INTRODUCTION

Psoriasis is an immune-mediated chronic skin disease with a prevalence of approximately 2–3% worldwide¹. Psoriatic arthritis may accompany in up to 30% of the patients¹¹. Patients with psoriasis tend to have systemic comorbidities such as cardiovascular diseases, diabetes, hypertension, hypercholesterolemia, and psychological disorders^2,3. Biological agents which are effective in the management of psoriasis target certain inflammatory cytokines and modify immune system⁴. It has been suggested that early treatment of psoriasis with biological agents might prevent psoriasis comorbidities such as psoriatic arthritis, cardiovascular diseases, and metabolic disorders².

Monocyte to high-density lipoprotein (HDL) cholesterol ratio (MHR) has been reported as a novel biomarker which indicated systemic inflammation and oxidative stress⁵. It has been suggested that MHR was a good indicator of inflammation since it may present both inflammatory and pro-oxidant activities of monocytes and anti-inflammatory functions of HDL cholesterol⁶. MHR has been associated with various inflammatory disorders such as cardiovascular diseases, hypertension, metabolic syndrome, and psychological diseases^5,7,8. MHR has also been used to predict vascular damage in patients with diabetes or prognosis in patients with cardiovascular diseases^5,9,10. Moreover, it has been suggested that MHR might indicate inflammation in patients with psoriasis since systemic inflammation plays a crucial role in the development of psoriasis and systemic comorbidities¹¹. In the light of this information, within this study, we aimed to evaluate the effect of biological agent treatment on MHR in patients with psoriasis.

MATERIALS AND METHODS

Gazi University Ethics Committee approval was obtained before this study (approval number 2022-955). Between April 2019 and August 2022, medical records of patients with psoriasis who were treated with infliximab, adalimumab, etanercept, ixekizumab, secukinumab, and ustekinumab were reviewed retrospectively. Age, gender, psoriasis type, psoriasis duration, accompanying psoriatic arthritis, systemic comorbidities, biological agent treatment, complete blood count, and biochemistry panel were evaluated. MHR was calculated as the ratio of absolute monocyte count (× 10³/µL) to serum level of HDL cholesterol (mg/dL), which was obtained from complete blood count and biochemistry panel. MHR was evaluated before and 3 months after the initiation of biological agent treatment. Exclusion criteria were pregnancy, lactation, acute infection, hematological diseases, and using cholesterol-lowering medicines.

Statistical analysis was performed using SPSS version 20.0. Quantitative variables were presented as mean±standard deviation or median (interquartile range) and categorical variables were presented as counts and percentages. Kolmogorov–Smirnov test was used to determine whether continuous variables were normally distributed or not. Differences between two groups were evaluated with Mann–Whitney U-test, Wilcoxon signed-rank test, and Kruskal–Wallis test. p < 0.05 were considered as statistically significant.

RESULTS

The study included 128 patients, 53 (41.4%) females and 75 (58.6%) males. The mean age of the patients was 51.47 ± 11.98 years (range: 20-77 years). 102 (79.7%) patients had psoriasis vulgaris, 14 (10.9%) had generalized pustular psoriasis, 9 (7%) had palmoplantar psoriasis, and 3 (2.3%) had palmoplantar pustular psoriasis. The mean psoriasis duration was 18.28 ± 11.62 years (range: 1–52 years). The mean disease duration was 19.98 ± 11.83 years in men and 15.88 ± 10.97 years in women (p = 0.049). 32 (25%) patients had psoriatic arthritis. The past medical history was unremarkable in 88 (68.8%) patients. However, 17 (13.3%) patients had hypertension, 12 (9.4%) had diabetes, 8 (6.3%) had coronary artery disease, 8 (6.3%) had hepatitis B carriage, 4 (3.1%) had chronic kidney disease, 3 (2.3%) had anxiety disorder, and 3 (2.3%) had hypothyroidism. 39 (30.5%) patients were treated with infliximab, 26 (20.3%) with adalimumab, 8 (6.3%) with etanercept, 18 (14.1%) with ixekizumab, 12 (9.4%) with secukinumab, and 25 (19.5%) with ustekinumab.

The median MHR was statistically significantly higher in men than in women (p = 0.011). The median MHR before treatment was 0.0125 (0.0081-0.0151) in patients with psoriatic arthritis and 0.0139 (0.0110-0.0198) in patients without psoriatic arthritis (p = 0.036). The median MHR 3 months after treatment was 0.0129 (0.0099-0.0151) in patients with psoriatic arthritis and 0.0143 (0.0109-0.0191) in patients without psoriatic arthritis (p = 0.227). The median MHR before treatment in patients with and without comorbidities was 0.0147 (0.0119-0.0179) and 0.0134 (0.0099-0.0229), respectively (p = 0.141). The median MHR after treatment in patients with and without comorbidities was 0.0142 (0.0098-0.0192) and 0.0138 (0.0109-0.0183), respectively (p = 0.873).

