Effect of SC placebo on MMDs according to type of migraine and prior treatment failures
In episodic migraine, the meta-regression showed a relationship (P <0.001) between the percentage of patients with ≥2 treatment failures and the reduction in MMDs from baseline with placebo: placebo-treated patients who failed 2 or more therapies had a lower MMD reduction (1.78 MMDs), compared with patients who did not previously fail any therapies and who had almost no placebo response (-0.26 MMDs) (Table 2 and Figure 2A ).
Furthermore, there was a relationship between the percentage of patients with ≥2 treatment failures and the reduction in MMDs from baseline with placebo in chronic migraine, although there was a greater level of uncertainty (wider CIs and P =0.057; Table 2 andFigure 2B ). This may reflect the smaller number of trials and data points available for chronic migraine compared with episodic migraine. However, the coefficient estimates of the impact of the proportion of patients with ≥2 treatment failures were comparable between chronic migraine (1.88) and episodic migraine (1.77).
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In the sensitivity analyses, which included the data from the publications of phase 3 trials reporting subgroup analyses of patients with ≥2 treatment failures, the point estimate for episodic migraine was unaffected (see Table S1 ) and the CIs were narrowed (seeFigure S1 ). Adding the subgroup data for chronic migraine slightly modified the coefficient estimate of prior treatment failure (from 1.87 to 1.81), which became closer to that of episodic migraine, and the P -value was less than 0.05; however, the 95% CI of the impact of prior treatment failure remained wider in chronic migraine than in episodic migraine.