The 'Act when Mild' (AwM) study: a step forward in our understanding of early treatment in acute migraine.
An important issue in the management of migraine is the advice given to patients as to when to take their treatment in the course of the attack. While it seems common sense almost to take treatment early in the attack, the evidence base for that advice is not as robust as could be expected. The 'Act when Mild' (AwM) Study was a randomized, four-arm, multicentre, multinational, double-blind, placebo-controlled trial of almotriptan (12.5 mg) to compare outcomes after administration of treatment when pain intensity was mild and within 1 h of headache onset (mild/early) with outcomes when pain had become moderate or severe. Of 491 migraineurs enrolled, 403 were evaluable with an intention-to-treat population (ITT) of 404. At the primary end-point, 2 h pain free, on the ITT analysis 49% of patients in the almotriptan 12.5 mg treat early/mild group and 40% in the treat moderate/severe group had responded (P = 0.21). Of these patients, 43 did not take medication according to their randomly allocated baseline pain intensity (mild or moderate/severe) and were subsequently reassigned, prior to study unblinding, to the appropriate group (AwM population) for re-analysis of the primary outcome measure: 2-h pain-free rates. In the almotriptan arms, 53% of the mild/early group and 37.5% of the moderate/severe group were pain free at 2 h (P = 0.02; AwM population). The corresponding proportions in the placebo groups were 24.7% and 17.5% (significantly lower than the respective almotriptan arms; P </= 0.01). Considering the ITT population, secondary end-points were also significantly in favour of treatment with almotriptan in the mild/early vs. the moderate/severe stage, including: sustained pain-free, 45.6% vs. 30.5% (P = 0.02); headache recurrence at 24 h, 6% vs. 24% (P = 0.0124). Adverse events were reported in < 5% of patients, with no significant differences between almotriptan and placebo and no serious events in any group. Treatment with almotriptan while migraine pain is still mild and within 1 h of onset provides statistically significant and clinically relevant enhancements in efficacy compared with waiting until pain has reached higher severity levels.
Goadsby
P J
PJ
Headache Group, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. peter.goadsby@ucsf.edu
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D010147:Pain Measurement; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014363:Tryptamines / Q000008:administration & dosage / Q000627:therapeutic use*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D000700:Analgesics; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D014662:Vasoconstrictor Agents; C409045:almotriptan