Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2024;14(1):e2024065 1 Effect of Treatment With Biologic Agents on the Novel Inflammatory Biomarkers Systemic Immune Inflammation Index and Systemic Inflammation Response Index for Psoriasis Funda Tamer1, Yusuf Can Edek1, Ahmet Burhan Aksakal1 1 Department of Dermatology, Gazi University School of Medicine, Ankara, Turkey Key words: biological agents, psoriasis, systemic immune inflammation index, systemic inflammation response index, treatment Citation: Tamer F, Edek YC, Aksakal AB. Effect of Treatment With Biologic Agents on the Novel Inflammatory Biomarkers Systemic Immune Inflammation Index and Systemic Inflammation Response Index for Psoriasis. Dermatol Pract Concept. 2024;14(1):e2024065. DOI: https://doi.org/10.5826/dpc.1401a65 Accepted: April 9, 2023; Published: January 2024 Copyright: ©2024 Tamer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Funda Tamer, Gazi Universitesi Hastanesi, Emniyet Mahallesi, 29, 06560, Ankara/ Turkey. Tel: +903122026129. E-mail: fundatmr@yahoo.com. Introduction: Psoriasis is a chronic cutaneous disorder with underlying systemic inflammation. The systemic immune inflammation (SII) and systemic inflammation response indexes (SIRI) are novel biomarkers that indicate systemic inflammation. Objectives: We aimed to evaluate the effect of biological agent treatment on SII and SIRI in psoriasis patients. Methods: Between April 2019 and October 2022, SII and SIRI were retrospectively evaluated in pa- tients with psoriasis before and three months after the initiation of biological agents. Results: This study included 220 patients, 101 females and 119 males. SIRI was significantly higher in male patients compared to females (P < 0.001). Although not statistically significant, SII and SIRI were higher in obese patients, patients with severe psoriasis, longer disease duration, nail involvement and patients who received previous biological agent treatment. SII was also higher in patients with hypertension, diabetes, hepatic steatosis, depression and coronary artery disease (P = 0.801, P = 0.752, P = 0.706, P = 0.079, P = 0.861, respectively), whereas SIRI was higher in patients with diabetes and de- pression (P = 0.263, P = 0.777, respectively). Both SII and SIRI statistically significantly decreased after treatment with adalimumab, infliximab, ixekizumab, secukinumab, ustekinumab and risankizumab. ABSTRACT 2 Original Article | Dermatol Pract Concept. 2024;14(1):e2024065 Introduction Psoriasis is a chronic inflammatory cutaneous disorder which has been related to comorbidities such as psoriatic ar- thritis, diabetes, obesity, cardiovascular diseases and depres- sion due to underlying systemic inflammation [1]. It has been suggested that proinflammatory cytokines, which have been implicated in the development of cutaneous findings such as tumor necrosis factor (TNF)-α, interleukin (IL)-17, IL-23, were increased in both skin and the circulation [2]. Although the systemic inflammatory response, which is not limited to the skin, may lead to tissue and organ dysfunction, the risk for the development of the disease and pathogenesis of the systemic involvement have not been fully understood [3]. It has been suggested that biological agents used in the treat- ment of psoriasis might reduce the risk of the development of systemic comorbidities and prevent the progression of exist- ing comorbidities due to their anti-inflammatory effects [4]. It is important to identify biomarkers that can indicate disease activity and remission in psoriasis. Inflammatory biomarkers, especially obtained from blood samples, may be easily