Coluzzi Flaminia, Ruggeri Matteo
Dept. Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome , Italy.
Curr Med Res Opin. 2014 Jun;30(6):1139-51. doi: 10.1185/03007995.2014.894501. Epub 2014 Mar 3.
Chronic pain is a leading cause of disability and represents a relevant societal burden. Opioids are widely used for managing chronic non-cancer pain; however, the high incidence of side effects is often the main reason for discontinuation. Two formulations have recently been studied to improve the tolerability of opioids (tapentadol extended release [ER] and oxycodone/naloxone ER), but a direct comparison between these drugs is not available in the literature. The comparative cost effectiveness of these two drugs has not previously been assessed. The objective of this meta-analysis is a clinical and economic evaluation of tapentadol ER and oxycodone/naloxone ER for the treatment of musculoskeletal pain, by indirect comparison with controlled release (CR) oxycodone.
A structured literature review was conducted to identify published data for the health-economic model. The authors performed a meta-analysis on three selected randomized controlled trials (RCTs) for each treatment (tapentadol ER and oxycodone/naloxone ER). As measure of treatment effect, risk ratio was calculated, compared to the control active treatment (CR oxycodone), for the following outcomes: discontinuation rate due to adverse events, due to gastrointestinal (GE) side effects and central nervous system (CNS) side effects. A Markov model was developed to compare the cost effectiveness of tapentadol ER and oxycodone/naloxone ER. Four health states were defined: (1) patients still on treatment; (2) occurrence of adverse events (gastroenterology, central nervous system); (3) treatment discontinuation as consequence of ineffectiveness of treatment; and (4) treatment discontinuation as consequence of adverse events.
Both drugs showed a significant clinical advantage over the active control, CR oxycodone; however, tapentadol ER resulted in a better risk ratio reduction for the primary outcome of discontinuation rate due to adverse events and for the secondary outcome nausea and vomiting. The two drugs gave equivalent results in the capacity of reduction of constipation risk. In the economic evaluation both interventions were cost effective compared with CR oxycodone. However, tapentadol ER showed the most favorable results as in 65% of cases it was less costly and produced a considerable quality adjusted life years (QALY) gain. The higher impact of tapentadol ER on the cost effectiveness results was probably due to the price and the lower incidence of adverse events and related discontinuation rate, resulting in a further economic advantage.
Both tapentadol ER and oxycodone/naloxone ER are cost effective interventions compared with CR oxycodone; however, tapentadol ER was shown to provide better clinical outcomes at lower costs.
慢性疼痛是导致残疾的主要原因，也是一项重大的社会负担。阿片类药物被广泛用于治疗慢性非癌性疼痛；然而，副作用发生率高往往是停药的主要原因。最近对两种制剂进行了研究，以提高阿片类药物的耐受性（缓释曲马多和羟考酮/纳洛酮缓释剂），但文献中尚无这两种药物的直接比较。此前尚未评估这两种药物的比较成本效益。本荟萃分析的目的是通过与控释羟考酮进行间接比较，对缓释曲马多和羟考酮/纳洛酮缓释剂治疗肌肉骨骼疼痛进行临床和经济学评估。
进行了结构化文献综述，以确定健康经济模型的已发表数据。作者对每种治疗方法（缓释曲马多和羟考酮/纳洛酮缓释剂）的三项选定随机对照试验（RCT）进行了荟萃分析。作为治疗效果的衡量指标，计算了与对照活性治疗（控释羟考酮）相比的风险比，用于以下结果：因不良事件、胃肠道（GE）副作用和中枢神经系统（CNS）副作用导致的停药率。开发了一个马尔可夫模型来比较缓释曲马多和羟考酮/纳洛酮缓释剂的成本效益。定义了四种健康状态：（1）仍在接受治疗的患者；（2）发生不良事件（胃肠病学、中枢神经系统）；（3）因治疗无效而停药；（4）因不良事件而停药。
两种药物均显示出优于活性对照控释羟考酮的显著临床优势；然而，对于因不良事件导致的停药率这一主要结局以及恶心和呕吐这一次要结局，缓释曲马多的风险比降低效果更好。在降低便秘风险方面，两种药物的效果相当。在经济学评估中，与控释羟考酮相比，两种干预措施均具有成本效益。然而，缓释曲马多显示出最有利的结果,因为在65%的情况下，它成本更低，并产生了相当可观的质量调整生命年（QALY）增益。缓释曲马多对成本效益结果的影响更大，可能是由于其价格以及不良事件发生率较低和相关停药率较低，从而带来了进一步的经济优势。
与控释羟考酮相比，缓释曲马多和羟考酮/纳洛酮缓释剂都是具有成本效益的干预措施；然而，缓释曲马多被证明能以更低的成本提供更好的临床结果。
