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

Högl B, Oertel WH, Stiasny-Kolster K, Geisler P, Beneš H, García-Borreguero D, Trenkwalder C, Poewe W, Schollmayer E, Kohnen R - BMC Neurol (2010)

Bottom Line: 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 responder rate in the CGI change item 2 ("much" and "very much" improved) was 95% after year 2.NCT00498186.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. birgit.ho@i-med.ac.at

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.

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Related in: MedlinePlus

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.
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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.

Mentions: Rotigotine transdermal patch rapidly improved the IRLS severity rating; the baseline sum score of 27.8 ± 5.9 was reduced by 18.8 ± 8.6 during the 4-week titration phase of the open-label trial (Figure 2). This result is comparable to the data recorded during rotigotine titration in the preceding double-blind, placebo-controlled trial [13]. Figure 3 shows the changes in IRLS severity over 2 years of rotigotine treatment. At month 12 and month 24, mean IRLS sum scores of 8.7 ± 8.0 and 10.3 ± 9.3, respectively, were calculated. Mean reduction after 2 years of rotigotine maintenance treatment was 15.4 ± 10.3 for all patients entering this extension trial (n = 295, LOCF) and 17.2 ± 9.2 for all patients completing the 2-year period (n = 190). CGI-1 and RLS-6 daytime at rest scores closely follow this pattern (Figure 2). All other efficacy variables also improved over the 2-year period (Table 3) and remained stable during the second year when compared with the year 1 results [16]. Responder rates indicate that the majority of patients benefited from rotigotine treatment (Table 4). Overall, 30% of all patients who completed the 2-year treatment were free of symptoms according to IRLS (total score = 0) and 30% were free of symptoms according to CGI-1 (not ill at all). Therapeutic efficacy of rotigotine was rated as 'good' to 'very good' in 95% (n = 209) of year 1 completers and 89% (n = 170) of year 2 completers.


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

Högl B, Oertel WH, Stiasny-Kolster K, Geisler P, Beneš H, García-Borreguero D, Trenkwalder C, Poewe W, Schollmayer E, Kohnen R - BMC Neurol (2010)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2958158&req=5

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.
Mentions: Rotigotine transdermal patch rapidly improved the IRLS severity rating; the baseline sum score of 27.8 ± 5.9 was reduced by 18.8 ± 8.6 during the 4-week titration phase of the open-label trial (Figure 2). This result is comparable to the data recorded during rotigotine titration in the preceding double-blind, placebo-controlled trial [13]. Figure 3 shows the changes in IRLS severity over 2 years of rotigotine treatment. At month 12 and month 24, mean IRLS sum scores of 8.7 ± 8.0 and 10.3 ± 9.3, respectively, were calculated. Mean reduction after 2 years of rotigotine maintenance treatment was 15.4 ± 10.3 for all patients entering this extension trial (n = 295, LOCF) and 17.2 ± 9.2 for all patients completing the 2-year period (n = 190). CGI-1 and RLS-6 daytime at rest scores closely follow this pattern (Figure 2). All other efficacy variables also improved over the 2-year period (Table 3) and remained stable during the second year when compared with the year 1 results [16]. Responder rates indicate that the majority of patients benefited from rotigotine treatment (Table 4). Overall, 30% of all patients who completed the 2-year treatment were free of symptoms according to IRLS (total score = 0) and 30% were free of symptoms according to CGI-1 (not ill at all). Therapeutic efficacy of rotigotine was rated as 'good' to 'very good' in 95% (n = 209) of year 1 completers and 89% (n = 170) of year 2 completers.

Bottom Line: 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 responder rate in the CGI change item 2 ("much" and "very much" improved) was 95% after year 2.NCT00498186.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. birgit.ho@i-med.ac.at

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.

Show MeSH
Related in: MedlinePlus