performed and used in the follow-up of patients with psoriasis [5]. Various biomarkers such as neutrophil/ lymphocytes ratio, platelet/lymphocytes ratio and systemic immune inflammation index have been proposed to be used to detect systemic inflammation in patients with psoria- sis [1,5]. However, there is no consensus on the biomarkers that can be used to create an optimized treatment strategy in the management of psoriasis [5]. Systemic immune inflammation index (SII) and systemic inflammation response index (SIRI) are new biomarkers that have been reported to indicate systemic inflammation [6]. SII and SIRI have been associated with various disorders such as hepatic steatosis, cardiovascular diseases, risk of cancer devel- opment and depression [6-9]. In a few studies, high SII levels have been reported in patients with psoriasis [10,11]. Recently, Sugimoto et al reported that patients with psoriatic arthritis were likely to have high SIRI levels [1]. However, SII and SIRI have not been adequately studied in patients with psoriasis. Objectives The aim of this study was to evaluate the SII and SIRI in patients with psoriasis treated with biological agents. Methods Gazi University Ethics Committee approved this study (approval number: 2022-1108). Medical records of patients who were admitted for the treatment of psoriasis between April 2019 and October 2022 were retrospectively reviewed. Patients with psoriasis aged 18 years and over and who were treated with biological agents were included in this study. Psoriasis type, psoriasis duration, accompanying psoriatic arthritis and systemic diseases, psoriasis treatment, psoriasis area and severity index (PASI) and body mass index (BMI) were noted. PASI less than 10 was regarded as mild to moderate psoriasis, whereas PASI greater than 10 was severe dis- ease  [12]. Obesity was defined as body mass index (BMI) ≥ 30 kg/m2  [13]. In addition, SII and SIRI were evaluated before and three months after treatment with biological agents. SII and SIRI were calculated using the data obtained from complete blood count; SII= platelet count (x103/µL) X neutrophil count (x103/µL) / lymphocyte count (x103/µL) and SIRI= neutrophil count (x103/µL) X monocyte count (x103/µL) / lymphocyte count (x103/µL) [14,15]. Statistical analysis was performed using SPSS version 25.0. Continuous variables were presented as mean ± stan- dard deviation or median (interquartile range), whereas cat- egorical variables were presented as counts and percentages. Kolmogorov-Smirnov test was used to detect the normality of the distribution of the variables. The differences between the groups were evaluated by Mann-Whitney U test and Wilcoxon signed ranks test. P < 0.05 was considered statis- tically significant. Results This study included 220 patients, 101 (45.9%) females and 119 (54.1%) males with a mean age of 49.61±13.29 years (range: 20-77 years) (Table 1). The median psoriasis duration was 20 (16) years in male patients and 15 (18) years in females (p=0.006). The median PASI and BMI was 14  (8.5) and 28.6 (8) kg/m2, respectively. Sixty-six (30%) patients were treated with ustekinumab, 56 (25.5%) with ixekizumab, 43 (19.5%) with adalimumab, 24 (10.9%) with secukinumab, 15 (6.8%) with infliximab, 11 (5%) with ri- sankizumab and 5 (2.3%) with guselkumab. Conclusions: SII and SIRI may indicate the severity of psoriasis as well as SII may be associated with psoriatic arthritis, hypertension, hepatic steatosis and coronary artery disease in patients with psoriasis. There is no consensus on the biomarkers that can be used to create an optimized treatment strategy in psoriasis. Therefore, SII and SIRI may be helpful in making the choice of treatment and in the follow-up of patients with psoriasis treated with biological agents. Original Article | Dermatol Pract Concept. 