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Xiao Zhang,1 Huji Xu,2 Zhiyi Zhang,3 Yang Li,4 Lynne Pauer,5 Shanmei Liao,6 Fengchun Zhang7 1Department of Rheumatology, Guangdong General Hospital, Guangdong, People’s Republic of China; 2Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Affiliated to Second Military Medical University, Shanghai, People’s Republic of China; 3School of Clinical Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Department of Rheumatology and Immunology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 5Global Research and Development, Pfizer, Groton, CT, USA; 6Pfizer China Statistics Department, Global Innovative Pharma Business, Shanghai, People’s Republic of China; 7Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, People’s Republic of ChinaCorrespondence: Fengchun ZhangPeking Union Medical College Hospital, No. 9, Dongdan Santiao, Dongcheng District, Beijing, People’s Republic of ChinaTel/Fax +8610-69155416Email zhangfccra@aliyun.comPurpose: 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.ClinicalTrials.gov Identifier: NCT01387607.Keywords: China, chronic pain, FM, Lyrica, pain management, sleep

Primary efficacy measure of this 13-week randomized clinical trial of pregabalin 600 mg/d (BID) as treatment of painful DPN was endpoint (EP) mean pain score (MPS) on an 11-point numeric rating scale (NRS) derived from patients' daily pain diaries. Secondary efficacy measures included weekly MPS and EP and weekly sleep-interference scores (on an 11-point NRS). Primary safety endpoints were amplitude and conduction velocity for 4 nerves (median-motor, median-sensory, ulnar-sensory, and peroneal-motor) assessed at baseline (BL), EP, and 2-week follow-up. 82 patients were randomized to pregabalin, 85 to placebo (PBO). After 1-week dose escalation, pregabalin patients received 600 mg/d for 12 weeks. EP MPS was significantly lower in pregabalin treated patients than in PBO-treated patients (mean difference, - 1.28; P=.0003). Significant pain improvement among pregabalin patients was evident at Week 1 and every weekly timepoint thereafter. Pregabalin was statistically significantly superior to PBO for reducing pain-related sleep-interference score at every weekly timepoint (except Weeks 9,10) and at EP (mean difference, - 1.08; P=.0019). No statistically significant differences in amplitude or velocity were observed for any of the 4 nerves tested. In an open-label (OL) extension of this trial, patients received 150-600 mg/d pregabalin (BID), adjusted to optimize efficacy and tolerability, for up to 6 months. 97% of patients received dosages of ≥300 mg/d. Pregabalin was generally well tolerated, with 70/104 patients completing 24 weeks of treatment. 15 patients (14%) withdrew from OL treatment because of AEs. Peripheral edema, dizziness, and somnolence were the most common AEs associated with treatment. In conclusion, pregabalin 600 mg/d (BID) showed robust and sustained efficacy in pain improvement with no meaningful effect on nerve conduction during 13 weeks of double-blind treatment. Pregabalin was generally well tolerated during both 13-week double-blind and 6-month OL treatment. [ABSTRACT FROM AUTHOR]

Objective: There is increasing demand for prediction of chronic pain treatment outcomes using machine-learning models, in order to improve suboptimal pain management. In this exploratory study, we used baseline brain functional connectivity patterns from chronic pain patients with fibromyalgia (FM) to predict whether a patient would respond differentially to either milnacipran or pregabalin, 2 drugs approved by the US Food and Drug Administration for the treatment of FM., Methods: FM patients participated in 2 separate double-blind, placebo-controlled crossover studies, one evaluating milnacipran (n = 15) and one evaluating pregabalin (n = 13). Functional magnetic resonance imaging during rest was performed before treatment to measure intrinsic functional brain connectivity in several brain regions involved in pain processing. A support vector machine algorithm was used to classify FM patients as responders, defined as those with a ≥20% improvement in clinical pain, to either milnacipran or pregabalin., Results: Connectivity patterns involving the posterior cingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC) individually classified pregabalin responders versus milnacipran responders with 77% accuracy. Performance of this classification improved when both PCC and DLPFC connectivity patterns were combined, resulting in a 92% classification accuracy. These results were not related to confounding factors, including head motion, scanner sequence, or hardware status. Connectivity patterns failed to differentiate drug nonresponders across the 2 studies., Conclusion: Our findings indicate that brain functional connectivity patterns used in a machine-learning framework differentially predict clinical response to pregabalin and milnacipran in patients with chronic pain. These findings highlight the promise of machine learning in pain prognosis and treatment prediction., (© 2021 Pfizer. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: Pregabalin, an α2-δ agonist, is approved for the treatment of fibromyalgia (FM) in the United States, Japan, and 37 other countries. The purpose of this article was to provide an in-depth, evidence-based summary of pregabalin for FM as demonstrated in randomized, placebo-controlled clinical studies, including open-label extensions, meta-analyses, combination studies and post-hoc analyses of clinical study data., Methods: PubMed was searched using the term "pregabalin AND fibromyalgia" and the Cochrane Library with the term "pregabalin". Both searches were conducted on 2 March 2017 with no other date limits set., Results: Eleven randomized, double-blind, placebo-controlled clinical studies were identified including parallel group, two-way crossover and randomized withdrawal designs. One was a neuroimaging study. Five open-label extensions were also identified. Evidence of efficacy was demonstrated across the studies identified with significant and clinically relevant improvements in pain, sleep quality and patient status. The safety and tolerability profile of pregabalin is consistent across all the studies identified, including in adolescents, with dizziness and somnolence the most common adverse events reported. These efficacy and safety data are supported by meta-analyses (13 studies). Pregabalin in combination with other pharmacotherapies (7 studies) is also efficacious. Post-hoc analyses have demonstrated the onset of pregabalin efficacy as early as 1-2 days after starting treatment, examined the effect of pregabalin on other aspects of sleep beyond quality, and shown it is effective irrespective of the presence of a wide variety of patient demographic and clinical characteristics., Conclusions: Pregabalin is a treatment option for FM; its clinical utility has been comprehensively demonstrated.