Efficacy and Safety of Pregabalin for Fibromyalgia in a Population of Chinese Subjects

Xiao Zhang, Huji Xu, Zhiyi Zhang, Yang Li, Lynne Pauer, Shanmei Liao, Fengchun Zhang, Xiao Zhang, Huji Xu, Zhiyi Zhang, Yang Li, Lynne Pauer, Shanmei Liao, Fengchun Zhang

Abstract

Purpose: Fibromyalgia (FM) may go underdiagnosed and untreated in China in part due to a lack of awareness and understanding of the condition, and limited available treatments.

Patients and methods: This randomized, double-blind, Phase III local registration trial compared the efficacy and safety of pregabalin (flexibly dosed 300-450 mg/day) versus placebo for the management of pain in Chinese adults diagnosed with FM according to American College of Rheumatology 1990 criteria, across 22 centers within China. Patients reported pain score of ≥40 mm on 100-mm scale (from 0 "no pain" to 100 "worst possible pain"). The primary efficacy endpoint was change from baseline to Week 14 in mean pain score (MPS). Secondary endpoints included measures of sleep and sleep interference. Safety and tolerability were monitored throughout.

Results: Median pregabalin dose was 335 mg/day. A significant reduction from baseline to Week 14 in weekly MPS was seen for patients treated with pregabalin (n=170) versus placebo (n=164) (least-squares mean difference [95% confidence interval]: -0.73 [-1.10 to -0.36]; P=0.0001). Significantly greater proportions of patients experienced ≥30% and ≥50% reductions in MPS at Week 14 with pregabalin versus placebo. Pregabalin-treated subjects demonstrated improvements in measures of sleep and sleep interference. Pregabalin was generally well tolerated. The most common adverse events were dizziness and somnolence; no serious adverse events (SAEs) occurred in pregabalin-treated subjects. Nine placebo-treated subjects experienced SAEs.

Conclusion: Pregabalin (300-450 mg/day) is a safe and effective treatment for reducing pain and improving sleep in native Chinese subjects with FM.

Clinicaltrialsgov identifier: NCT01387607.

Keywords: China; FM; Lyrica; chronic pain; pain management; sleep.

Conflict of interest statement

LP is an employee of Pfizer and has stock options in Pfizer. SL was employed by Pfizer during the study and initial development of the manuscript. All other authors were investigators of the study and have no conflicts of interest to declare regarding the content of this article.

© 2021 Zhang et al.

Figures

Figure 1
Figure 1
Patient dispositiona.
Figure 2
Figure 2
Change from baseline in weekly mean pain score (FAS, MMRM). *All P<0.05 vs placebo.

