New Study Published In The Lancet Neurology Shows Topamax(R) Provides Sustained Reduction In Monthly Migraine Days For Up To One Year

Main Category: Headache / Migraine
Also Included In: Neurology / Neuroscience
Article Date: 04 Dec 2007 - 2:00 PDT

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A new long-term study into migraine prevention published in The Lancet Neurology shows that patients who continued with Topamax(R) (topiramate) for migraine prophylaxis for up to a year experienced a sustained reduction in the number of migraine days per month, with significant associated benefits on quality of life measures.1 The study also found that there was a significant increase in the number of monthly migraine days following discontinuation of topiramate, however, the number did not return to pre-treatment levels.1

Migraine is a very common disorder affecting around 11% of the adult population in the Western world.2 One UK study estimated that 5.85 million people in the UK, aged 16-65 years, experience 190,000 migraine attacks everyday resulting in the loss of 25 million days from work or school each year.3

The PROMPT (PROlonged Migraine Prevention with Topiramate) study was a 12-month, multicentre, double-blind, randomised, placebo-controlled study conducted to investigate the continued effectiveness of topiramate in reducing the number of migraine days beyond six months, compared with the impact of stopping treatment at six months. All patients received open-label Topamax for the first 6 months, and then were randomised to either continue Topamax or take placebo for the second 6 months in a double-blind design.

After 6 months of open-label topiramate treatment, the mean number of monthly migraine days fell significantly from 8.93 to 5.83, a reduction of 3.1 migraine days per month (p<0.0001):

- After 12 months, the reduction in the mean number of monthly migraine days seen during the first six months was maintained and remained almost unchanged in the group that continued on topiramate (+0.1 migraine days per 4 weeks; [p=0.5756]). However, patients who had been switched to placebo at six months experienced a significant increase in migraine days, with an average rise of more than 1 migraine day per month by endpoint (+1.2 migraine days per 4 weeks; [p<0.0001]).

- Although there was a significant increase in the mean number of monthly migraine days in the placebo group following discontinuation of topiramate, the number did not return to pre-treatment values by the 12 month endpoint.

Dr Brendan Davies from North Midlands Regional Headache Clinic, University Hospital of North Staffordshire, one of the investigators in the PROMPT study commented; "Many migraine prevention trials examine patients over a three-month period which is why this new 12-month data is so important. The longer evaluation used in the PROMPT study is more reflective of clinical practice, so these new results may offer physicians and patients more meaningful data when considering migraine prevention treatment. This is also one of the first controlled studies to systematically investigate what happens when prophylactic treatment is stopped."

After 6 months of open-label treatment with topiramate, quality of life (measured using the Migraine Disability Assessment Questionnaire, MIDAS) was also significantly improved, with mean MIDAS scores reduced by 21.18 to 15.40 (p<0.0001). This represents a change from 'severe disability' (score > 20) to 'moderate disability' (score < 21). At 12 months, quality of life had deteriorated significantly following the switch to placebo, with mean MIDAS scores increasing by 6 points in this group (p<0.05). However improvements seen in the first 6 months were maintained in those patients who continued on topiramate, with no change in mean MIDAS scores.

Wendy Thomas, from the patient advocacy group Migraine Trust, commented "One of the most confining aspects of migraine is the debilitating impact it has on the patient and their lives: affecting their ability to do their job properly or even enjoy social and leisure activities. Anything that reduces this effect and enables people with migraine to carry on with their day to day existence is highly welcomed by the Migraine Trust".

About PROMPT

The PROMPT study was conducted in 21 countries throughout Europe and the Middle East by Janssen-Cilag, the makers of Topamax® A total of 818 adults were enrolled in PROMPT, and 559 patients completed the initial 6-month open-label phase. Of that total, 514 progressed to the double-blind phase. All patients were treated with topiramate for the first 6 months of the trial, and then either continued with topiramate treatment for the second 6-month stage of the study or switched to placebo. The primary endpoint in the PROMPT trial was the difference in the number of migraine days during the last 4 weeks of the double-blind phase versus the last 4 weeks of the open-label phase.

Secondary efficacy parameters included number of withdrawals, change in the duration and severity of migraine headaches, change in the number of acute medication intakes, change in Quality of Life (QoL) questionnaire scores, and change in patient satisfaction over the double-blind phase.

MIDAS4

The Migraine Disability Assessment Questionnaire (MIDAS) measures headache-related disability by counting the number of days lost and limited activity due to migraine. Activities are classed into three areas:

- Paid work and education (school / college)
- Household work (housework / shopping / caring for children and others)
- Family, social and leisure activities

Adverse Events

Open-label phase:
Adverse events (AEs) were reported in 85% of patients. Those reported in 10% or more of patients were: Paraesthesia (50%), fatigue (12%), disturbance in attention (12%), decreased appetite (11%)

Double-blind phase:
AEs were reported by 68 percent of topiramate-treated patients versus 59 percent of patients in the placebo group. AEs reported in 5% or more of patients were:
Paraesthesia (30% topiramate, 21% placebo), fatigue (7%, 4%), disturbance in attention (4%, 5%), decreased appetite (5%, 3%), weight decreased (9%, 7%), depression (5%, %5) and nausea was reported in 4% of both groups. Serious AEs occurred in 3% of topiramate patients and 4% of placebo patients.

About Topamax®

In the UK, Topamax® is licensed for migraine prevention in adults only, in situations such as adults experiencing three or more migraine attacks per month or frequent migraine attacks that significantly interfere with the patient's daily routine. It is not licensed for the acute treatment of migraines. Topamax must be initiated under the supervision of a specialist conversant with migraine or via a shared care arrangement. A six-month review is recommended once treatment has been initiated.

About Janssen-Cilag

Janssen-Cilag has a long track record in developing treatments for central nervous system disorders, pain management, oncology, fungal infections and gastrointestinal conditions. Products include Concerta® XL (ADHD), Durogesic® DTrans® (pain management), Eprex® (anemia), Topamax® (epilepsy, migraine prevention), Risperdal® (schizophrenia, bipolar disorder), Risperdal® Consta® (schizophrenia) and Velcade® (progressive multiple myeloma). More information can be found at http://www.janssen-cilag.co.uk and http://www.janssen-cilag.com

References

1. Diener, HC., Agnosti, R., Allais, G. et al. Cessation versus continuation of 6-month migraine preventive therapy with topiramate(PROMPT): a randomised,double-blind,placebo-controlled trial. The Lancet Neurology, 2007; 6: 1054-1062

2. Lipton RB, Stewart WF, Scher AI. Epidemiology and economic impact of migraine. Curr Med Res Opin 2001; 17 (Suppl 1): S4-S12.

3. Steiner TJ, et al. The prevalence and disability burden of adult migraine in England and their relationships to age, gender and ethnicity. Cephalalgia, 2003, 23, 519-527

4. Migraine Disability Assessment Questionnaire

Janssen-Cilag