Meta-analysis of rizatriptan efficacy in randomized controlled clinical trials

Data from seven randomized, placebo-controlled, double-blind phase III clinical trials were analysed to further evaluate the efficacy of rizatriptan 10 mg (n = 2068) in comparison with placebo (n = 1260) and rizatriptan 5 mg (n = 1486) for the acute treatment of a migraine attack. Migraine was diagnosed according to International Headache Society criteria. Headache severity, associated migraine symptoms and functional disability were measured immediately before dosing and at 0.5, 1, 1.5 and 2 h. Headache recurrence (return of moderate or severe headache after an initial response) was also recorded. In addition to conventional pain relief (reduction of moderate or severe headache to mild or none) and pain free measures, the analysis looked at the elimination of associated migraine symptoms and disability in patients who had symptoms or disability at baseline. Maintenance of pain relief or pain-free status over 24 h was also analysed. At 2 h, rizatriptan 10 mg was significantly more effective than placebo for pain relief (71% vs. 38%, P < 0.001), and for elimination of pain, nausea, photophobia, phonophobia and functional disability. The benefit was maintained over 24 h; 37% of patients on rizatriptan 10 mg had sustained pain relief vs. 18% for placebo (P < 0.001). Rizatriptan 10 mg was also more effective than rizatriptan 5 mg, with a significant superiority at 2 h on all measures except for elimination of nausea. The benefit was maintained over 24 h; 38% of patients on rizatriptan 10 mg had sustained pain relief vs. 32% for rizatriptan 5 mg (P = 0.001).     

Rizatriptan 10-mg wafer versus usual nontriptan therapy for migraine: analysis of return to function and patient preference

BACKGROUND: More than half of patients with migraine suffer moderate to severe functional disability during migraine attacks. OBJECTIVE: To compare effects on functional disability at 2 hours after treating a migraine with rizatriptan 10-mg wafer versus usual nontriptan therapy for triptan-na?ve patients with migraine. DESIGN: Open-label, prospective, two-attack study conducted at 111 neurology clinics. METHODS: Adult patients with migraine treated two migraine attacks, the first with their usual nontriptan therapy (nonsteroidal anti-inflammatory drugs, 57%; analgesics, 27%; or ergot derivatives, 16%) and the second with rizatriptan 10-mg wafer. Patients recorded pain intensity and functional disability at the start, and functional disability at 2 hours, as well as the time of return to normal function. RESULTS: A total of 1353 patients, 76% of them female, completed the study and were considered evaluable. During first and second migraine attacks, 55% and 63% of patients, respectively, reported severe disability or requiring bed rest. At 2 hours after treatment, the likelihood of experiencing any disability was more than five times greater after usual nontriptan therapy than after rizatriptan (odds ratio, 5.68; 95% confidence interval (CI), 4.66 to 6.94; P < .001). Rizatriptan was twice as likely to return patients to normal function than usual nontriptan therapy after adjusting for confounding factors (adjusted hazard ratio, 2.08; 95% CI, 1.92 to 2.25; P < .001). Assessed over all time points up to 6 hours, the speed of return to normal function was 52% faster after rizatriptan therapy (P < .001). Significantly more patients preferred rizatriptan than usual nontriptan therapy (78.8% vs. 21.2%; P < .001). The most common reasons cited for preference for rizatriptan were faster relief of headache pain and faster return to normal function. CONCLUSIONS: Patients in this study were more likely to experience a return to normal function at 2 hours after receiving rizatriptan than after their usual nontriptan therapy for migraine. The results of this study, using patient-oriented, clinically relevant endpoints such as functional disability and preference, will help to guide practitioners in making recommendations for acute migraine treatment.     

