Stratified cave vs step care strategies for migraine -: The disability in strategies of care (DISC) study:: A randomized trial

Context Various guidelines recommend different strategies for selecting and sequencing acute treatments for migraine. In step care, treatment is escalated after first-line medications fail. In stratified care, initial treatment is based on measurement of the severity of illness or other factors. These strategies for migraine have not been rigorously evaluated. Objective To compare the clinical benefits of 3 strategies: stratified care, step care within attacks, and step care across attacks, among patients with migraine. Design and Setting Randomized, controlled parallel-group clinical trial conducted by the Disability in Strategies Study group from December 1997 to March 1999 in 88 clinical centers in 13 countries. Patients A total of 835 adult migraine patients with a Migraine Disability Assessment Scale (MIDAS) grade of II, III, or IV were analyzed as the efficacy population; the safety analysis included 930 patients. Interventions Patients were randomly assigned to receive(1) stratified care (n=279), in which patients with MIDAS grade II treated up to 6 attacks with aspirin, 800 to 1000 mg, plus metoclopramide, 10 mg, and patients with MIDAS grade III and IV treated up to 6 attacks with zolmitriptan, 2.5 mg; (2) step care across attacks (n = 271), in which initial treatment was with aspirin, 800 to 1000 mg, plus metoclopramide, 10 mg. Patients not responding in at least 2 of the first 3 attacks switched to zolmitriptan, 2.5 mg, to treat the remaining 3 attacks; and (3) step care within attacks (n = 285), in which initial treatment for all attacks was with aspirin, 800 to 1000 mg, plus metoclopramide, 20 mg. Patients not responding to treatment after 2 hours in each attack escalated treatment to zolmitriptan, 2.5 mg. Main Outcome Measures Headache response, achieved if pain intensity was reduced from severe or moderate at baseline to mild or no pain at 2 hours; and disability time per treated attack at 4 hours for all 6 attacks, compared among the 3 groups. Results Headache response at 2 hours was significantly greater across 6 attacks in the stratified care treatment group (52.7%) than in either the step care across attacks group (40.6%; P<.001) or the step care within attacks group (36.4%; P<.001). Disability time (6 attacks) was significantly lower in the stratified care group (mean area under the curve [AUC], 185.0 mm.h) than in the step care across attacks group (mean AUG, 209.4 mm.h; P<.001) or the step care within attacks group (mean AUG, 199.7 mm.h; P<.001). The incidence of adverse events was higher in the stratified care group (321 events) vs both step care groups (159 events in across-attack group; 217 in within-attack group), although most events were of mild-to-moderate intensity. Conclusion Our results indicate that as a treatment strategy, stratified care provides significantly better clinical outcomes than step care strategies within or across attacks as measured by headache response and disability time.