Prevention of episodic migraine with topiramate: a prospective 24-week, open-label, flexible-dose clinical trial with optional 24 weeks follow-up in a community setting

Abstract

Objective:

To explore efficacy and safety outcomes of topiramate for episodic migraine prevention in community practice.

Research design and methods:

Open-label, multicenter, flexible-dose clinical trial consisting of a 4-week baseline phase, 24-week core phase and an optional 24-week follow-up phase in patients (18–80 years) with episodic migraine treated in community practices outside tertiary care centers.

Main outcome measures:

The primary efficacy endpoint was the change in the number of migraine days/28 days (baseline vs. the last 4 weeks of core treatment) Secondary efficacy parameters included aspects of quality of life (QoL) and subjective patient ratings.

Results:

A total of 360 patients entered the core phase (ITT population); 37.6% (97 patients) discontinued prematurely, mainly due to adverse events (AEs; 23.6%). Mean topiramate dosage was 90 mg/day. Migraine days decreased from 8.30/28 days to 5.65/28 days and QoL (HIT-6 and MIDAS) was improved. Efficacy, tolerability and satisfaction were rated as ‘good’ or better by 56, 61 and 63% of patients, respectively. A total of 321 of 364 patients (88.2%) reported at least one treatment emergent AE, and the most common during the core phase were paraesthesia (46.4% of 364 patients), fatigue (17.0%), nausea (15.4%), dizziness (12.9%), viral infection (12.9%), weight decrease (12.6%) and impaired concentration (10.2%). Of 227 patients completing the core phase, 199 (88%) participated in the follow-up phase. A total of 187 patients received topiramate and 38 (20.3%) of these stopped treatment prematurely due to insufficient efficacy (6.4%), AEs (4.8%) or other reasons (10.2%). Reduction in migraine days and improvements in QoL (HIT-6) were maintained or improved (MIDAS) during follow-up, and 84% rated their satisfaction with topiramate therapy as ‘good to very good’.

Conclusions:

This community practice study showed that long-term treatment with topiramate in the prevention of episodic migraine was effective and well-tolerated, and it was associated with clinically relevant improvements in several aspects of QoL.

Key words::

• HIT-6
• MIDAS
• Migraine prevention
• Open-label trial
• Topiramate

Transparency

Declaration of funding

The study was sponsored by Janssen-Cilag, Neuss, Germany.

Declaration of financial/other relationships

R.M. has received lecture fees from Eli Lilly, Mundipharma, BiogenIdec, Pfizer, Wyeth, MSD, Berlin-Chemie and clinical trial honoraria from Boehringer Ingelheim, BiogenIdec, Servier and CSL Behring. L.S. has received lecture fees from Mundipharma and clinical trial fees from Boehringer Ingelheim, BiogenIdec, Eli Lilly, Janssen-Cilag and Mundipharma. B. Steinberg and A.G. have nothing to disclose. K.B., M.D. and B. Schäuble are employees of Janssen-Cilag.

Peer reviewers may receive honoraria from CMRO for their review work. Peer Reviewers 1 and 2 have disclosed that they have no relevant financial relationships.

Acknowledgements

Editorial support was provided by Dr. Felicitas Deget and Content Ed Net, and was funded by Janssen-Cilag. The authors gratefully acknowledge the participation of following investigators:

Adam, Heidrun; Altenkirch, Holger; Andree, Karin; Angerer, Michael; Becker, Veit Ulrich; Bek, Jan; Binsfeld, Heinrich; Bodenschatz, Ralf; Böhringer, Johannes; Bornhövd, Karin; Brand, Jan-R.; Buder, Petra; Eger, Robert; Emrich, Peter; Fegers, Stephan; Finkelstein-Conea, Nana; Flöter, Thomas; Franz, Peter; Freier, Joachim; Frieling, Rolf-R.; Göbel, Hartmut; Gromoll, Heike; Harrer-Haag, Judith; Hartmann, Alexander; Hein, Albert; Heise, Marina; Hermanns, Kai; Horlemann, Johannes; Horn, Rolf; Hubbertz, Ludwig J.; Humbert, Thomas; Jaber, Nizar; Jansen, Jan-Peter; Käfferlein, Wolfgang; Kausch, Ulrich; Kessel, Jörg; Klein, Martin; Klimmek, Verena; Klotz, Jürgen; Köhn, Ralph D.; Koppai-Reiner, Joachim; Krauspe, Ulrike; Kühn, Frank; Kukowski, Borries; Küster-K., Michael; Längler, Klaus; Lefèbre, Johann-Christoph; Leinisch, Elke; Malessa, Rolf; Marziniak, Martin; Mattern, Wolfgang; Moser, Christiane; Müllner, Eckhart; Niedhammer, Mathias; Oehler, Klaus-Ulrich; Peglau, Ines; Pfaffenrath, Volker; Prange, Ernst; Rautenberg, Wolfgang; Salem, Kamal; Sallach, Klaus; Saschowa, Stephan; Schellenberg, Rüdiger; Schlinsog, Kerstin; Schmidt, Gerald; Schmitt, Lukas; Schulze, Alexander; Siever, Arno; Sohn, Wolfgang; Springub, Joachim; Stahl, Angela; Steinberg, Bastian; Steinwachs, Klaus-Christian; Stoenescu, Adrian; Stotz, W. G.; Tegenthoff, M.; van Heys, Rurik; Vogt, Jürgen; von Goeldel, Rudolph; Wallasch, Thomas-Martin; Wallesch, C.-W.; Wencker, H.-V.; Wenzel, Wilhelm; Wieden, Elke; Witte, O. W.; Wollenhaupt, Elke; Wunderlich, Hans-Peter; Zierz, Stephan