By Sarah A. Friedman, MD, and Matthew S. Robbins, MD, FAAN, FAHS
Dr. Friedman is a Senior Resident in Neurology at New York Presbyterian Hospital/Weill Cornell Medical Center.
Dr. Robbins is Neurology Residency Program Director; Associate Professor of Neurology, Weill Cornell Medical College, New York-Presbyterian Hospital.
SYNOPSIS: In a big data-driven observational study that compared 3 million treated migraine attacks captured from a migraine diary smartphone app, triptans were found to be the most efficacious treatment class. Among the triptans, eletriptan had the highest rate of success. Consistent with clinical practice and recent consensus statements, the success of triptans was followed by ergots and antiemetics.
SOURCE: Chiang CC, Fang X, Horvath Z, et al. Simultaneous comparisons of 25 acute migraine medications based on 10 million users’ self-reported records from a smartphone application. Neurology 2023;101:e2560-e2570.
Migraine consistently is one of the highest contributors to years lived with disability globally. Consequently, the development and use of effective acute migraine treatments play a pivotal role in minimizing functional disability by mitigating symptom severity and reducing attack duration. Various acute medications have been employed to address migraine, including triptans, ergots, nonsteroidal anti-inflammatory drugs (NSAIDs), combination analgesics, acetaminophen, antiemetics, certain opioids, and newer agents, such as calcitonin gene-related peptide (CGRP) receptor antagonists (gepants). However, the efficacy of these medications has been challenging to compare comprehensively because of limited head-to-head trials, often with small sample sizes. Although some meta-analyses have attempted to compare acute migraine medications based on randomized controlled trials, these indirect comparisons may not fully capture real-world effectiveness, considering diverse patient populations and comorbidities.
To address this gap, Chiang et al leveraged patient-generated health data from Migraine Buddy, a smartphone headache diary app with more than 3 million users globally. Analyzing more than 10 million migraine attacks with nearly 3 million unique medication-outcome pairs recorded by 278,000 users, the study directly compared the treatment effectiveness of 25 acute migraine medications across the United States, United Kingdom, and Canada.
Triptans emerged as the most helpful class of medication, particularly eletriptan (odds ratio, 6.1; 95% confidence interval, 6.0-6.3, compared to ibuprofen, which was used as the reference treatment), followed by zolmitriptan and sumatriptan. Triptans were followed by ergots and antiemetics. Other studied agents, including certain opioids, other NSAIDs, and combination analgesics, all were found to be more effective than ibuprofen.
COMMENTARY
While acknowledging the subjectivity of user-reported outcomes and potential limitations in dosage and formulation information, this real-world study provides valuable insights into the comparative effectiveness of acute migraine medications. A particular strength of this study is its immense sample size, which potentially is the largest international dataset of medically managed migraine to date. Although the patient population was 90.7% women, which could limit its generalizability, this parallels most clinical trial populations.
The limited demographic information impedes the stratification of outcomes for historically underserved groups, including racial, ethnic, and gender minorities, limiting insights on existing disparities in treatment efficacy. Socioeconomic factors, such as low income, may compound these issues, with restricted access to smartphones and treatment options. The multinational scope of the study, while enhancing generalizability, introduces potential bias as the result of varying treatment access across countries. For instance, medication availability and prescription requirements differ between the United States and the United Kingdom.
Another consideration is the grouping of medication doses and formulations in the analysis, which raises concerns about the precision of outcomes. Not capturing differences in migraine severity among diary users may affect the interpretation of treatment efficacy. Factors such as attack intensity influence medication choice and success rates, leading to variations in preferences for specific triptans or ergots. Further, caution is urged in interpreting results related to opioid efficacy compared to ibuprofen, given concerns about medication overuse headache and dependence. The authors noted that these findings should not deter clinicians from using NSAIDs for migraine, which is justified given the efficacy of newer NSAID formulations, such as liquid celecoxib and oral diclofenac powder.
Although the study highlights the success of eletriptan in a large patient population, the exclusion of newer agents, such as CGRP-targeted treatments, limits the study relevance to evolving clinical practices. Comparative data across trials suggest triptans’ higher efficacy compared to gepants and lasmiditan, indicating the need for future studies incorporating these newer medications. Nonetheless, the conclusions from this study align with existing guidelines and meta-analyses, reinforcing the significance of triptans as a primary choice for treating acute migraine attacks. Additionally, the study emphasizes the importance of considering real-world data alongside traditional clinical trials for a more comprehensive understanding of treatment effectiveness. This study highlights the feasibility of real-world observational data to be considered alongside more traditional clinical trials.
