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.

Background 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). Objectives 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 992 randomised patients and ECLIPSE 1048 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 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. Clinical trial registration VOYAGE I: NCT02207231; VOYAGE II: NCT02207244; ECLIPSE: NCT03090100.