Outcome for headache and pain-free nonresponders to treatment of the first attack: a pooled post-hoc analysis of four randomized trials of eletriptan 40 mg.

OBJECTIVE: The objective of this article is to evaluate, in first attack eletriptan headache and pain-free nonresponders, the efficacy of treating a second and third attack with the same dose of eletriptan 40 mg (ELE-40). METHODS: Data were pooled from four randomized, double-blind, placebo-controlled, multiple attack studies of eletriptan in the treatment of migraine. The first-attack eletriptan headache (HNR) and pain-free (PFNR) nonresponder samples consisted of patients who did not achieve headache or pain-free responses at two hours, or sustained headache or pain-free responses at 24 hours. The efficacy of the same dose of eletriptan (vs placebo; PBO) in treating the second and third attacks was evaluated using a logistic regression model. RESULTS: Among Attack 1 eletriptan HNRs, treatment with ELE-40 (vs PBO) was associated with significantly higher two-hour headache response and pain-free rates, respectively, on both Attack 2 (48.8% vs 20.2%; 17.0% vs 3.9%; P < 0.0001 for both comparisons) and Attack 3 (37.4% vs 15.5%; 18.8% vs 3.2%; P < 0.0001 for both comparisons). Significantly higher sustained headache response and pain-free rates at 24 hours were also observed on both Attack 2 and Attack 3. CONCLUSIONS: The results of this pooled analysis suggest that patients who have HNR or PFNR to an initial dose of eletriptan may respond when a second and third attack is treated with the same dose.

Early intervention in migraine with sumatriptan tablets 50 mg versus 100 mg: a pooled analysis of data from six clinical trials.

BACKGROUND: In clinical trials evaluating sumatriptan in the treatment of moderate or severe migraine pain, the 50- and 100-mg doses have been comparably effective and well tolerated. OBJECTIVE: To assess the dose-efficacy relationship of sumatriptan tablets given early for mild pain, data from 6 randomized, double-blind, placebo-controlled, early-intervention studies of sumatriptan tablets 50 mg and 100 mg (5 of which have been published) were pooled for analysis. These constitute all the studies conducted to date of sumatriptan tablets prospectively given early for mild pain. METHODS: The primary efficacy end point in all the studies was the proportion of patients reporting a pain-free result (ie, mild, moderate, or severe pain reduced to none) 2 hours postdose. Other efficacy end points included the proportion of patients who were migraine free (ie, no pain and no associated symptoms of nausea, vomiting, photophobia, or phonophobia) 2 hours postdose; the proportion reporting worsening of pain (ie, moderate or severe pain) 2 hours postdose; and the proportion with a sustained pain-free result (ie, pain free from 2-24 hours postdose with no use of a second dose of study medication or of rescue medication). Tolerability was assessed by evaluating the incidence of individual adverse events. The investigators assessed each adverse event's relationship to study medication. RESULTS: The number of patients in the intent-to-treat population was 2297 (771 sumatriptan 50 mg, 759 sumatriptan 100 mg, 767 placebo). Patients' mean age ranged from 39.4 to 39.8 years across groups, and most patients were female (90%-92%) and white (89%-90%). A pain-free result 2 hours post dose was reported by significantly more patients who took either dose of sumatriptan tablets compared with placebo and by significantly more patients who took the 100-mg dose compared with the 50-mg dose (50 mg, 49%; 100 mg, 58%; placebo, 24%; P < 0.001, both sumatriptan doses vs placebo, and 100 mg vs 50 mg). A similar pattern was observed for migraine-free results 2 hours postdose (50 mg, 42%; 100 mg, 47%; placebo, 20%; P < 0.05, both sumatriptan doses vs placebo, and 100 mg vs 50 mg), worsening of pain 2 hours postdose (50 mg, 26%; 100 mg, 21%; placebo, 46%; P < 0.05, both sumatriptan doses vs placebo, and 100 mg vs 50 mg), and sustained pain-free results from 2 through 24 hours postdose (50 mg, 30%; 100 mg, 35%; placebo, 12%; P < 0.05, both sumatriptan doses vs placebo, and 100 mg vs 50 mg). Both doses of sumatriptan were well tolerated, and no dose-related trends in the incidence of individual drug-related adverse events were observed. CONCLUSIONS: In this analysis of pooled data from 6 clinical trials, sumatriptan tablets 50 mg and 100 mg administered early in a migraine attack while the pain was mild were well tolerated and significantly more effective than placebo. The 100-mg dose of sumatriptan was significantly more effective than the 50-mg dose.

Pain-free efficacy after treatment with sumatriptan in the mild pain phase of menstrually associated migraine.

