Direct and Indirect Effect of Guselkumab on Anxiety, Depression, and Quality of Life in Patients with Moderate-to-Severe Plaque Psoriasis: A Mediation Analysis.

IF 3.5 3区医学 Q1 DERMATOLOGY

Dermatology and Therapy Pub Date : 2024-09-01 Epub Date: 2024-08-23 DOI:10.1007/s13555-024-01250-9

April W Armstrong, Peter Foley, Yan Liu, Megan Miller, Rachel E Teneralli, Anthony Bewley, Kenneth B Gordon, Kim A Papp, Chenglong Han

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Abstract

Introduction: Treating plaque psoriasis (PsO) with guselkumab (GUS) promotes skin clearance and is associated with improvements in health-related quality of life (HRQoL), anxiety, and depression. It is unclear whether improvements in patient-reported outcomes are due to resolution of skin symptoms or the direct result of GUS treatment.

Methods: Two phase 3, placebo- and active-comparator-controlled studies randomized patients with moderate-to-severe PsO to GUS, placebo (crossing over to GUS at week 16), or adalimumab. Post hoc mediation analyses examined direct and indirect effects of GUS, versus adalimumab, on Dermatology Life Quality Index (DLQI) or Hospital Anxiety and Depression Scale (HADS) after adjusting for indirect effects mediated by skin clearance, evaluated via Psoriasis Area and Severity Index (PASI), to determine the direct effect of GUS on dermatology HRQoL, depression, and anxiety.

Results: Compared with adalimumab, the natural direct effect (NDE) of GUS on change in DLQI from baseline was - 2.04 (P < 0.001), using PASI improvement as a mediator, indicating 89.2% of the total treatment effect was due to direct effects of GUS; using PASI 90 as a mediator, NDE of GUS was - 1.43 (P < 0.001), with 62.2% of the total treatment effect attributed to direct effects of GUS. Compared with adalimumab, 25.5% of change in HADS anxiety score was mediated through PASI improvement (NDE - 0.74; P = 0.002), indicating 74.5% of the total effect was independent of PASI improvement. Similarly, 24% of treatment effect was mediated through PASI 90 (NDE - 0.76; P = 0.002). Comparable proportions of the total improvement in HADS depression scores were due to direct and indirect effects of GUS mediated through PASI improvement (direct, 50.2%; indirect, 49.8%) or PASI 90 (direct, 59.5%; indirect, 40.5%).

Conclusions: GUS-mediated improvements in anxiety, depression, and overall HRQoL are not solely mediated by resolution of PsO signs, suggesting GUS use has a potential direct effect on anxiety and depression.

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古舍库单抗对中重度斑块状银屑病患者焦虑、抑郁和生活质量的直接和间接影响：中介分析

简介：使用古舍库单抗（GUS）治疗斑块状银屑病（PsO）可促进皮肤清除，并与改善健康相关生活质量（HRQoL）、焦虑和抑郁有关。目前还不清楚患者报告结果的改善是由于皮肤症状的缓解还是GUS治疗的直接结果：两项三期安慰剂和活性对比剂对照研究将中重度PsO患者随机分配到GUS、安慰剂（第16周转为GUS）或阿达木单抗治疗中。事后中介分析检查了GUS与阿达木单抗相比对皮肤科生活质量指数（DLQI）或医院焦虑和抑郁量表（HADS）的直接和间接影响，然后调整了皮肤清除率（通过银屑病面积和严重程度指数（PASI）评估）中介的间接影响，以确定GUS对皮肤科HRQoL、抑郁和焦虑的直接影响：结果：与阿达木单抗相比，GUS对DLQI基线变化的自然直接效应（NDE）为-2.04（P 结论：GUS能改善焦虑、抑郁和抑郁症：GUS介导的焦虑、抑郁和整体 HRQoL 的改善并非仅由 PsO 征兆的缓解所介导，这表明 GUS 的使用对焦虑和抑郁有潜在的直接影响。

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来源期刊

Dermatology and Therapy Medicine-Dermatology

CiteScore

6.00

自引率

8.80%

发文量

187

审稿时长

6 weeks

期刊介绍： Dermatology and Therapy is an international, open access, peer-reviewed, rapid publication journal (peer review in 2 weeks, published 3–4 weeks from acceptance). The journal is dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of dermatological therapies. Studies relating to diagnosis, pharmacoeconomics, public health and epidemiology, quality of life, and patient care, management, and education are also encouraged. Areas of focus include, but are not limited to all clinical aspects of dermatology, such as skin pharmacology; skin development and aging; prevention, diagnosis, and management of skin disorders and melanomas; research into dermal structures and pathology; and all areas of aesthetic dermatology, including skin maintenance, dermatological surgery, and lasers. The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports/case series, trial protocols, and short communications. Dermatology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an International and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of quality research, which may be considered of insufficient interest by other journals. The journal appeals to a global audience and receives submissions from all over the world.