Comparative efficacy of eletriptan 40 mg versus sumatriptan 100 mg

OBJECTIVE: To confirm the efficacy advantage of eletriptan 40 mg over sumatriptan 100 mg. Background.-Eletriptan 80 mg has demonstrated significantly greater efficacy when compared to both sumatriptan 50 mg and 100 mg in two studies. Eletriptan 40 mg demonstrated significantly greater efficacy than sumatriptan 100 mg in one previous trial. METHODS: Two thousand one hundred thirteen patients with a diagnosis of migraine according to International Headache Society criteria were randomized using a double-blind, double-dummy, parallel-group design, and treated for a single migraine attack with either eletriptan 40 mg, sumatriptan 100 mg, or placebo. The primary endpoint was 2-hour headache response. Secondary endpoints included headache response rates at 1 hour, pain-free rates, absence of associated symptoms, functional response at 1 and 2 hours, and sustained headache response. RESULTS: Headache response rates at 2 hours postdose were significantly higher for eletriptan 40 mg (67%) than for sumatriptan 100 mg (59%; P <.001) and placebo (26%; P <.0001). Eletriptan 40 mg consistently showed significant (P <.01) efficacy over sumatriptan 100 mg across secondary clinical outcomes, including 1-hour headache response; 2-hour pain-free response; absence of nausea, photophobia, and phonophobia; functional improvement; use of rescue medication; treatment acceptability; and sustained headache response (P <.05). Overall, treatment-related adverse events were low, nausea being the only adverse event with an incidence of 2% or higher (4.9% with eletriptan, 4.2% sumatriptan, 2.8% placebo). CONCLUSION: This trial confirmed that eletriptan 40 mg offers superior efficacy in treating migraine pain and associated symptoms and in restoring patient functioning when compared with sumatriptan 100 mg.     

Efficacy of eletriptan in migraineurs with persistent poor response to nonsteroidal anti-inflammatory drugs

BACKGROUND/OBJECTIVE: Nonsteroidal anti-inflammatory drugs continue to be one of the most widely used therapies for migraine, but their efficacy in treating moderate to severe migraine headache has not been well documented. In contrast, the efficacy of triptans in this group of patients is well documented, although no systematic research is available that evaluates the effectiveness of switching to a triptan in patients who respond poorly to nonsteroidal anti-inflammatory drugs. METHODS: One hundred thirteen patients who met International Headache Society criteria for migraine and who did not experience satisfactory response to nonsteroidal anti-inflammatory drugs, received open-label treatment with a 40-mg dose of eletriptan for one migraine attack. Efficacy assessments were made at 1, 2, 4, and 24 hours postdose and consisted of headache and pain-free response rates, absence of associated symptoms, and functional response. Global ratings of treatment effectiveness and preference were obtained at 24 hours. RESULTS: The pain-free response rate at 2 hours postdose was 25% and at 4 hours postdose, 55%; the headache response rate at 2 hours was 66% and at 4 hours, 87%. At 2 hours postdose, relief of baseline associated symptoms was achieved by 41% of patients with nausea compared to 82% of patients at 4 hours; for patients with phonophobia, 67% were relieved at 2 hours and 93% at 4 hours, and for patients with photophobia, 70% were relieved at 2 hours and 91% at 4 hours. Functional response was achieved by 70% of patients by 2 hours postdose. The high level of acute response was maintained over 24 hours, with only 24% of patients experiencing a headache recurrence and only 10% using rescue medication. At 24 hours postdose, 74% of patients rated eletriptan as preferable to any previous treatment for migraine. The most frequent reasons cited for this treatment preference were faster headache improvement (83%) and functional response (78%). Overall, eletriptan was well tolerated; most adverse events were transient and mild to moderate in severity. No serious adverse events were reported. CONCLUSION: Results of this open-label trial found the 40-mg dose of eletriptan to have a high degree of efficacy and tolerability among patients who responded poorly to nonsteroidal anti-inflammatory drugs.     

Treatment of mild headache in disabled migraine sufferers: results of the Spectrum Study

OBJECTIVE: To evaluate the effectiveness of sumatriptan, 50-mg tablets, versus placebo for early intervention while head pain was mild in patients with disabling migraine. METHODS: A post hoc analysis was performed in a subgroup of patients from a large, randomized, placebo-controlled study of patients with disabling headache who treated while pain was mild. Pain-free response 2 and 4 hours postdose, headache recurrence, and safety were examined. Significance tests were performed only for the first-treated attacks. RESULTS: Twenty-six patients with disabling headache treated 46 mild and 166 moderate or severe headaches. For the first-treated headaches while pain was mild, pain-free rates were significantly higher for sumatriptan than placebo 4 hours postdose (78% versus 0%, P =.02), but not 2 hours postdose (52% versus 0%, P =.22). Across all headaches treated while pain was mild, pain-free responses were higher for sumatriptan than placebo 4 hours (85% versus 17%) and 2 hours (50% versus 0%) postdose compared with placebo. When the same patients treated headaches while pain was moderate or severe, pain-free rates were lower than that reported for treatment during mild pain. There was a trend toward lower headache recurrence in headaches treated while pain was mild compared with moderate or severe pain (13% versus 18%). No drug-related adverse events were reported in the headaches treated while pain was mild. CONCLUSIONS: Patients with disabling migraine may benefit from early intervention with sumatriptan, 50 mg, while pain is mild.     

Identification of negative predictors of pain-free response to triptans: analysis of the eletriptan database

Thirty to forty percent of migraineurs do not respond to any given triptan treatment. We identified clinical variables that significantly predict therapeutic non-response and evaluated the efficacy of eletriptan (20, 40 and 80 mg) and sumatriptan (100 mg) vs. placebo in a subgroup of patients with all predictor variables. First-attack data were pooled from 10 randomized, double-blind, placebo-controlled migraine trials ( n  = 8473). Multivariate regression analyses identified three significant baseline predictors of failure to achieve 2-h pain-free response: severe headache pain, presence of photophobia/phonophobia and presence of nausea. Time of dosing following headache onset did not influence 2-h pain-free response. Among patients with all three risk factors ( n  = 2010; 24% of total sample), 2-h pain-free response was significantly higher in patients receiving all three doses of eletriptan or sumatriptan vs. placebo (all P  < 0.01). Thus, eletriptan and sumatriptan are efficacious in difficult-to-treat patients at high risk for non-response to triptans.     

Eletriptan for the acute treatment of migraine in adolescents: results of a double-blind, placebo-controlled trial

BACKGROUND: Eletriptan is a potent 5-HT(1B/1D) agonist with proven efficacy in the acute treatment of migraine in adults. OBJECTIVE: To evaluate the efficacy and tolerability of eletriptan 40 mg versus placebo in adolescent patients (aged 12-17). METHODS: A multicenter, double-blind, parallel-group, placebo-controlled trial was conducted comparing 40 mg of oral eletriptan with placebo for the treatment of migraine in adolescent patients. The primary efficacy endpoint was 2-hour headache response, and a number of secondary endpoints were also evaluated. An exploratory analysis evaluated which clinical and demographic characteristics might be correlated with high placebo response. RESULTS: Of 274 patients who treated a migraine attack, 267 were evaluated for efficacy (n = 138 eletriptan; n = 129 placebo) at 2 hours post-dose. There was no significant difference in 2-hour headache response for eletriptan 40 mg versus placebo (57% vs 57%), and no significant improvements were observed for any of the outcomes at 1 or 2 hours post-dose. By contrast, there was a significant advantage for eletriptan 40 mg in reducing headache recurrence within 24 hours post-dose (11% vs 25%, P= .028), and post hoc analyses showed statistically significant differences for sustained headache response rates (52% vs 39%; P= .04) and sustained pain-free response rates (22% vs 10%; P= .013). The strongest clinical predictor of placebo response was triptan-na?ve status (i.e., no previous use of any triptan). Eletriptan 40 mg was well tolerated in this population, and the profile of adverse events was similar to that observed in Phase III trials in adult patients. CONCLUSIONS: The high placebo response rates reported here for 1- and 2-hour outcomes are in accordance with other studies of triptans in adolescent patients. The evaluation of treatment effect in adolescent migraine might benefit from use of more stringent outcome measures, such as headache recurrence, sustained headache response, and sustained pain-free response at 24 hours post-dose.     

Efficacy,safety, and tolerability of oral eletriptan for treatment of acute migraine: a multicenter,double-blind,placebo-controlled study conducted in the United States

OBJECTIVE: To investigate the efficacy, consistency, safety, and tolerability of oral eletriptan in the acute treatment of three migraine attacks. BACKGROUND: Eletriptan is a selective 5-HT1B/1D agonist member of a class of agents known to be effective in the acute treatment of migraine. METHODS: Thirteen hundred thirty-four patients were randomized to 20 mg, 40 mg, or 80 mg of eletriptan, or placebo and could treat up to three attacks. The primary efficacy endpoint was 2-hour headache response for the first attack. Secondary endpoints included associated symptom relief, and pain-free, sustained pain-free, and consistency of response. RESULTS: Eletriptan 20 mg, 40 mg, and 80 mg achieved significantly (P <.0001) better headache response rates than placebo at 2 hours (47%, 62%, and 59%, respectively, versus 22%) and 4 hours (64%, 76%, and 79%, respectively, versus 25%). Headache response was observed to be rapid, showing improvement at 0.5 hour and 1 hour. Two-hour pain-free response rates for eletriptan 20 mg, 40 mg, and 80 mg were 14%, 27%, and 27%, respectively, compared with 4% for placebo. Sustained pain-free response rates were significantly (P <.001) better for eletriptan 20 mg (10%), 40 mg (20%), and 80 mg (18%) compared with placebo (3%). Eletriptan had a higher consistency of intrapatient response than placebo in two of three (68% to 82%) and three of three attacks (32% to 60%) versus 16% and 8%, respectively. All eletriptan doses yielded significant functional improvement at 2 hours. Adverse events were generally mild or moderate and transient, with eletriptan 20 mg having an adverse event profile comparable to placebo. CONCLUSIONS: Eletriptan is efficacious, displaying high consistency of response over multiple attacks, and is well tolerated for the acute treatment of migraine.     

2000 Wolfe Award. Sumatriptan for the range of headaches in migraine sufferers: results of the Spectrum Study

BACKGROUND: Migraineurs experience a spectrum of headaches: migraine, migrainous, and episodic tension-type as defined by the International Headache Society (IHS). OBJECTIVE: To evaluate the effectiveness of sumatriptan, 50-mg tablets, in treating the spectrum of headaches in IHS-diagnosed migraineurs. DESIGN/METHODS: Migraineurs with severe disability (Headache Impact Questionnaire score 250 or greater) were enrolled in a randomized, double-blind, placebo-controlled, crossover study. Patients treated up to 10 headaches with sumatriptan, 50 mg, or placebo (4:1). Headache features, recorded prior to treatment, were used to classify each headache using IHS criteria. Headache response (moderate or severe pain reduced to mild or no pain) and pain-free response were recorded at 2 and 4 hours postdose (primary endpoint). Because patients treated multiple attacks, statistical methods controlling for within-subject correlation were used. RESULTS: Two hundred forty-nine migraineurs treated 1576 moderate or severe headaches: migraine (n = 1110), migrainous (n = 103), and tension-type (n = 363). Sumatriptan was superior to placebo for headache response 4 hours postdose (primary endpoint) across all headache types (migraine, 66% versus 48%; P<.001; migrainous, 71% versus 39%; P<.01; tension-type, 78% versus 50%, P<.001). Sumatriptan was also superior to placebo for pain-free response 4 hours postdose for migraine (41% versus 24%, P<.001) and tension-type headaches (56% versus 36%, P =.001). Sumatriptan provided superior pain-free response 2 hours postdose for migraine (18% versus 7%, P<.0001) and tension-type headache (28% versus 14%, P =.0005) compared with placebo. CONCLUSION: Sumatriptan, 50-mg tablets, are effective for the full spectrum of headaches experienced by patients with disabling migraine due to a sumatriptan-responsive mechanism.     