OBJECTIVE: To estimate the efficacy of sumatriptan 50-mg and 100-mg tablets in menstrually associated migraine when treatment is administered during the mild pain phase. METHODS: A randomized, double-blind, placebo-controlled, single-attack study was conducted. Menstrually associated migraine was defined as any migraine beginning on or between day -2 and day 4, with day 1 = first day of flow. Patients had at least a 1-year history of migraine as defined by International Headache Society criteria and reported regularly occurring menstrually associated migraines typically having a mild pain phase. Patients treated attacks within 1 hour of the onset of pain but only if the pain was mild at onset and while the pain was still mild. RESULTS: In the 349 women with menstrually associated migraine, sumatriptan was significantly more effective than placebo: 61% and 51% of patients who used sumatriptan 100 mg and 50 mg, respectively, were pain-free 2 hours after treatment compared with 29% of patients who used placebo (P <.001 for both comparisons). At 2 hours, 51% and 45% of patients who used sumatriptan 100 mg and 50 mg were free of pain and associated symptoms (photophobia, phonophobia, nausea, vomiting) compared with 25% of placebo patients (P <.001 for both comparisons). Adverse events were low for sumatriptan 100 and 50 mg, and both doses were generally well tolerated. CONCLUSION: Sumatriptan 50-mg and 100-mg tablets are generally well tolerated and effective in providing pain-free relief and relief of the associated symptoms of menstrually associated migraine when administered in the mild pain phase.

Efficacy and tolerability of naratriptan for short-term prevention of menstrually related migraine: data from two randomized, double-blind, placebo-controlled studies.

BACKGROUND: In a pilot study, naratriptan was significantly more effective than placebo in preventing menstrually related migraine (MRM) when given as 1 mg twice daily for 5 days beginning 2 days before the predicted onset of MRM for up to 4 menstrual cycles. OBJECTIVE: To evaluate the efficacy and tolerability of naratriptan for short-term prevention of MRM in 2 large, identically designed, randomized, double-blind, placebo-controlled, parallel-group studies. METHODS: MRM was defined as any migraine beginning during the perimenstrual period (PMP). By definition, the PMP consisted of Days -2, -1, 1, 2, 3, and 4, with Day 1 being the first day of menstrual flow. Adult women were eligible if they reported a history of MRM, had regular menstrual cycles, and could predict within 2 days both the onset of menstrual flow and MRM. The studies comprised a baseline phase and a treatment phase. During the baseline phase, patients prophylactically treated their first PMP after the screening visit with single-blind placebo. Patients who documented an MRM while receiving placebo were eligible for the treatment phase. During the treatment phase, patients were randomized to receive either naratriptan 1 mg twice daily or placebo beginning 3 days before the predicted onset of MRM for a total of 6 days for 4 PMPs or 6 months, whichever occurred sooner. The primary efficacy endpoint was the mean percentage of treated PMPs without MRM per patient. Secondary efficacy endpoints included the percentage of patients who were free of MRM during all treated PMPs, the median number of days with MRM over 4 PMPs, and patient satisfaction. Safety and tolerability measures included adverse events, standard clinical laboratory tests, and vital signs. RESULTS: The intent-to-treat population was 287 in Study 1 (149 in the naratriptan group and 138 in the placebo group) and 346 in Study 2 (173 in each treatment group). Approximately 20% of randomized patients in each treatment group in Study 1 and 10% in each treatment group in Study 2 withdrew prematurely from the studies over the 4-month treatment period. The mean percentage of PMPs without MRM per patient was 38% and 34% among naratriptan-treated patients treating at least 1 PMP compared with 29% and 24% among placebo-treated patients in each respective study (P < .05 naratriptan vs placebo for both studies). Efficacy of naratriptan did not vary as a function of age, use of oral contraceptives, or use of migraine prophylaxis. More patients who had received naratriptan reported attacks posttreatment compared to patients who had received placebo. Among patients treating at least 1 PMP, the percentage of patients with no MRM in any treated PMP was significantly (P < .05) higher in the naratriptan group (11%; 19/173) than the placebo group (3%; 6 of 173) in Study 2. There were no differences in the percentages of patients with no MRM in any treated PMP in Study 1. The number of MRM days per patient across 4 PMPs was significantly lower in the naratriptan group than in the placebo group in both studies (median 5.0 days vs 6.5 days in Study 1 [P= .005] and 5.3 days vs 6.0 days in Study 2 [P= .018]). Significantly more patients receiving naratriptan were satisfied with the ability of naratriptan to control MRM either by preventing their occurrence or reducing their severity or duration compared with patients receiving placebo. No single drug-related adverse event was reported by more than 2% of patients in a treatment group in either study, and no serious drug-related adverse events were reported. CONCLUSIONS: Naratriptan 1 mg twice daily for 6 days per month is effective and well tolerated when used for short-term prevention of MRM. More patients receiving naratriptan than placebo were satisfied with treatment. The observed increase in posttreatment attacks needs further study.