2024;14(1):e2024065 3 Although not statistically significant, higher SII levels were detected in male patients, patients with severe psori- asis, psoriasis duration longer than 20 years, patients with psoriatic arthritis, nail involvement, obese patients and patients previously treated with biological agents (P = 0.855, P =  0.267, P = 0.466, P = 0.968, P = 0.210, P = 0.071, P = 0.921, respectively). SII was also higher in patients with hypertension, diabetes, hepatic steatosis, depression and coronary artery disease (P = 0.801, P = 0.752, P = 0.706, P = 0.079, P = 0.861, respectively) (Table 2). SIRI was statistically significantly higher in male patients compared to females (P < 0.001). Although not statistically sig- nificant, higher SIRI levels were detected in patients with severe psoriasis, nail findings, psoriasis duration longer than 20 years, obese patients and patients previously treated with biological agents (P = 0.295, P = 0.904, P = 0.381, P = 0.185, P = 0.921, respectively). SIRI was also higher in patients with diabetes and depression (P = 0.263, P = 0.777, respectively) (Table 3). SII statistically significantly decreased in all patients with psoriasis three months after biological agent treat- ment (P < 0.001). In addition, SII significantly decreased in treatment groups such as TNF-α inhibitors, IL-17 inhibitors and IL-12/23 inhibitor (P < 0.001, P < 0.001, P < 0.001, respectively). SII also statistically significantly decreased in patients treated with adalimumab, infliximab, ixekizumab, secukinumab, ustekinumab and risankizumab (P < 0.001, P = 0.002, P < 0.001, P = 0.004, P < 0.001, P = 0.013, respec- tively) (Table 4) (Figure 1). SIRI statistically significantly decreased in all patients with psoriasis three months after biological agent treat- ment (P < 0.001). SIRI also significantly decreased in pa- tients treated with adalimumab, infliximab, ixekizumab, secukinumab, ustekinumab and risankizumab (P < 0.001, P = 0.001, P = 0.002, P = 0.018, P < 0.001, P = 0.041, respec- tively) (Table 5 and Figure 2). Conclusions SII and SIRI have been proposed as novel biomarkers which might indicate systemic inflammation, however, the use of SII and SIRI in patients with psoriasis was evaluated in lim- ited studies [1]. For instance, Yorulmaz et al reported higher SII levels in patients with psoriasis compared to healthy in- dividuals as well as SII was positively correlated with PASI and presence of psoriatic arthritis [10]. Similarly, Melikoglu et al reported an association between disease severity and SII levels in patients with psoriasis. In addition, Melikoglu et al reported no difference in SII levels in patients with different Table 1. The characteristics of the patients with psoriasis. Characteristics Gender, N (%) Female, 101 (45.9%) Male, 119 (54.1%) Mean age±SD (years) 49.61±13.29 Psoriasis type, N (%) Psoriasis vulgaris, 195 (88.6%) Palmoplantar psoriasis, 13 (5.9%) Generalized pustular, 12 (5.5%) Psoriasis duration, median (IQR) (years) 18 (16) Psoriatic arthritis, N (%) Present, 66 (30%) None, 154 (70%) Nail findings, N (%) Present, 104 (47.3%) None, 116 (52.7%) Past medical history, N (%) Unremarkable, 100 (45.5%) Hypertension, 59 (26.8%) Hyperlipidemia, 45 (20.5%) Diabetes mellitus, 32 (14.5%) Hepatic steatosis, 24 (10.9%) Hepatitis B virus carriage, 20 (9.1%) Depression, 19 (8.6%) Coronary artery disease, 16 (7.3%) Thyroid disease, 9 (4.1%) Asthma, 6 (2.7%) Previous treatment, N (%) Conventional treatment, 214 (97.3%) Biological agents, 93 (42.3%) Phototherapy, 70 (31.8%) IQR = interquartile range; SD = Standard deviation. This study included 220 patients with a mean age of 49.61±13.29 years. Most of the patients (88.6%) had psoriasis vulgaris. The frequency of psoriatic arthritis was 30%. 