Fluctuations in episodic and chronic migraine status over the course of 1 year: implications for diagnosis, treatment and clinical trial design

Abstract

Background: Relatively little is known about the stability of a diagnosis of episodic migraine (EM) or chronic migraine (CM) over time. This study examines natural fluctuations in self-reported headache frequency as well as the stability and variation in migraine type among individuals meeting criteria for EM and CM at baseline.

Methods: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study was a longitudinal survey of US adults with EM and CM identified by a web-questionnaire. A validated questionnaire was used to classify respondents with EM (<15 headache days/month) or CM (≥15 headache days/month) every three months for a total of five assessments. We described longitudinal persistence of baseline EM and CM classifications. In addition, we modelled longitudinal variation in headache day frequency per month using negative binomial repeated measures regression models (NBRMR).

Results: Among the 5464 respondents with EM at baseline providing four or five waves of data, 5048 (92.4%) had EM in all waves and 416 (7.6%) had CM in at least one wave. Among 526 respondents with CM at baseline providing four or five waves of data, 140 (26.6%) had CM in every wave and 386 (73.4%) had EM for at least one wave. Individual plots revealed striking within-person variations in headache days per month. The NBRMR model revealed that the rate of headache days increased across waves of observation 19% more per wave for CM compared to EM (rate ratio [RR], 1.19; 95% CI, 1.13-1.26). After adjustment for covariates, the relative difference changed to a 26% increase per wave (RR, 1.26; 95% CI, 1.2-1.33).

Conclusions: Follow-up at three-month intervals reveals a high level of short-term variability in headache days per month. As a consequence, many individuals cross the CM diagnostic boundary of ≥15 headache days per month.Nearly three quarters of persons with CM at baseline drop below this diagnostic boundary at least once over the course of a year. These findings are of interest in the consideration of headache classification and diagnosis, the design and interpretation of epidemiologic and clinical studies, and clinical management.

Keywords: Chronic migraine; Episodic migraine; Longitudinal; Migraine; Remission.

Conflict of interest statement

Competing interests

Daniel Serrano is an employee of Endpoint Outcomes. This work was initiated while he was serving as a consultant for Vedanta Research and completed while Associate Director of Psychometrics at Endpoint Outcomes. He has received support funded by Allergan plc, CoLucid, Endo Pharmaceuticals, GlaxoSmithKline, MAP Pharmaceuticals, Merck & Co., Inc., NuPathe, Novartis, and Ortho-McNeil, via grants to the National Headache Foundation. In addition, he has received funding from Allergan plc, Astellas, Genenteck, Lumena, Neurocrine, Shire and Supernus. Richard B. Lipton serves on the editorial board of Neurology and as senior advisor to Headache. He has received research support from the NIH. He also receives support from the Migraine Research Foundation and the National Headache Foundation. He has reviewed for the NIA and NINDS, serves as consultant, advisory board member, or has received honoraria from: Alder, Allergan, Amgen, Autonomic Technologies, Avanir, Boston Scientific, Colucid, Dr. Reddy’s, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Pfizer, Teva, and Vedanta. He receives royalties from Wolff’s Headache, 8th Edition, Oxford University Press, 2009 and Informa. He holds stock options in eNeura Therapeutics and Biohaven. Ann I Scher, in the past 12 months has received honoraria from and is an advisory board member for Allergan, Inc., receives grant support from CDMRP and CNRM, and is on the editorial boards of Cephalalgia and Pain Medicine. The Views expressed are those of the author (s) and do not necessarily reflect the official views of the Uniformed Services University of the Health Sciences or the Department of Defense. Michael Reed is Managing Director of Vedanta Research, which has received research funding from Allergan, Amgen, CoLucid, Dr. Reddy’s Laboratories, Endo Pharmaceuticals, GlaxoSmithKline, Merck & Co., Inc., NuPathe, Novartis, and Ortho-McNeil, via grants to the National Headache Foundation. Vedanta Research has received funding directly from Allergan for work on the CaMEO Study. Walter (Buzz) F. Stewart consulted for Amgen and received support for research from Astra-Zeneca. Aubrey Manack Adams is a full-time employee of Allergan plc and owns stock in the company. Dawn C. Buse in the past 12 months, has received grant support and honoraria from Allergan, Avanir, Amgen, and Dr. Reddy’s Laboratories. She has served as a consultant for Eli Lilly. She is an employee of Montefiore Medical Center, which in the past 12 months, has received research support funded by Allergan, Alder, Avanir, CoLucid, Dr. Reddy’s Laboratories, and Labrys via grants to the National Headache Foundation and/or Montefiore Medical Center. She is on the editorial board of Current Pain and Headache Reports, the Journal of Headache and Pain, Pain Medicine News, and Pain Pathways magazine.

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Figures

Fig. 1

CaMEO study design, reprinted from Manack Adams A, et al. Cephalalgia 2015;35:563–578. [8]

Fig. 2

Longitudinal study sample flow

Fig. 3

Observed monthly headache frequency over 15 months compared with that predicted using IBLUP = approach HAFREQ = observed monthly headache frequency: IBLUP = inverse link function best linear unbiased predictor

Fig. 4

Episodic- and chronic migraine-specific longitudinal trajectories. Time by chronic migraine interaction plot