Efficacy and Contextual (Placebo) Effects of CGRP Antibodies for Migraine: Systematic Review and Meta-analysis

CGRP Antibodies are high-cost newly licensed migraine preventatives.

To calculate the overall reduction in monthly migraine days and the proportion contextual effect (PCE) using meta-analysis. The PCE is the ratio between the reduction in Monthly Migraine Days in the placebo group and the reduction in Monthly Migraine Days in the CGRP-Ab group after 3 months of treatment.

Meta-analysis of randomized double-blind placebo-controlled trials of anti-CGRP antibodies in people with episodic migraine (EM) or chronic migraine (CM) in persons aged 18 or over. Non-randomized trials and trials in persons under 18 years excluded. Search of National Clinical Trials Register 2000-2019, MEDLINE to September 2019, Hand search of major headache conference abstract books 2012-2019. Two investigators used standard proforma to reach consensus. Trial quality assessed using Cochrane Collaboration risk of bias tool. PRISMA guidelines followed.

21 completed trials with 13367 participants (8075 EM, 5292 CM). Compared to placebo, pooled reduction in MMD was 1.50 days in 15 EM trials (95%CI 1.16, 1.84; I²  = 69%, P_{hetereogeneity}  < .001) and 2.24 days in 7 CM trials (95%CI 1.82, 2.65, I²  = 15%, P_{hetereogeneity}  = .320). In EM trials, pooled PCE was 0.66 (95%CI 0.59,0.75; I²  = 64%, P_{hetereogeneity}  = .001). In CM trials the PCE was .68 (95%CI 0.61, 0.75; I²  = 20%, P_{hetereogeneity}  = .280). Industry funded every study, but risk of bias was low.

CGRPAbs are effective but sixty-six percent of the benefit is from contextual effects, including placebo effect. Contextual effects merit further scrutiny as a means of improving migraine headache.