Are IL-17 inhibitors superior to IL-23 inhibitors in reducing systemic inflammation in moderate-to-severe plaque psoriasis? A retrospective cohort study

Abstract

IL-17 and IL-23 inhibitors have shown successful results in improving skin lesions in the treatment of moderate-to-severe plaque psoriasis. However, psoriasis is a chronic inflammatory disease characterized by systemic inflammation including joints in addition to skin lesions. Therefore, in this retrospective and observational cohort study, we aimed to evaluate the effect of IL-17 inhibitors (secukinumab and ixekizumab) and IL-23 inhibitors (risankizumab and guselkumab) on systemic inflammation in psoriasis. We included 214 treatment courses with IL-17 inhibitors (n = 116, 54.2%) and IL-23 inhibitors (n = 98, 45.8%) and compared the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-monocyte ratio (PMR), systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) at baseline and Week 16 of treatment. In patients receiving IL-17 inhibitor, NLR, d-NLR, PLR, SII, SIRI, and AISI were significantly decreased at Week 16 (p = 0.003, p = 0.001, p = 0.024, p = 0.001, p = 0.008, and p = 0.002, respectively). There was no significant reduction in systemic inflammatory markers in the anti-IL-23 group. At week 16, the anti-IL-17 group showed a significantly higher mean decrease from the baseline values of NLR, d-NLR, SII, SIRI, and AISI than the anti-IL-23 group (p = 0.021, p = 0.009, p = 0.012, p = 0.028, and p = 0.021, respectively). The PASI75/90/100 scores didn’t significantly differ between the IL-17 and IL-23 groups. Achieving PASI90 response at Week 16 in the IL-17 group was associated with the change in AISI (p = 0.037). The PASI75 response at Week 16 in the IL-23 group was associated with the change in NLR, d-NLR, and SII (p = 0.044, p = 0.037, and p = 0.031, respectively). NLR (rho = 0.173, p = 0.014), d-NLR (rho = 0.189, p = 0.007), SII (rho = 0.158, p = 0.024), SIRI (rho = 0.156, p = 0.026), and MLR (rho = 0.165, p = 0.019) showed positive correlations with the baseline PASI, but no correlation was found with the change in systemic inflammatory markers and the change in PASI score. In the treatment of moderate-to-severe psoriasis, IL-17 inhibitors appear to have a greater decreasing effect on systemic inflammatory markers than IL-23 inhibitors. However, more evidence-based data are needed to conclude that IL-17 inhibitors are superior to IL-23 inhibitors in suppressing systemic inflammation in psoriatic disease.