4 Original Article | Dermatol Pract Concept. 2024;14(1):e2024065 Table 2. Systemic immune inflammation index in patients with psoriasis. Systemic Immune Inflammation Index median (IQR) P value Female 618 (513) Male 655 (400) 0.855 With arthritis 656 (430) Without arthritis 642 (419) 0.968 Psoriasis vulgaris 644 (426) Other types 705 (363) 0.456 Nail involvement 696 (434) Without nail involvement 600 (401) 0.210 Psoriasis duration (≤20 years) 643 (429) Psoriasis duration (>20 years) 656 (428) 0.466 Mild/ moderate psoriasis 624 (388) Severe psoriasis 652 (490) 0.267 Non-obese 642 (428) Obese 718 (619) 0.071 Previous biological treatment 658 (411) Biologic-naïve 642 (436) 0.921 Unremarkable medical history 645 (395) With a chronic disease 648 (461) 0.763 With hypertension 687 (566) Without hypertension 642 (411) 0.801 With hyperlipidemia 598 (388) Without hyperlipidemia 658 (436) 0.113 With diabetes mellitus 651 (611) Without diabetes mellitus 645 (403) 0.752 With hepatic steatosis 735 (461) Without hepatic steatosis 643 (418) 0.706 With hepatitis B virus carriage 608 (431) Without hepatitis B virus carriage 650 (421) 0.915 With depression 782 (239) Without depression 608 (418) 0.079 With coronary artery disease 692 (521) Without coronary artery disease 643 (416) 0.861 IQR = interquartile range. Higher SII levels were detected in male patients, patients with severe psoriasis, patients with psoriatic arthritis, nail findings and obese patients. SII may indicate the severity of psoriasis. Table 3. Systemic inflammation response index in patients with psoriasis. Systemic inflammation response index median (IQR) P value Female 1.02 (0.83) Male 1.28 (1.10) <0.001 With arthritis 1.09 (0.75) Without arthritis 1.21 (0.99) 0.07 Psoriasis vulgaris 1.18 (0.90) Other types 1.19 (1.06) 0.956 Nail involvement 1.20 (0.87) Without nail involvement 1.16 (0.91) 0.904 Psoriasis duration (≤20 years) 1.13 (0.91) Psoriasis duration (>20 years) 1.25 (0.99) 0.381 Mild/ moderate psoriasis 1.13 (0.75) Severe psoriasis 1.19 (1.07) 0.295 Non-obese 1.05 (0.74) Obese 1.30 (1.08) 0.185 Previous biological treatment 1.25 (1.19) Biologic-naïve 1.16 (0.76) 0.921 Unremarkable medical history 1.16 (1.01) With a chronic disease 1.19 (0.79) 0.753 With hypertension 1.16 (1.00) Without hypertension 1.19 (0.87) 0.607 With hyperlipidemia 1.18 (0.67) Without hyperlipidemia 1.20 (1.01) 0.806 With diabetes mellitus 1.23 (1.11) Without diabetes mellitus 1.16 (0.89) 0.263 With hepatic steatosis 1.13 (0.98) Without hepatic steatosis 1.19 (0.90) 0.472 With hepatitis B virus carriage 1.13 (0.98) Without hepatitis B virus carriage 1.19 (0.90) 0.424 With depression 1.39 (1.22) Without depression 1.18 (0.89) 0.777 With coronary artery disease 1.01 (0.85) Without coronary artery disease 1.20 (0.90) 0.185 IQR = interquartile range. SIRI was statistically significantly higher in male patients compared to females. This result may be related to longer psoriasis duration in male patients than in females. types of psoriasis [16]. However, Ibrahim et al reported that patients with pustular psoriasis had higher SII levels com- pared to those with psoriasis vulgaris and erythrodermic psoriasis [17]. Dincer Rota et al reported higher SII levels in patients with psoriasis compared to patients with dermato- logical disorders other than psoriasis. SII was also associated with nail changes due to psoriasis [11]. Kelesoglu Dincer et al reported higher SII levels in patients with psoriatic arthritis Original Article | Dermatol Pract Concept. 