References

    1. Branco JC, Bannwarth B, Failde I, et al. Prevalence of fibromyalgia: a survey in five European countries. Semin Arthritis Rheum. 2010;39(6):448–453. doi:10.1016/j.semarthrit.2008.12.003
    1. Carmona L, Ballina J, Gabriel R, Laffon A. The burden of musculoskeletal diseases in the general population of Spain: results from a national survey. Ann Rheum Dis. 2001;60(11):1040–1045. doi:10.1136/ard.60.11.1040
    1. Walitt B, Nahin RL, Katz RS, Bergman MJ, Wolfe F. The prevalence and characteristics of fibromyalgia in the 2012 National Health Interview Survey. PLoS One. 2015;10(9):e0138024. doi:10.1371/journal.pone.0138024
    1. Wolfe F, Brahler E, Hinz A, Hauser W. Fibromyalgia prevalence, somatic symptom reporting, and the dimensionality of polysymptomatic distress: results from a survey of the general population. Arthritis Care Res. 2013;65(5):777–785. doi:10.1002/acr.21931
    1. McNally JD, Matheson DA, Bakowsky VS. The epidemiology of self-reported fibromyalgia in Canada. Chronic Dis Can. 2006;27(1):9–16.
    1. Queiroz LP. Worldwide epidemiology of fibromyalgia. Curr Pain Headache Rep. 2013;17(8):356. doi:10.1007/s11916-013-0356-5
    1. Schaefer C, Mann R, Masters ET, et al. The comparative burden of chronic widespread pain and fibromyalgia in the United States. Pain Pract. 2016;16(5):565–579. doi:10.1111/papr.12302
    1. Wolfe F, Clauw DJ, Fitzcharles MA, et al. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 2016;46(3):319–329. doi:10.1016/j.semarthrit.2016.08.012
    1. Wolfe F, Clauw DJ, Fitzcharles MA, et al. The American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia and Measurement of Symptom Severity. Arthritis Care Res. 2010;62(5):600–610. doi:10.1002/acr.20140
    1. Wolfe F, Walitt B. Culture, science and the changing nature of fibromyalgia. Nat Rev Rheumatol. 2013;9(12):751–755. doi:10.1038/nrrheum.2013.96
    1. Arnold LM, Clauw DJ, Dunegan LJ, Turk DC. A framework for fibromyalgia management for primary care providers. Mayo Clin Proc. 2012;87(5):488–496. doi:10.1016/j.mayocp.2012.02.010
    1. Arnold LM, Clauw DJ, McCarberg BH. Improving the recognition and diagnosis of fibromyalgia. Mayo Clin Proc. 2011;86(5):457–464. doi:10.4065/mcp.2010.0738
    1. Choy E, Perrot S, Leon T, et al. A patient survey of the impact of fibromyalgia and the journey to diagnosis. BMC Health Serv Res. 2010;10:102. doi:10.1186/1472-6963-10-102
    1. Mist SD, Jones KD. Randomized controlled trial of acupuncture for women with fibromyalgia: group acupuncture with traditional Chinese medicine diagnosis-based point selection. Pain Med. 2018;19(9):1862–1871. doi:10.1093/pm/pnx322
    1. Mist S, Wright C, Jones KD, Carson JW, Shih J. Traditional Chinese medicine for fibromyalgia. Pract Pain Manag. 2010;10(7):1–7.
    1. Mist SD, Wright CL, Jones KD, Carson JW. Traditional Chinese medicine diagnoses in a sample of women with fibromyalgia. Acupunct Med. 2011;29(4):266–269. doi:10.1136/acupmed-2011-010052
    1. Russell IJ. The prevalence of the fibromyalgia syndrome in China. J Musculoskelet Pain. 2006;14(2):1–2.
    1. Scudds RA, Li EKM, Scudds RJ. The prevalence of fibromyalgia syndrome in Chinese people in Hong Kong. J Musculoskelet Pain. 2006;14(2):3–11. doi:10.1300/J094v14n02_02
    1. Mu R, Li C, Zhu JX, et al. National survey of knowledge, attitude and practice of fibromyalgia among rheumatologists in China. Int J Rheum Dis. 2013;16(3):258–263. doi:10.1111/1756-185X.12055
    1. Lyrica® (pregabalin), capsule and solution [prescribing information]. New York: Pfizer Inc; 2004.
    1. Pfizer Japan Inc, Eisai Co, Ltd [Internet]. New indication approved in Japan for Lyrica® capsules; 2013. Available from: . Accessed August28, 2020.
    1. Häuser W, Walitt B, Fitzcharles M-A, Sommer C. Review of pharmacological therapies in fibromyalgia syndrome. Arthritis Res Ther. 2014;16(1):201. doi:10.1186/ar4441
    1. Arnold LM, Russell IJ, Diri EW, et al. A 14-week, randomized, double-blinded, placebo-controlled monotherapy trial of pregabalin in patients with fibromyalgia. J Pain. 2008;9(9):792–805. doi:10.1016/j.jpain.2008.03.013
    1. Crofford LJ, Rowbotham MC, Mease PJ, et al. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2005;52(4):1264–1273. doi:10.1002/art.20983
    1. Mease PJ, Russell IJ, Arnold LM, et al. A randomized, double-blind, placebo-controlled, phase III trial of pregabalin in the treatment of patients with fibromyalgia. J Rheumatol. 2008;35(3):502–514.
