Placebo effects in clinical trials of anti-CGRP monoclonal antibodies for migraine prevention

Abstract text (incl. figure legends and references)

OBJECTIVE: Commonly used indirect treatment comparison (ITC) methods, such as network meta-analyses, assume the presence of a common comparator across trials. For placebo (PBO)-controlled trials, PBO usually serves as the common comparator. Recent literature indicates that differences in route of administration (ROA) across PBO arms of clinical trials in pain disorders may contribute to differences in PBO effect. We conducted a meta-regression on PBO data from anti-CGRP monoclonal antibody (mAb) trials for migraine prevention to quantify the potential impact of ROA on PBO reduction in monthly migraine days (MMDs) across weeks 1–12.

METHODS: A systematic literature review was conducted in June 2021 to identify relevant PBO data from randomized clinical trials of anti-CGRP mAbs in migraine prevention. A generalized linear model was fitted to the extracted PBO data, with migraine type (EM/CM) and proportion of patients with ≥2 failed preventives as covariates.

RESULTS: An IV ROA for the PBO arm was a predictor for higher MMD reduction while episodic migraine, and a higher proportion of patients having ≥2 failed preventives were predictors of lower MMD reduction over weeks 1–12 in the PBO arms of studies investigating anti-CGRP mAbs.

CONCLUSIONS: Our results indicate that PBO ROA differences may warrant the use of ITC methods which do not assume the presence of a common comparator when comparing anti-CGRP mAbs in migraine prevention. Further research should be considered.