Treatment of moderate to severe restless legs syndrome: 2-year safety and efficacy of rotigotine transdermal patch

Birgit Högl, Wolfgang H Oertel, Karin Stiasny-Kolster, Peter Geisler, Heike Beneš, Diego García-Borreguero, Claudia Trenkwalder, Werner Poewe, Erwin Schollmayer, Ralf Kohnen, Birgit Högl, Wolfgang H Oertel, Karin Stiasny-Kolster, Peter Geisler, Heike Beneš, Diego García-Borreguero, Claudia Trenkwalder, Werner Poewe, Erwin Schollmayer, Ralf Kohnen

Abstract

Background: Rotigotine is a unique dopamine agonist with activity across D1 through D5 receptors as well as select adrenergic and serotonergic sites. This study reports the 2-year follow-up safety and efficacy data of an ongoing open-label multicenter extension study (NCT00498186) of transdermal rotigotine in patients with moderate to severe restless legs syndrome (RLS).

Methods: Patients received a once-daily patch application of an individually optimized dose of rotigotine between 0.5 mg/24 h to 4 mg/24 h. Safety assessments included adverse events (AEs) and efficacy was measured by the International RLS Study Group Severity Rating Scale (IRLS), RLS-6 scales and Clinical Global Impression (CGI). Quality of life (QoL) was measured by QoL-RLS.

Results: Of 310 patients who completed a 6-week placebo-controlled trial (SP709), 295 (mean age 58 ± 10 years, 66% females) were included in the open-label trial SP710. 64.7% (190/295 patients) completed the 2-year follow-up; 29 patients discontinued during the second year. Mean daily rotigotine dose after 2 years was 2.93 ± 1.14 mg/24 h with a 2.9% dose increase from year 1. Rotigotine was generally well tolerated. The rate of typical dopaminergic side effects, nausea and fatigue, was low (0.9% and 2.3%, respectively) during the second year; application site reactions were frequent but lower than in year 1 (16.4% vs. 34.5%). The IRLS total score improved from baseline of SP709 (27.8 ± 5.9) by 17.2 ± 9.2 in year 2 completers. Similar improvements were observed in RLS-6 scales, CGI scores and QoL-RLS. The responder rate in the CGI change item 2 ("much" and "very much" improved) was 95% after year 2.

Conclusions: Transdermal rotigotine is an efficacious and well-tolerated long-term treatment option for patients with moderate to severe RLS with a high retention rate during 2 years of therapy.

Trial registration: NCT00498186.

Figures

Figure 1
Figure 1
Mean daily rotigotine dose over the 2-year maintenance period (safety population).
Figure 2
Figure 2
Mean IRLS total score, CGI item 1 (severity of illness), and RLS-6 item 4 (severity during the day at rest) scores over 2 years of rotigotine maintenance treatment (data as observed). B, baseline; CGI, Clinical Global Impression; IRLS, International RLS Severity Scale; RLS, restless legs syndrome S, start of maintenance phase.
Figure 3
Figure 3
Changes in IRLS severity over 2 years of rotigotine maintenance treatment (data as observed).