Efficacy of eletriptan in triptan-naïve patients: results of a combined analysis

OBJECTIVE: To compare the efficacy and tolerability of eletriptan 20 mg, 40 mg, and 80 mg in triptan-na?ve patients (who have not previously used triptans) versus triptan-experienced patients (who have previously used triptans). METHODS: Efficacy and tolerability data for eletriptan 20 mg, 40 mg, and 80 mg were pooled from 10 similarly designed, randomized, parallel-group studies, and triptan-na?ve and triptan-experienced patients were compared with placebo across the 3 triptan doses. The primary efficacy endpoint was headache response at 2 hours postdose. Secondary efficacy endpoints were 2-hour pain-free response, 2-hour absence of associated symptoms, 2-hour functional response, 24-hour sustained headache response, and 24-hour sustained pain-free response. RESULTS: For eletriptan 20 mg, 40 mg, and 80 mg versus placebo, respectively, triptan-na?ve patients showed significantly higher 2-hour headache response (54%, 61%, 66% vs. 31%; P < .0001), 2-hour pain-free response (20%, 28%, and 31% vs. 8%; P < .0001), and 24-hour sustained headache response (34%, 45%, and 51% vs. 20%; P < .0001). A similarly significant efficacy advantage was also observed in the triptan-experienced subgroup for 2-hour headache response (46%, 63%, 69% vs. 21%; P < .0001), 2-hour pain-free response (13%, 32%, and 38% vs. 4%; P < .0001), and 24-hour sustained headache response (29%, 41%, and 45% vs. 9%; P < .0001). Previous treatment status did not influence tolerability, and all 3 doses of eletriptan were well tolerated. CONCLUSIONS: These data suggest that eletriptan has comparable efficacy versus placebo among both triptan-na?ve and triptan-experienced patients.     

Eletriptan for the treatment of migraine in patients with previous poor response or tolerance to oral sumatriptan

To determine the tolerability and efficacy of eletriptan in patients who had discontinued oral sumatriptan due to lack of efficacy or intolerable adverse events (AEs) during previous clinical treatment (not a controlled trial). Eletriptan is a potent, selective 5-HT1B/1D receptor agonist with beneficial pharmacokinetic properties compared with sumatriptan. In a double-blind, parallel group, placebo-controlled multicentre study, patients with and without aura (n = 446) were randomized to 40 mg eletriptan (E40, n = 188), 80 mg eletriptan (E80, n = 171) or placebo (n = 87) for treatment of up to three migraine attacks. Two-hour headache response, based on first-dose, first-attack data, was 59% for eletriptan 40 mg, 70% for eletriptan 80 mg, and 30% for placebo (P < 0.0001 for both doses of eletriptan vs. PBO; P < 0.05 for E80 vs. E40). Onset of action was rapid, with 1-h headache response rates significantly superior for E40 and E80 vs. placebo (40%, 48%, 15%; P < 0.0005). Both E40 and E80 were significantly superior to placebo, based on first-dose, first-attack data, for 2-h pain-free response (35%, 42%, and 7%; P < 0.0001). Both E40 and E80 demonstrated significant consistency of response, with headache relief rates at 2 h on at least two of three attacks in 66% and 72% vs. 15% on placebo (P < 0.001). AEs were mild to moderate in severity and dose related. The most commonly reported AEs included nausea, vomiting, asthenia, and chest symptoms. E40 and E80 produce an effective response in patients who had previously discontinued treatment with sumatriptan due to lack of efficacy or side-effects.     

