Contextual Effects Have Role in Benefits of CGRP Antibodies for Migraine

A woman suffers from a migraine headache.
While calcitonin gene related peptide antibodies are effective for episodic and chronic migraine, most of its benefits are from contextual effects.

While calcitonin gene related peptide (CGRP) antibodies are effective for adults with episodic and chronic migraine, most of the reduction in monthly migraine days (MMD) is from contextual effects, including placebo effect, according to study results published in Headache.

Previous studies have shown that CGRP antibodies are effective for adults with migraine. The treatment effect is due to the CGRP blockade (specific treatment effect) and the context in which the treatment is given (contextual treatment effect).

The goal of this systematic review was to assess the overall efficacy and the proportion contextual effect (PCE) of CGRP antibodies in patients with episodic and chronic migraine. Using meta-analysis, study researchers assessed the overall reduction in MMD and the PCE, calculated as the ratio between the reduction in MMD in the placebo and the CGRP antibodies treatment groups at 3 months.

The systematic review and meta-analysis included randomized, double-blind, placebo-controlled trials in adults with episodic or chronic migraine, reporting MMD as an outcome measure.

The meta-analysis included 21 trials, of which 14 trials included patients with episodic migraine, 6 trials included patients with chronic migraine, and 1 study included both types of patients. Of 13,367 participants, 8075 had episodic migraine and 5292 had chronic migraine.

In patients with episodic migraine, treatment with CGRP antibodies reduced MMD by 1.50 (95% CI, 1.16-1.85; P <.001) compared to placebo (effect size, 0.37; 95% CI, 0.30-0.43). In those with chronic migraine, the active treatment was associated with 2.23 fewer MMD (95% CI, 1.79-2.67; P =.320) than placebo (effect size, 0.34; 95% CI, 0.26-0.41).

Approximately two-thirds of the benefit of CGRP antibodies was due to the contextual effects rather than the direct effect of CGRP blockade. The pooled PCE was calculated to be 0.66 (95% CI, 0.59-0.75; P =.001) in episodic migraine and 0.68 (95% CI, 0.61-0.73; P =.280) in chronic migraine.

The primary limitation of this study was that it was the first of its kind for neurologic disorders; consequently, it could not be compared to previous estimates of contextual effects in neurologic disease. An additional limitation included the short duration of the randomized-controlled studies on CGRP antibodies.

“Contextual effects may offer a means to improve health outcomes for a modest investment by paying attention to patient expectations, physician behavior, clinical environment, and health system culture,” concluded the researchers.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Forbes RB, McCarron M, Cardwell CR. Efficacy and contextual (placebo) effects of CGRP antibodies for migraine: systematic review and meta-analysis. Headache. Published online July 15, 2020. doi:10.1111/head.13907