    1. Ohta H, Oka H, Usui C, Ohkura M, Suzuki M, Nishioka K. A randomized, double-blind, multicenter, placebo-controlled phase III trial to evaluate the efficacy and safety of pregabalin in Japanese patients with fibromyalgia. Arthritis Res Ther. 2012;14(5):R217. doi:10.1186/ar4056
    1. Pauer L, Winkelmann A, Arsenault P, et al. An international, randomized, double-blind, placebo-controlled, phase III trial of pregabalin monotherapy in treatment of patients with fibromyalgia. J Rheumatol. 2011;38(12):2643–2652. doi:10.3899/jrheum.110569
    1. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 1990;33(2):160–172. doi:10.1002/art.1780330203
    1. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum. 1995;38(1):19–28. doi:10.1002/art.1780380104
    1. Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001;94(2):149–158. doi:10.1016/S0304-3959(01)00349-9
    1. Arnold LM, Whitaker S, Hsu C, Jacobs D, Merante D. Efficacy and safety of mirogabalin for the treatment of fibromyalgia: results from three 13-week randomized, double-blind, placebo- and active-controlled, parallel-group studies and a 52-week open-label extension study. Curr Med Res Opin. 2019;35(10):1825–1835. doi:10.1080/03007995.2019.1629757
    1. Clauw DJ, Mease P, Palmer RH, Gendreau RM, Wang Y. Milnacipran for the treatment of fibromyalgia in adults: a 15-week, multicenter, randomized, double-blind, placebo-controlled, multiple-dose clinical trial. Clin Ther. 2008;30(11):1988–2004. doi:10.1016/j.clinthera.2008.11.009
    1. Lian YN, Wang Y, Zhang Y, Yang CX. Duloxetine for pain in fibromyalgia in adults: a systematic review and a meta-analysis. Int J Neurosci. 2020;130(1):71–82. doi:10.1080/00207454.2019.1664510
    1. Han M, Cui J, Xiao Y, et al. Acupuncture for primary fibromyalgia: study protocol of a randomized controlled trial. Trials. 2020;21(1):538. doi:10.1186/s13063-020-04317-y
    1. Cao H, Liu J, Lewith GT. Traditional Chinese medicine for treatment of fibromyalgia: a systematic review of randomized controlled trials. J Altern Complement Med. 2010;16(4):397–409. doi:10.1089/acm.2009.0599
    1. Galvez-Sánchez CM, Reyes Del Paso GA. Diagnostic criteria for fibromyalgia: critical review and future perspectives. J Clin Med. 2020;9(4):1219. doi:10.3390/jcm9041219
    1. Sarzi-Puttini P, Atzeni F, Masala IF, Salaffi F, Chapman J, Choy E. Are the ACR 2010 diagnostic criteria for fibromyalgia better than the 1990 criteria? Autoimmun Rev. 2018;17(1):33–35. doi:10.1016/j.autrev.2017.11.007
    1. Vanderschueren S, Van Wambeke P, Morlion B. Fibromyalgia: do not give up the tender point count too easily: comment on the article by Wolfe et al. Arthritis Care Res (Hoboken). 2010;62(11):1675. doi:10.1002/acr.20293
    1. Guang’anmen Hospital of China Academy of Chinese Medical Sciences [Internet]. Chinese version of fibromyalgia criteria and severity scales study. Available from: . Accessed December11, 2020.
    1. Finan PH, Goodin BR, Smith MT. The association of sleep and pain: an update and a path forward. J Pain. 2013;14(12):1539–1552. doi:10.1016/j.jpain.2013.08.007
    1. Klinger R, Stuhlreyer J, Schwartz M, Schmitz J, Colloca L. Clinical use of placebo effects in patients with pain disorders. Int Rev Neurobiol. 2018;139:107–128.
    1. Enck P, Klosterhalfen S, Weimer K, Horing B, Zipfel S. The placebo response in clinical trials: more questions than answers. Philos Trans R Soc Lond B Biol Sci. 2011;366(1572):1889–1895. doi:10.1098/rstb.2010.0384
    1. Serpell M, Latymer M, Almas M, Ortiz M, Parsons B, Prieto R. Neuropathic pain responds better to increased doses of pregabalin: an in-depth analysis of flexible-dose clinical trials. J Pain Res. 2017;10:1769–1776.
    1. Freynhagen R, Baron R, Kawaguchi Y, et al. Pregabalin for neuropathic pain in primary care settings: recommendations for dosing and titration. Postgrad Med. 2021;133(1):1–9. doi:10.1080/00325481.2020.1857992
    1. Laursen DRT, Paludan-Muller AS, Hrobjartsson A. Randomized clinical trials with run-in periods: frequency, characteristics and reporting. Clin Epidemiol. 2019;11:169–184. doi:10.2147/CLEP.S188752
    1. Silverman SL, Backonja M, Pauer L, et al. Effect of baseline characteristics on the pain response to pregabalin in fibromyalgia patients with comorbid depression. Pain Med. 2018;19(3):419–428. doi:10.1093/pm/pnx091

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere