Pfizer, New York, NY, USA.
Health Services Consulting Corporation, Boxborough, MA, USA.
Adv Ther. 2018 Mar;35(3):382-394. doi: 10.1007/s12325-018-0664-6. Epub 2018 Feb 23.
Achieving a therapeutic response to pregabalin in patients with painful diabetic peripheral neuropathy (pDPN) requires adequate upward dose titration. Our goal was to identify relationships between titration and response to pregabalin in patients with pDPN.
Data were integrated from nine randomized, placebo-controlled clinical trials as well as one 6-week open-label observational study conducted by 5808 physicians (2642 patients with pDPN) in standard outpatient settings in Germany. These studies evaluated pregabalin for treatment of pDPN. Using these data, we examined "what if" scenarios using a microsimulation platform that integrates data from randomized and observational sources as well as autoregressive-moving-average with exogenous inputs models that predict pain outcomes, taking into account weekly changes in pain, sleep interference, dose, and other patient characteristics that were unchanging.
Final pain levels were significantly different depending on dose changes (P < 0.0001), with greater proportions improving with upward titration regardless of baseline pain severity. Altogether, 78.5% of patients with pDPN had 0-1 dose change, and 15.2% had ≥ 2 dose changes. Simulation demonstrated that the 4.8% of inadequately titrated patients who did not improve/very much improve their pain levels would have benefited from ≥ 2 dose changes. Patient satisfaction with tolerability (range 90.3-96.2%) was similar, regardless of baseline pain severity, number of titrations, or extent of improvement, suggesting that tolerability did not influence treatment response patterns.
Upward dose titration reduced pain in patients with pDPN who actually received it. Simulation also predicted pain reduction in an inadequately titrated nonresponder subgroup of patients had they actually received adequate titration. The decision not to uptitrate must have been driven by factors other than tolerability.
Pfizer, Inc.
在患有糖尿病周围神经痛（pDPN）的患者中，要实现普瑞巴林的治疗反应，需要进行充分的剂量递增滴定。我们的目标是确定 pDPN 患者的滴定与普瑞巴林反应之间的关系。
数据来自德国标准门诊环境中 5808 名医生（2642 名 pDPN 患者）进行的 9 项随机、安慰剂对照临床试验和 1 项为期 6 周的开放性观察性研究。这些研究评估了普瑞巴林治疗 pDPN 的效果。使用这些数据，我们使用一个整合了来自随机和观察性来源的数据以及自回归移动平均外加输入模型的微模拟平台，检查了“假设”情况，这些模型预测了疼痛结局，同时考虑了每周疼痛变化、睡眠干扰、剂量和其他不变的患者特征。
最终疼痛水平因剂量变化而显著不同（P < 0.0001），无论基线疼痛严重程度如何，向上滴定都能使更多的患者得到改善。总体而言，78.5%的 pDPN 患者有 0-1 次剂量变化，15.2%的患者有≥2 次剂量变化。模拟结果表明，4.8%的滴定不足的患者，如果增加≥2 次剂量，他们的疼痛水平会有所改善。患者对耐受性的满意度（90.3%-96.2%）相似，无论基线疼痛严重程度、滴定次数或改善程度如何，这表明耐受性没有影响治疗反应模式。
向上剂量滴定降低了实际接受治疗的 pDPN 患者的疼痛水平。模拟还预测，如果未充分滴定的无反应亚组患者实际接受了充分的滴定，他们的疼痛也会减轻。未进行滴定的决定可能是由耐受性以外的因素驱动的。
辉瑞公司。
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