Eletriptan in the early treatment of acute migraine: influence of pain intensity and time of dosing

This double-blind, placebo-controlled study was designed to evaluate the efficacy and tolerability of early treatment of a single migraine attack, when headache pain was mild, with two doses (20 mg and 40 mg) of eletriptan. Patients (N = 613; female 79%; mean age 39 years) meeting International Headache Society criteria for migraine were encouraged, but not required, to utilize early treatment, thus providing an opportunity to assess the relative contribution to efficacy of pain severity and timing of dose. For the total patient sample (mild-to-severe headaches), 2-h pain-free rates were significantly higher than placebo (22%) on both eletriptan 20 mg (35%; P < 0.01) and eletriptan 40 mg (47%; P < 0.0001). For the cohort of patients who treated their headache when the pain intensity was mild, the 2-h pain-free rate on eletriptan 40 mg was 68% compared with 25% on placebo (P < 0.0001). Pain intensity at the time of taking eletriptan appeared to influence outcome more than the timing of the dose relative to headache onset. Eletriptan was well-tolerated, with adverse event rates similar to placebo when mild headaches were treated.     

Effectiveness of eletriptan in acute migraine: primary care for Excedrin nonresponders

OBJECTIVE: To evaluate the effectiveness of eletriptan as a treatment for acute migraine in patients who were poor responders to Excedrin and had not yet been exposed to a triptan. BACKGROUND: Self-medication with over-the-counter drugs, such as Excedrin, is the most common treatment for migraine. Guidelines, however, recommend that triptans be used as first-line treatment of moderate to severe migraine--the severity affecting approximately 80% of migraineurs. Since over-the-counter medications, such as Excedrin, continue to be used in many patients, it is important that clinicians have information on the efficacy of triptans as first-line treatment and on treatment of migraineurs who have shown poor response to over-the-counter medications. METHODS: One hundred ten patients meeting criteria for migraine who were poor responders to Excedrin received open-label treatment with a 40-mg dose of eletriptan for one migraine attack. Efficacy assessments were made at 1, 2, 4, and 24 hours postdose and consisted of headache and pain-free response rates, absence of associated symptoms, and functional response. RESULTS: At 1 hour, the headache response rate was 44%; at 2 hours, 81%. The pain-free response rate at 1 hour was 14% and at 2 hours, 48%. At 2 hours, relief of baseline-associated symptoms ranged from 74% to 80%. Functional response was achieved by 82% of patients by 2 hours, and 68% of patients achieved relief of migraine that was sustained across 24 hours with no need for a second dose of eletriptan or for rescue medication. Eletriptan was well tolerated with adverse events being transient and mild to moderate in intensity. CONCLUSION: Previous studies have established the efficacy of eletriptan as a first-line treatment for migraine. The results of this open-label trial demonstrate that the 40-mg dose of eletriptan had a high degree of efficacy and tolerability among patients who were poor responders to Excedrin.     

Pharmacology and efficacy of eletriptan for the treatment of migraine attacks

Sumatriptan, a 5-HT 1B/1D agonist, was introduced 10 years ago and was the most effective therapy for migraine attacks at that time. Eletriptan is a new 5-HT 1B/1D agonist with high potency and selectivity at 5-HT 1B/1D receptors. It is effective in animal models in which the vascular and neurogenic mechanisms implicated in migraine were measured. Eletriptan is selective for the intracranial blood vessels over other extracranial vasculature, in particular coronary arteries. Eletriptan has a rapid and complete oral absorption and a good oral bioavailability in migraineurs. In comparative trials 20 mg, 40 mg and 80 mg eletriptan, 100 mg sumatritpan and placebo were compared for the treatment of migraine attacks. All three doses of eletriptan were statistically superior to placebo for headache response and headache-free patients. The 80 mg dose of eletriptan was also superior to sumatriptan 100 mg. Headache recurrence, defined as return of moderate or severe headache within 24 hours of dosing and following a headache response at two hours after initial dosing, occurred in 33% of the patients following 100 mg sumatriptan and in 28%, 34% and 32% after 20 mg, 40 mg and 80 mg eletriptan. In another large trial, headache response rates were significantly higher for both doses of eletriptan (64% for 40 mg and 67% for 80 mg) than for two doses of sumatriptan (50% for 50 mg and 53% for 100 mg). Eletriptan 40 mg or 80 mg was also superior to ergotamine plus caffeine (Cafergot). In summary, eletriptan is a highly effective and fast-acting drug for the treatment of acute migraine attacks.     