The median MHR in all patients before and 3 months after treatment was 0.0136 (0.0102-0.0183) and 0.0138 (0.0107-0.0186), respectively (p = 0.761). The median MHR before treatment was the highest in patients received secukinumab. However, no statistically significant difference was detected in median MHR before treatment according to the biological agent received (p = 0.473). The median MHR after treatment was the highest in patients received infliximab. In addition, the median MHR after treatment was statistically significantly higher in patients received infliximab compared to patients received ustekinumab and etanercept (p = 0.006, p = 0.011, respectively). The median MHR in treatment groups such as TNF-α inhibitors, IL-17 inhibitors, and IL-12/23 inhibitor was stated in table 1. The median MHR decreased after treatment with adalimumab, ixekizumab, secukinumab, and ustekinumab, whereas it increased after treatment with infliximab and etanercept (p = 0.790, p = 0.015, p = 0.754, p = 0.221, p = 0.276, p = 0.889, respectively). The change in median MHR after treatment was 0.0013 (-0.00009-0.0024) in ixekizumab group which was statistically significant (p = 0.015). The median MHR before and after treatment with infliximab, adalimumab, etanercept, ixekizumab, secukinumab and ustekinumab was stated in table 2. The effect of biological agent treatment on MHR in patients with different types of psoriasis has also been evaluated and stated in table 3.

DISCUSSION

Monocytes have been related to chronic inflammation and thus development of skin lesions and systemic comorbidities in patients with psoriasis¹¹. It has been suggested that monocytes might show increased cytokine synthesis, adhesion, and aggregation in patients with psoriasis^12,13. The severity of psoriasis has been associated, especially with peripheral blood intermediate monocytes¹¹. Nevertheless, the role of monocytes in the etiopathogenesis of psoriasis has not been fully elucidated¹¹. In addition, HDL cholesterol exhibits anti-inflammatory effects and immunomodulatory functions by regulating monocytes, macrophages, lymphocytes, and dendritic cells. However, chronic inflammation may lead to deterioration in lipid metabolism. Functional and structural changes in HDL cholesterol have been reported in patients with psoriasis¹⁵.

MHR is a novel inflammatory biomarker, especially used in cardiovascular diseases⁵. Nevertheless, a limited number of studies have investigated whether MHR indicated inflammatory status in psoriasis^11,16. Sirin et al. reported increased MHR levels in patients with psoriasis compared to healthy individuals as well as relationship between MHR and severity of psoriasis¹¹. Karabay et al. reported higher MHR levels in patients with psoriasis compared to hospital employees without an inflammatory disease. MHR was higher in patients with moderate to severe psoriasis compared to patients with mild disease¹¹. On the other hand, Yamanaka et al. suggested that biological agents might be effective in the treatment of psoriasis by inhibiting monocyte and neutrophil activation¹⁴.

Within this study, MHR was evaluated in patients with psoriasis treated with infliximab, adalimumab, etanercept, ixekizumab, secukinumab, and ustekinumab. The median MHR decreased 3 months after treatment with adalimumab, ixekizumab, secukinumab, and ustekinumab. However, statistically significant decrease in MHR was detected only in patients who received ixekizumab (p = 0.015). Since high MHR levels have been associated with poor clinical outcomes in cardiovascular diseases, ixekizumab may have a positive impact in the treatment of psoriasis patients who had cardiovascular diseases⁵. IL-17 which has a crucial role in the etiopathogenesis of psoriasis also released from T-cell infiltrated coronary artery. Therefore, it has been suggested that inhibition of IL-17 might prevent atherosclerosis¹⁷. On the other hand, Egeberg et al. reported neutral impact of ixekizumab treatment on factors related to cardiovascular diseases in patients with psoriasis¹⁸.

Furthermore, cardiovascular diseases have an increased incidence in men compared to women^19,20. However, gender differences on the risk for the development of cardiovascular diseases in patients with psoriasis have been evaluated in a few studies^20,21. For instance, Garshick et al. reported that atherosclerotic cardiovascular diseases and deep vein thrombosis were more frequent in young female patients with psoriasis compared to male psoriasis patients²¹. Sondermann et al. reported that cardiometabolic risk factors were more common in female psoriasis patients than in males. Nevertheless, the effect of gender on relationship between psoriasis and cardiometabolic diseases has not been fully elucidated²². Within this study, the median MHR was statistically significantly higher in male patients with psoriasis than in females (p = 0.011). The high MHR levels in male patients may be related to the longer psoriasis duration in males than in females. Taking into consideration that MHR has been related to cardiovascular diseases, our result may indicate higher risk in male psoriasis patients for cardiovascular diseases than in female psoriasis patients.

Early treatment of psoriasis decreases inflammatory load and thus may have a protective role from cardiometabolic diseases. However, no inflammatory biomarker has been widely accepted to be used in the course of psoriasis²³. Within this study, MHR significantly decreased in patients with psoriasis after treatment with ixekizumab. Since high MHR levels have been associated with poor prognosis in patients with cardiovascular diseases¹⁶, ixekizumab may have a positive impact in the treatment of psoriasis patients who have cardiovascular diseases. This study is unique that the effect of biological agent treatment on MHR has been evaluated in patients with psoriasis. We suggest that MHR may be useful both in establishing appropriate biological agent treatment and in the follow-up of patients with psoriasis treated with biological agents.