Treatment of Plaque Psoriasis with Guselkumab Reduces Systemic Inflammatory Burden as Measured by Neutrophil/Lymphocyte Ratio, Platelet/Lymphocyte Ratio, and Monocyte/Lymphocyte Ratio: A post hoc Analysis of Three Randomised Clinical Trials

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Biologics; Biomarker; Guselkumab; Neutrophil-to-lymphocyte ratio; Platelet-to-lymphocyte ratio; Psoriasis; Systemic inflammation.

Fig. 1.

Diagram depicting the study designs for VOYAGE I (a), VOYAGE II (through Week 16) (b), and ECLIPSE (through Week 12) (c). In VOYAGE I, patients were randomised 2:1:2 to receive guselkumab 100 mg at Weeks 0, 4, and 12 (three active injections, n = 329), placebo at Weeks 0, 4, and 12 (no active injections, n = 174), or adalimumab 80 mg at Week 0, 40 mg at Week 1, then q2w (nine active injections, n = 334). In VOYAGE II, patients were randomised 2:1:2 to receive guselkumab 100 mg at Weeks 0, 4, and 12 (three active injections, n = 496), placebo at Weeks 0, 4, and 12 (no active injections, n = 248) or adalimumab 80 mg at Week 0, 40 mg at Week 1, then q2w (nine active injections, n = 248). In ECLIPSE, patients were randomised 1:1 to receive guselkumab 100 mg at Weeks 0, 4, and 12 (three active injections, n = 534) or secukinumab 2 × 150 mg at Weeks 0, 1, 2, 3, 4, 8, and 12 (14 active injections, n = 514). Ra, randomisation; q2w, every 2 weeks; W, week.

Fig. 2.

Plots of meanneutrophil/lymphocyte ratio (NLR) (a), platelet/lymphocyte ratio (PLR) (b), and monocyte/lymphocyte ratio (MLR) (c) values over time in VOYAGE I, VOYAGE II, and ECLIPSE, stratified by treatment group. The mean NLR decreased from 2.680 to 2.415 in VOYAGE I and from 2.726 to 2.253 in VOYAGE II following 16 weeks of guselkumab treatment and decreased from 2.804 to 2.453 in ECLIPSE following 12 weeks of guselkumab treatment. In VOYAGE I and II, these reductions were greater than with placebo but less than those with adalimumab at Week 16. In ECLIPSE, reductions were similar between guselkumab and secukinumab at Week 12. Similar trends were generally observed for PLR and MLR (except in VOYAGE II, where the decrease in MLR was not greater with adalimumab vs. guselkumab).