Eletriptan treatment of migraine in patients switching from barbiturate-containing analgesics: results from a multiple-attack study

The aim of this study was to examine efficacy and tolerability of eletriptan in patients switched from barbiturate-containing combinations (Fiorinal), Fioricet. Migraineurs (n = 160) meeting IHS criteria, with unsatisfactory response in the past year to butalbital-containing combinations, treated up to 16 attacks over 3 months with eletriptan 40 mg. Assessments included headache response and pain-free rates and functional impairment at baseline and 2 h postdose, and global ratings of treatment satisfaction at 24 h. At 2 h postdose, average headache response and pain-free rates were 71% (95% CI, 69-74%) and 37% (95% CI, 35-40%), respectively; 68.5% of patients (95% CI, 65-72%) reported functional response. Within-patient analysis found no efficacy diminution over time (no tolerance). Average headache recurrence rate was 20% (95% CI, 18-23%). Eletriptan was well-tolerated; 6 (3.7%) patients discontinued due to adverse events. There were no serious treatment-related adverse events. We conclude that in poor responders to butalbital-caffeine combinations, switching to eletriptan 40 mg was well-tolerated and efficacious.     

Comparative efficacy of eletriptan vs. naratriptan in the acute treatment of migraine

This was a randomized, double-blind study designed to evaluate the comparative efficacy and tolerability of the 40-mg dose of eletriptan and the 2.5-mg dose of naratriptan. Patients (n = 548) meeting International Headache Society (IHS) criteria for migraine were randomized to treat a single migraine attack with either eletriptan 40 mg, naratriptan 2.5 mg, or placebo. Headache response rates at 2 h and 4 h, respectively, were 56% and 80% for eletriptan, 42% and 67% for naratriptan (P < 0.01 for both time-points vs. eletriptan), and 31% and 44% for placebo (P < 0.0001 vs. both active drugs at both time-points). Eletriptan also showed a significantly greater pain-free response at 2 h (35% vs. 18%; P < 0.001) as well as lower use of rescue medication (15% vs. 27%; P < 0.01) and higher sustained headache response at 24 h (38%) compared with naratriptan (27%; P < 0.05) and placebo (19%; P < 0.01). Both eletriptan and naratriptan were well tolerated. The results confirm previous meta-analyses that have suggested the superiority of eletriptan vs. naratriptan in the acute treatment of migraine.     

Efficacy, safety and tolerability of oral eletriptan in the acute treatment of migraine: results of a phase III, multicentre, placebo-controlled study across three attacks

The efficacy, safety and tolerability of the 5-HT1B/D receptor agonist eletriptan (40 mg and 80 mg) in acute treatment of migraine was evaluated in a multinational, randomized, double-blind, parallel-group, placebo-controlled, three-attack study treating 1153 patients. In the initial attack, significantly more eletriptan patients reported headache relief and complete pain relief at 2 h vs. placebo (40 mg 62% and 32%, 80 mg 65% and 34%, placebo 19% and 3%; P < 0.0001). Headache relief occurred faster after eletriptan, with more patients at both doses reporting relief 30 min (P < 0.01) and 1 h (P < 0.0001) after treatment than after placebo. There was a significantly lower recurrence rate with eletriptan 80 mg compared with placebo (P < 0.01). Adverse events for all treatments were generally mild or moderate and self-limiting. Eletriptan 40 mg and eletriptan 80 mg both appear to be effective and well-tolerated acute migraine treatments.     

