Unit of Pain and Palliative Care, Hospital Universitario Virgen de las Nieves, Granada, Spain.
Unit Pain, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
Pain Physician. 2021 Jan;24(1):E75-E85.
The central analgesic tapentadol prolonged release (PR) has proven effective and generally well tolerated in a broad range of chronic pain conditions. Long-term data of its use are still scarce.
To evaluate long-term effectiveness, tolerability, and safety of tapentadol PR in patients with severe chronic osteoarthritis (OA) knee pain or low back pain (LBP) who responded to tapentadol in 1 of 4 preceding 12-week phase 3b clinical trials.
Open-label, uncontrolled, observational extension study of up to 72 weeks.
Fourteen centers in Spain. Protocol approval by the reference ethics committee for all the participating centers.
Eligible patients started the extension trial on the tapentadol PR dosage optimized for them in the preceding trial; dose adjustments were permitted throughout the extension. Treatment effectiveness outcomes included changes in pain intensity, sleep, state of health, quality of life, patient and clinician global impression of change, and patients' satisfaction with treatment. Patients with OA knee pain also answered the Western Ontario and McMaster Universities OA index, and patients with LBP with a possible neuropathic pain component completed neuropathic pain-related questionnaires.
Eighty-three patients were enrolled: 40 with OA knee pain, 43 with LBP. The full analysis set consisted of 81 patients. Mean pain intensity remained relatively stable over the 72-week extension period with mean increases from baseline of 0.44 (95% confidence interval [CI], -0.1,1.0; Numeric Rating Scale) for all patients, 0.2 (95% CI, -0.5, 0.9) for patients with OA, and 0.68 (95% CI, -0.2, 1.6) for patients with LBP. State of health and quality of life baseline ratings were maintained; overall impression of change was "improved." Most patients (88.9%) reported at least good treatment satisfaction at the end of treatment. Mean daily tapentadol PR doses slightly increased from 313.3 ± 139.5 mg at baseline to 315.7 ± 140.1 mg at end of study. Uptitration was required for 8.4% of the patients, 4.8% had a dose reduction during the trial. Adverse events considered probably/likely or certainly related to tapentadol PR treatment by the investigator were documented for 18.1% of all patients, most commonly constipation (7.2%). Seven patients (8.4%) experienced adverse events leading to premature discontinuation.
An open-label design, stable concomitant analgesics (World Health Organization step I), and dose adjustments were allowed during the study. All patients had benefitted from tapentadol PR in preceding trials.
Sustained pain relief and quality of life for up to 72 treatment weeks under relatively stable dosing, as well as the good safety profile, indicate the usefulness of tapentadol PR for patients who suffer from severe chronic OA knee pain and LBP with limited risk for tolerance development.
中枢性镇痛药酒石酸布托啡诺控释片（PR）已被证明在广泛的慢性疼痛病症中具有有效性和良好的耐受性。其长期使用的数据仍相对较少。
评估对酒石酸布托啡诺 PR 有反应的 4 项为期 12 周的 3b 期临床试验中，严重慢性骨关节炎（OA）膝关节疼痛或腰痛（LBP）患者长期使用酒石酸布托啡诺 PR 的有效性、耐受性和安全性。
长达 72 周的开放标签、非对照、观察性扩展研究。
西班牙的 14 个中心。所有参与中心的参考伦理委员会均批准了方案。
符合条件的患者在前一个试验中开始使用为他们优化的酒石酸布托啡诺 PR 剂量进行扩展试验；整个扩展期间允许进行剂量调整。治疗效果的评估包括疼痛强度、睡眠、健康状况、生活质量、患者和医生对治疗改变的总体印象以及患者对治疗的满意度的变化。OA 膝关节疼痛患者还回答了西部安大略省和麦克马斯特大学骨关节炎指数，而可能存在神经病理性疼痛成分的腰痛患者则完成了与神经病理性疼痛相关的问卷。
共纳入 83 例患者：40 例 OA 膝关节疼痛，43 例 LBP。全分析集包括 81 例患者。在 72 周的扩展期间，平均疼痛强度相对稳定，所有患者的平均疼痛强度从基线增加了 0.44（95%置信区间 [CI]，-0.1，1.0；数字评分量表），OA 患者为 0.2（95%CI，-0.5，0.9），LBP 患者为 0.68（95%CI，-0.2，1.6）。健康状况和生活质量的基线评分保持不变；总体印象为“改善”。治疗结束时，大多数患者（88.9%）报告至少有良好的治疗满意度。酒石酸布托啡诺 PR 的平均日剂量从基线时的 313.3±139.5mg 略微增加到研究结束时的 315.7±140.1mg。需要对 8.4%的患者进行滴定，4.8%的患者在试验期间减少了剂量。研究者认为可能/很可能或肯定与酒石酸布托啡诺 PR 治疗有关的不良事件发生在 18.1%的所有患者中，最常见的是便秘（7.2%）。有 7 名患者（8.4%）发生了导致提前停药的不良事件。
开放性设计，稳定的伴随镇痛药物（世界卫生组织第 I 步），以及在研究期间允许进行剂量调整。所有患者在前一个试验中都受益于酒石酸布托啡诺 PR。
在相对稳定的剂量下持续缓解疼痛和提高生活质量长达 72 周，以及良好的安全性，表明酒石酸布托啡诺 PR 对患有严重慢性 OA 膝关节疼痛和 LBP 的患者有用，这些患者的耐受性发展风险有限。