Cost-effectiveness of almotriptan and rizatriptan in the treatment of acute migraine

BACKGROUND: Migraine is a common disorder that costs US employers billions of dollars each year in missed workdays and reduced productivity. Seven triptans, including almotriptan and rizatriptan, are recommended as first-line therapy for acute migraine. OBJECTIVE: The aim of this study was to assess the relative cost-effectiveness of almotriptan and rizatriptan in the treatment of acute migraine. METHODS: A model was built to compare almotriptan 12.5 mg and rizatriptan 10 mg for the treatment of a single, acute migraine attack. Cost-effectiveness (in year-1999 US dollars) was evaluated from the perspective of a US health care payer. Mean and incremental cost-effectiveness ratios (CERs) were calculated. The effectiveness measure was the proportion of patients who achieved sustained freedom from pain with no adverse events (SNAE). Data on sustained pain-free outcomes and adverse-event rates were obtained from a meta-analysis of oral triptan trials. Efficacy and tolerability were assumed to be independent in the base-case scenario, so the total direct cost of treating a single migraine attack was calculated, adding drug costs to health service costs per attack. RESULTS: In the base-case analysis, the mean CERs for almotriptan 12.5 mg and rizatriptan 10 mg were 91.12 dollars and 131.26 dollars, respectively, per attack at which SNAE was achieved after treatment. The incremental CER for almotriptan (compared with rizatriptan 10 mg) was 6.94 dollars per additional SNAE achieved. The economic benefit of almotriptan 12.5 mg was robust in a range of sensitivity analyses. CONCLUSION: Almotriptan 12.5 mg was more cost-effective than rizatriptan 10 mg for the treatment of acute migraine in this analysis based on published data.     

Disability in migraine patients: Italian experience

Migraine is associated with functional impairment. The migraine disability assessment (MIDAS) scale is a scientific instrument which captures headache–related disability. The Italian version of MIDAS was developed through a multi–step standardized methodology. Studies on Italian clinical samples showed that migraine patients were disabled in all activity domains. Non–work activities were more affected than work activities. Among patients in paid work, most continued working with a headache attack, although productivity was significantly reduced. The Italian MIDAS was used also in patients with transformed migraine and drug overuse. These patients were markedly disabled. MIDAS scores were higher than those found in migraine patients. When disability was assessed after 6 months from withdrawal therapy, MIDAS scores were significantly lower than at baseline. Our results confirmed the negative impact of the lives of headache patients, and suggest the use of MIDAS as a sensitive outcome measure for monitoring patients’ progress.     

Efficacy of rizatriptan for menstrual migraine in an early intervention model: a prospective subgroup analysis of the rizatriptan TAME (Treat A Migraine Early) studies

OBJECTIVE: A prospective subgroup analysis of the TAME (Treat A Migraine Early) studies examined the efficacy of rizatriptan in patients treating a menstrual migraine attack. METHODS: Both TAME studies were randomized, placebo-controlled, and double-blind. Adults with migraine were assigned (2:1) to either rizatriptan 10-mg tablet or placebo. Patients were instructed to treat within 1 hour of migraine onset and when the pain was mild. The primary endpoint was 2-hour pain freedom. The diagnosis of menstrual migraine was established according to the revised 2004 International Headache Society (IHS) diagnostic criteria. Data from both studies were pooled for logistic regression analyses. A test for interaction was performed to compare rates of 2-hour pain freedom between patients treating a menstrual and non-menstrual attack. RESULTS: A total of 94 patients (63 in the rizatriptan group and 31 in the placebo group) met IHS criteria for menstrual migraine and treated a menstrual attack. The percentage of patients reporting 2-hour pain freedom was significantly greater for rizatriptan than for placebo (63.5% vs 29.0%; odds ratio = 4.5; 95% confidence interval: 1.7, 11.9; P = .002) in those treating a menstrual attack. In those treating with rizatriptan, the percentage of patients with 2-hour pain freedom did not statistically differ between those treating a menstrual or non-menstrual migraine attack (63.5% vs 57.5%; P = .454). CONCLUSION: Rizatriptan 10 mg was effective for the treatment of menstrual migraine in an early intervention model, as measured by 2-hour pain freedom. Rates of 2-hour pain freedom were comparable for patients treating menstrual and non-menstrual migraine attacks with rizatriptan.     

