Poster Abstracts Friday, November 11, 2005 $489

1527 Eletriptan and headache recurrence

Sakai, F 1, Hamada, j 1 Li, C 2, Almas, M 2, Albert, KS 2, Pal'sons, B 2. ~Department of Neurology, Kitasato University, Kanagawa, Japan; 2Pfizer Inc., New York, USA

The recommended dose of eletriptan is 20 mg (E20) in Japan and 40 mg (E40) in the US and Europe. The current analysis evaluates the effect of dose on headache recurrence in patients with mild and moderate-to-severe headache in both settings. Data were pooled from 3 placebo-controlled trials in migraine conducted in Western countries comparing E20 ( IN- 322) and placebo (PBO; N -- 183); and one study of E20 (IN - 51) and placebo (IN - 46) in Japan. In the pooled Western studies, recurrence rates were not different on E20 (31%) compared with PBO (31%) in patients with moderate-to-severe headache. However, in patients with mild headache, recurrence rates were reduced on E20 compared with PBO (14"/o vs 41%). In contrast, in Japan, reduction in recurrence was achieved on E20 (10%) compared with placebo (24%; p - 0.06) regardless of headache severity. The 20 mg dose of eletriptan provides reduction of recurrence in Japan regardless of headache severity, and the 20 mg dose appears effective in Western settings when headache pain is mild.

1528 An economic evaluation of Triptan products for Migraine

Perfetto, EM 1, Wets, K A z, Mullins, CD 3, Subedi, P~, Healey, PJZ, Parsons, B 2. 1The Weinberg Group Inc., Washington, DC, USA; 2Pfizer Inc., New York, USA; 3 University of Maryland School of Pharmacy, Baltimore, MD, USA

A composite outcome measure in migraine treatment is useful to healthcare authorities because it provides a more accurate reflection of effectiveness and allows for more complete modeling of the economic value. This composite measure must consider both short- and long- term treatment effects, as well as placebo effects. To compare the total triptan cost to treat 100 migraine-patient attacks and cost per successfully treated patient (CPSTP) for marketed triptans in France, Italy, Spain and Switzerland using a composite measure of effective- ness, the 'successfully treated" migraine (defined as requiring only one triptan dose to treat one migraine attack during a 24-hour period). Clinical data were abstracted from the published meta-analysis by Ferrari. Two-hour response, pain-free response, and recurrence rates were used to calculate the number of doses used by treatment successes and failures. The country-specific price per dose was then used to calculate total triptan cost. Of the oral triptan doses compared, eletriptan 40 mg was associated with the lowest total triptan cost for treating 100 migraine attacks and with the lowest CPSTP. The relative CPSTP for migraine therapies is dependent on the definition of treatment success and pricing in each country. When success is defined as using one triptan dose to treat one migraine attack in a 24-hour period, the triptans with the most value are eletriptan 40 mg (USD$56.39), zolmitriptan 2.5 mg (USD$75.62) and sumatriptan 50 mg (USD$77.59). These were comparable in rank order when country-specific drug prices were used.

1529 Efficacy and safety of Oral Eletriptan for the treatment of acute migraine in adolescents

Winner, p1 Linder, S 2, Lipton, R 3, Parsons, B 4, Pitman, V 4. ~Nova Southeastern University, Fort Lauderdale, FL, USA; 2Medical City Hospital, Dallas, TX, USA; 3Department of Neurology, Albert Ebtstein College of Medicine, New York, USA; 4Pfizer Inc., New York, USA

Eletriptan is a potent 5-HTm/1D agonist that has shown efficacy for the acute treatment of migraine in adults. This was a mulfi-center, double-blind, placebo-controlled study comparing 40 mg of oral eletriptan with placebo for the treatment of migraine in adolescent

patients, 12-17 years of age. 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. Of 274 patients who treated a migraine attack, 267 were evaluated for efficacy (in - 138 eletriptan; n -- 129 placebo). The standard measure of headache response at 2 h showed a very kigh response to placebo (57%), and a similar response to eletriptan (1577,';). By contrast, there was a significant advantage for eletriptan in headache recurrence (11% vs. 25%, p - 0.028). Post-hoe analyses showed statistically significant differences for sustained headache response rates when comparing eletriptan (52%) and placebo (39°,5) (p - 0.04). Additionally, sustained pain-free response rates were also significantly higher in patients receiving eletriptan (22%) vs. placebo (110%) (i3 - 0.013). It may be necessary to use alternative primary endpoints for determining efficacy of migraine therapy in adolescent patients.

