Early intervention with almotriptan:: Results of the AEGIS trial (AXERT® early migraine intervention study)

Objective.-To evaluate prospectively the efficacy and safety of almotriptan 12.5 mg as compared to placebo when administered within 1 hour of headache pain onset for the acute treatment of 3 migraine headaches. Background.-Although clinical trials have reported improved outcomes when triptans were used early or to treat mild pain, acceptance of this treatment strategy has been hampered by both efficacy and tolerability issues. Methods.-In this multicenter, double-blind, placebo-controlled, parallel-group trial, patients with IHS-migraine were randomized in a 1:1 ratio to treat 3 consecutive migraine attacks with either almotriptan 12.5 mg or placebo. Patients were instructed to take their study medication at the first sign of headache pain of any intensity, within 1 hour of onset, and to record their symptoms at multiple time points during their headaches using a personal digital assistant. Clinical trial efficacy results for the first study headache and safety data for the entire study are presented. Results.-A total of 378 patients were randomized, 189 to each group; 162 almotriptan-treated patients, and 155 placebo-treated patients were evaluable for efficacy. Almotriptan treatment, compared to placebo, resulted in a significantly greater proportion of patients achieving 2-hour pain free (37.0% vs 23.9%, P= .010), 2-hour pain relief (72.3% vs 48.4%, P < .001) and sustained pain free (24.7% vs 16.1%, P = .040). Significant differences in pain free (P = .026) and pain relief (P = .019) between almotriptan and placebo also were observed at 1 hour. At 2 to 4 hours and 4 to 24 hours after treatment, the mean intensity of phonophobia and photophobia were significantly lower in the patients treated with almotriptan compared to the placebo-treated patients. A greater proportion of patients treating with almotriptan versus placebo reported normal functionality within 2 hours postdose (54.4% vs 38.1%, P = .007) and 4 hours postdose (74.5% vs 54.3%, P < .001). The percentage of patients experiencing 1 or more treatment-emergent adverse events (AE) was 9.8% for almotriptan and 6.4% for placebo. The only treatment-emergent AEs that occurred with a frequency of at least 1% (equivalent to 2 or more patients) in the almotriptan and placebo groups, respectively, were somnolence (1.1% and 2.3%), nausea (1.1% and 1.7%), vomiting (1.1% and 0.6%), and fatigue (1.1% and 0%). Conclusion.-Treatment with almotriptan within 1 hour of migraine onset resulted in significantly better clinical outcomes than placebo and tolerability similar to placebo. Acute medications, such as almotriptan, that are both effective and well tolerated may encourage patients to access acute treatment earlier.