New data confirm pramipexole relieves symptoms and significantly improves patients’ quality of life
Athens/Greece, 19 September 2005 – New data, reported for the first time today at the European Federation of Neurological Societies (EFNS) Annual Meeting, have confirmed the vital future role of Boehringer Ingelheim’s dopamine agonist, pramipexole, in treating patients suffering from Restless Legs Syndrome (RLS)1,2. New research also demonstrates that two key assessment scales for RLS are equivalent in outcomes, giving clinicians wider scope for assessing the impact of the disease3. Restless Legs Syndrome is one of the most common, but treatable neurological conditions in the world. It is estimated that RLS affects up to one in ten of the population aged between 30 to 79 years4.
The latest results from the large, double-blind, placebo-controlled European study1,2 in 345 patients have shown that pramipexole is highly effective in reducing the severity of RLS symptoms, over a six-week period, and is well tolerated. Furthermore, pramipexole treatment brings about significant improvements in patients’ quality of life.
“Restless Legs Syndrome is a surprisingly common, but underdiagnosed condition, that adversely affects the lives of millions of people worldwide”, explained Professor Wolfgang Oertel, MD, Chairman of the Department of Neurology, Centre of Nervous Diseases, Philipps University, Marburg, Germany. “The reason why these data presented today are so important, is that they strengthen the evidence for the beneficial effect of pramipexole, not just in relieving the primary symptoms of the condition, but in reducing the high impact of the disease on patients’ quality of life”.
Efficacy in relieving symptoms Efficacy was demonstrated in this study using two measurement criteria: the International RLS Rating Scale of severity (IRLS) and the Clinical Global Impressions – Improvement (CGI – I) scale. Results after six weeks of trial therapy showed that: • Improvement in the IRLS was significantly greater for the pramipexole group, compared to the placebo group (adjusted mean change from baseline -12.3 vs -5.7, p=0.0001). • On the CGI-I scale almost two-thirds (62.9%) of patients taking pramipexole were classified as “improved” or “much improved”, compared to only one-third (32.5%) of patients treated with placebo (p<0.0001).
Quality of life Patients with RLS commonly find that their quality of life is severely impacted by the condition. The motor restlessness during the evening and night can cause considerable disruption to sleep5. Additionally, social activities such going to a theatre or cinema, can also be severely impacted6.
A new subanalysis of the European study, also presented for the first time today, has shown that pramipexole treatment significantly improves patients’ quality of life, as measured by the SF-36 (Medical Outcomes Study 36 –Item Short Form health survey)2. This assessment test has eight sub-scales upon which patients are scored. Low scores on this scale indicate poor or worsening quality of life; high scores indicate better quality of life. After six weeks of study treatment, compared to placebo, patients treated with pramipexole had statistically significant higher scores for ‘Vitality’ (i.e. fatigue), ‘Social Functioning’ (i.e. interference with normal social activities with family, friends and others) and ‘Bodily Pain’ (i.e. bodily pain during the past four weeks on a six-point verbal rating scale). For the other five subscales, pramipexole showed an improvement on scores over placebo, but these data did not reach statistical significance. These data are important as recent studies have shown that the Quality of Life impact of RLS is comparable to that of other chronic diseases. When the quality of life of patients with different chronic conditions was assessed using the SF-36 test, the results revealed7: • RLS patients had significantly lower scores (indicating worse quality of life) on all 8 scores of the SF-36 compared with patients with hypertension; • RLS patients had lower scores on 7 out of the 8 scales when compared to patients with diabetes mellitus • RLS patients had lowers scores on 6 out of the 8 scales than patients with other cardiovascular conditions (congestive heart failure, myocardial infarction within the past year and angina).
Accurately measuring efficacy of treatments in RLS: CGI-I is equivalent to PGI The Clinical Global Impression (CGI) scale is a widely used instrument, used by clinicians to measure the impact of certain disorders or the efficacy of a treatment across a range of diseases, including depression and schizophrenia, as well as movement disorders, such as Parkinson’s Disease and RLS. The CGI has four sub-scales and the most commonly used sub-scale in RLS is the CGI – Improvement (CGI-I), whereby a physician can rate the change in severity of a patient’s RLS symptoms. When the CGI-I scale is used in RLS, clinicians make their assessment by interviewing the patient, relying on the patients’ own description of their symptoms. An alternative instrument is the Patient Global Improvement (PGI) score. The PGI involves a questionnaire completed by the patients themselves. In an additional study presented for the fist time today3, the CGI-I and the PGI scales were shown to be closely correlated, both with each other, and with the specific RLS severity scale. This correlation indicates that both scales can convincingly be used as outcome measures in clinical trials. Furthermore, the PGI could serve as an independent, yet patient-based assessment of a treatment effect in RLS, broadening the opportunities for clinicians in assessing this common condition.
