005-2006, 2006-2007, 2007-2008, and 2008-2009). The first eligible couplet was analyzed for each respondent. Medication regimens studied included: (1) maintaining current triptan use (consistent group); (2) adding a different triptan; (3) adding an NSAID; or (4) adding a combination analgesic containing opioids or barbiturates. We assessed change in Migraine Disability Assessment (MIDAS) score from the first to the second year of a couplet, contrasting scores of participants with consistent use with those who added an acute treatment to their triptan regimen.
The study sample (N = 2128) included 111 individuals who added another triptan, 118 who added an opioid or barbiturate, and 69 who added an NSAID, with referent groups of approximately 600 cases in each group who remained consistent. In general, MIDAS scores were higher among those who made changes from one year to the next compared with those who did not make changes in therapy. In fully adjusted models, adding triptans or NSAIDs was associated with increased disability for HFEM/CM cases at follow-up but decreased disability at follow-up for MFEM cases, resulting in significant interaction effects for both adding triptans and NSAIDs, respectively (15.88, 95% confidence interval [CI] 0.75, 31.01, 38.52, 95% CI 12.43, 64.61).
While the effects of adding vs staying consistent on the outcome of headache-related disability varied by medication type added and headache frequency strata, in general, these results suggest that for individuals with migraine, adding acute therapies to current triptan use is generally not associated with reductions in headache-related disability. The results were strongest among persons with HFEM and CM. These results identify important unmet medical needs in current migraine management, especially among patients with high-frequency migraine, and suggest that alternative treatment strategies are needed to improve patient outcomes.
尽管曲坦类药物是偏头痛最常用的急性治疗药物,但治疗反应有时并不理想。曲坦类药物治疗常通过添加其他急性治疗药物来增强疗效。这种做法的益处尚未在大规模的真实世界观察性研究中得到检验。
按添加治疗的类别评估在曲坦类药物治疗方案中添加其他急性治疗药物后与头痛相关残疾的变化,添加的治疗类别包括:第二种曲坦类药物、非甾体抗炎药(NSAID)、阿片类药物或巴比妥类药物。
研究对象为美国偏头痛患病率与预防研究的参与者,这是一项基于美国人群的针对“重度”头痛患者的纵向研究。根据国际头痛疾病分类第3版β标准符合偏头痛诊断的受访者,根据其自我报告正在使用曲坦类药物,且使用同一种曲坦类药物,并提供了至少连续两年的头痛相关残疾数据。根据每月头痛天数将受试者分为3组:低频发作性偏头痛(LFEM,0 - 4天)、中频发作性偏头痛(MFEM,5 - 9天)和高频发作性偏头痛/慢性偏头痛(HFEM/CM,每月≥10天头痛日)。由于样本量限制,HFEM和CM合并为一组进行分析。在接下来的几年对(2005 - 2006年、2006 - 2007年、2007 - 2008年和2008 - 2009年)的偏头痛急性治疗模式进行逐年监测。对每位受访者分析其第一个符合条件的年份对。研究的药物治疗方案包括:(1)维持当前曲坦类药物使用(持续用药组);(2)添加不同的曲坦类药物;(3)添加NSAID;或(4)添加含阿片类药物或巴比妥类药物的复合镇痛药。我们评估了年份对中第一年到第二年偏头痛残疾评估(MIDAS)评分的变化,对比持续用药组参与者与在曲坦类药物治疗方案中添加急性治疗药物的参与者的评分。
研究样本(N = 2128)包括111名添加了另一种曲坦类药物的患者、118名添加了阿片类药物或巴比妥类药物的患者以及69名添加了NSAID的患者,每组的参照组约有600例持续使用原治疗方案的患者。总体而言,与未改变治疗方案的患者相比,逐年改变治疗方案的患者MIDAS评分更高。在完全调整模型中,添加曲坦类药物或NSAID与随访时HFEM/CM病例的残疾增加相关,但与MFEM病例随访时的残疾减少相关,分别导致添加曲坦类药物和NSAID时均有显著的交互作用(15.88,95%置信区间[CI] 0.75,31.01;38.52,95% CI 12.43,64.61)。
虽然添加治疗与维持原治疗方案对头痛相关残疾结局的影响因添加的药物类型和头痛频率分层而异,但总体而言,这些结果表明,对于偏头痛患者,在当前曲坦类药物治疗基础上添加急性治疗药物通常与头痛相关残疾的减少无关。这些结果在HFEM和CM患者中最为明显。这些结果揭示了当前偏头痛管理中重要的未满足医疗需求,尤其是在高频偏头痛患者中,并表明需要替代治疗策略来改善患者结局。