Incremental IV placebo effect
The results of the meta-regression of the placebo effect with route of administration, type of migraine, and percentage of patients with ≥2 treatment failures are shown in Table 3 . The MMD reduction with IV placebo was 1.34 days lower (95% CI -1.86, -0.81;P <0.001) than with SC placebo. When the interaction term between administration and migraine type was added, theP -value just missed the 5% threshold (P =0.071). Directionally, the data indicate that an IV route of administration generated a higher incremental placebo response in chronic migraine (1.96 MMDs) than in episodic migraine (1.01 MMDs). The IV effect was numerically lower in patients with ≥2 prior treatment failures (0.47 MMDs) than in those with <2 prior treatment failures, but theP -value was 0.44. After splitting the trial results into <2 and ≥2 treatment failures, the IV effect remained similar (1.37 MMDs; P <0.001) (see Table S2 andTable S3 ).
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