Research indicates that Chronic migraine (CM; ≥15 monthly headache days with 8 or more linked to migraine) is associated with higher rates of disability and comorbidities, as well as reductions in health-related quality of life compared with episodic migraine (EM; <15 monthly headache days). Approximately 2.5% of patients with EM develop CM each year.  “Identifying individuals at risk for progression from EM to CM and optimizing treatment plans in the hopes of preventing progression is a promising strategy for reducing the public health burden of migraine,” explain Richard B. Lipton, MD, and Dawn C. Buse, PhD. In a study published in Neurology, Dr. Lipton, Dr. Buse, and colleagues sought to test the hypothesis that subgroups of migraine identified by comorbidity constellations vary in rates of progression from EM to CM. The study team used data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, which surveyed 16,789 people with migraine every 3 months from 2012 to 2013. CaMEO tracked comorbidities and patterns of treatment. In a previous report, the group used latent class analysis (LCA) to identify eight naturally occurring subgroups of people with EM based on comorbidities and symptoms and showed that the groups differed at baseline in demographic features, disability, and headache characteristics.

Identifying Progression Risk

The eight LCA-defined migraine subgroups included: many comorbidities (most comorbidities); respiratory/psychiatric; respiratory/pain; respiratory; psychiatric; cardiovascular; pain; few comorbidities (fewest comorbidities). Discrete time hazard modeling was used to analyze the migraine subgroups and to estimate rates of progression from EM to CM, adjusting for a range of variables, including demographics (Table). During the study period, 6.7% of patients identified with EM progressed to CM.

Among people with EM at baseline, the subgroup with the fewest comorbidities had the lowest risk of progressing from EM to CM. Conversely, the subgroup with the most comorbidities had the highest risk of progression, with a hazard ratio (HR) of 5.34, when compared with the fewest comorbidities group in models adjusted for demographics excluding race. The subgroup with a combination of respiratory and pain comorbidities had the second highest rate of progressing to CM (HR, 3.64). However, when a respiratory or pain comorbidity was the sole comorbidity, HRs for new-onset CM were significantly lower (1.53 and 1.93, respectively). “This result suggests that when certain comorbidities occur together, the risk for progression to CM is increased,” says Dr. Lipton. “We hypothesize that subgroups defined by comorbidity profiles may differ in disease biology in a prognostically significant way.” These findings suggest that treating comorbidities could have a significant impact on migraine patients’ quality of life and risk of progression.

Looking to the Future

The study findings suggest that physicians should be aware of how migraine comorbidities can impact their patients’ disease course and quality of life, according to Dr. Buse. “The clinical importance of the subgroups we have identified is demonstrated by the differences among the groups in the risk of progression to CM over time,” adds Dr. Lipton. He believes that identifying migraine subgroups and observing their relationship with the disease over time could provide a greater understanding of the heterogeneity of migraine.

“This analysis forms an early step in the identification of naturally occurring subgroups of migraine that are related to prognosis,” says Dr. Lipton. “Future research on this topic should look to externally validate comorbidity classes and determine whether we can predict responses to different types of treatments for each comorbidity group. Additionally, future studies should determine whether treatment of these risk factors can prevent or reduce rates of progression and target which comorbidities have the greatest impact and which treatments are most effective.”