Sodium oxybate (SXB) is a drug sold as Xyrem in the United States by Jazz Pharmaceuticals, in Europe by UCB Pharma, and in Canada by Valeant Pharmaceuticals. It is approved in the United States in adults for the treatment of excessive daytime sleepiness (EDS) and cataplexy associated with narcolepsy (NwC) or the EDS associated with narcolepsy without cataplexy (Nw/oC), in Europe for the treatment of only NwC, and in Canada for EDS associated with narcolepsy. Xyrem is also being studied for different indications, such as for narcolepsy in children and adolescents and for chronic fatigue syndrome. A different formulation of SXB is being studied as a once-a-night dose for the treatment of narcolepsy by Flamel Technologies. SXB has not previously been studied for the treatment of idiopathic hypersomnia (IH).
Who were the research participants and what did they do?
Forty-six patients with IH and 47 patients with narcolepsy type 1 (narcolepsy with cataplexy or hypocretin deficiency or both; N1) underwent overnight polysomnography followed by a five-nap Multiple Sleep Latency Test (MSLT). Most of the patients with IH had their sleep monitored for an extended period of time after their MSLT, as did some of the patients with N1. All of the patients also completed Epworth Sleepiness Scales and had their HLA status determined.
Who were the researchers and what did they do?
Dr. Leu-Semenescu and her colleagues treat more than 300 patients with IH at their national referral center for IH in Paris. In 2012, they began prescribing SXB to patients with IH on a compassionate use basis. They recently reviewed the medical records of all patients at their center with IH and N1 who were treated with SXB. They compared polysomnography and MSLT findings, HLA typing, and questionnaire results between both groups of patients.
What were the results of the study?
People with IH took, on average, 3.2 different stimulants before trying SXB, as compared with 2.2 in the N1 group. At baseline, before they were treated with SXB, all of the people with IH had sleep inertia; with treatment, 71% of them had an improvement in sleep inertia. The people with N1 were slightly sleepier before treatment with SXB (N1: 17.7 vs IH: 15.7, ESS scores), but ESS scores fell to a similar level after treatment in both groups (13.9 vs 13). People with IH were more likely to take only one nightly dose of SXB (66%) than were those with N1 (21%) and were also more likely to continue treatment with SXB (47% vs 32%). More people with IH, as compared with those with N1, reported a good to very good response on SXB (IH: 65% vs N1: 48%). People with IH, as compared with those with N1, were also more likely to report an impact on sleep inertia (71% vs 43%), decreased sleep-onset latency (67% vs 50%), and shortened night-time sleep (52% vs 17%).
What were the authors’ conclusions?
“In this chart review, we found that SXB treatment improved sleepiness in IH to the same degree as it did in narcolepsy, but it also improved some extremely disabling symptoms proper to IH, including severe morning inertia, difficulty falling asleep at night, and prolonged sleep time duration. This important benefit was counterbalanced by an average safety profile, with frequent nausea and dizziness. Overall, half of the patients with IH, all refractory to other stimulants, continued the SXB treatment for the long term because of a favorable benefit/risk ratio. This study should help clinicians treat difficult patients with IH and should prompt pharmaceutical companies to design large size, placebo-controlled studies for this poorly studied condition.”
Leu-Semenescu S, Louis P, Arnulf I. Benefits and risk of sodium oxybate in idiopathic hypersomnia versus narcolepsy type 1: a chart review. Sleep Med 2015.