Efficacy and safety of erenumab (AMG334) in episodic migraine patients with prior preventive treatment failure: A subgroup analysis of a randomized, double-blind, placebo-controlled study

Background Erenumab was effective and well tolerated in a pivotal clinical trial of episodic migraine that included subjects both naive to, and those who had failed, previous preventives. Here we evaluated the efficacy and safety of erenumab (70mg or 140mg) versus placebo in the subgroup of patients who had previously failed preventive treatment(s): 1 or 2 prior failed migraine preventive categories, and in patients who had never failed. Methods Prespecified subgroup analyses evaluated change from baseline to months 4-6 (the primary endpoint of the blinded study phase) in monthly migraine days, achievement of 50% and 75% reduction in monthly migraine days, and change from baseline in acute migraine-specific medication days. Adverse events were also evaluated. Results Treatment with both doses of erenumab resulted in greater reductions in monthly migraine days at months 4-6 (treatment difference versus placebo [95% CI], never failed subgroup: -0.9 [-1.5, -0.3] for 70mg and -1.3 [-1.9, -0.7] for 140mg; 1 prior failed medication categories subgroup: -2.0 [-2.8, -1.2] for 70mg and -2.5 [-3.4, -1.7] for 140mg; 2 prior failed medication categories subgroup: -1.3 [-2.6, 0.0] for 70mg and -2.7 [-4.0, -1.4] for 140mg). Similar results were observed in the monthly acute migraine-specific medication days endpoint, and in the achievement of 50% and 75% reduction in monthly migraine days. For the 50% reduction in monthly migraine day endpoint, placebo response in the no prior treatment failed group was 32.6%, in the 1 failed treatment 17.5%, and in the 2 failed treatments 11.1%. Conclusion Erenumab showed consistent efficacy in episodic migraine patients who had failed prior preventive treatments and was well tolerated across subgroups. The data suggest prior patients with prior treatment failures have lower placebo response rates.