1530 Efficacy and Tolerability of Eletriptan in Triptan-Naive vs. Triptan-Experienced Patients: Results of a Combined Analysis

Martin, VT 1, Valade, D a, Almas, M ~, Salonen, R 3, Albert, KS 3, Parsons, B 3. 1Division of General lnternal Medicine, University of Cincinnati, Cincinnati, USA; 2Centre d'Urgence Cephalees, Hopital Lariboisiere, Paris, France; 3Pfizer Inc., New York, USA

Triptan-na'fve (TN) patients (starting a triptan for the first time) represent a clinical subgroup with different treatment needs than triptan-experienced (TE) patients. The goal of the current study is to evaluate the efficacy and tolerability of eletriptan in TN vs. TE patients. Efficacy and tolerability data were analyzed from 10 double- blind trials in patients treated with eletriptan 20 mg (E20; TN vs. TE, N -- 179 vs. 255), eletriptan 40 mg (E40; TN vs. TE, N -- 1381 vs. 1971), and placebo (PBO; TN vs. TE, N -- 735 vs. 988). 2-h headache response rates were significantly higher in TN and TE patients, respectively, on E20 (154"/o and 46°,5) and E40 (61 °,5 and 63"/0) vs. PBO (31% and 21%; p < 0.0001 for all comparisons to PBO). Sustained response at 24 h was also significantly higher in TN and TE patients on E20 (34% and 29%) and E40 (45% and 41%) vs. PBO (20% and 9%; p < 0.0001 for all comparisons to PBO). Tolerability was similar for TiN and TE patients, respectively, regardless of whether they were treated with E20 (any severe adverse event -- 6.1"/o vs. 3.9"/0), E40 (4.6°,5 vs. 4.5°,5) or placebo (5.4°,5 vs. 5.9°,5). E20 and E40 are highly effective and well-tolerated in both TN and TE patients.

1531 Efficac~ of Elelriptan in migraine patients reporting unsatisfactory Ie~pO[lSe to Rizatriptan

Goldstein, j1, Tiseo, p2, Li, C 2, Salonen, R 2, Parsons, B 2, Albert, KS 2. 1San Francisco Headache Clinic, San Francisco, USA," 2Pfizer Inc., New York, USA

The selection of treatment for use in non-responders to triptan therapy is an important clinical problem. This open-label study evaluated the efficacy of switctting poor responders on rizatriptan (N - 123) to eletriptan 40 mg (E40) to treat up to 2 migraine attacks (eletriptan 80 mg [E80] could be used for the second attack). Reasons for dissatisfaction with rizatriptan (> 1 could be cited) included inade- quate (184%) or slow (50%) onset of pain relief, and high recurrence rate (69"/0). On a work productivity questionnaire (PQ-7), the proportion of patients reporting attack-related impairment > 50"/0 of the time on rizatriptan ranged from 70-80% across the 7 assessment items. On E40, 2-hour headache response was 64%, while 2-hour pain- free response was 30% (first attack). Absence of nausea increased, baseline-to-2 hours, from 50% to 78%, absence ofphotophobia from 30% to 72% and absence of phonophobia from 39% to 77% (first attack). Functional response at 2 hours was 63% (first attack), with 41% o f patients at normal functioning. On the PQ-7, patients reported a 27-40% reduction in attack-related impairment. Using a prospective

$490 Friday, November 11, 2005 Poster Abstracts

time-loss recording method, there was a 48?,'; reduction in the relative risk of losing more than 4 hours of work time on E40 compared with previous treatment with rizatriptan. Overall, 72°,5 of patients rated eletriptan as a "good-to-excellent" treatment, and 79% reported overall satisfaction with the degree of headache relief after treating 2 attacks. The results of tiffs study suggest that eletriptan is an efficacious treatment option for patients who are poor responders to rizatriptan.

1532 Functional ~esponse in inig~aine: efficacy of Eletfiptan using 4 concurrently adndtdstered thnctional assessment measures

Lipton, RB ~, Almas, M ~, Parsons, B 2, Albert, KS a. 1Department of Neurology, Albert Einstein College of Medicine, New York, USA; :Pfizer Inc., New York, USA

Functional response is an important assessment measure for diag- nosing migrane. The goal of the current study is to evaluate the efficacy of eletriptan in normalizing functional impairment using 4 concurrently administered scales: the 7-item Work Productivity Questionnaire (PQ-7), the FAIM Activities and Participation subscale (FAIM-A&P), the FAIM Mental Functioning subscale (FAIM- IMMF), and the traditional 4-point global functional impairment scale (FIS). Outpatients with an IHS diagnosis of migraine were randomized to double-blnid treatment with either eletriptan 40 mg (E40; N -- 196) or placebo (N -- 194). Patients with mo derate-to-severe impairment were identified on each of the 4 disability scales, and 2h functional response was compared for E40 vs. PBO. Functional response at 2 h was significantly higher on E40 vs. PBO on the measure of work productivity (PQ-7: 56% vs. 34°,5; p < 0.011), on mental functioning (FAIM-IMMF: 50% vs. 34%; p _< 0.015), and on the ability to participate in a range of activities (FAIM-A&P: 63% vs. 36%; p _< 0.0001). These rates were similar to functional response rates on the traditional 4-point FIS: 75°,5 vs. 45°,5, p < 0.0001. Impairment in mental functioning showed a somewhat more delayed time-to- remission on eletriptan compared with work productivity and other non-mental functional activities. Eletriptan is effective in normalizing functioning across multidimensional domains in individuals experien- cing attack-related disability.