MIGRAINE TREATMENT

Clinical trials of migraine therapy often require treatment when migraine pain intensity is moderate or severe, but many physicians find this practice artificial and patients often prefer to treat while pain is mild. This randomized, placebo-controlled study assessed the efficacy of zolmitriptan 2.5 mg in treating migraine while pain is mild, in patients who typically experience migraine attacks that are initially mild, but progress to moderate or severe. The intent-to-treat population comprised 280 patients (138 zolmitriptan; 148 placebo), with mean MIDAS grades of 29.6 (zolmitriptan) and 27.6 (placebo). Zolmitriptan 2.5 mg provided a significantly higher pain-free rate at 2 hours (43.4% vs 18.4% placebo; P < .0001). Significantly fewer zolmitriptan patients reported progression of headache pain to moderate or severe intensity 2 hours postdose (53.7% vs 70.4% placebo; P < .01), or required further medication within 24 hours (46.4% vs 71.1% placebo; P < .0001). The efficacy of zolmitriptan was more pronounced in patients treating during the first 15 minutes following pain onset. Adverse events were reported in 31.2% of patients treated with zolmitriptan (vs 11.3% for placebo), and the incidence was lower in patients who treated early after attack onset. Zolmitriptan provides high efficacy when treating migraine while pain is mild, with the clinical benefits being more pronounced when treating early after migraine onset.     

Valdecoxib for treatment of a single, acute, moderate to severe migraine headache

OBJECTIVE: To evaluate the analgesic efficacy and safety of a single 20- or 40-mg dose of valdecoxib compared with placebo in treatment of a single, acute, moderate or severe migraine headache, with or without aura. BACKGROUND: Valdecoxib, an oral COX-2 specific inhibitor, is indicated for relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis and treatment of primary dysmenorrhea. This study assessed the optimal dose of valdecoxib for treatment of a single, acute, moderate to severe migraine headache. METHODS: This was a double-blind, randomized, placebo- and active-controlled, multicenter, single-dose (primary end point) and multiple-dose (secondary end point), 56-day study of valdecoxib in the treatment of a single, acute, moderate or severe migraine headache, with or without aura. Migraine headaches were diagnosed according to International Headache Society (IHS) criteria. The primary efficacy end point was headache response (defined as reduction of headache pain intensity from moderate or severe to mild or none) at 2 hours postdose. Patients assessed their headache pain intensity and presence or absence of migraine-associated nausea, vomiting, phonophobia, and photophobia at intervals from 0 to 24 hours postdose. Sumatriptan 50 mg (encapsulated, in standard method, to maintain blinding) was included as a positive control for assay sensitivity. No statistical comparisons were performed between active treatment arms (valdecoxib 20 mg, valdecoxib 40 mg, and sumatriptan 50 mg). Adverse events and safety parameters were monitored throughout the study. RESULTS: In the intent-to-treat population of 570 patients (135 valdecoxib 20 mg, 151 valdecoxib 40 mg, 143 sumatriptan, and 141 placebo), no significant differences in baseline demographics among treatment groups were observed. The headache response rate with valdecoxib 40 mg and sumatriptan 50 mg was significantly greater than that with placebo at all time points from 2 to 24 hours postdose. With valdecoxib 20 mg, headache response rate was significantly greater than placebo from 2 to 4 hours. Significantly fewer patients treated with valdecoxib 40 mg, compared with placebo, experienced nausea, vomiting, and phonophobia at 2 hours postdose. CONCLUSIONS: A single 40-mg dose of valdecoxib is effective and well tolerated in treatment of migraine headache pain and associated symptoms.     

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.     

