Efficacy and Safety of Topical Roflumilast for the Treatment of Psoriasis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

IF 2.9 3区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical Drug Investigation Pub Date : 2024-09-01 Epub Date: 2024-08-22 DOI:10.1007/s40261-024-01368-w

Rafaela de Moraes-Souza, Regina Chahine Chater, Izabela Pera Calvi, Yasmin Mesquita, Rubiana Sarto, Izadora Lapenda, Lívia Figueiredo Pereira, Luana Moury, Pedro Herranz-Pinto

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引用次数: 0

Abstract

Background and objective: Plaque psoriasis is commonly treated topically with glucocorticoids and vitamin D derivatives. However, potential side effects such as skin atrophy underscore the need for safe and effective alternative topical therapies. Recently, the US Food and Drug Administration (FDA) and Health Canada approved roflumilast 0.3% cream as an option for treating this disease. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to assess the efficacy and safety of topical roflumilast 0.3% compared with vehicle for plaque psoriasis.

Methods: PubMed, Embase, ClinicalTrials.gov, and Cochrane databases were searched from inception to 1 May 2024, assessing the outcomes of Investigator's Global Assessment (IGA) or body-IGA success (clear or almost clear status plus an at least 2-grade improvement from baseline), Psoriasis Area and Severity Index (PASI)-50, PASI-75, PASI-90, intertriginous-IGA success (clear or almost clear status on the intertriginous-IGA plus an at least 2-grade improvement from baseline), and adverse events (AEs). Statistical analysis was performed using Review Manager, R software, and RStudio. Heterogeneity was determined using the Cochran Q test and I² statistics.

Results: Four RCTs were included, comprising a total of 1403 patients, of whom 885 (63.1%) received topical roflumilast 0.3% and 518 (36.9%) received vehicle. At week 8, the achievement of IGA or body-IGA success was significantly higher among those treated with topical roflumilast than in the vehicle group [relative risk (RR) 5.07; 95% confidence interval (CI) 3.55-7.23; p < 0.01]. Similar findings were observed at week 8 for PASI-50 (RR 2.73; 95% CI 2.27-3.29; p < 0.01), PASI-75 (RR 4.48; 95% CI 2.26-8.89; p < 0.01), and PASI-90 (RR 5.61; 95% CI 2.57-12.25; p < 0.01). Corresponding outcomes were found at weeks 2, 4, and 6. Additionally, a higher percentage of patients treated with topical roflumilast 0.3% once daily achieved intertriginous-IGA success, compared with those receiving vehicle, at week 8 (71.9% versus 20.5%; RR 3.32; 95% CI 2.11-5.22; p < 0.01), with similar findings at weeks 2, 4, and 6. While a significant difference was observed in the overall incidence of AEs between the topical roflumilast and vehicle groups, there was no difference in treatment-related AEs, serious AEs, or AEs leading to study discontinuation.

Conclusion: These findings support the superiority of topical roflumilast 0.3% over vehicle and suggest its use as a valuable asset for the treatment of plaque psoriasis.

Protocol registration: International Prospective Register of Systematic Reviews (PROSPERO), CRD42023456494.

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外用罗氟司特治疗银屑病的有效性和安全性：随机对照试验的系统回顾和元分析》。

背景和目的：斑块状银屑病通常采用糖皮质激素和维生素 D 衍生物进行局部治疗。然而，皮肤萎缩等潜在副作用凸显了对安全有效的替代外用疗法的需求。最近，美国食品药品管理局（FDA）和加拿大卫生部批准将 0.3% 罗氟司特乳膏作为治疗这种疾病的一种选择。我们对随机对照试验（RCTs）进行了系统回顾和荟萃分析，以评估局部使用 0.3% 罗氟司特乳膏与使用药物治疗斑块状银屑病相比的疗效和安全性：方法：PubMed、Embase、ClinicalTrials.gov 和 Cochrane 数据库进行了检索，评估了研究者全球评估（IGA）或身体-IGA 成功率（清除或几乎清除状态，以及与基线相比至少 2 级的改善）的结果、银屑病面积和严重程度指数 (PASI)-50、PASI-75、PASI-90、三叉神经间-IGA 成功率（三叉神经间-IGA 清晰或基本清晰，且与基线相比至少改善 2 个等级）和不良事件 (AE)。统计分析使用Review Manager、R软件和RStudio进行。异质性采用 Cochran Q 检验和 I2 统计法确定：共纳入了四项研究，共有1403名患者，其中885人（63.1%）接受了局部罗氟司特0.3%治疗，518人（36.9%）接受了药物治疗。第 8 周时，接受局部罗氟司特治疗的患者的 IGA 或身体-IGA 成功率明显高于药物组[相对风险 (RR) 5.07；95% 置信区间 (CI) 3.55-7.23；P < 0.01]。第 8 周时，PASI-50（RR 2.73；95% CI 2.27-3.29；p <0.01）、PASI-75（RR 4.48；95% CI 2.26-8.89；p <0.01）和 PASI-90（RR 5.61；95% CI 2.57-12.25；p <0.01）也出现了类似的结果。在第 2、4 和 6 周也发现了相应的结果。此外，与接受药物治疗的患者相比，接受 0.3% 罗氟司特外用药治疗的患者在第 8 周达到三叉神经间-IGA 成功的比例更高（71.9% 对 20.5%；RR 3.32；95% CI 2.11-5.22；p <0.01），在第 2、4 和 6 周也有类似结果。虽然局部罗氟司特组和载体组的AEs总发生率有明显差异，但治疗相关AEs、严重AEs或导致研究中止的AEs没有差异：这些研究结果表明，外用罗氟司特0.3%的疗效优于载体，建议将其作为治疗斑块状银屑病的重要药物：协议注册：系统综述国际前瞻性注册（PROSPERO），CRD42023456494。

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来源期刊

Clinical Drug Investigation 医学-药学

CiteScore

5.90

自引率

3.10%

发文量

108

审稿时长

6-12 weeks

期刊介绍： Clinical Drug Investigation provides rapid publication of original research covering all phases of clinical drug development and therapeutic use of drugs. The Journal includes: -Clinical trials, outcomes research, clinical pharmacoeconomic studies and pharmacoepidemiology studies with a strong link to optimum prescribing practice for a drug or group of drugs. -Clinical pharmacodynamic and clinical pharmacokinetic studies with a strong link to clinical practice. -Pharmacodynamic and pharmacokinetic studies in healthy volunteers in which significant implications for clinical prescribing are discussed. -Studies focusing on the application of drug delivery technology in healthcare. -Short communications and case study reports that meet the above criteria will also be considered. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Clinical Drug Investigation may be accompanied by plain language summaries to assist readers who have some knowledge, but non in-depth expertise in, the area to understand important medical advances.