1533 Comparative efficacy of Elelriptan and Suinatfiptan in redudng Headache recurrence in high-risk migraine patients

Goadsby, PJ~, Dodick, D'~V ~, Lipton, RB ~, Tfelt-Hansen, p4, Ferrari, MD 5, Diener, H-C s, Almas, M y, Albert, KS:, Parsons, B 7. 1Institute of Neurology, London, UK," ~Departrnent of Neurology, Mayo Clinic, Scottsdale, Arizona, USA; 3Department of Neurology, Albert Einstein College of Medicine, New York, USA; 4Department of Neurology, Glostrup Hospital Glostrup, Denmark; S Leiden University Medical Centre, Leiden, The Netherlcotds; eDepartrnent of Neurology, University of Essen, Germany; 7 Pfizer Inc., New York, USA

Eletriptan has been shown to significantly reduce recurrence rates among patients achieving a headache response witlffn 2 h. The goal of the current study was to compare the efficacy of eletriptan and sumatriptan in redudng recurrence in patients at high risk for recurrence. Data were pooled from 10 double-blnid, placebo- controlled trials in migraine. Multivariate regression analyses identi- fied significant predictors of recurrence witlffn 24 h of initial treatment response. Patients qualified for inclusion in the lffgh-risk subgroup if they had at least 3 of the most significant predictors of recurrence (high baseline pain severity, female, age _>35 years). Among patients qualifying for the high-risk subgroup, recurrence rates at 24 h were lower on eletriptan 40 mg (E40; 35%) compared with both sumatriptan 100 mg (S100; 51°,5; p < 0.005) and placebo (48°,5; p -- 0.058) when the analysis was limited to patients with severe headache pain at baseline (N -- 511). Recurrence rates at 24 h were

also lower on E40 (29%) compared with both SI00 (140%; p < 0.005) and placebo (43%; p < 0.001) when the analysis was limited to patients with moderate headache pain at baseline (IN - 1314). Eletriptan was more effective than sumatriptan in reducing the risk of headache recurrence among lffgh-risk patients.

1534 Precipitating factors of migraine in young migraine sufferers in Southern Sri Lanka

Patlfi~ana, K 1, Basnayake, L 1, Liyanage, pZ. 1University Medical Unit, Faculty" of medicine, Gall: Sri Lanka

Background: Precipitating factors of migraine attacks are different in different studies. The objective of this study is to identify the common precipitating factors in young migraine sufferers in Sri Lanka. Method: A pre tested self administered structured questionnaire is given to 139 subjects previously identified as having migraine according to IHS 2004 criteria. There were 92 senior secondary school children and 47 university students. Ninety students are from Galle and49 are from Matara. They were asked to tick off from alist of common and presumed triggers and to write a Results: There were 139 subjects with 91 (165.4°,5) were females and 48 (34.5%) were males. Age range was 16.0 to 28.5 years. Exposure to sunlight was a precipitating factor in 84 (49.7%) closely followed by traveling in vehicles in 67 (48.2%), sleep deprivation in 64 (146.0%), hunger in 55 (39.5%), food items in 43 (25.4%) physical activity in 15 (10.7%). Among those who had precipitant as food items cheese (20°,5) and chocolates (144°,5) are the common single items. There were differences in the frequency of precipitating factors according to locality and whether they are fi'om university or high school. Discussion: The precipitating factors for migraine are different from those reported elsewhere. Young Sri Lanka migraine sufferers have triggers like exposure to sunlight and traveling in vehicles which are not commonly described elsewhere. The explanation of the differences may be due to the differences in chance of exposure and lifestyles

1535 A randomized, double-blind comparison of Botulinum Toxin type a (Botox ~) and Divalproex Sodium (Depakote ~) for the prophylactic lreatulent of ulig~aine headaches: a pilot study

Porter, j 1 2 Sale m Neurological Center, Winston-Salem, USA

Background: There is a need for effective, well-tolerated prophylactic migraine treatment. Method: This was a single-center, randomized, double-blnid pilot study comparing the efficacy and safety of botulinum toxin type A (BoNTA) (200 U) and divalproex sodium (DVPX) (250 mg/bid the first week and 500 mg/bid thereafter) as prophylactic treatment of episodic migraine headaches. The primary outcome measure was the mean change from baseline in the number of headache-free days per month. The HIT-6, measuring the effect of headache and its treatment on function and well-being, was administered. Adverse events were assessed. Patients were assessed every 30 days for 3-months. Results: 44 patients (n -- 22 each group; mean age 43 years, 90.9% female) were enrolled. Treatment with BoNTA or DVPX resulted in statistically significant mean improvements from baseline in the number of headache-free days at days 30 (3.4, 1.9, p - 0.0189), 60 (4.4, 5.7) and 90 (4.5, 4.7) (p < 0.0001, both time-points), respectively. BoNTA and DVPX treatment resulted in statistically significant improvements in HIT-6 scores at all assessments (p < 0.0001). Differences between the groups were not significant. Adverse events were mild to moderate in both groups but significantly more adverse events possibly related to treatment were reported in the DVPX group (195.5% vs. 37.5%, p -- 0.0021), causing 2 patients to discontinue treatment. Conclusion: BoNTA and DVPX were safe and effective in the treatment of episodic migraine. These results suggest BoNTA