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Kazutaka Nozawa,1 Yusuke Karasawa,1 Yuka Shidahara,2 Takahiro Ushida3 1Medical Affairs, Viatris Pharmaceuticals Japan Inc., Minato-ku, Tokyo, Japan; 2Bioscience Business Division, KAC Co., Ltd, Ritto, Shiga, Japan; 3Multidisciplinary Pain Center, Aichi Medical University, Nagakute, Aichi, JapanCorrespondence: Kazutaka Nozawa, Medical Affairs, Viatris Pharmaceuticals Japan Inc, Minato-ku, Tokyo, Japan, Tel +81 80-5001-3029, Email Kazutaka.Nozawa@viatris.comPurpose: Neuropathic pain is sometimes difficult to manage because of limited efficacy of analgesic monotherapy even at high doses. Combination therapy may help address this issue, but there is little evidence for its effectiveness. Therefore, we evaluated the efficacy of combination therapy with pregabalin, an anchor drug for treating neuropathic pain, using the rat L5 spinal nerve ligation model.Methods: Experiments were performed on four-week-old L5 spinal nerve ligated male Sprague-Dawley rats. Mechanical allodynia was assessed using the von Frey test, where the 50% withdrawal threshold was evaluated for five drugs: pregabalin, duloxetine, venlafaxine, tramadol, and celecoxib. The single-drug experiment included 112 rats, where each drug was tested independently. Median effective doses (ED50s) were determined. Combinations of pregabalin with each of the other four drugs were tested (n=84). The 50% withdrawal threshold in the von Frey test was evaluated. The ED50 of each combination was determined experimentally. Isobolographic analyses were conducted to assess the synergistic potential of the drug combinations, excluding pregabalin-celecoxib, since the ED50 of celecoxib could not be determined.Results: In the single-drug experiment, all drugs except celecoxib resulted in a dose-dependent increase in the 50% withdrawal threshold 2 h after administration, with a maximum possible effect ranging from 4.4% to 79.6%. Similarly, all pregabalin combinations demonstrated a dose-dependent increase in the 50% withdrawal t

Toshihiko Taguchi,1 Shogo Nakano,2 Kazutaka Nozawa2 1Japan Organization of Occupational Health and Safety, Yamaguchi Rosai Hospital, Sanyo-Onoda, Yamaguchi, Japan; 2Pfizer Japan, Inc., Tokyo, JapanCorrespondence: Kazutaka Nozawa Email kazutaka.nozawa@pfizer.comPurpose: Neuropathic pain (NeP) is common among patients with chronic pain associated with spine diseases. Practical effectiveness of pregabalin, one of the first-line treatments for NeP, has not been evaluated in an entire population of patients with spine diseases, including various pathophysiological conditions. This pooled analysis aimed to evaluate the therapeutic value of pregabalin for chronic pain with NeP component in patients with spine diseases in routine primary care settings.Patients and Methods: We pooled data from two 8-week prospective observational cohort studies for patients with chronic low back pain with accompanying lower limb pain (NeP component), and patients with chronic cervical pain and accompanying upper limb radiating pain (NeP component) in routine primary care settings in Japan. For both studies, patients were treated for 8 weeks with pregabalin (alone/with other analgesics) or usual care with conventional analgesics (eg, non-steroidal anti-inflammatory drugs). Changes in pain numerical rating scale (NRS), Pain-Related Sleep Interference Scale (PRSIS), and EuroQol 5-dimension 5-level (EQ-5D-5L) scores from baseline to week 8 were summarized and compared between the pregabalin and usual care groups, and also for subgroups of primary diagnosis. Safety was evaluated by adverse events (AEs) in the pregabalin group.Results: The pooled dataset comprised 700 patients (pregabalin group: 302; usual care group: 398). All patient-reported outcomes (PRO) scores significantly improved from baseline to week 8 in the pregabalin than in the usual care group (NRS: P< 0.0001; PRSIS: P< 0.0001, and EQ-5D-5L: P=0.0006). Overall, all three PRO measures showed greater improvement in the p

