Criteria for Gauging Response to Sodium Oxybate for Narcolepsy

Our objective was to define responder criteria using an anchor-based approach for frequency of cataplexy attacks and excessive daytime sleepiness in narcolepsy patients undergoing sodium oxybate treatment. We used pooled data from two randomized, placebo-controlled, double blind, multi-center 4-week and 8-week trials of sodium oxybate for narcolepsy with cataplexy and analyzed using receiver operator characteristics analysis. Percent change in frequency of weekly cataplexy attacks and the Epworth Sleepiness Scale outcomes were compared to Clinical Global Impression of Change ratings, used as the anchor to define true response. Participants (n=336) were 39% male, 89% white, with a mean age of 41.5 (15.3), reporting a median of 20.5 cataplexy attacks per week and a mean Epworth Sleepiness score of 17.5 at baseline. A majority (51%) were much or very much improved based on Clinical Global Impression of Change ratings, considered a true response to treatment. Area under the curve values for % reduction in cataplexy attacks (77%) and % change in sleepiness score (78%) supported response definition thresholds of 46% and 12%, respectively. Classification using either response definition agreed with the anchor for approximately 71% of participants. Cataplexy response definition was more sensitive (Cataplexy=0.77, ESS=0.69) while sleepiness was more specific (Cataplexy=0.66, ESS=0.75). Both responder definitions showed a dose response relationship with sodium oxybate demonstrating their validity using an external criterion. Weekly cataplexy attacks and ESS can be used to help document clinical response to narcolepsy treatment using criteria of 46% and 12% reductions, respectively.