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

DOI: https://doi.org/10.1186/s10194- 017- 0787- 1

Abstract-Summary This study examines natural fluctuations in self-reported headache frequency as well as the stability and variation in migraine type among individuals meeting crite- ria for EM and CM at baseline.

The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study was a lon- gitudinal survey of US adults with EM and CM identified by a web-questionnaire. A validated questionnaire was used to classify respondents with EM (<15 head- ache 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. 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.

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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).

Many individuals cross the CM diagnostic boundary of ≥15 headache days

per month.

Extended: These findings have implications for classification and diagnosis, the design and conduct of observational studies, and for the design, management, and interpretation of randomized controlled trials (RCTs).

Background Within-person variation in headache days per month logically influences the epide- miologic estimates of EM and CM incidence and persistence reported in the litera- ture [150–153], as well as the assessment of treatment response.

The natural within-person variation in headache day frequency, which is the fun- damental driver of the instability in diagnostic classification for EM and CM reported in the literature, has been studied inadequately, if at all.

To better characterize within-person change in headache days we analyzed lon- gitudinal data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study [154].

Of primary importance, we modelled natural history of self-reported headache

day variation in quarterly assessments across the span of 15 months.

Natural history of headache frequency was modeled accounting for both within-

person and between-person changes in headache days per month.

Methods Among those with migraine, respondents were classified as having CM if they reported ≥15 headache days per month averaged over the preceding 90 days (i.e., the Silberstein-Lipton approach [155]), otherwise they were classified as having EM. Of the 58,418 respondents to the baseline survey, 16,789 met criteria for EM or CM and received follow-up surveys at three-month intervals from September 2012 to November 2013.

Analysis was also completed to model variation in average monthly headache

days using the longitudinal negative binomial mixed effect models.

The first was an unadjusted model that included only the repeated measures trend terms and main effects and interactions between the repeated measures trend terms and EM/CM status (with EM as reference).

For the adjusted models, EM and CM status varied over time while all other

covariates were entered as predictors based on their baseline status.

3.2 Medical history

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Results The significant linear trend by headache status interaction indicated that headache days per wave changed differently for those with EM vs CM.

Headache days per wave decreased slightly in the EM group and increased

slightly in the CM group.

This difference in change resulted in a rate of headache day increase of 19% more per wave for CM compared to EM (rate ratio [RR], 1.19; 95% CI 1.13–1.26). After adjustment, the headache status by linear trend interactions revealed that headache days per month increased 26% more per wave for CM compared to EM (RR, 1.26; 95% CI, 1.20–1.33).

Headache frequency oscillates for CM, but the overall trend is one of subtle

increase.

The reported rate ratios of 1.19 and 1.26 (adjusted) arise from this difference between headache frequency decreasing over time for EM while increasing over time for CM.

Discussion This study demonstrates that in persons with migraine assessed at three-month intervals, there are frequent transitions between CM and EM with substantial within-person variation in the number of headache days per month over the course of 15 months.

We found that 73.4% of people with CM at baseline and four or five follow-up waves of data had at least 1 three-month period when they did not meet the 15 or more headache day per month criteria for CM.

Among persons with EM at baseline and four or five waves of follow-up, 7.6%

had at least one period when they met the headache frequency criteria for CM.

Among people with EM at baseline, when assessed every three months, 7.6% of individuals met headache day criteria for CM at least once over a 15-month period.

Conclusions Results confirm that there is substantial variation in headache day frequency in peo- ple with EM and CM followed at three-month intervals.

Transitions from EM to CM are more common (7.6%) than previously observed when sampled less frequently; in addition, nearly 75% of people with CM will remit to EM at some point during a 12-month period.

This natural variation should be considered when designing epidemiologic and

clinical trials and when clinicians diagnose, treat and study CM.

Acknowledgement A machine generated summary based on the work of Serrano, Daniel; Lipton, Richard B.; Scher, Ann I.; Reed, Michael L.; Stewart, Walter F.; Adams, Aubrey Manack; Buse, Dawn C. 2017 in The Journal of Headache and Pain.

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Prolonged migraine aura: new insights from a prospective diary-aided study