Background: The clinical efficacy of roflumilast, an oral phosphodiesterase-4 inhibitor, has been demonstrated in patients with severe chronic obstructive pulmonary disease (COPD). However, roflumilast has shown frequent adverse drug reactions (ADRs). This study was performed to investigate the dosing strategy that will improve adherence to roflumilast in COPD.
Methods: We conducted a systematic review and meta-analysis using PubMed, Embase, and Cochrane Central Register. The dosing strategy for roflumilast was classified into a dose-escalation group and a low-dose group. We investigated clinical outcomes according to dosing strategy.
Results: Five clinical trials involving 2424 patients were included. Both the dose-escalation and the low-dose groups showed a decrease in discontinuation rate compared to the standard dosing group for roflumilast (risk ratio [RR], 0.81; 95% confidence interval [CI], 0.67– 0.97; P = 0.02 and RR, 0.62; 95% CI, 0.48– 0.80; P < 0.01, respectively). In the two strategies, the pooled proportions of discontinuation were 27.9% and 11.7%, respectively. Although the pooled proportion of any ADR was not statistically decreased in the two strategies, diarrhea was significantly reduced in the low-dose group compared to the standard group (RR, 0.58; 95% CI, 0.42– 0.82; P < 0.01). The pooled incidence of acute exacerbations was similar between the low-dose and the standard groups (22.9% and 20.1%, respectively; P = 0.27).
Conclusion: Our findings show that the two alternative dosing strategies might have the benefit of improving adherence to roflumilast in COPD. Further large-scale trials are required to support our findings.



中文翻译：

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提高罗氟司特治疗慢性阻塞性肺病依从性的剂量策略：系统评价和荟萃分析

背景：罗氟司特（一种口服磷酸二酯酶 4 抑制剂）的临床疗效已在严重慢性阻塞性肺疾病 (COPD) 患者中得到证实。然而，罗氟司特经常出现药物不良反应（ADR）。本研究旨在探讨可提高慢性阻塞性肺病患者罗氟司特依从性的给药策略。
方法：我们使用 PubMed、Embase 和 Cochrane Central Register 进行了系统评价和荟萃分析。罗氟司特的给药策略分为剂量递增组和低剂量组。我们根据剂量策略研究了临床结果。
结果：纳入了 5 项临床试验，涉及 2424 名患者。与罗氟司特标准剂量组相比，剂量递增组和低剂量组的停药率均有所下降（风险比 [RR]，0.81；95% 置信区间 [CI]，0.67–0.97；P = 0.02， RR，0.62；95% CI，0.48-0.80；P < 0.01）。在这两种策略中，停药的汇总比例分别为 27.9% 和 11.7%。尽管两种策略中任何不良反应的汇总比例没有统计学上下降，但与标准组相比，低剂量组的腹泻显着减少（RR，0.58；95% CI，0.42-0.82；P < 0.01 ）。低剂量组和标准组的急性加重汇总发生率相似（分别为 22.9% 和 20.1%；P = 0.27）。
结论：我们的研究结果表明，两种替代给药策略可能有利于提高慢性阻塞性肺病患者对罗氟司特的依从性。需要进一步的大规模试验来支持我们的发现。