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Jiang W, Li Q, Zheng W. The impact of biologics targeting the IL-17 and IL-23 pathways on metabolic indicators in plaque psoriasis. Arch Dermatol Res 2025; 317:643. [PMID: 40148675 DOI: 10.1007/s00403-025-04174-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 03/04/2025] [Accepted: 03/09/2025] [Indexed: 03/29/2025]
Abstract
This study aims to compare the efficacy of IL-17 and IL-23 biologics in the treatment of plaque psoriasis (Psoriasis vulgaris) in patients with metabolic syndrome (MetS) and to explore the effects of different biologics on metabolic indicators, particularly regarding the differences in efficacy during long-term treatment. This is a randomized controlled clinical trial involving 120 moderates to severe plaque psoriasis patients, of which 60 have metabolic syndrome and 60 do not. The patients were randomly assigned to three groups: IL-17 biologics group, IL-23 biologics group, and cyclosporine control group. Treatment lasted for three months, with evaluation indicators including psoriatic lesion assessment (PASI score), blood glucose levels, lipid profile (triglycerides, HDL-C), inflammatory markers (CRP, ESR, IL-6), etc. Patients were assessed at baseline, after one month, and after three months of treatment for both clinical efficacy and changes in metabolic indicators. Both IL-17 and IL-23 biologics demonstrated superior efficacy compared to cyclosporine in treating plaque psoriasis. After one month and three months of treatment, PASI scores in the IL-17 and IL-23 groups were significantly lower than in the control group, and the therapeutic effects were more pronounced (P < 0.05). The IL-17 and IL-23 groups also showed better improvements in blood glucose, blood lipids (TG and HDL-C), and inflammatory markers (CRP, ESR, IL-6) compared to the control group. After three months of treatment, fasting blood glucose, fasting insulin, triglycerides, and CRP levels were significantly lower in the IL-17 and IL-23 groups than in the control group (P < 0.05). Metabolic syndrome had some impact on treatment outcomes, with the efficacy of IL-17 and IL-23 biologics being lower in patients with metabolic abnormalities compared to those without metabolic syndrome. However, the IL-23 biologic showed less impact from metabolic syndrome. IL-17 biologics had a rapid effect in the short term, while IL-23 biologics demonstrated superior efficacy in long-term treatment, particularly at the three-month mark, where both efficacy and metabolic improvements were better than the IL-17 group. Both IL-17 and IL-23 biologics are more effective than cyclosporine in treating plaque psoriasis and can improve metabolic indicators in patients. Although metabolic syndrome impacts the efficacy of IL-17 biologics, IL-23 biologics are less affected by metabolic syndrome and demonstrate better long-term efficacy. Therefore, IL-23 biologics are recommended for long-term treatment in plaque psoriasis patients with metabolic syndrome.
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Affiliation(s)
- Wenzhuo Jiang
- Department of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, No. 1, Renmin Avenue East, Guangxi Zhuang Autonomous Region, Nanning, 530021, China
| | - Qiujv Li
- Department of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, No. 1, Renmin Avenue East, Guangxi Zhuang Autonomous Region, Nanning, 530021, China
| | - Wenjun Zheng
- Department of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, No. 1, Renmin Avenue East, Guangxi Zhuang Autonomous Region, Nanning, 530021, China.
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Chandratre P, Sabido-Sauri R, Zhao SS, Abhishek A. Gout, Hyperuricemia and Psoriatic Arthritis: An Evolving Conundrum. Curr Rheumatol Rep 2025; 27:22. [PMID: 40146321 DOI: 10.1007/s11926-025-01187-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/05/2025] [Indexed: 03/28/2025]
Abstract
PURPOSE OF REVIEW The co-existence of gout and psoriatic disease (PD) is long standing but more recently frequently encountered in clinical settings due to increased awareness of their shared comorbidities and clinical phenotypes, often posing diagnostic and management challenges. Here we review the overlap in gout and PD focusing on shared clinical features, common inflammatory pathophysiology and comorbidities which may prompt a diagnosis of 'Psout' and lead to changes in management. RECENT FINDINGS Several epidemiological studies have highlighted the increased incidence of hyperuricemia and gout in those with PD and vice versa. Although the role of monosodium urate (MSU) crystals is well recognized in activation of innate immunity via inflammasome and NETosis, it is likely that they have a role in triggering adaptive immunity via antigen presenting cells and their autocrine effect on keratinocytes in psoriasis (PSO), ultimately leading to T cell secretion of proinflammatory cytokines such as IL17. Hyperuricemia (HU) is common in PD (up to 30%) and underpins metabolic syndrome comorbidities that are common to both gout and PD. Shared clinical phenotypes and co-morbidities are routinely observed in clinical practice yet there is a paucity of evidence evaluating the effect of treating hyperuricemia/gout on PD activity, with small scale clinical trials showing a positive effect. There were no studies to our knowledge assessing gout disease activity with concurrent treatment of PD. The association between gout and PD is likely due to shared multimorbidity and perhaps to a smaller extent, the direct role of HU in triggering the release of proinflammatory cytokines in PD. There is often a significant overlap in clinical and radiological presentation of gout and Psoriatic arthritis (PsA). In those with atypical response to standard treatments of the primary condition (either gout or PsA), it would be plausible to investigate and treat for the other 'secondary' condition. This is particularly relevant and relatively feasible in those with PsA (and features of HU and multimorbidity) who respond poorly to standard immunomodulating treatments.
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Affiliation(s)
- Priyanka Chandratre
- Department of Medicine, Division of Rheumatology, The Ottawa Hospital and Ottawa Hospital Research Institute, Ottawa, Canada.
| | - Ricardo Sabido-Sauri
- Department of Medicine, Division of Rheumatology, The Ottawa Hospital and Ottawa Hospital Research Institute, Ottawa, Canada
| | - Sizheng Steven Zhao
- Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology Medicine and Health, Centre for Musculoskeletal Research, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
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Smith A, Karahasan A, Yi D, Yapabandara S, Elhindi J, Fernandez-Penas P, Chow C, Zaman S. Biologic Therapy and Cardiometabolic Risk in Psoriasis: A Retrospective Review. Dermatol Ther (Heidelb) 2025; 15:201-212. [PMID: 39843708 PMCID: PMC11785865 DOI: 10.1007/s13555-024-01327-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 12/11/2024] [Indexed: 01/24/2025] Open
Abstract
INTRODUCTION Psoriasis is a systemic inflammatory disease with increased cardiometabolic risk including dyslipidaemia and diabetes. Biologic therapy effectively treats the cutaneous inflammatory burden of psoriasis and evolving evidence suggests potential to reduce systemic inflammatory sequalae that can elevate cardiovascular risk. This study aimed to assess the change in cardiometabolic risk markers in a cohort of patients with psoriasis treated with 1 year of continuous biologic treatment. METHODS A retrospective review was conducted of patients receiving biologic therapy for chronic plaque psoriasis in a single dermatology centre at a major tertiary hospital in Sydney, Australia. The effect of biologic therapy on psoriasis was assessed using the psoriasis area severity index (PASI). Cardiometabolic risk markers assessed included lipid profile (total cholesterol [TC], low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol and triglycerides [TG]) and haemoglobin A1c (HbA1c). Measurements at baseline and 1 year were compared using paired t tests for analysis of the parameters which approximated normal distribution (TC, LDL, HDL) and Wilcoxon signed-rank test for analysis of those which did not (TG, HbA1c, PASI). Two-tailed P values < 0.05 were considered significant. RESULTS A total of 200 patients were reviewed, of which 39 had complete data sets. The participants' ages ranged from 21 to 85 years (mean 51, SD 16.9). Of the 39 participants, 31 (79.5%) were male, 8 (20.5%) were female; 26 (67%) were biologic experienced (BE) and 13 (33%) were biologic naïve (BN). The mean PASI at baseline (for BN + BE) was 13.4 (SD 9.8). The biologic agents used, according to frequency, included risankizumab, with 14 participants (35.9%), secukinumab by 7 (17.9%), ustekinumab by 6 (15.4%), ixekizumab by 6 (15.4%), guselkumab by 3 (7.7%), infliximab by 2 (5.1%), and adalimumab by 1 (2.6%). After 12 months, significant skin improvement was seen [PASI reduced from 13.43 (SD 9.8) to 1.1 (SD 2.1), p < 0.001]. There was no significant change in lipid profile, including TC (mean difference - 0.1 mmol/L, p = 0.532), LDL-C (mean difference = - 0.1 mmol/L, p = 0.476), HDL (mean difference = - 0.1 mmol/L, p = 0.125), triglycerides (mean difference = 0.0 mmol/l, p = 0.748) or HbA1c (mean difference 0.38%, p = 0.468). CONCLUSION Markers of cardiometabolic risk (lipid profile and HbA1c) did not significantly improve after 1 year of biologic therapy despite significant reduction in psoriasis skin severity. Further research in larger cohorts is needed to elucidate the benefits, if any, of biologic therapy on cardiometabolic parameters in individuals with psoriasis, in order to optimise care for this vulnerable cohort.
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Affiliation(s)
- Annika Smith
- Department of Dermatology, Westmead Hospital, Sydney, NSW, Australia.
- Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
- Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
| | - Aidin Karahasan
- Department of Dermatology, Westmead Hospital, Sydney, NSW, Australia
- Research and Education Network, Western Sydney Local Health District, Sydney, NSW, Australia
| | - Deborah Yi
- Department of Dermatology, Westmead Hospital, Sydney, NSW, Australia
- Research and Education Network, Western Sydney Local Health District, Sydney, NSW, Australia
| | - Sanjay Yapabandara
- Department of Dermatology, Westmead Hospital, Sydney, NSW, Australia
- Research and Education Network, Western Sydney Local Health District, Sydney, NSW, Australia
| | - James Elhindi
- Research and Education Network, Western Sydney Local Health District, Sydney, NSW, Australia
| | - Pablo Fernandez-Penas
- Department of Dermatology, Westmead Hospital, Sydney, NSW, Australia
- Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
- Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - Clara Chow
- Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
- Department of Cardiology, Westmead Hospital, Sydney, NSW, Australia
| | - Sarah Zaman
- Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
- Department of Cardiology, Westmead Hospital, Sydney, NSW, Australia
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Wilkinson MJ, Shapiro MD. Immune-Mediated Inflammatory Diseases, Dyslipidemia, and Cardiovascular Risk: A Complex Interplay. Arterioscler Thromb Vasc Biol 2024; 44:2396-2406. [PMID: 39479765 PMCID: PMC11602385 DOI: 10.1161/atvbaha.124.319983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2024]
Abstract
Individuals with autoimmune inflammatory diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and psoriasis, are at increased risk for cardiovascular disease. While these diseases share common features of systemic inflammation, the impact of individual autoimmune inflammatory conditions on circulating lipids and lipoproteins varies by specific disease, disease activity, and the immune-suppressing medications used to treat these conditions. A common feature observed in many autoimmune inflammatory diseases is the development of a proatherogenic dyslipidemic state, characterized by dysfunctional HDLs (high-density lipoproteins) and increased oxidation of LDLs (low-density lipoproteins). Various disease-modifying antirheumatic drugs also have complex and variable effects on lipids, and it is critical to take this into consideration when evaluating lipid-related risk in individuals with immune-mediated inflammatory conditions. This review aims to critically evaluate the current understanding of the relationship between immune-mediated inflammatory diseases and dyslipidemia, the underlying mechanisms contributing to atherogenesis, and the impact of various pharmacotherapies on lipid profiles and cardiovascular risk. We also discuss the role of lipid-lowering therapies, particularly statins, in managing residual risk in this high-risk population and explore the potential of emerging therapies with complementary anti-inflammatory and lipid-lowering effects.
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Affiliation(s)
- Michael J. Wilkinson
- Division of Cardiovascular Medicine, Department of Medicine, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA
| | - Michael D. Shapiro
- Center for Prevention of Cardiovascular Disease, Section on Cardiovascular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
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Merzel Šabović EK, Kraner Šumenjak T, Janić M. Residual metabolic burden in young psoriasis patients successfully treated with biologics. Arch Dermatol Res 2024; 316:647. [PMID: 39331218 PMCID: PMC11436468 DOI: 10.1007/s00403-024-03403-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 07/25/2024] [Accepted: 09/14/2024] [Indexed: 09/28/2024]
Abstract
Metabolic disorders are common in patients with psoriasis and contribute significantly to an increased cardiovascular risk. While biologic therapy is very successful in clearing skin lesions, its impact on metabolic parameters is uncertain. Our aim was to investigate the residual metabolic burden in psoriasis patients successfully treated with biologic therapy. We conducted a cross-sectional study of 80 young patients (54 men, 26 women, aged 30-45 years) successfully treated with either adalimumab, secukinumab or guselkumab and topical therapy or methotrexate, and 20 healthy controls. Anthropometric parameters, lipid levels and metabolic indices (HOMA-IR, TyG index and FIB-4 index) were measured. Patients did not receive any other treatments to exclude confounding effects. After analysis, we found that patients treated with three different biologics had similar metabolic status, only the FIB-4 index was higher in the adalimumab group than in the secukinumab and guselkumab treatment groups. There were no significant differences between the patients treated with biologics and the control group. The comparison with patients treated topically or with methotrexate showed that only triglyceride levels, HOMA-IR, TyG index, and FIB-4 index were elevated in patients treated with adalimumab compared to patients treated with topical therapy. Finally, metabolic status was also similar in patients treated with methotrexate or topical therapy. In conclusion, this study suggests that psoriasis patients successfully treated with biologics have similar metabolic parameters to the control group and patients treated with topical therapy or methotrexate. This indicates that there is no significant residual metabolic burden in young patients successfully treated with biologics. These results are clinically relevant and should be considered in the treatment of psoriasis patients.The study is registered at http://clinicaltrials.gov (identifier: NCT05957120). Date of registration: 24th of July 2023.
