Objectives: To evaluate the safety and efficacy of oxybate for management of FMS. Oxybate is currently approved for the treatment of cataplexy in patients with narcolepsy. Since it provides restorative sleep, it was believed to have therapeutic potential for insomnia in FMS, but FMS is defined by pain, with an uncertain relationship to insomnia. A controlled clinical study by one investigator disclosed benefit in FMS, so a proof-of-principle study was designed, reviewed by the FDA, and conducted.
Methods: Patients with primary FMS [ACR criteria] were withdrawn from medications used to treat their FMS symptoms and were randomized to receive oxybate or matching placebo for 8 weeks. The dosage of oxybate was 4.5g or 6g per day, taken in 2 equally-divided doses [bedtime and 2.5-4 hours later]. The primary outcome variable [POV] was a composite of changes from baseline in three co-primary, self-report measures: Pain Visual Analog Scale [PVAS], captured with electronic diaries; Fibromyalgia Impact Questionnaire [FIQ]; and Patient Global Assessment [PGA]. A beneficial POV response was defined by 20% improvement in the PVAS and FIQ, plus “much better” or “very much better” on the PGA. Secondary outcome measures included changes in sleep quality [SLP], measured by the Jenkins scale, and in an examination measure of tenderness [the total Tender Point Count, TTP]. The prospectively planned intent-to-treat analyses examined changes from baseline. A post-hoc, linear correlation analysis sought a relationship between the PVAS and SLP.
Results: The intent-to-treat population included 188 patients [placebo, n=64; oxybate 4.5g, n=58; oxybate 6g, n=66], of whom 147 [78%] completed the trial. Significant benefit in the POV was seen with both doses of oxybate compared with placebo [illustrated by 4.5g, p=0.005]. Sleep quality [SLP] was improved with both dosages of oxybate [4.5g, p=0.004]. The TTP was significantly improved only with the 6g dose [p = 0.05]. A significant correlation was seen between change in PVAS and change in SLP [r=0.55, p<0.001]. Oxybate was well tolerated, as illustrated by the high rate of study completion. As expected, nausea and dizziness were oxybate dose-related [4.5g, 15% and 6.7%, respectively; placebo, 9.2% and 1.5%] but no unexpected adverse events were observed.
Conclusion: Oxybate therapy of FMS was safe and significantly improved the POV. It improved the major symptoms of FMS [pain, tenderness, insomnia]. The direct relationship between changes in pain and insomnia suggested that the improved quality of sleep induced by oxybate was responsible for the reduction in pain. Sodium oxybate represents a novel therapeutic option for the care of patients with FMS and warrants further study.