L A Smith1, A D Oldman, H J McQuay, R A Moore. 1. Oxford Brookes University, School of Health and Social Care, Jack Straws Lane, Marston, Oxford, UK, OX3 0FL. lesleysmith@brookes.ac.uk
Abstract
BACKGROUND:Eletriptan (Relpax) is a new triptan soon to be made available by prescription for the treatment of acute migraine. Currently five triptans are available by prescription and more are under development. In light of the many drugs for treating acute migraine, there is a need for evidence-based assessments to help determine the relative efficacy and harm of these treatments. OBJECTIVES: To determine the efficacy of eletriptan for treating a single migraine attack using the outcomes of headache response and pain-free response at 0.5, 1, 2 and 4 hours, and sustained relief over 24 hours. To express efficacy in terms of number-needed-to-treat (NNT). To determine the adverse effects of a single dose of eletriptan and express this in terms of number-needed-to-harm (NNH). To allow for the comparison of the efficacy of eletriptan with other migraine treatments evaluated systematically in the same way. SEARCH STRATEGY: Data from all Phase III randomised placebo-controlled trials were made available by the manufacturer, Pfizer Inc. To date, these trials comprise the only data on eletriptan relevant to this review in a published or unpublished form; thus, searches of electronic databases for further trials of eletriptan were not conducted. Date of last search: January 2000. SELECTION CRITERIA: Trials of eletriptan for acute migraine; randomised allocation to treatment groups, including a placebogroup; double-blind design; International Headache Society diagnostic criteria for migraine with or without aura; single migraine attack; single-dose treatment at standard doses; adult population; baseline pain of moderate or severe intensity using a 4-point standardised rating scale (0 = no pain, 1 = mild pain, 2 = moderate pain and 3 = severe pain); and dichotomous or percentage data for at least one of the main efficacy outcomes. DATA COLLECTION AND ANALYSIS: Trials were scored for quality and data extracted by two independent reviewers. Dichotomous or percentage data were extracted and pooled to calculate the relative benefit (RB) or relative risk (RR) and NNTs or NNHs for a number of outcomes for eletriptan 20 mg, 40 mg and 80 mg. The main outcomes considered were headache response at 1 and 2 hours, pain-free response at 2 hours, sustained relief over 24 hours and adverse effects. Minor outcomes considered were headache response at 0.5 and 4 hours, and pain-free response at 0.5, 1 and 4 hours. MAIN RESULTS: Six trials met the inclusion criteria. Significant benefit of eletriptan over placebo was shown for eletriptan 20 mg, 40 mg and 80 mg for the primary efficacy outcomes of headache response and pain-free response at 2 hours. For headache response at 2 hours, the NNTs (with 95% confidence intervals) were 4.4 (3.4 to 6.2), 2.9 (2.6 to 3.3) and 2.6 (2.4 to 3.0) for eletriptan 20 mg, 40 mg and 80 mg, respectively. For pain-free response at 2 hours, the NNTs were 9.9 (6.9 to 18), 4.0 (3.6 to 4.5) and 3.7 (3.4 to 4.2), for eletriptan 20 mg, 40 and 80 mg, respectively. There was no significant difference in the incidence of major adverse effects between any dose of eletriptan and placebo. The incidence of minor adverse effects was significantly higher for all eletriptan doses than for placebo, with NNHs of 11 (95% confidence interval, 6.2 to 39), 7.0 (5.2 to 11) and 3.7 (3.1 to 4.5) for eletriptan 20 mg, 40 mg and 80 mg, respectively. AUTHORS' CONCLUSIONS:Eletriptan 20 mg, 40 mg and 80 mg are effective for the treatment of an acute migraine attack. Effectiveness is dose-related, with statistically significant differences between doses for pain-free response and 24-hour outcomes. Eletriptan compares well with other triptans available for outcomes measured up to 2 hours and provides meaningful relief for 24 hours. Taken as a single dose, eletriptan was well tolerated and caused no major harm. The incidence of minor harm was dose-dependent, with 80 mg giving significantly more adverse effects than 40 mg.