2024;14(1):e2024065 5 Table 4. The effect of biological agent treatment of psoriasis on systemic immune inflammation index. Systemic immune inflammation index median (IQR) P value Before treatment After treatment All patients 646 (420) 492 (324) <0.001 TNF-α inhibitors 607 (384) 408 (341) <0.001 IL-17 inhibitors 703 (485) 528 (298) <0.001 IL-12/23 inhibitor 603 (468) 512 (344) <0.001 IL-23 inhibitor 689 (390) 467 (182) 0.056 Adalimumab 532 (278) 374 (327) <0.001 Infliximab 867 (356) 487 (469) 0.002 Ixekizumab 682 (432) 539 (314) <0.001 Secukinumab 744 (624) 454 (276) 0.004 Ustekinumab 603 (468) 512 (344) <0.001 Risankizumab 559 (392) 443 (145) 0.013 Guselkumab 859 (468) 501 (1147) 0.893 IL = interleukin; IQR = interquartile range;TNF-α = tumor necrosis factor-α. Systemic immune inflammation index decreased in patients treated with adalimumab, infliximab, ixekizumab, secukinumab, usteki- numab and risankizumab. Systemic immune inflammation index may be useful in the follow-up of patients treated with biological agents. Figure 1. The effect of biological agents on systemic immune inflammation index. Systemic immune inflammation index decreased in all treatment groups. Table 5. The effect of biological agent treatment of psoriasis on systemic inflammation response index. Systemic inflammation response index median (IQR) P value Before treatment After treatment All patients 1.18 (0.90) 0.95 (0.74) <0.001 TNF-α inhibitors 1.15 (0.73) 0.8 (0.58) <0.001 IL-17 inhibitors 1.16 (1.08) 1.00 (0.88) <0.001 IL-12/23 inhibitor 1.17 (0.79) 0.95 (0.68) <0.001 IL-23 inhibitor 1.52 (1.42) 0.97 (0.78) 0.056 Adalimumab 1.05 (0.68) 0.78 (0.58) <0.001 Infliximab 1.73 (1.14) 0.88 (1.04) 0.001 Ixekizumab 1.17 (1.14) 1.00 (0.93) 0.002 Secukinumab 1.07 (1.27) 1.01 (0.94) 0.018 Ustekinumab 1.17 (0.79) 0.95 (0.68) <0.001 Risankizumab 1.75 (1.69) 0.88 (1.08) 0.041 Guselkumab 1.28 (0.79) 0.98 (3.03) 0.686 IL = interleukin; IQR = interquartile range; TNF-α = tumor necrosis factor-α. Systemic inflammation response index decreased in treatment groups such as TNF-α inhibitors, IL-17 inhibitors and IL-12/23 in- hibitor. Systemic inflammation response index may be useful in the follow-up of patients treated with biological agents. than in healthy controls as well as positive correlation be- tween SII and severity of psoriatic arthritis [18]. Sugimoto et al reported no significant difference in SII and SIRI levels in patients with psoriasis vulgaris and psoriatic arthritis and in healthy individuals. On the other hand, a positive rela- tionship was detected between PASI and both SII and SIRI. Sugimoto et al also revealed that SIRI might indicate higher possibility of the diagnosis of psoriatic arthritis. In addition, 6 Original Article | Dermatol Pract Concept. 2024;14(1):e2024065 with adalimumab, infliximab, ixekizumab, secukinumab, ustekinumab and risankizumab significantly reduced SII and SIRI levels in patients with psoriasis. Herein, we presented a unique and comprehensive study on SII and SIRI in patients with psoriasis treated with biological agents. Although a va- riety of biological agents have been developed to be used in the treatment of psoriasis, there is lack of biomarkers widely preferred to asses disease severity, psoriatic arthritis and co- morbidities and to be used during the course of treatment of psoriasis with biological agents [5,19-21]. Our results will contribute to the literature on the use of SII and SIRI in the