References

    1. Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J. Restless Legs Syndrome Diagnosis and Epidemiology workshop at the National Institutes of Health; International Restless Legs Syndrome Study Group. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med. 2003;4:101–119. doi: 10.1016/S1389-9457(03)00010-8.
    1. Trenkwalder C, Paulus W, Walters AS. The restless legs syndrome. Lancet Neurol. 2005;4:465–475. doi: 10.1016/S1474-4422(05)70139-3.
    1. Kushida C, Martin M, Nikam P, Blaisdell B, Wallenstein G, Ferini-Strambi L, Ware JE Jr. Burden of restless legs syndrome on health-related quality of life. Qual Life Res. 2007;16:617–624. doi: 10.1007/s11136-006-9142-8.
    1. Oertel WH, Trenkwalder C, Zucconi M, Benes H, Borreguero DG, Bassetti C, Partinen M, Ferini-Strambi L, Stiasny-Kolster K. State of the art in restless legs syndrome therapy: practice recommendations for treating restless legs syndrome. Mov Disord. 2007;22(Suppl 18):S466–475. doi: 10.1002/mds.21545.
    1. Hening WA. Current guidelines and standards of practice for restless legs syndrome. Am J Med. 2007;120(1A):S22–S27. doi: 10.1016/j.amjmed.2006.11.004.
    1. Trenkwalder C, Hening WA, Montagna P, Oertel WH, Allen RP, Walters AS, Costa J, Stiasny-Kolster K, Sampaio C. Treatment of restless legs syndrome: An evidence-based review and implications for clinical practice. Mov Disord. 2008;23:2267–2302. doi: 10.1002/mds.22254.
    1. Partinen M, Hirvonen K, Jama L, Alakuijala A, Hublin C, Tamminen I, Koester J, Reess J. Open-label study of the long-term efficacy and safety of pramipexole in patients with Restless Legs Syndrome (extension of the PRELUDE study) Sleep Med. 2008;9:537–541. doi: 10.1016/j.sleep.2007.12.004.
    1. Garcia-Borreguero D, Grunstein R, Sridhar G, Dreykluft T, Montagna P, Dom R, Lainey E, Moorat A, Roberts J. A 52-week open-label study of the long-term safety of ropinirole in patients with restless legs syndrome. Sleep Med. 2007;8:742–752. doi: 10.1016/j.sleep.2006.09.009.
    1. Scheller D, Ullmer C, Berkels R, Gwarek M, Lübbert H. The in vitro receptor profile of rotigotine: a new agent for the treatment of Parkinson's disease. Naunyn-Schmiedeberg's Arch Pharmacol. 2009;379:73–86. doi: 10.1007/s00210-008-0341-4.
    1. Watts RL, Jankovic J, Waters C, Rajput A, Boroojerdi B, Rao J. Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson disease. Neurology. 2007;68:272–276. doi: 10.1212/01.wnl.0000252355.79284.22.
    1. Poewe WH, Rascol O, Quinn N, Tolosa E, Oertel WH, Martignoni E, Rupp M, Boroojerdi B. SP 515 Investigators. Efficacy of pramipexole and transdermal rotigotine in advanced Parkinson's disease: a double-blind, double-dummy, randomised controlled trial. Lancet Neurology. 2007;6:513–520. doi: 10.1016/S1474-4422(07)70108-4.
    1. Stiasny-Kolster K, Kohnen R, Schollmayer E, Möller JC, Oertel WH. The Rotigotine SP 666 Study Group. Patch application of the dopamine agonist rotigotine to patients with moderate to advanced stages of restless legs syndrome: a double-blind, placebo-controlled pilot study. Mov Disord. 2004;19:1432–1438. doi: 10.1002/mds.20251.
    1. Oertel WH, Benes H, Garcia-Borreguero D, Geisler P, Högl B, Saletu B, Trenkwalder C, Sommerville KW, Schollmayer E, Kohnen R, Stiasny-Kolster K. Rotigotine SP 709 Study Group. Efficacy of rotigotine transdermal system in severe restless legs syndrome: a randomized, double-blind, placebo-controlled, six-week dose-finding trial in Europe. Sleep Med. 2008;9:228–239. doi: 10.1016/j.sleep.2007.04.010.
    1. Trenkwalder C, Benes H, Poewe W, Oertel WH, Garcia-Borreguero D, de Weerd AW, Ferini-Strambi L, Montagna P, Odin P, Stiasny-Kolster K, Högl B, Chaudhuri KR, Partinen M, Schollmayer E, Kohnen R. SP790 Study Group. Efficacy of rotigotine for treatment of moderate-to-severe restless legs syndrome: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2008;7:595–604. doi: 10.1016/S1474-4422(08)70112-1.
    1. Hening WA. Effective treatment of idiopathic RLS with 24-hour rotigotine transdermal patch: results of a 6-month, multicenter, double-blind, placebo-controlled trial in the USA. Eur J Neurol. 2008;15(Suppl 3):111. (abstract P1297)
    1. Oertel WH, Benes H, Garcia-Borreguero D, Geisler P, Högl B, Trenkwalder C, Tacken I, Schollmayer E, Kohnen R, Stiasny-Kolster K. Rotigotine SP710 Study Group. One year open-label safety and efficacy trial with rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome. Sleep Med. 2008;9:865–873. doi: 10.1016/j.sleep.2008.04.012.
    1. National Institute of Mental Health. 028 CGI. Clinical Global Impressions. In: Guy W, editor. ECDEU Assessment Manual for Psychopharmacology. Rockville, MD: National Institute of Mental Health; 1976. pp. 217–222.
    1. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14:540–545.
    1. The International Restless Legs Syndrome Study Group. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med. 2003;4:121–132. doi: 10.1016/S1389-9457(02)00258-7.
    1. Kohnen R, Stiasny-Kolster K, Oertel WH, Beneš H, Trenkwalder C. Severity Rating of Restless Legs Syndrome: validation of the RLS-6 scales. Sleep. 2004;27(Abstract Suppl):A342.
    1. Kohnen R, Beneš H, Heinrich CR, Kurella B. Development of the disease-specific Restless Legs Syndrome Quality of Life (RLS-QoL) questionnaire. Mov Disord. 2002;17(Suppl 5) P743Abs.
    1. Beneš H, Heinrich CR, Ueberall MA, Kohnen R. Long-term safety and efficacy of cabergoline for the treatment of idiopathic restless legs syndrome: results from an open-label 6-month clinical trial. Sleep. 2004;27:674–682.
    1. Trenkwalder C, Benes H, Grote L, Happe S, Högl B, Mathis J, Saletu-Zyhlarz GM, Kohnen R. CALDIR Study Group. Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: results from a multi-center, randomized, active controlled trial. Mov Disord. 2007;22:696–703. doi: 10.1002/mds.21401.
    1. García-Borreguero D, Allen RP, Benes H, Earley C, Happe S, Högl B, Kohnen R, Paulus W, Rye D, Winkelmann J. Augmentation as a treatment complication of restless legs syndrome: concept and management. Mov Disord. 2007;22(Suppl 18):S476–484. doi: 10.1002/mds.21610.
    1. Vaillant L, Biette S, Machet L, Constans T, Monpere C. Skin acceptance of transcutaneous nitroglycerin patches: a prospective study of 33 patients. Contact Dermatitis. 1990;23:142–145. doi: 10.1111/j.1600-0536.1990.tb04774.x.
    1. Donner B, Zenz M, Strumpf M, Raber M. Long-term treatment of cancer pain with transdermal fentanyl. J Pain Symptom Manage. 1998;15:168–175. doi: 10.1016/S0885-3924(97)00361-8.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren