Meta-Analysis of Rizatriptan Efficacy in Randomized Controlled Clinical Trials

Abstract

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).

Overview of Triptans in the Treatment of Acute Migraine

“…49 Ferrari et al conducted a meta-analysis of seven randomised, placebocontrolled, double-blind phase III trials of rizatriptan (10 mg, n=2,068 or 5 mg, n=1,486) versus placebo (n=1,260) for treating an acute migraine attack. 50 Rizatriptan (10 mg) was significantly better compared with placebo for pain relief at 2 hours (71 versus 38%, p<0.001) and for the elimination of pain, nausea, photophobia, phonophobia and functional disability. In addition, more patients treated with rizatriptan than placebo had sustained pain relief over 24 hours (37 versus 18% respectively, p<0.001).…”

“…Except for the elimination of nausea, the 10 mg dose was significantly more effective than 5 mg on all endpoints at 2 hours and maintained over 24 hours (38 versus 32% for rizatriptan 10 mg and 5 mg, respectively, p=0.001). 50 Rizatriptan (5 mg for body weight 20-39 kg, 10 mg >40 kg) has also been evaluated in 96 young patients aged 6-17 years in a double-blind, placebo-controlled, cross-over trial. 51 Patients receiving either dose of rizatriptan achieved headache relief by two grades at 2 hours compared with placebo (p<0.001).…”

All triptans are not the same

“…In terms of sustained headache response, defined as relief of headache pain within 2 hours, and no recurrence or use of rescue medication within 24 hours, eletriptan appears to offer a clear advantage over all the other triptans, with the 80-mg dose showing a sustained response rate of 57%, while rizatriptan offers the highest sustained pain-free response, in the range of 25% [13]. Sustained headache response and sustained pain-free response results are highly correlated with restoration of normal levels of functioning, and is important from a pharmacoeconomic standpoint because it is the outcome measure that best determines the average number of pills taken per migraine attack.…”

Ten Years of Rizatriptan: From Development to Clinical Science and Future Directions

“…A summary of the efficacy of rizatriptan on these measures in a pooled analysis of the phase 3 trials plus other randomized controlled trials performed up to 1998 is shown in Table 2. 58 The trials also demonstrated that rizatriptan had a fast onset of action with benefits over placebo being seen from 30 minutes in some cases. In addition to looking at effects on migraine symptoms, the trials also assessed patient satisfaction with medication at 2 hours.…”

“…58 Clinical adverse experiences were typically mild and short-lasting (2-3 hours). The tolerability profile of rizatriptan 10 mg in the longterm extensions was similar to that observed in the short-term studies and few patients (less than 5%) discontinued due to clinical adverse events, although the overall discontinuation rate for any reason was higher.…”