Comprehensive evidence base Previous studies in RLS have confirmed that pramipexole provides rapid relief from symptoms, within one week of starting treatment and that efficacy is sustained over at least a six month period8. Pramipexole is highly efficacious at the starting dose of 0.125mg single dose per day and up to 0.75mg single dose per day9 and is well tolerated10,11. Data from one study have also suggested that pramipexole may also be effective in patients who have not tolerated other treatments, such as levodopa or other dopamine agonists12. These data, coupled with the new data presented today, form a comprehensive base of evidence confirming the real-life benefits that pramipexole may bring to patients with RLS.
The efficacy and tolerability of pramipexole in RLS continues to be investigated in a comprehensive ongoing clinical trials programme with more than 1,000 patients, to further assess the therapeutic potential in this condition. Boehringer Ingelheim, the discoverer of the molecule, has recently submitted for international approval of pramipexole in the treatment of Restless Legs Syndrome (RLS).
About pramipexole Pramipexole, a compound from Boehringer Ingelheim research, was jointly developed by Boehringer Ingelheim and Pharmacia Corp. (today Pfizer). Currently, pramipexole is approved for the treatment of the signs and symptoms of idiopathic Parkinson`s Disease, as monotherapy or in combination with levodopa.
About the European Flexible Does Study The European Flexible dose study is a multi-centre, double-blind, placebo controlled study. It was designed to evaluate efficacy and safety of pramipexole in a large population, in a clinical setting over a six week treatment period. The study included a total of 345 patients, from 37 centres, with idiopathic Restless Legs Syndrome. Patients were randomised to receive either pramipexole or placebo. The study had two primary endpoints: mean change from baseline in the RLSRS scale and responder status using the CGI-I score at week 6.
Notes • RLS o Restless Legs Syndrome RLS is a neurological disorder characterised by an uncontrollable urge to move the legs, usually accompanied by unpleasant and sometimes painful sensations in the legs. It is estimated that RLS affects up to one in ten of the population aged between 30 to 79 years4 and around one-third of sufferers experience symptoms more than twice weekly causing moderate to severe distress13. The motor-restlessness worsens during the evening and night causing difficulty initiating and maintaining sleep. The sleep disruption can lead to excessive daytime sleepiness and compromise work performance. RLS also has considerable impact on social activities that require immobility5,6. • IRLS o International RLS Rating Scale • CGI o Clinical Global Impression ScaleThe CGI scale is a clinical-rated instrument that consists of four subscales. The CGI-Improvement is traditionally used as an endpoint in clinical trials for responder analyses while the other subscales are less used. The global assessment of overall severity of illness, of the overall therapeutic effect and of interference of side effects with functioning, provides additional information of the overall effectiveness of a drug treatment • SF-36 o Short-form 36 items quality of life assessment
References: 1 Oertel W, Stiasny-Kolster K. Effective treatment of Restless Legs Syndrome (RLS) with pramipexole: Results of a 6 week, multi-centre, double blind and placebo controlled study. Presented 19 September 2005, 9th EFNS Congress, Athens, Greece; Abstract # P2205 2 Leissner L et al Pramipexole improves Quality of Life (QoL) in patients with Restless Legs Syndrome (RLS). Presented 19 September 2005, 9th EFNS Congress, Athens, Greece; Abstract # P2207 3 Hoegl B et al Clinical global impression- improvement (CGI-I) and patient global improvement (PGI) are equivalent and useful tools in measuring treatment effects in RLS patients. Presented 19 September 2005, 9th EFNS Congress, Athens, Greece; Abstract # P2202 4 Phillips B et al Epidemiology of restless legs symptoms in adults. Arch Intern Med 2000; 160(14): 2137-2141 5 Allen RP Earley CJ Restless legs syndrome: a review of clinical and pathophysiologic features. J Clin Neurophysiol 2001; 18(2): 128-147 6 Earley CJ Clinical practice. Restless legs syndrome. New Engl J Med 2003: 348(21) ; 2103-2109 7 L Abetz et al Evaluating the quality of life of patients with restless legs syndrome. Clinical Therapeutics 2004 26: 925-935. 8 Partinen et al Beneficial effect of PPX in RLS patients after 6 months treatment-Results from a prospective open label study; presented 22 June 2005, 1:30 - 2:15pm APSS 19th Annual Meeting, Denver, Colorado; Abstract, ID # 132978 9 Oertel W, Stiasny-Kolster K. Early and persistent effect of pramipexole in RLS patients already with the starting dose. Movement Disorders 2005, 20 (Suppl 10): S58 10 Silber MH et al Pramipexole in the management of restless legs syndrome. Sleep 2003; 26(7): 819-821 11 Ferini-Strambi L Restless legs syndrome augmentation and pramipexole treatment. Sleep Medicine 2002; 3(1): S23-S25. 12 Stiasny-Kolster K Oertel WH Low-dose pramipexole in the management of restless legs syndrome. An open-label trial. Neuropsychobiol 2004; 50(1): 65-70. 13 Hening W et al Impact, diagnosis and treatment of restless legs syndrome in a primary care population: the REST (RLS epidemiology, symptoms and treatment) primary care study. Sleep Med 2004; 5(3): 237-246
