Assess the nature of interictal burden in migraine, and whether treatment with galcanezumab can reduce it.

Typical migraine clinical trial endpoints assess only ictal burden.

Adult patients (N=462) with episodic or chronic migraine who experienced failure of 2-4 prior preventive medication categories in the past 10 years were randomized 1:1 to 3 months of double-blind treatment with placebo or galcanezumab 120mg. Primary endpoint was mean change from baseline in number of monthly migraine headache days. The Migraine Interictal Burden Scale-4 (MIBS-4) measured burden of migraine on non-headache days over the past 4 weeks (0=no burden, 1-2=mild, 3-4=moderate, 5-12=severe). Migraine Disability Assessment (MIDAS), Migraine-Specific Quality of Life Questionnaire v.2 (MSQ), Patient Global Impression of Severity (PGI-S), and symptoms of depression (Patient Health Questionaire-9 [PHQ-9]) and anxiety (Generalized Anxiety Disorder Scale [GAD-7]) were assessed. We evaluated the relationship between MIBS-4 and these outcome measures using Spearman’s rank correlation coefficient for total population at baseline.

At baseline, MIBS-4 was moderately correlated with PHQ-9 (r=.55) and MSQ total (r=-.53) but showed low correlation  with GAD-7 (r=0.42), MIDAS (r=0.41), and PGI-S (r=0.32), and negligible correlation with monthly migraine headache days (0.22).

After 3 months, from a mean baseline of 13.2 monthly migraine headache days, galcanezumab patients improved by 4.4 days vs 1.3 days for placebo (p<.0001). From mean baseline MIBS-4 score of 5.5, galcanezumab patients improved by 1.8 points vs 0.8 points for placebo (p<.0001).

In addition to reducing ictal burden, galcanezumab treatment significantly reduces interictal burden of migraine as measured by MIBS-4. The lack of strong correlation between MIBS-4 and other trial outcomes supports previous validation work and suggests that interictal burden in migraine is a distinct effect of the disease that is not fully captured by other constructs.