management of psoriasis patients with biological agents. Since SII and SIRI can be easily performed, in clinical prac- tice both biomarkers may be helpful in making treatment choice and in the follow-up of patients with psoriasis treated with biological agents. References 1. Sugimoto E, Matsuda H, Shibata S, et al. Impact of pretreatment systemic inflammatory markers on treatment persistence with bi- ologics and conventional systemic therapy: a retrospective study of patients with psoriasis vulgaris and psoriatic arthritis. J Clin Med. 2023;12(8):3046. DOI: 10.3390/jcm12083046. PMID: 37109382. PMCID: PMC10145777. 2. Korman NJ. Management of psoriasis as a systemic disease: what is the evidence? Br J Dermatol. 2020;182(4):840-848. DOI: 10.1111/bjd.18245. PMID: 31225638.  PMCID: PMC7187293. 3. Tashiro T, Sawada Y. Psoriasis and systemic inflammatory disorders. Int J Mol Sci. 2022;23(8):4457. DOI: 10.3390 /ijms23084457. PMID: 35457278. PMCID: PMC9028262. adherence to biological agent treatment of patients with pso- riasis vulgaris and psoriatic arthritis was not related to high SII or SIRI levels [1]. Within this study, SII was higher in males, obese patients, patients with severe psoriasis and longer disease duration, patients with psoriatic arthritis, nail findings and patients who received previous biological agent treatment. SII was also higher in patients with comorbidities such as hyperten- sion, diabetes, hepatic steatosis, depression and coronary artery disease. On the other hand, SIRI was statistically sig- nificantly higher in male patients compared to females. This result may be related to longer psoriasis duration in male pa- tients than in females. SIRI was also higher in obese patients, patients with severe psoriasis, longer disease duration and nail involvement and patients who received previous biolog- ical agent treatment. In addition, SIRI was higher in patients with comorbidities such as diabetes and depression. SII and SIRI were similar in patients with psoriasis vulgaris and in patients with other types of psoriasis. Both SII and SIRI sig- nificantly decreased after treatment with TNF-α inhibitors such as adalimumab and infliximab, IL-17 inhibitors such as ixekizumab and secukinumab, IL-23 inhibitor such as ri- sankizumab, as well as ustekinumab. Our results revealed that both SII and SIRI might in- dicate severity of psoriasis, however, SII might also be as- sociated with psoriatic arthritis. Furthermore, SII may be associated with hypertension, diabetes, hepatic steatosis, depression and coronary artery disease in patients with pso- riasis, whereas SIRI with diabetes and depression. Treatment Figure 2. The effect of biological agents on systemic inflammation response index. Systemic inflammation response index decreased in all treatment groups. Original Article | Dermatol Pract Concept. 2024;14(1):e2024065 7 higher cardiovascular risk according to seven risk algorithms: results of a 10-year single-center retrospective study and clini- cal management of psoriatic patients with cardiovascular risk. Dermatol Ther. 2020;33(6):14451. DOI: 10.1111/dth.14451. PMID: 33098612. 13. Liu N, Birstler J, Venkatesh M, Hanrahan L, Chen G, Funk L. Obe- sity and BMI cut points for associated comorbidities: electronic health record study. J Med Internet Res. 2021;23(8):24017. DOI: 10.2196/24017. PMID: 34383661. PMCID: PMC8386370. 14. He L, Xie X, Xue J, Xie H, Zhang Y. Association of the systemic immune-inflammation index with all-cause mortality in patients with arteriosclerotic cardiovascular disease. Front Cardiovasc Med. 2022;9:952953. DOI: 10.3389/fcvm.2022.952953. PMID: 36172591.  