Sodium oxybate therapy provides multidimensional improvement in fibromyalgia: results of an international phase 3 trial
- 1Rheumatologische Schwerpunktpraxis, Gräfelfing, Germany
- 2Fibromyalgia Research Unit, Oregon Health and Science University, Portland, Oregon, USA
- 3Jazz Pharmaceuticals, Palo Alto, California, USA
- 4Cardiff University School of Medicine, Cardiff, UK
- Correspondence to Michael Spaeth, Rheumatologische Schwerpunktpraxis, Bahnhofstrasse 95, Gräfelfing, Munich 82166, Germany;
Contributors MS, RMB and EHC collected or assembled data. EHC, RMB, CL, MS, BAB and YGW undertook or supervised analysis and interpretation of data. CL conducted statistical analysis. MS, RMB, EHC, BAB and YGW contributed to the writing of the manuscript. All authors had access to the data, contributed substantially to the writing of the report and reviewed and approved the final draft. MS had final responsibility for the decision to submit this manuscript for publication.
- Received 6 July 2011
- Accepted 29 November 2011
- Published Online First 31 January 2012
Background Fibromyalgia 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.
Methods 573 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.
Results Significant 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.
Conclusion These 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.
Funding This study and report was sponsored and funded by Jazz Pharmaceuticals, Inc.
Competing interests MS, RMB and EHC are consultants to and have received research support from Jazz Pharmaceuticals for this study. MS has also acted as a consultant to Allergan and has been a consultant and participated on the speakers' bureaux of Eli Lilly, Pierre Fabre Médicament, Pfizer and UCB. RMB has also acted as a consultant to Cypress Bioscience, Eli Lilly and Pfizer, and has received research support from Merck and Schwarz Pharma. BAB, YGW and CL are employees and stockholders of Jazz Pharmaceuticals. EHC has also acted as a consultant to and has been a member of the speakers' bureaux of Abbott Laboratories, Chugai Pharma, Eli Lilly, MSD, Pfizer, Pierre Fabre Médicament, Roche and UCB, and has been a consultant to Allergan, AstraZeneca, Boehringer Ingelheim, Chelsea Therapeutics, GlaxoSmithKline, Merrimack Pharmaceutical, Schering Plough, Synovate and UCB Celltech. His institution has received research support from Chelsea Therapeutics, Chugai Pharma, Jazz Pharmaceuticals, MSD, Pfizer, Roche and UCB. The lead/corresponding author had final responsibility for the decision to submit this manuscript for publication.
Ethics approval This study was approved by the ethics committee or institutional review board of each study site.
Patient consent Obtained.
Study investigators France: P Hatron, S Perrot, B Rioult, E Serra, N Cantagrel, M Lanteri-Minet, A Dumolard. Germany: R Alten, U Jaeger, G Neeck, F Petzke, M Spaeth, T Weiss, W Sohn, B Wiedeking, H Zug. Italy: L Bazzichi, P Sarzi Puttini. The Netherlands: M van de Laar, R van Seventer. Poland: J Brzezicki, A Filipowicz-Sosnowska, S Jeka, E Kucharz, W Samborski, M Brzosko. Spain: C Alegre, A Fernandez Nebro, F Francisco, J Gomez-Reino, V Poca, R Queiro, A Rodriguez de la Serna, J Vidal. UK: A Adebajo, A Bhalla, E Choy, D Walker, S Richards, P Taylor, K Adams. USA: P Alder, R DiGiovanni, AE Massey, E Ekman, N Feldman, J Fidelholtz, O Florete, HS Fung, W George, A Goldstein, D Haselwood, D Johnson, L Lavelle, B Long, P Manolukas, V Mehra, D Mehta, L Perez-Limonte, D Sikes, J Silverfield, M Tark, D Weiss, C Wiesenhutter, H Williams, J Winfield, K Hackshaw, G Forde, T Johnson, JK Schwab, M McNett, R Bennett, S Sitar, M Abeles, N Rosenthal, B Cleeremans, M Barber, R Nielsen, R Ziman, M Dempsey, M Colvard, M Liebowitz, J Greenwald, R Staud, A Ellenbogen, P Mease, E Walko, K Willingham, S Silverman, S Choi, J Borders, R Guthrie, T Swick, D Young, R Rauck, T Wade, T Smith, C Curtis, D Ferrera, T Sligh, L Sharp, S Flitman, S Cohen, M Hassman, JD Hudson, R Pucillo, M Hagen, M Dunn.
Provenance and peer review Not commissioned; externally peer reviewed
This paper is freely available online under the BMJ Journals unlocked scheme, see http://ard.bmj.com/info/unlocked.dtl