Prevention of migraine episodes, Topamax shows promise - New long-term clinical studies

Main Category: Headache / Migraine
Article Date: 28 Sep 2005 - 0:00 PDT

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Results from two large clinical trials demonstrate that patients with frequent migraine who were treated with TOPAMAX® (topiramate) for up to 14 months (6 months double blind followed by 8 months open label) had a persistent reduction in the frequency of migraine headaches.1 In addition, analyses from the three 26-week placebo-controlled pivotal trials of topiramate in migraine prevention showed that topiramate improves health-related quality of life (HRQoL).2 These data were presented at the ninth congress of the European Federation of Neurological Societies (EFNS), in Athens, Greece.

Efficacy and tolerability results presented from the 8 month open-label extension (OLE) phases of two (*) pivotal, 6-month, randomised, double-blind (DB), placebo-controlled trials with topiramate, demonstrated there was persistent reduction in monthly migraine frequency that was consistent with the initial 6-month maintenance period (100mg/d topiramate change from baseline; -2.5 by end of DB phase, and -3.7 by end of OLE phase).1

A separate analysis of the three pivotal, 26-week, randomised, double-blind, migraine prevention trials with topiramate highlighted that 100 mg/d significantly improved health-related quality of life for patients with migraine for up to six months following initiation of treatment.2 HRQoL was evaluated via a Migraine-Specific Questionnaire (MSQ) which measured the degree to which migraine limited and interrupted patients' daily performance, and via the SF-36 which assess the impact of general medical disorders on HRQoL.

Significant improvement in MSQ scores were observed for all domains as early as week 8 and at every time point thereafter. Topiramate-associated improvements on SF-36 subscales were seen for physical functioning, bodily pain, vitality, general health perceptions, and social functioning compared with placebo.

Dr Domenico D'Amico from the Neurological Institute C. Besta in Milan (Italy), commented: "While acute treatments can lessen the symptoms of a migraine attack once it has started, these trials show that using topiramate as preventative therapy reduces the frequency of migraine attacks. These results offer new hope for patients with frequent migraine in terms of controlling their condition and bring them one step closer to leading a normal, healthy life."

Benefits of preventative therapy were also reinforced when a pooled analysis of the three pivotal trials found that 46.3% of patients on topiramate 100 mg/d achieved at least 50% reduction in the number of monthly migraine periods compared with 22.8% on placebo (p<0.001), and similarly a reduction in both the mean frequency and duration of monthly migraine attacks. 3

Topiramate demonstrated acceptable tolerability across all three pivotal trials in migraine prevention at the target dose of 100mg/day in two divided doses3. The most common side effects experienced by patients taking 100 mg of topiramate included paresthesia (mild tingling sensations in the extremities), loss of appetite, fatigue, nausea, taste alteration, diarrhoea, cognitive side effects and weight loss. The most common adverse events leading to discontinuation during the OLE phase of the trials were fatigue (1.8%), paresthesia (1.6%) and language problems (1.6%).

When these side effects occurred, most were mild to moderate in severity and resolved once the medication was discontinued. Topiramate is not associated with treatment-induced weight gain, unlike many other migraine preventative agents.

Daily migraine preventative therapy can reduce the risk of migraine occurrence, allowing people with frequent migraine greater reassurance and control over their daily life. International Headache Society guidelines recommend that preventative therapy be prescribed when migraines occur three or more times per month or are particularly debilitating and severe for patients.4 Of all cases who met consensus guideline criteria for preventative treatment (regardless of their current treatment status) only 20% were receiving it.5

The World Health Organisation has rated migraine as one of the top 20 leading causes of disability world-wide.6 It is a very common disorder which affects around 11% of the adult population in the Western world.7 Often the impact of migraine can be underestimated and the full disabling extent of the condition misjudged, both by physicians and the public. This can place additional pressure on people with migraine who may feel stigmatised by their condition and unable to seek support where needed.

TOPAMAX® is approved worldwide as adjunctive treatment for a variety of epileptic seizures. In addition, more than 60 countries have approved its use for monotherapy treatment of epilepsy and TOPAMAX® has been approved for migraine prophylaxis in 41 countries. To date, more than 4 million patients worldwide have been treated with TOPAMAX®.

In Europe, TOPAMAX® is marketed by Janssen-Cilag, a member of the Johnson & Johnson family of companies, 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.

References
1 H.C. Diener et al. Long-Term Effectiveness of Topiramate for Migraine Prevention: Analyses of Open-Label Extension-Phase Data from Two Pivotal Studies. Poster presented at EFNS Congress, Athens, Greece 20th September, 2005: poster reference P2138.
Subject eligible for the OLE phase had completed the DB phase (8 weeks titration followed by an 18 weeks maintenance period) or withdrew prematurely after completing at least 4 weeks of the maintenance period due to lack of efficacy .
2 C. Dahlöf et al. Analyses of Quality of Life Indicators from 3 Placebo-Controlled Trials of Topiramate for Migraine Prevention. Poster presented at EFNS Congress, Athens, 20th September, 2005: poster reference P1158.
3 G. Bussone et al. 'Topiramate 100 mg/day in migraine prevention: a pooled analysis of double-blind randomised controlled trials'. Int J Clin Pract. 2005; 59, 8, 961-968.
4 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
5 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, Philidelphia, 23-26 June 2005: abstract reference F38
6 Headache Class Subcommittee of the International Headache Society. The International Classification of Headache Disorders 2nd Edition. Cephalalgia 2004; 24: Suppl 1:1-151.
7 Lipton RB, Stewart WF, Scher AI. Epidemiology and economic impact of migraine. Curr Med Res Opin 2001; 17(Suppl 1): S4-S12.