HOW MUCH OF ANTI-CGRP MONOCLONAL ANTIBODY PREVENTIVE THERAPY FOR MIGRAINE IS CONTEXTUAL (PLACEBO) EFFECT?

Background Randomised Controlled Trials (RCTs) of Anti-CGRP monoclonal antibodies prove their efficacy in preventing Episodic Migraine (EM) and Chronic Migraine (CM), but will cost c£350 per patient per month. Many headache interventions have significant placebo responses. The aim is to quantify the contribution of placebo and other non-specific effects by estimating the Proportion Contextual Effects from available RCTs. Methods Search of clinicaltrials.gov for RCTs in adults with EM or CM. Data extracted from peer reviewed publications, conference abstracts and company websites January 2013-Sep 2018. Primary outcome - Reduction in Monthly Migraine Days. Effect Size (Standardised Mean Difference - SMD) and Proportion Contextual Effect (Response Ratio) calculated with 95%CI. Risk of bias not estimated. Results 56 registered studies identified, of which 28 were RCTs (8 incomplete or non-migraine and 2 in children). 18 included trials tested 19 doses of CGRP-antibody in EM and 9 doses in CM. Effect Sizes were small (SMD 0.2–0.49) in 12/19 EM and 7/9 CM doses, moderate (0.5–0.79) in 5/19 EM and 1/9 CM. Proportion Contextual Effects were between 50–70% in 13/19 EM and 8/9 CM doses, and >70% in 5/19 EM and 2/9 CM doses. Discussion Anti-CGRP antibodies are effective treatments for EM and CM, but this is primarily due to contextual effects. >50% of the benefit accrued is attributable to health service personnel and infrastructure, not a direct drug effect.