Study Finds Bidirectional Relationship Between Migraine, Rheumatoid Arthritis

Migraine increases the risk of rheumatoid arthritis (RA) and RA is associated with an increased risk of migraine, according to results of 2 longitudinal follow-up studies with a national sample cohort. Findings were published in BMJ Open.

Although the complete underlying mechanism of migraine pathophysiology is still unknown, “a variety of factors, including those involving the central nervous system, the immune system, inflammation, genetics and vascular ischemia, can contribute to the development of migraine attacks,” authors explained.

In addition, several causative genetic, environmental, and immunological factors have been implicated in the development of RA.

Few studies have reported an association between migraine and RA, but previous research suggests that a shared mechanism involving inflammatory processes and immune responses may account for the link between the 2 conditions. Common comorbidities among patients with RA and migraine include depression, obesity, and sleep disturbance.

“Based on the common pathophysiologic mechanisms of inflammation, vascular endothelial cells and the immune system between migraine and RA, we hypothesized that there might be a bidirectional association between migraine and RA,” researchers wrote.

To test this hypothesis, they conducted 2 longitudinal follow-up studies, each with a control group matched with a study group based on age, sex, income, and region of residence. Adjusted analyses took the Charlson Comorbidity Index (CCI), body mass index (BMI), smoking, alcohol consumption, and autoimmune disease histories into account.

Deidentified data were amassed from the Korean National Health Insurance Service-Health Screening Cohort between January 2002 and December 2013. Individuals were divided into 2 cohorts to determine risk for incident RA in those with migraine, and risk for incident migraine in those with RA.

The migraine cohort was matched 1:4 with control group 1 (n = 31,589 and 126,356, respectively) and those with a history of RA were excluded from both groups. Similarly, the RA group was matched 1:4 with control group 2 (n =9287 and 37,148, respectively) and any individual previously diagnosed with migraine was excluded.

Among those with migraine:

• Incidence of RA was higher in the migraine group (2.0% [640/31,589]) than in control group 1 (1.4% [1709/126,356]; P < .001).
• The adjusted HR for RA in the migraine without aura group was 1.48 (95% CI, 1.34-1.63; P < .001); adjusted HR for RA in the migraine with aura group was 1.23 (95% CI, 0.91-1.67; P = .183).
• In all subgroup analyses (age, income level, urban vs rural), higher adjusted HRs for RA were observed in the migraine group (each P < .05).

Analyses of those with RA showed:

• Incidence of migraine was higher in the RA group (6.4% [590/9287]) than in control group 2 (4.6% [1721/37,148]; P < .001).
• Adjusted HR for migraine without aura in the RA group was 1.35 (95% CI, 1.23-1.49; P < .001) and the adjusted HR for migraine with aura in the RA group was 1.36 (95% CI, 0.95-1.96; P = .094).
• Higher adjusted HRs for migraine were observed in the RA group, except in men 60 years and older (each P < .05).
• Adjusted HRs were 1.38 (95% CI, 1.21-1.57) in the low-income group and 1.33 (95% CI, 1.16-1.53) in the high-income group, while both urban and rural categories in the RA group had higher adjusted HRs for migraine.

“In addition, Kaplan-Meier survival analysis showed that the cumulative proportion of patients with RA increased over time in the group with migraines, and the cumulative proportion of patients with migraine also increased over time in the group with RA,” researchers wrote.

Authors noted that the finding that RA was not associated with an increased risk of migraine in men over the age of 60 may be due to the age- and sex-specific prevalence of migraine, as the condition is more often found in women and in those aged 25 to 55 years.

Researchers also noted that although the adjusted HR for RA was 1.46, the adjusted HR for RA among those with migraine with aura was not significant. In addition, as glucocorticoids are used in patients with severe migraine, their presence may have affected prevalence of RA. However, detailed histories of medications used for migraine were not included in the study, marking a limitation.

Overall, “this national cohort study is the first to show a bidirectional association between migraine and RA,” they concluded.

Reference

Kim YH, Lee JW, Kim Y, et al. Bidirectional association between migraine and rheumatoid arthritis: two longitudinal follow-up studies with a national sample cohort. BMJ Open. Published online June 8, 2021. doi:10.1136/bmjopen-2020-046283