O0044 On the definition of response, non-response and relapse to drug treatment in restless legs syndrome

Introduction: Several drug treatments for Restless Legs Syndrome (RLS) have been evaluated in clinical trials during the recent years, using mean changes from baseline. Especially in the context of augmentation and tolerance, but also to evaluate clinical relevance of drug-induced changes in outcome measures, a need for definition of qualitative treatment outcome is recognized. Based on IRLS data (International RLS Severity Scale) we propose the following categories: • Non-response (NR): condition unchanged or worsened compared to baseline; • Minimal improvement (MI): change >0% and 20% and 50% and <100%; • Remitter (R0): change 100%, symptom-free or IRLS total score <10 • Relapse (R10): worsening by at least 2 categories or NR during longterm therapy (e.g., after 3 months) compared to an at least moderate initial response (e.g., after 4 weeks). Methods: IRLS data from a double-blind, multi-center dose-finding study comparing 3 doses of the dopamine agonist lisuride in its transdermal application (1, 2, or 4mg/24 h lisuride) and placebo during a 12-week treatment period in 210 severely disabled RLS patients. Results: There was a clear dose–response relationship in the categories RS, R10, and R0 with increasing rates of patients with increasing dose. NR and MI occurred most frequently in the placebo group; in category MO, also the lowest lisuride dose was frequently present, indicating that efficacy was not sufficient to treat severely disabled RLS patients in this group. Under all lisuride treated patients, 7% fulfilled the criteria for relapse compared to 10% under placebo. Conclusions: Our classification should harmonize qualitative outcome research in RLS treatments. The response categories demonstrate the clinical relevance of treatment efficacy, analysis of non-response or poor efficacy is not yet addressed. The relapse definition might help to identify patients with augmentation and tolerance.