Toshihiko Taguchi,1 Kazutaka Nozawa,2 Shigeki Zeniya,3 Tatsunori Murata,3 Thomas Laurent,4 Takahiro Hirano,4 Koichi Fujii2 1Japan Organization of Occupational Health and Safety, Yamaguchi Rosai Hospital, Sanyo-Onoda, Yamaguchi, Japan; 2Medical Affairs, Pfizer Japan Inc, Tokyo, Japan; 3CRECON Medical Assessment Inc., Tokyo, Japan; 4Clinical Study Support, Inc, Nagoya, JapanCorrespondence: Kazutaka NozawaPfizer Japan Inc., Shibuya Bunka Quint Bldg., 22-7, Yoyogi 3-chome, Shibuya-ku, Tokyo, 150-8589, JapanTel +81-3-5309-7000Email kazutaka.nozawa@pfizer.comBackground: Chronic low back pain or chronic cervical pain often has a neuropathic pain (NeP) component and patients with these conditions complain of sleep deprivation, loss of physical function, and reduced productivity due to pain. The objective of this study was to clarify the pathway by which pain, sleep disturbance due to pain, and physical function status influence QOL measures in chronic low back pain patients with NeP associated with lumbar spine diseases (CLBP-NeP) and in chronic cervical pain patients with NeP associated with cervical spine diseases (CCP-NeP).Methods: A model assuming pain numeric rating scale (NRS), pain-related sleep interference scale (PRSIS), and functional indices (Roland Morris Disability Questionnaire [RMDQ], Neck Disability index [NDI]) as factors that can affect outcomes such as QOL (calculated using EuroQoL 5 Dimensions (EQ-5D)), the Patient Global Impression of Change (PGIC), and the Clinical Global Impression of Change (CGIC) was developed using structural equation modeling.Results: Overall trends were frequently observed in both patients with CLBP-NeP and CCP-NeP. Pain NRS had the largest comprehensive direct impact on QOL based on EQ-5D and an overall impression of changing symptoms. The effects of pain NRS on each outcome were largely due to direct pain-related effects; however, for EQ-5D, an indirect effect via functional improvement was the primary factor.Conclusion: Althou

Toshihiko Taguchi,1 Kazutaka Nozawa,2 Bruce Parsons,3 Tamotsu Yoshiyama,4 Nozomi Ebata,2 Ataru Igarashi,5 Koichi Fujii21Japan Organization of Occupational Health and Safety, Yamaguchi Rosai Hospital, Sanyo-Onoda, Yamaguchi, Japan; 2Medical Affairs, Pfizer Japan Inc, Tokyo, Japan; 3Global Medical Product Evaluation, Pfizer Inc, New York, NY, USA; 4Biometrics and Data Management, Development Japan, Pfizer R&D Japan G.K., Tokyo, Japan; 5Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, JapanBackground: Despite high prevalence of chronic neck pain in Japan and the negative impact pain has on patient’s quality of life (QoL), the therapeutic value of pregabalin for chronic neck pain with a neuropathic pain (NeP) component has not been assessed in a typical Japanese health care setting.Methods: An 8-week, non-interventional, multicenter, observational study of Japanese adults (≥20 years) with chronic refractory cervical pain including a NeP element (for ≥12 weeks) and sleep disturbance on the Pain-Related Sleep-Interference Scale (PRSIS) ≥1 (from 0 “does not interfere with sleep” to 10 “completely interferes”). Patients received either usual care with conventional analgesics or pregabalin (150–600 mg/day) for 8 weeks. “Usual care” with analgesics or other treatment(s) was determined based on physician’s best clinical judgment. Primary endpoint was change from baseline to week 8 in PRSIS. Secondary endpoints included: change from baseline to week 4 in PRSIS, and to week 4 and 8 in pain Numerical Rating Scale (NRS; from 0 “no pain” to 10 “worst possible pain”), and on the Neck Disability Index (NDI). Other assessments of QoL were undertaken. Safety was monitored.Results: Overall, 369 patients received pregabalin (n=145) or usual care (n=224). The media