RCT Entities:
BACKGROUND:Eletriptan (Relpax) is a new triptan soon to be made available by prescription for the treatment of acute migraine. Currently five triptans are available by prescription and more are under development. In light of the many drugs for treating acute migraine, there is a need for evidence-based assessments to help determine the relative efficacy and harm of these treatments. OBJECTIVES: To determine the efficacy of eletriptan for treating a single migraine attack using the outcomes of headache response and pain-free response at 0.5, 1, 2 and 4 hours, and sustained relief over 24 hours. To express efficacy in terms of number-needed-to-treat (NNT). To determine the adverse effects of a single dose of eletriptan and express this in terms of number-needed-to-harm (NNH). To allow for the comparison of the efficacy of eletriptan with other migraine treatments evaluated systematically in the same way. SEARCH STRATEGY: Data from all Phase III randomised placebo-controlled trials were made available by the manufacturer, Pfizer Inc. To date, these trials comprise the only data on eletriptan relevant to this review in a published or unpublished form; thus, searches of electronic databases for further trials of eletriptan were not conducted. Date of last search: January 2000. SELECTION CRITERIA: Trials of eletriptan for acute migraine; randomised allocation to treatment groups, including a placebo group; double-blind design; International Headache Society diagnostic criteria for migraine with or without aura; single migraine attack; single-dose treatment at standard doses; adult population; baseline pain of moderate or severe intensity using a 4-point standardised rating scale (0 = no pain, 1 = mild pain, 2 = moderate pain and 3 = severe pain); and dichotomous or percentage data for at least one of the main efficacy outcomes. DATA COLLECTION AND ANALYSIS: Trials were scored for quality and data extracted by two independent reviewers. Dichotomous or percentage data were extracted and pooled to calculate the relative benefit (RB) or relative risk (RR) and NNTs or NNHs for a number of outcomes for eletriptan 20 mg, 40 mg and 80 mg. The main outcomes considered were headache response at 1 and 2 hours, pain-free response at 2 hours, sustained relief over 24 hours and adverse effects. Minor outcomes considered were headache response at 0.5 and 4 hours, and pain-free response at 0.5, 1 and 4 hours. MAIN RESULTS: Six trials met the inclusion criteria. Significant benefit of eletriptan over placebo was shown for eletriptan 20 mg, 40 mg and 80 mg for the primary efficacy outcomes of headache response and pain-free response at 2 hours. For headache response at 2 hours, the NNTs (with 95% confidence intervals) were 4.4 (3.4 to 6.2), 2.9 (2.6 to 3.3) and 2.6 (2.4 to 3.0) for eletriptan 20 mg, 40 mg and 80 mg, respectively. For pain-free response at 2 hours, the NNTs were 9.9 (6.9 to 18), 4.0 (3.6 to 4.5) and 3.7 (3.4 to 4.2), for eletriptan 20 mg, 40 and 80 mg, respectively. There was no significant difference in the incidence of major adverse effects between any dose of eletriptan and placebo. The incidence of minor adverse effects was significantly higher for all eletriptan doses than for placebo, with NNHs of 11 (95% confidence interval, 6.2 to 39), 7.0 (5.2 to 11) and 3.7 (3.1 to 4.5) for eletriptan 20 mg, 40 mg and 80 mg, respectively. AUTHORS' CONCLUSIONS:Eletriptan 20 mg, 40 mg and 80 mg are effective for the treatment of an acute migraine attack. Effectiveness is dose-related, with statistically significant differences between doses for pain-free response and 24-hour outcomes. Eletriptan compares well with other triptans available for outcomes measured up to 2 hours and provides meaningful relief for 24 hours. Taken as a single dose, eletriptan was well tolerated and caused no major harm. The incidence of minor harm was dose-dependent, with 80 mg giving significantly more adverse effects than 40 mg.