Improvement in migraine-specific quality of life in a clinical trial of rizatriptan

A validated migraine-specific questionnaire (24-h Migraine Quality of Life Questionnaire1: 24-h MQoLQ) was used to assess the impact of migraine and migraine therapy on health related quality of life during an acute migraine attack. Male and female migraineurs aged 18-55 years were randomized to placebo ( n = 41), rizatriptan 2.5 mg ( n = 47), 5 mg ( n = 74), or 10 mg ( n = 85) in a triple-blind, placebo-controlled clinical trial. Rizatriptan 5 mg and 10 mg were significantly more efficacious than placebo on pain relief and functional disability. After accounting, for multiple comparisons to placebo, rizatriptan 10 mg showed significantly better responses compared to placebo on three of five domains of 24-h MQoLQ (social functioning, migraine symptoms, and feelings/concerns). The O'Brien's Rank Sum Test statistic showed a statistically significant overall difference on the 24-h MQoLQ between the 10 mg rizatriptan and placebo groups ( p = 0.005) and for the overall close trend ( p 0.001).     

Long-term tolerability of telcagepant for acute treatment of migraine in a randomized trial

(Headache 2011;51:73‐84) Objective.— To evaluate the long‐term tolerability of telcagepant for acute treatment of intermittent migraine attacks. Background.— Telcagepant is a calcitonin gene‐related peptide (CGRP) receptor antagonist being investigated for the acute treatment of migraine. Methods.— Migraine patients were randomized 2:1 to double‐blind treatment with telcagepant 280/300 mg or rizatriptan 10 mg for an acute mild, moderate, or severe migraine. Patients could administer a second dose within 2‐24 hours for nonresponse or migraine recurrence. Patients could treat up to 8 attacks per month for up to 18 months. Safety assessments included spontaneous reports of adverse events and collection of vital signs, electrocardiograms, and laboratory assessments. The primary endpoint was the percentage of patients with ≥1 triptan‐related adverse events in the 14‐day period post dose. Results.— Of 1068 patients randomized, 641 (90%) patients treated ≥1 attack with telcagepant and 313 (88%) treated ≥1 attack with rizatriptan. A total of 19,820 attacks were treated with telcagepant (mean per patient = 31) and 10,981 with rizatriptan (mean per patient = 35). Fewer triptan‐related adverse events (difference: ?6.2%; 95% CI ?10.4, ?2.6; P < .001) and drug‐related adverse events (difference: ?15.6%; 95% CI ?22.2, ?9.0) were reported for telcagepant vs rizatriptan. The most common adverse events appeared to have generally similar incidence proportions between the treatment groups. Those with an incidence >5% in the telcagepant group were dry mouth (9.7%, rizatriptan = 13.7%), somnolence (9.2%, rizatriptan = 16.6%), dizziness (8.9%, rizatriptan = 10.2%), and nausea (9.0%, rizatriptan = 6.4%). Conclusions.— Telcagepant was generally well tolerated when administered for the acute intermittent treatment of migraine for up to 18 months. The incidences of triptan‐related and drug‐related adverse events favored telcagepant over rizatriptan.     

Rizatriptan for treatment of acute migraine in patients taking topiramate for migraine prophylaxis