Bruce Parsons,1 Koichi Fujii,2 Kazutaka Nozawa,2 Tamotsu Yoshiyama,3 Marie Ortiz,4 Edward Whalen4 1Global Medical Product Evaluation, Pfizer Inc, New York, NY, USA; 2Medical Affairs, Pfizer Japan Inc, Shibuya-ku, Tokyo, Japan; 3Clinical Statistics, Pfizer R&D Japan GK, Shibuya-ku, Tokyo, Japan; 4Global Statistics, Pfizer Inc, New York, NY, USA Purpose: Although analyses of pooled clinical trial data have reported how international populations respond to pregabalin by baseline neuropathic pain (NeP) severity, no studies have evaluated this specifically in patients from Japan. Thus, this post hoc pooled analysis evaluated the efficacy of pregabalin in Japanese subjects for treating moderate or severe baseline NeP.Patients and methods: Data were pooled from three placebo-controlled trials enrolling Japanese subjects with postherpetic neuralgia (PHN), diabetic peripheral neuropathy (DPN), and spinal cord injury (SCI). The efficacy of pregabalin was evaluated by baseline pain severity (moderate or severe NeP). The trials on PHN and DPN included a 1-week titration of pregabalin from 150 mg/day to 300 or 600 mg/day; the SCI trial included a 4-week dose optimization phase (150 mg/day, titrated up to 600 mg/day). Treatment durations were 13–16 weeks (excluding 1-week taper periods), and pregabalin was administered in two divided doses per day.Results: Mean baseline pain scores and demographic characteristics were comparable between treatment cohorts. Pregabalin treatment significantly reduced pain scores from baseline to endpoint compared with placebo in subjects with both moderate (P<0.001) and severe (P<0.05) baseline pain. Significant improvements in mean sleep scores from baseline to endpoint were associated with pregabalin compared with placebo in subjects with both moderate and severe baseline pain (both P<0.0001). A greater proportion of subjects in both pain cohorts achieved a ≥30% reduction in pain from baseline with pre

Toshihiko Taguchi,1 Ataru Igarashi,2 Stephen Watt,3 Bruce Parsons,3 Alesia Sadosky,3 Kazutaka Nozawa,4 Kazuhiro Hayakawa,4 Tamotsu Yoshiyama,4 Nozomi Ebata,4 Koichi Fujii4 1Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan; 2Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan; 3Pfizer Inc., New York, NY, USA; 4Pfizer Japan, Inc., Tokyo, Japan Objective: To evaluate the impact of pregabalin on sleep, pain, function, and health status in patients with chronic low back pain with accompanying neuropathic pain (CLBP-NeP) under routine clinical practice. Methods: This prospective, non-interventional, observational study enrolled Japanese adults (≥18 years) with CLBP-NeP of duration ≥3 months and severity ≥5 on a numerical rating scale (0= no pain, 10= worst possible pain). Treatment was 8 weeks with pregabalin (n=157) or usual care alone (n=174); choice of treatment was determined by the physician. The primary efficacy outcome was change from baseline to 8 weeks in pain-related interference with sleep, assessed using the Pain-Related Sleep Interference Scale (PRSIS; 0= did not interfere with sleep, 10= completely interferes with sleep). Secondary endpoints were changes in PRSIS at week 4, and changes at weeks 4 and 8 in pain (numerical rating scale), function (Roland-Morris Disability Questionnaire), and quality of life (EuroQol 5D-5L); global assessments of change were evaluated from the clinician and patient perspectives at the final visit. Results: Demographic characteristics were similar between cohorts, but clinical characteristics suggested greater disease severity in the pregabalin group including a higher mean (standard deviation) pain score, 6.3 (1.2) versus 5.8 (1.1) (P<0.001). For the primary endpoint, pregabalin resulted in significantly greater improvements in PRSIS at week 8, least-squares mean changes o