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).
<<<Note to Journal Editors: Place Table 2
here.>>>
<<<Note to Journal Editors: Place Fig. 2
here.>>>
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.