Objective.— To assess efficacy and tolerability of rizatriptan orally disintegrating tablet (ODT) for treatment of acute migraine in patients using topiramate for migraine prophylaxis. Background.— There are limited data from prospective controlled trials demonstrating the benefit of triptans in patients who experience migraine attacks while taking prophylactic medication. Methods.— This was a worldwide, randomized, placebo‐controlled, double‐blind, multiple‐attack study in adults with a >1‐year history of migraine taking a stable dose of topiramate for migraine prophylaxis and experiencing ≥2 moderate/severe attacks per month. Participants treated 3 moderate/severe attacks in crossover fashion (2 with rizatriptan 10‐mg ODT, 1 with placebo) following random assignment to 1 of 3 treatment sequences. The primary end point was 2‐hour pain relief. Results.— Two‐hour pain relief was significantly greater with rizatriptan compared with placebo (55.0% vs 17.4%, P < .001). Response rates also favored rizatriptan for sustained pain relief from 2‐24 hours (32.6% vs 11.1%, P < .001), 2‐hour pain freedom (36.0% vs 6.5%, P < .001), normal functional ability at 2 hours (42.2% vs 12.7%, P < .001), and overall treatment satisfaction at 24 hours (60.8% vs 33.6%, P < .001). Few participants reported adverse experiences (16 [15.8%] with rizatriptan, 3 [3.2%] with placebo); none were serious. Conclusion.— Rizatriptan 10‐mg ODT was superior to placebo at all pain end points for treatment of acute migraine in patients using topiramate for migraine prophylaxis. Rizatriptan was generally well tolerated in this population. These results are comparable with those from clinical trials in patients not using prophylaxis, suggesting that the use of topiramate does not affect the efficacy or tolerability of rizatriptan for acute migraine treatment.     

Effects on productivity and quality of life of rizatriptan for acute migraine: a workplace study

OBJECTIVE: To evaluate the impact of treatment with rizatriptan 10 mg on jobs and quality of life of patients with migraine. METHODS: Prospective, open-label study at 27 work sites of 20 companies representing diverse labor sectors in Spain. Eligible patients according International Headache Society (IHS) criteria were recruited for the study by on-site physicians and instructed to treat moderate or severe migraine attacks with one tablet of rizatriptan 10 mg. They were asked to complete the study questionnaires (ML-96, SF-36) at baseline, and then 3 months later. RESULTS: A total of 259 patients (83 men and 176 women) of a mean age of 39 (range 18 to 61 years) completed the study. Only 7% had taken triptans before for treatment of their migraine attacks. After 3 months of rizatriptan therapy, the use of medical services was significantly lower and all tested domains of quality of life had improved (P<.001). Absenteeism and days worked during migraine attacks also fell significantly during 3 months of rizatriptan therapy as compared with the 3 months before the study (P<.001). The improvement in productivity was reflected in the significant decreases in lost workday equivalents (decrease from 3.32 to 1.21 days; P<.001) and also in the total number of workdays lost (decrease from 5.16 to 1.82 days; P<.001). Two-thirds of patients described the efficacy of oral rizatriptan as excellent or very good (62%), and 89% preferred it over their usual medications for acute treatment of migraine attacks. CONCLUSION: For this employed population of patients with migraine, treatment with rizatriptan significantly improved parameters measuring direct medical costs, work and productivity, and health-related quality of life. In accordance with these findings, direct and indirect costs related to migraine could be substantially reduced by gathering detailed information about the nature of headache, eliminating triggering factors, and instituting effective treatment of migraine attacks.     

Rizatriptan <Emphasis Type="Italic">vs.</Emphasis> ibuprofen in migraine: a randomised placebo-controlled trial

The objective of this study was to compare the efficacy of rizatriptan and ibuprofen in migraine. The study was a randomised placebo-controlled trial in a tertiary care teaching hospital. Migraine patients with <8 attacks/months were included. One hundred and fifty-five migraine patients were randomised to rizatriptan 10 mg (53), ibuprofen 400 mg (52) and placebo (50). Efficacy was assessed by headache relief, and headache freedom at 2 h and 24 h. Two-hour headache relief, was noted in 73% in rizatriptan, 53.8% in ibuprofen and 8% in placebo groups. Headache freedom was achieved in 37.7% in rizatriptan, 30.8% in ibuprofen and 2% in placebo groups. Rizatriptan was superior to ibuprofen and placebo in relieving headache at 2 h but not at 24 h. Side effects were noted in 9 patients in rizatriptan, 8 in ibuprofen and 3 in placebo, all of which were nonsignificant. Rizatriptan and ibuprofen are superior to placebo. Rizatriptan is superior to ibuprofen in relieving headache, associated symptoms and functional disability.