Sodium oxybate therapy provides multidimensional improvement in fibromyalgia: results of an international phase 3 trial

Abstract

BackgroundFibromyalgia is characterised by chronic musculoskeletal pain and multiple symptoms including fatigue, multidimensional function impairment, sleep disturbance and tenderness. Along with pain and fatigue, non-restorative sleep is a core symptom of fibromyalgia. Sodium oxybate (SXB) is thought to reduce non-restorative sleep abnormalities. This study evaluated effects of SXB on fibromyalgia-related pain and other symptoms.Methods573 patients with fibromyalgia according to 1990 American College of Rheumatology criteria were enrolled at 108 centres in eight countries. Subjects were randomly assigned to placebo, SXB 4.5 g/night or SXB 6 g/night. The primary efficacy endpoint was the proportion of subjects with ≥30% reduction in pain visual analogue scale from baseline to treatment end. Other efficacy assessments included function, sleep quality, effect of sleep on function, fatigue, tenderness, health-related quality of life and subject's impression of change in overall wellbeing.ResultsSignificant improvements in pain, sleep and other symptoms associated with fibromyalgia were seen in SXB treated subjects compared with placebo. The proportion of subjects with ≥30% pain reduction was 42.0% for SXB4.5 g/night (p=0.002) and 51.4% for SXB6 g/night (p<0.001) versus 26.8% for placebo. Quality of sleep (Jenkins sleep scale) improved by 20% for SXB4.5 g/night (p≤0.001) and 25% for SXB6 g/night (p≤0.001) versus 0.5% for placebo. Adverse events with an incidence ≥5% and twice placebo were nausea, dizziness, vomiting, insomnia, anxiety, somnolence, fatigue, muscle spasms and peripheral oedema.ConclusionThese results, combined with findings from previous phase 2 and 3 studies, provide supportive evidence that SXB therapy affordsimportant benefits across multiple symptoms in subjects with fibromyalgia.

Fibromyalgia Syndrome: Novel Therapeutic Targets

“…In view of evidence indicating a positive effect of this compound on the quality and quantity of slow wave sleep [84] it has repeatedly been studied for the treatment of FMS. Thus, in an international Phase III trial recruiting 573 patients, sodium oxybate treatment was associated with multidimensional improvement in FMS symptoms, including pain and sleep [85]. While this and other studies on sodium oxybate raised considerable hopes regarding the potential of this medication [86,87], serious concerns regarding the safety and abuse potential of this medication have hampered its further development which currently does not appear to be likely [88].…”

Recent strategies for drug development in fibromyalgia syndrome

“…Each used a primary endpoint of ≥30% reduction of pain by the visual analog scale (VAS) at week 14 of treatment. Both studies [11,12] demonstrated that significantly more patients achieved the primary endpoint in both dosage options for sodium oxybate compared to placebo, as well as for improvement in several secondary endpoints. However, when the data from these clinical trials was presented to an advisory committee of the FDA on August 20, 2010 the request to allow sodium oxybate to be prescribed for FMS was rejected by a vote of 20-2.…”

Current Treatments to Counter Sleep Dysfunction as a Pathogenic Stimulus of Fibromyalgia

“…Hitherto, it is the only treatment, which has been trialed in fibromyalgia that targets specifically sleep dysfunction. Several randomized placebo-controlled trials of sodium oxybate have been conducted in fibromyalgia [67][68][69][70]. Sodium oxybate reduced sleep disturbance and fatigue with a medium effect size.…”