Meta-analysis of the efficacy and safety of zolmitriptan in the acute treatment of migraine

OBJECTIVE: To assess the relative efficacy and safety of zolmitriptan in the treatment of acute migraine attacks. BACKGROUND: Zolmitriptan is a second-generation triptan developed for the treatment of migraine. Numerous randomized controlled trials (RCTs) have been carried out to compare different dosages and formulations of zolmitriptan against other treatments for acute migraine. METHODS: Random effects meta-analysis of 24 RCTs, including 15,408 patients suffering from acute migraine attacks. Subgroup analyses compared differences in response between different dosages and formulations of zolmitriptan, and other triptan comparators. RESULTS: Zolmitriptan 2.5 mg tablet was found to be as effective as almotriptan 12.5 mg, eletriptan 40 mg, sumatriptan 50 mg and 100 mg and more effective than naratriptan 2.5 mg in terms of 2-hour pain-free rates. Likewise, zolmitriptan 5 mg tablet was as effective as sumatriptan 50 mg and 100 mg in 2-hour pain-free rates. Compared against zolmitriptan 2.5 mg tablet, eletriptan 80 mg was more effective in achieving headache relief, pain-free and sustained pain-free responses, and rizatriptan 10 mg was more effective in terms of sustained pain-free rates. Zolmitriptan 2.5 mg tablet was associated with a lower risk of adverse events than eletriptan 80 mg but higher risk than naratriptan 2.5 mg and rizatriptan 10 mg. Zolmitriptan 5 mg tablet was superior to zolmitriptan 2.5 mg tablet in achieving 1- and 2-hour pain-free response. There were no significant differences in 1- and 2-hour headache relief and adverse event rates between the different formulations of zolmitriptan 2.5 mg. CONCLUSIONS: Zolmitriptan 2.5 mg tablet is an effective treatment for acute attacks of migraine showing similar efficacy to almotriptan 12.5 mg, eletriptan 40 mg, and sumatriptan 50 mg, and being more effective than naratriptan 2.5 mg in terms of pain-free response at 2 hours post dose. Zolmitriptan 2.5 mg tablet was also as effective as rizatriptan 10 mg in terms of headache relief and pain-free response but less effective in terms of sustained pain-free response.     

Treatment-emergent CNS symptoms following triptan therapy are part of the attack

If treatment-emergent central nervous system (CNS) symptoms following triptan therapy represent direct pharmacological effects of the drug, they should occur independent of response to active drug. However, if they represent unmasking of neurological symptoms of the migraine attack after pain is relieved, they should be more common in responders both to active drug and to placebo. To explore this issue, we evaluated the relationship between the CNS adverse events and treatment response following triptan or placebo treatment. We used pooled data from seven double-blind, placebo-controlled trials involving eletriptan 20 mg (E20, n = 402), eletriptan 40 mg (E40, n = 1870), eletriptan 80 mg (E80, n = 1393), sumatriptan 100 mg (S100, n = 275) and placebo (Pbo, n = 1024). Somnolence was more prevalent among 2 h headache responders than non-responders for all treatments, including E80 (8.8% vs. 5.0%; P < 0.05), E40 (6.4% vs. 5.0%; NS), E20 (4.0% vs. 2.0%; NS), S100 (4.7% vs. 3.2%; NS) and Pbo (7.6% vs. 3.0%; P < 0.05). Similarly, the incidence of asthenia was higher among patients who responded to treatment compared with those who did not respond to E80 (15.2% vs. 7.8%; P < 0.05), E40 (6.5% vs. 3.6%; P < 0.05), E20 (6.5% vs. 1.0%; P < 0.05), S100 (10.1% vs. 4.7%; NS) and Pbo (4.4% vs. 2.7%; NS). The generally higher rates of somnolence and asthenia in patients who respond to treatment suggests that these treatment-emergent neurological symptoms may represent the unmasking of CNS symptoms associated with the natural resolution of a migraine attack, rather than simply representing drug-related side-effects. The rate of somnolence in placebo responders is comparable to that in responders to E40 and E80, indicating that somnolence is related, at least in some important part, to headache relief and not treatment.