Kearney Niamh, Gorecki Patricia, Acciarri Lorenzo, Buyze Jozefien, Akawung Alianu, Merola Joseph F, Kirby Brian
Department of Dermatology, St. Vincent's University Hospital, Dublin, Ireland.
Janssen-Cilag Ltd, High Wycombe, UK.
Dermatology. 2025 Apr 10:1-15. doi: 10.1159/000545148.
Psoriasis is associated with an increased risk of cardiovascular disease (CVD). Previous studies have found that treatment with tumour necrosis factor or interleukin (IL)-17 inhibitors leads to reductions in the systemic inflammation biomarkers neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR). The primary aim of this study was to evaluate changes in NLR, PLR and MLR with guselkumab compared with placebo (VOYAGE I/II), adalimumab (VOYAGE I/II), and secukinumab (ECLIPSE). The secondary aims were to assess correlation with disease severity, C-reactive protein (CRP) levels, and treatment response.
This was a post hoc analysis of VOYAGE I, VOYAGE II, and ECLIPSE Phase III randomised trial data on guselkumab for moderate-to-severe plaque psoriasis. NLR, PLR, and MLR were evaluated at baseline and Week 16 in VOYAGE I and II and at baseline and Week 12 in ECLIPSE. Mean changes were compared between groups using a Student's t test; Pearson's test was used for correlation analyses.
VOYAGE I included 837 randomised patients, VOYAGE II included 992 randomised patients, and ECLIPSE included 1,048 randomised patients. In VOYAGE I, NLR (p = 0.011), PLR (p = 0.015), and MLR (p = 0.004) decreased significantly following 16 weeks of guselkumab treatment vs. placebo. In VOYAGE II, reductions in NLR (p = 0.003), PLR (p = 0.006), and MLR (p = 0.001) were greater at Week 16 in patients treated with guselkumab vs. placebo. Treatment with adalimumab was associated with a greater reduction (p < 0.001) in the three biomarkers vs. guselkumab, while secukinumab resulted in a similar reduction in NLR, PLR, and MLR compared with guselkumab (p = 0.413, 0.650, and 0.498, respectively). All biomarkers weakly correlated with Psoriasis Area and Severity Index (PASI) at baseline and showed modest correlations with CRP levels. Biomarkers in patients who were PASI90 responders were consistent between all active treatment groups at baseline.
Guselkumab is a highly efficacious treatment for plaque psoriasis; the study has demonstrated the potential benefit of treatment with guselkumab in reducing systemic inflammation as measured by NLR, PLR, and MLR, which appeared to be independent of psoriasis response, suggesting that reducing systemic inflammation with guselkumab may decrease CVD risk.
银屑病与心血管疾病（CVD）风险增加相关。既往研究发现，使用肿瘤坏死因子或白细胞介素（IL）-17抑制剂治疗可使全身炎症生物标志物中性粒细胞/淋巴细胞比值（NLR）、血小板/淋巴细胞比值（PLR）和单核细胞/淋巴细胞比值（MLR）降低。本研究的主要目的是评估与安慰剂（VOYAGE I/II）、阿达木单抗（VOYAGE I/II）和司库奇尤单抗（ECLIPSE）相比，古塞库单抗治疗对NLR、PLR和MLR的影响。次要目的是评估其与疾病严重程度、C反应蛋白（CRP）水平及治疗反应的相关性。
这是一项对VOYAGE I、VOYAGE II和ECLIPSE这三项关于古塞库单抗治疗中度至重度斑块状银屑病的III期随机试验数据的事后分析。在VOYAGE I和II中于基线和第16周评估NLR、PLR和MLR，在ECLIPSE中于基线和第12周评估。使用学生t检验比较组间平均变化；采用Pearson检验进行相关性分析。
VOYAGE I纳入837例随机分组患者，VOYAGE II纳入992例随机分组患者，ECLIPSE纳入1048例随机分组患者。在VOYAGE I中，与安慰剂相比，古塞库单抗治疗16周后NLR（p = 0.011）、PLR（p = 0.015）和MLR（p = 0.004）显著降低。在VOYAGE II中，与安慰剂相比，接受古塞库单抗治疗的患者在第16周时NLR（p = 0.003）、PLR（p = 0.006）和MLR（p = 0.001）的降低幅度更大。与古塞库单抗相比，阿达木单抗治疗使这三种生物标志物的降低幅度更大（p < 0.001），而司库奇尤单抗与古塞库单抗相比，NLR、PLR和MLR的降低幅度相似（分别为p = 0.413、0.650和0.498）。所有生物标志物在基线时与银屑病面积和严重程度指数（PASI）呈弱相关，与CRP水平呈中度相关。在所有活性治疗组中，达到PASI90缓解的患者基线时的生物标志物情况一致。
古塞库单抗是治疗斑块状银屑病的高效药物；该研究证明了古塞库单抗治疗在降低以NLR、PLR和MLR衡量的全身炎症方面的潜在益处，这似乎与银屑病反应无关，提示用古塞库单抗降低全身炎症可能降低CVD风险。
