The APPRAISE randomized clinical trial compared the efficacy, tolerability, patient adherence, and satisfaction between erenumab and nonspecific oral migraine preventive medications (OMPMs) in patients with episodic migraine (EM) who had previously failed 1 or 2 preventive treatments. The 12-month, global, multicenter, active-controlled, randomized trial included 621 patients, with a 2:1 randomization ratio to erenumab and OMPMs. The primary endpoint was the proportion of patients completing 1 year of treatment and achieving a 50% or greater reduction in monthly migraine days (MMDs) at month 12. Secondary endpoints included cumulative MMD changes and responder rates on the Patients' Global Impression of Change (PGIC) scale. Results showed that significantly more patients assigned to erenumab achieved the primary endpoint (56.2% vs 16.8%; odds ratio [OR], 6.48; 95% CI, 4.28-9.82; P < .001) and had a higher responder rate on the PGIC scale (76.0% vs 18.8%; OR, 13.75; 95% CI, 9.08-20.83; P < .001). The erenumab group also reported a greater reduction in cumulative average MMDs (−4.32 vs −2.65 days; treatment difference [SE]: −1.67 [0.35] days; P < .001). Fewer patients in the erenumab group switched medication (2.2% vs 34.6%) and discontinued treatment due to adverse events (2.9% vs 23.3%). No new safety signals were identified. The study concluded that early use of erenumab provided greater and sustained efficacy, safety, and adherence compared to continuous OMPMs.The APPRAISE randomized clinical trial compared the efficacy, tolerability, patient adherence, and satisfaction between erenumab and nonspecific oral migraine preventive medications (OMPMs) in patients with episodic migraine (EM) who had previously failed 1 or 2 preventive treatments. The 12-month, global, multicenter, active-controlled, randomized trial included 621 patients, with a 2:1 randomization ratio to erenumab and OMPMs. The primary endpoint was the proportion of patients completing 1 year of treatment and achieving a 50% or greater reduction in monthly migraine days (MMDs) at month 12. Secondary endpoints included cumulative MMD changes and responder rates on the Patients' Global Impression of Change (PGIC) scale. Results showed that significantly more patients assigned to erenumab achieved the primary endpoint (56.2% vs 16.8%; odds ratio [OR], 6.48; 95% CI, 4.28-9.82; P < .001) and had a higher responder rate on the PGIC scale (76.0% vs 18.8%; OR, 13.75; 95% CI, 9.08-20.83; P < .001). The erenumab group also reported a greater reduction in cumulative average MMDs (−4.32 vs −2.65 days; treatment difference [SE]: −1.67 [0.35] days; P < .001). Fewer patients in the erenumab group switched medication (2.2% vs 34.6%) and discontinued treatment due to adverse events (2.9% vs 23.3%). No new safety signals were identified. The study concluded that early use of erenumab provided greater and sustained efficacy, safety, and adherence compared to continuous OMPMs.