PMCID: PMC9510918. 15. Han K, Shi D, Yang L, et al. Prognostic value of systemic inflam- matory response index in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Ann Med. 2022;54(1):1667-1677. DOI: 10.1080/07853890.2022.2083671. PMID: 35695557. PMCID: PMC9225721. 16. Melikoglu M, Pala E. Systemic Immune-inflammation in- dex as a biomarker of psoriasis severity. Arch Basic Clin Res. 2023;5(2):291-295. DOI: 10.5152/ABCR.2023.22124. 17. Ibrahim SH, Guan M, Li S. Systemic immune inflammatory index is associated with pustular psoriasis: a single center retrospective study. J Cosmet Dermatol Sci Appl. 2022;12(4):174-186. DOI: 10.4236/jcdsa.2022.124015. 18. Kelesoglu Dincer AB, Sezer S. Systemic Immune inflammation index as a reliable disease activity marker in psoriatic arthritis. J Coll Physicians Surg Pak. 2022;32(6):773-778. DOI: 10.29271 /jcpsp.2022.06.773. PMID: 35686411. 19. Ramessur R, Corbett M, Marshall D, et al. Biomarkers of disease progression in people with psoriasis: a scoping review. Br J Der- matol. 2022;187(4):481-493. DOI: 10.1111/bjd.21627.PMID: 35482474. PMCID: PMC9796834. 20. Molteni RE. Biomarkers in the pathogenesis, diagnosis, and treatment of psoriasis. Psoriasis (Auckl). 2012;2:55-66. DOI: 10.2147/PTT.S24995. 21. Jiménez C, Bordagaray MJ, Villarroel JL, et al. Biomarkers in oral fluids as diagnostic tool for psoriasis. Life. 2022;12(4):501. DOI: 10.3390/life12040501. PMID: 35454992.  PMCID: PMC9027180. 4. Wu JJ, Kavanaugh A, Lebwohl MG, Gniadecki R, Merola JF. Psoriasis and metabolic syndrome: implications for the man- agement and treatment of psoriasis. J Eur Acad Dermatol Ve- nereol. 2022;36(6):797-806. DOI: 10.1111/jdv.18044. PMID: 35238067. PMCID: PMC9313585. 5. Honma M, Nozaki H. Molecular pathogenesis of psoria- sis and biomarkers reflecting disease activity. J Clin Med. 2021;10(15):3199. DOI: 10.3390/jcm10153199. PMID: 34361983.  PMCID: PMC8346978. 6. Xia Y, Xia C, Wu L, Li Z, Li H, Zhang J. Systemic immune in- flammation index (SII), system inflammation response index (SIRI) and risk of all-cause mortality and cardiovascular mortal- ity: a 20-year follow-up cohort study of 42,875 US adults. J Clin Med. 2023;12(3):1128. DOI: 10.3390/jcm12031128. PMID: 36769776. PMCID: PMC9918056. 7. Fest J, Ruiter R, Mulder M, et al. The systemic immune- inflammation index is associated with an increased risk of incident cancer-a population-based cohort study. Int J Can- cer. 2020;146(3):692-698. DOI: 10.1002/ijc.32303. PMID: 30924141. PMCID: PMC6916270. 8. Song Y, Guo W, Li Z, Guo D, Li Z, Li Y. Systemic immune-inflammation index is associated with hepatic ste- atosis: evidence from NHANES 2015-2018. Front Immunol. 2022;13:1058779. DOI: 10.3389/fimmu.2022.1058779. PMID: 36466832. PMCID: PMC9718528. 9. Li X, Huan J, Lin L, Hu Y. Association of systemic inflammatory biomarkers with depression risk: results from national health and nutrition examination survey 2005-2018 analyses. Front Psy- chiatry. 2023;14:1097196. DOI: 10.3389/fpsyt.2023.1097196. PMID: 36846218. PMCID: PMC9945233. 10. Yorulmaz A, Hayran Y, Akpinar U, Yalcin B. Systemic immune- inflammation index (SII) predicts increased severity in psoriasis and psoriatic arthritis. Curr Health Sci J. 2020;46(4):352-357. DOI: 10.12865/CHSJ.46.04.05. PMID: 33717509. PMCID: PMC7948012. 11. Dincer Rota D, Tanacan E. The utility of systemic-immune in- flammation index for predicting the disease activation in pa- tients with psoriasis. Int J Clin Pract. 2021;75(6):e14101. DOI: 10.1111/ijcp.14101. PMID: 33619821. 12. Conforti C, Currado D, Navarini L, et al. Moderate-to-severe plaque psoriasis, described by PASI ≥10%, can be associated with