Topamax(R) Reduces Number Of Monthly Migraine Days In Chronic Migraine Patients

Main Category: Headache / Migraine
Article Date: 30 Apr 2006 - 0:00 PDT

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A study presented today at the annual meeting of the 8th European Headache Federation (EHF) demonstrated that chronic migraine sufferers treated preventively with TOPAMAX(R) (topiramate) experienced fewer migraine-related days per month than those treated with placebo.

The TOP-CHROME (TOPiramate in CHROnic MigrainE) study was a 16-week, multicenter double-blind, randomised, placebo-controlled study involving 59 patients aged 18 to 65 who experienced chronic migraines, which are defined as a total of 15 or more migraine days every 4 weeks.

The primary endpoint of this trial was the change in number of migraine days in patients treated with TOPAMAX compared to those on placebo, and the results showed a significantly greater reduction in migraine days in TOPAMAX patients. Patients who experienced chronic migraines and who were treated with TOPAMAX experienced a significant decrease in the mean number of migraine days of 3.5 days per month, while patients on placebo experienced no meaningful changes (0.2 day increase per month).

In addition, a group of patients who overused acute medications1 also experienced a significant and clinically relevant reduction in migraine days. Moreover, significantly fewer patients treated with TOPAMAX had overused acute medication at the end of the trial compared to those on placebo. Improvements in quality of life were also observed.

In the TOP-CHROME study, there was a 4-week baseline observation period without trial medication followed by initiation of treatment with placebo or topiramate at a daily dose of 25mg. The dose was then increased in weekly 25 mg increments to a target dose of 100 mg/day (with a 200 mg/day maximum dose). Final doses ranged between 50 mg and 200 mg per day according to patients' individual needs, with a mode dose of 100 mg. Subjects were permitted to continue taking existing migraine prevention therapies throughout the course of the study, with the exception of anticonvulsant medication. The predetermined primary efficacy endpoint of the trial was change in the number of migraine days during the last 4 weeks of treatment in the double-blind phase, compared to the number of migraine days during the 4 weeks baseline observation period.

During the last 4 weeks of treatment with topiramate, the number of migraine days was reduced from a baseline of 15.5 days to just 12 days (-3.5), compared to patients on placebo who experienced a 0.2 day increase in their migraine frequency. Patients' rating of the impact of migraine on their quality of life, as assessed by MIDAS2 questionnaires, was also significantly better for TOPAMAX than placebo. Improvements in quality of life were found with the MSQ3 and HIT-64 questionnaires, but there were no statistically significant differences between the treatment groups.

Prof H-C Diener, from the University of Essen (Germany) and one of the two principal investigators of the CHROME study, commented, "This trial enhances our understanding of the role that topiramate may play in reducing the frequency of migraine attacks in chronic migraine sufferers and medication overuse patients. These data may be an important consideration for physicians and patients who are considering the use of TOPAMAX as preventive therapy to help alleviate the toll that frequent migraine takes on people's lives."

During the treatment period, a significantly greater number of patients (up to 29%) responded to treatment with TOPAMAX, compared to up to 4% of migraine sufferers who responded to placebo. Patients were considered responders if they reported a reduction in their migraine days of at least 50%. Satisfaction with the effectiveness of treatment among patients in the study was also significantly higher for TOPAMAX compared to placebo. Moreover, a significant and clinically relevant reduction in migraine days was also reported in a group of patients who overused acute medications. Significantly fewer patients treated with TOPAMAX had overused acute medication at the end of the trial compared to patients on placebo (topiramate therapy: baseline 63% of patients, end of trial 28%; placebo baseline: 67% of patients, end of trial 59%).

During the course of the study, TOPAMAX was shown to be generally well-tolerated. There was a higher incidence of adverse events in the TOPAMAX group (75%) compared to patients on placebo (37%). The most commonly reported side effects were paraesthesia (59%), vomiting (16%), dizziness (13%) and nausea (9%). There was no statistically significant difference in satisfaction reported in the tolerability of the treatments. 75% of patients treated with TOPAMAX completed the study, compared to 52% of subjects on placebo.

In Europe, TOPAMAX is marketed by Janssen-Cilag, a subsidiary of Johnson & Johnson, the world's most comprehensive manufacturer of health-care products and related services. More information about the company can be found at http://www.janssen-cilag.com.

About TOPAMAX

TOPAMAX is approved for migraine prevention in adults only and is not approved for the acute treatment of migraines.

Important safety information: Serious risks associated with TOPAMAX include lowered bicarbonate levels in the blood resulting in an increase in the acidity of the blood (metabolic acidosis), and hyperventilation (rapid, deep breathing) or fatigue. More severe symptoms of metabolic acidosis could include irregular heartbeat or changes in the level of alertness. Chronic, untreated metabolic acidosis may increase the risk for kidney stones or bone disease.

Other serious risks include increased eye pressure (glaucoma), decreased sweating, increased body temperature, kidney stones, sleepiness, dizziness, confusion, and difficulty concentrating.

More common side effects are tingling in arms and legs, loss of appetite, nausea, diarrhea, taste change and weight loss.

Please see full prescribing information.

Regulatory status of medications and indications as discussed in these materials can vary from country to country. For full prescribing and safety information please refer to the Topamax labeling in your country.

1 - Acute Medication Overuse as Defined in TOP-CHROME Trial: Triptan intake 10 days/4 weeks; opioid intake 10 days/4 weeks; analgesic intake 15 days/4 weeks; or any combination of these drugs 10 days/4 weeks.
2 - Migraine Disability Assessment Questionnaire (MIDAS)
3 - Migraine Specific Questinnaire (MSQ)
4 - Headache Impact Test (HIT-6)

ABOUT EHF

Since its foundation in 1992, the EHF has sought to improve the life of European headache sufferers by promoting awareness of headache disorders and their impact. The EHF 8th Headache Congress is an international event which aims to foster scientific communication and debate centered on all aspects of the research, teaching and treatment of headache. Topics singled out for special focus at this year's congress include clinical experience with new acute and preventive treatments for headache.

References
1. Diener H-C, Goadsby PJ, Bussone G et al. Assessing the efficacy and safety of topiramate for the prevention of chronic migraine. European Headache Federation (EHF) 8th Headache Congress, Valencia, Spain, April 26-29, 2006. Poster 39.
2. Lipton RB, Stewart WF, Scher AI. Epidemiology and economic impact of migraine. Curr Med Res Opin 2001; 17(Suppl 1): S4-S12.ff.
3. Headache Class Subcommittee of the International Headache Society. The International Classification of Headache Disorders 2nd Edition. Cephalalgia 2004; 24: Suppl 1:1-151.
4. National Headache Foundation. Advances in migraine prophylaxis - current state of the art and future therapies. Monograph 2001. Available at http://www.headaches.org/professional/educationresources/PDF/botoxcme.pdf.
5. Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias, and facial pain. Cephalalgia. 1988;8(suppl 7): 1-96.
6. Lipton RB et al. Migraine Prevention Patterns in a Community Sample: Results from the American Migraine Prevalence and Prevention (AMPP) Study. Abstract presented at AHS Congress, Philadelphia, 23-26 June 2005: abstract reference F38.