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Safety and efficacy of duloxetine in Japanese patients with chronic knee pain due to osteoarthritis: an open-label, long-term, Phase III extension study.

ABSTRACT: Purpose:To assess long-term safety, tolerability, and efficacy of duloxetine in Japanese patients with chronic knee pain due to osteoarthritis. Methods:In this open-label extension study (NCT02335346), Japanese patients with knee osteoarthritis and pain (Brief Pain Inventory [BPI] - Severity average pain score ?4 at start of randomized trial) who had previously received duloxetine 60 mg/day or placebo for 14 weeks in a double-blind randomized trial entered the extension and received duloxetine 60 mg/day for 48 weeks. The primary outcome was safety/tolerability, secondary outcomes were change in BPI-Severity (BPI-S) average pain, BPI-Interference (BPI-I), Patient Global Impression-Improvement (PGI-I), Clinical Global Impression-Improvement (CGI-I), 36-item Short-Form Health Survey (SF36), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and exploratory outcomes were knee range of motion (efficacy outcome) and Kellgren-Lawrence grade (safety outcome). Results:Of 323 patients who completed the randomized trial, 93 (50 placebo, 43 duloxetine) entered the extension. Most patients (85, 91.4%) experienced an adverse event, most commonly constipation, nasopharyngitis, somnolence, and dry mouth (?10% of patients). There were eight serious adverse events in seven patients and no deaths. No obvious duloxetine-related changes were observed in laboratory tests, vital signs, or electrocardiograms. The change from baseline in BPI-S average pain score was significant throughout the extension. Significant reductions in BPI-I, PGI-I, CGI-I, WOMAC, and SF36 scores were also maintained through 52 weeks. There were no substantial changes in range of motion or Kellgren-Lawrence grade. Conclusion:In Japanese patients with chronic knee pain due to osteoarthritis, long-term treatment with duloxetine was well tolerated and associated with sustained improvements in pain and health-related quality of life without radiographic deterioration.

SUBMITTER: Uchio Y

PROVIDER: S-EPMC6074806 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Safety and efficacy of duloxetine in Japanese patients with chronic knee pain due to osteoarthritis: an open-label, long-term, Phase III extension study.

Uchio Yuji Y Enomoto Hiroyuki H Ishida Mitsuhiro M Tsuji Toshinaga T Ochiai Toshimitsu T Konno Shinichi S

Journal of pain research 20180731

<h4>Purpose</h4>To assess long-term safety, tolerability, and efficacy of duloxetine in Japanese patients with chronic knee pain due to osteoarthritis.<h4>Methods</h4>In this open-label extension study (NCT02335346), Japanese patients with knee osteoarthritis and pain (Brief Pain Inventory [BPI] - Severity average pain score ≥4 at start of randomized trial) who had previously received duloxetine 60 mg/day or placebo for 14 weeks in a double-blind randomized trial entered the extension and receiv ...[more]

PMID: 30104894

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Project description:BACKGROUND:The objectives of this study were to assess the maintenance of effect of duloxetine 60?mg once-daily (QD) in Chinese patients with chronic pain due to osteoarthritis (OA) of the knee or hip and to provide additional long-term safety data. METHODS:This was an open-label, extension phase of a randomized, double-blind, placebo-controlled clinical trial. Eligible patients were outpatients who met the American College of Rheumatology clinical and radiographic criteria for OA with a rating??4 on Brief Pain Inventory (BPI) 24-h average pain. After completing the 13-week placebo-controlled phase, patients originally assigned to placebo were titrated to duloxetine 60?mg QD (PLA_DLX), whereas patients originally assigned to duloxetine 60?mg QD remained on the same dose of duloxetine (DLX_DLX) for another 13?weeks. The maintenance effect of duloxetine 60?mg QD during the extension phase was evaluated by a 1-sided 97.5% confidence interval (CI) of the baseline-to-endpoint change in the extension phase for patients who took duloxetine and reported ?30% reduction in BPI average pain at the end of placebo-controlled phase (placebo-controlled phase duloxetine responders). Other BPI severity and interference items, as well as safety and tolerability, were assessed. RESULTS:Of 342 patients entering the extension phase, 162 (97.6%) DLX_DLX-treated patients and 157 (89.2%) PLA_DLX-treated patients completed this phase. Most patients (76.0%) were female. Mean age was 60.6?years. Mean BPI average pain was 5.5 at baseline of the placebo-controlled phase. Among 113 placebo-controlled phase duloxetine responders, mean change in BPI average pain during the extension phase was -?0.59 (from 2.47 to 1.88); the upper bound of the 1-sided 97.5% CI was -?0.31 and less than the pre-specified non-inferiority margin of a 1.5-point increase (p?<?0.001). Significant within-group improvements in all BPI items were observed for both PLA_DLX and DLX_DLX groups during the extension phase (all p?<?0.01). No deaths or suicide-related events occurred. Seven (4.0%) PLA_DLX-treated patients and no DLX_DLX-treated patients discontinued due to an adverse event. CONCLUSION:The analgesic effect of duloxetine 60?mg QD among treatment responders was maintained for the entire duration of the extension phase. Duloxetine 60?mg QD was well tolerated during the extension phase. TRIAL REGISTRATION:ClinicalTrials.gov identification number NCT01931475 . Registered 29 August 2013.

