Effects Of Fremanezumab In Patients With Chronic Migraine And Comorbid Depression: Subgroup Analysis Of The Randomized Halo Cm Study

Objective To evaluate the efficacy of fremanezumab in patients with chronic migraine (CM) and moderate to severe depression.Background Fremanezumab, a fully humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, has been approved for the preventive treatment of migraine in adults. CM and depression are highly comorbid.Methods The 12-week, Phase 3 HALO trial randomized patients with CM to fremanezumab quarterly (675 mg/placebo/placebo), fremanezumab monthly (675/225/225 mg), or placebo. Post hoc analyses evaluated the effects of fremanezumab in patients with moderate to severe depression (baseline 9-item Patient Health Questionnaire sum score >= 10) on monthly number of headache days of at least moderate severity; monthly migraine days; Patient Global Impression of Change (PGIC); 6-item Headache Impact Test (HIT-6) scores; and depression.Results For the 219/1121 (19.5%) patients with moderate to severe depression at baseline, fremanezumab was associated with a significant reduction in monthly number of headache days of at least moderate severity for active treatment versus placebo (least-squares mean change +/- standard error for quarterly dosing: -5.3 +/- 0.77; for monthly dosing: -5.5 +/- 0.72; and for placebo: -2.2 +/- 0.81; both p < 0.001). More patients achieved a >= 50% reduction in headache days of at least moderate severity with fremanezumab (quarterly: 31/78 [39.7%]; monthly: 39/96 [40.6%]) than placebo (9/67 [13.4%]; both p < 0.001). Compared with placebo, fremanezumab improved PGIC and HIT-6 scores.Conclusions Fremanezumab demonstrated efficacy in the preventive treatment of CM and reduced headache impact in patients with comorbid depression.