1. Oral triptans (serotonin 5-HT 1B/1D agonists) in acute migraine treatment: A meta-analysis of 53 trials by Michel D. Ferrari, Krista I. Roon, Richard B. Lipton, Peter J. Goadsby (Lancet 2001;358:1668-1675)

2. 0204060 80 50701030 90100 What Patients Want From Migraine Drug Therapy Adapted from Lipton RB et al. Headache 1999;39(suppl 2):S20-S26. *Most commonly selected as important or very important. % Migraineurs reporting each attribute (n=688) No recurrence* Rapid onset* No side effects Relief of associated symptoms Route of administration Complete pain relief*87% 86% 83% 79% 76% 56%

3. Triptan Meta-Analysis: Background Objective To evaluate the available clinical trial evidence base for oral triptan (5HT 1B/1D agonist) drugs and provide a foundation for their use in managing acute migraine. Background Given that seven different triptans are clinically available, physicians need evidence-based guidelines to select the triptans with the highest likelihood of success. Methods Clinical trial databases for randomized and active- controlled studies provided by manufacturers of rizatriptan, sumatriptan, zolmitriptan, eletriptan, almotriptan, and naratriptan. This independent analysis includes 53 trials with a total of 24,089 patients and is published in the Lancet. Adapted from Ferrari MD et al. Lancet 2001;358:1668-1675.

4. 02040608050701030 Relief of Migraine Pain Adapted from Ferrari MD et al. Lancet 2001;358:1668-1675. *Comparison of recommended initial doses in SPC and standard comparator in the meta-analysis (sumatriptan 100 mg). Headache relief at 2 hours* (95% CI) Zolmitriptan 2.5 mg Almotriptan 12.5 mg Sumatriptan 50 mg Eletriptan 40 mg Naratriptan 2.5 mg Rizatriptan 10 mg Sumatriptan 100 mg % Patients (N=24,089)

5. Rizatriptan 10 mg Freedom from Migraine Pain Pain free at 2 hours* (95% CI) Adapted from Ferrari MD et al. Lancet 2001;358:1668-1675. *Comparison of recommended initial doses in SPC and standard comparator in the meta-analysis (sumatriptan 100 mg). Sumatriptan 100 mg Zolmitriptan 2.5 mg Sumatriptan 50 mg Eletriptan 40 mg Naratriptan 2.5 mg Almotriptan 12.5 mg 010203040 % Patients (N=24,089) 50

6. Almotriptan 12.5 mg Eletriptan 40 mg 010203040 Sustained Freedom from Migraine Pain Sustained pain free* (95% CI) % Patients (N=24,089) Adapted from Ferrari MD et al. Lancet 2001;358:1668-1675. *Comparison of recommended initial doses in SPC and standard comparator in the meta-analysis (sumatriptan 100 mg). Rizatriptan 10 mg Sumatriptan 100 mg Zolmitriptan 2.5 mg Sumatriptan 50 mg Naratriptan 2.5 mg

7. Consistency of Migraine Treatment 0 102030405060708090100 Headache relief at 2 hours in at least 2 out of 3 attacks* (95% CI) % Patients (N=24,089) Adapted from Ferrari MD et al. Lancet 2001;358:1668-1675. *Comparison of recommended initial doses in SPC and standard comparator in the meta-analysis (sumatriptan 100 mg). Rizatriptan 10 mg Sumatriptan 100 mg Sumatriptan 50 mg Eletriptan 40 mg Naratriptan 2.5 mg Almotriptan 12.5 mg

8. 0 102030405060 % Patients (N=24,089) Consistency of Migraine Treatment Pain free at 2 hours in at least 2 out of 3 attacks* (95% CI) Adapted from Ferrari MD et al. Lancet 2001;358:1668-1675. *Comparison of recommended initial doses in SPC and standard comparator in the meta-analysis (sumatriptan 100 mg). Rizatriptan 10 mg Sumatriptan 100 mg Sumatriptan 50 mg Eletriptan 40 mg Naratriptan 2.5 mg Almotriptan 12.5 mg

9. Tolerability and Safety Profile All oral triptans in the meta-analysis were well tolerated. “No triptan was demonstrably safer than the others.” Safety can only be reliably assessed after large-scale and long-term clinical exposure. Adapted from Ferrari MD et al. Lancet 2001;358:1668-1675.

10. Summary of Efficacy Results 020406080100 Headache relief at 2 hours* Consistency: pain free (2 out of 3 attacks)* Pain free at 2 hours* Sustained pain free* % Patients (N=24,089) Consistency: headache relief (2 out of 3 attacks)* Adapted from Ferrari MD et al. Lancet 2001;358:1668-1675. *Comparison of recommended initial doses in SPC and standard comparator in the meta-analysis (sumatriptan 100 mg). Rizatriptan 10 mg Sumatriptan 50 mg Zolmitriptan 2.5 mg Eletriptan 40 mg Almotriptan 12.5 mg Naratriptan 2.5 mg Sumatriptan 100 mg

11. Triptan Meta-Analysis: Implications for Migraine Treatment Largest independent analysis of migraine therapies provided evidence-based foundation for choosing a first-line triptan. At marketed doses, all oral triptans were effective and well tolerated. Rizatriptan 10 mg demonstrated high efficacy across key endpoints.* Rizatriptan 10 mg offered a high likelihood of success “when consistent and rapid freedom from pain is desired.” Adapted from Ferrari MD et al. Lancet 2001;358:1668-1675. *Comparison of recommended initial doses in SPC and standard comparator in the meta-analysis (sumatriptan 100 mg).