Project description:ObjectiveTo assess the effectiveness of duloxetine in addition to usual care in patients with chronic osteoarthritis (OA) pain. The cost-effectiveness and whether the presence of symptoms of centralized pain alters the response to duloxetine were secondary objectives.MethodsWe conducted an open-label, cluster-randomized trial. Patients with chronic hip or knee OA pain who had an insufficient response to acetaminophen and nonsteroidal antiinflammatory drugs were included. Randomization took place at the general practice level, and patients received duloxetine (60 mg/day) in addition to usual care or usual care alone. The presence of centralized pain was defined as a modified PainDETECT Questionnaire score >12. The primary outcome measure was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores (scale 0-20) at 3 months after the initiation of treatment. Our aim was to detect a difference between the groups of a clinically relevant effect of 1.9 points (effect size 0.4). We used a linear mixed model with repeated measurements to analyze the data.ResultsIn total, 133 patients were included, and 132 patients were randomized into treatment groups. A total of 66 patients (at 31 practices) were randomized to receive duloxetine in addition to usual care, and 66 patients (at 35 practices) were randomized to receive usual care alone. We found no differences in WOMAC pain scores between the groups at 3 months (adjusted difference -0.58 [95% confidence interval (95% CI) -1.80, 0.63]) or at 12 months (adjusted difference -0.26 [95% CI -1.86, 1.34]). In the subgroup of patients with centralized pain symptoms, we also found no effect of duloxetine compared to usual care alone (adjusted difference -0.32 [95% CI -2.32, 1.67]).ConclusionWe found no effect of duloxetine added to usual care compared to usual care alone in patients with chronic knee or hip OA pain. Another trial including patients with centralized pain symptoms should be conducted to validate our results.

Project description:BackgroundRecent studies indicate that the administration of open-label placebos (OLP) can improve symptoms in various medical conditions. The primary aim of this 3-week randomized controlled trial was to examine the effects of OLP treatments on pain, functional disability, and mobility in patients with arthritic knee pain.MethodsSixty patients (55% females; mean age, 66.9 ± 9.7 SD years) were randomized to one of two OLP treatments (n = 41) or no treatment (NT; n = 19). OLP treatments were accompanied by the verbal suggestion "to decrease pain" (OLP-pain, n = 20) or "to improve mood" (OLP-mood, n = 21). Pain and mood levels were monitored on 11-point Numeric Rating Scales (NRSs) in a patient diary, and global clinical improvement (CGI-I) was assessed at the end of the study. At baseline and after 21 days, patients filled in validated questionnaires to assess symptoms and functional disability of the knee (WOMAC), mental and physical quality of life (SF-36), state anxiety (STAI-state), perceived stress (PSQ-20), and self-efficacy (GSE). In addition, knee mobility (neutral zero-method), heart rate variability (HRV), and diurnal cortisol levels were evaluated before and after treatment.ResultsEvaluation of daily pain ratings indicated significant pain decrease in the OLP groups compared to NT (p = 0.013, d = 0.64), with no difference between the OLP-pain and the OLP-mood groups (p = 0.856, d = 0.05). OLP treatment also improved WOMAC pain (p = 0.036, d = 0.55), again with no difference between the two OLP groups (p = 0.65, d = 0.17). WOMAC function and stiffness, knee mobility, stress, state anxiety, quality of life, and self-efficacy did not change differently between groups.ConclusionOLP treatment improved knee pain in elderly patients with symptomatic knee osteoarthritis (OA), while functional disability and mobility of the knee did not change. The content of the verbal suggestion was of minor importance. OLP administration may be considered as supportive analgesic treatment in elderly patients with symptomatic knee OA.Trial registrationGerman Clinical Trials Register (https://www.drks.de/), DRKS00015191 (retrospectively registered).

Project description:IntroductionResidual pain is a major factor in patient dissatisfaction following total hip arthroplasty or total knee arthroplasty (THA/TKA). The proportion of patients with unfavourable long-term residual pain is high, ranging from 7% to 34%. There are studies indicating that a preoperative degree of central sensitisation (CS) is associated with poorer postoperative outcomes and residual pain. It is thus hypothesised that preoperative treatment of CS could enhance postoperative outcomes. Duloxetine has been shown to be effective for several chronic pain syndromes, including knee osteoarthritis (OA), in which CS is most likely one of the underlying pain mechanisms. This study aims to evaluate the postoperative effects of preoperative screening and targeted duloxetine treatment of CS on residual pain compared with care-as-usual.Methods and analysisThis multicentre, pragmatic, prospective, open-label, randomised controlled trial includes patients with idiopathic hip/knee OA who are on a waiting list for primary THA/TKA. Patients at risk for CS will be randomly allocated to the preoperative duloxetine treatment programme group or the care-as-usual control group. The primary end point is the degree of postoperative pain 6 months after THA/TKA. Secondary end points at multiple time points up to 12 months postoperatively are: pain, neuropathic pain-like symptoms, (pain) sensitisation, pain catastrophising, joint-associated problems, physical activity, health-related quality of life, depressive and anxiety symptoms, and perceived improvement. Data will be analysed on an intention-to-treat basis.Ethics and disseminationThe study is approved by the local Medical Ethics Committee (METc 2014/087) and will be conducted according to the principles of the Declaration of Helsinki (64th, 2013) and the Good Clinical Practice standard (GCP), and in compliance with the Medical Research Involving Human Subjects Act (WMO).Trial registration number2013-004313-41; Pre-results.

Dataset Information

Safety and efficacy of duloxetine in Japanese patients with chronic knee pain due to osteoarthritis: an open-label, long-term, Phase III extension study.

Publications

Safety and efficacy of duloxetine in Japanese patients with chronic knee pain due to osteoarthritis: an open-label, long-term, Phase III extension study.

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