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Affiliation(s)
- Eva Klara Merzel Šabović
- Department of Dermatovenerology, University Medical Centre Ljubljana, Gradiškova ulica 10, Ljubljana, Slovenia.
- Faculty of Medicine, University of Ljubljana, Vrazov trg 2, Ljubljana, Slovenia.
| | - Tadeja Kraner Šumenjak
- Faculty of Agriculture and Life Sciences, University of Maribor, Pivola 10, Hoče, Slovenia
| | - Miodrag Janić
- Faculty of Medicine, University of Ljubljana, Vrazov trg 2, Ljubljana, Slovenia
- Clinical Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Zaloška 7, Ljubljana, Slovenia
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Lebwohl M, Merola JF, Strober B, Armstrong A, Yoshizaki A, Gisondi P, Szilagyi B, Peterson L, de Cuyper D, Cross N, Davies O, Gottlieb AB. Bimekizumab safety in moderate to severe plaque psoriasis: Rates of hepatic events and changes in liver parameters over 2 years in randomized phase 3/3b trials. J Am Acad Dermatol 2024; 91:281-289. [PMID: 38588819 DOI: 10.1016/j.jaad.2024.03.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 02/23/2024] [Accepted: 03/12/2024] [Indexed: 04/10/2024]
Abstract
BACKGROUND Patients with psoriasis are at increased risk of liver function abnormalities. OBJECTIVE Explore rates of hepatic treatment-emergent adverse events (TEAEs) and changes in liver parameters in bimekizumab-treated patients with psoriasis. METHODS Data are reported from 5 phase 3/3b trials over 2 years. Hepatic TEAEs, laboratory elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST), and changes in clinical markers of liver fibrosis (Fibrosis-4 [FIB-4] Index and AST to Platelet Ratio Index [APRI]) are reported. TEAEs are presented using exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY). RESULTS 2186 patients received ≥1 bimekizumab dose. Over 2 years, the EAIR of hepatic TEAEs was 3.5/100 PY and did not increase from first to second year. 2-year EAIRs of ALT/AST elevations >3x and >5x the upper limit of normal were 2.3 and 0.6/100 PY; rates were similar to placebo, adalimumab, secukinumab, and ustekinumab during controlled study periods. FIB-4 and APRI scores did not increase through 2 years, regardless of fibrosis risk at baseline. LIMITATIONS Obesity, diabetes, dyslipidemia, chronic alcohol consumption, and medication changes are confounding factors for hepatic dysfunction. CONCLUSION Rates of hepatic adverse events (AEs) with bimekizumab were consistent through 2 years; incidences of transaminase elevations were similar to comparators during phase 3/3b controlled study periods.
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Affiliation(s)
- Mark Lebwohl
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.
| | - Joseph F Merola
- Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts
| | - Bruce Strober
- Department of Dermatology, Yale University, New Haven, Connecticut; Central Connecticut Dermatology Research, Cromwell, Connecticut
| | - April Armstrong
- University of California Los Angeles (UCLA), Los Angeles, California
| | - Ayumi Yoshizaki
- Department of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan; Department of Clinical Cannabinoid Research, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
| | - Paolo Gisondi
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy
| | | | | | | | | | | | - Alice B Gottlieb
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York
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Zhang M, Fan S, Hong S, Sun X, Zhou Y, Liu L, Wang J, Wang C, Lin N, Xiao X, Li X. Epidemiology of lipid disturbances in psoriasis: An analysis of trends from 2006 to 2023. Diabetes Metab Syndr 2024; 18:103098. [PMID: 39146906 DOI: 10.1016/j.dsx.2024.103098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 07/12/2024] [Accepted: 08/05/2024] [Indexed: 08/17/2024]
Abstract
INTRODUCTION A strong link has been established between psoriasis and lipid disturbances; however, no study has systematically examined their global epidemiology. METHODS We searched six databases from their inception up to October 1, 2023. Data analysis was conducted using Stata SE 15.1. We performed subgroup, meta-regression, and sensitivity analyses to assess the heterogeneity of the pooled studies. RESULTS Our review included 239 studies comprising 15,519,570 participants. The pooled prevalence rate of dyslipidemia among individuals with psoriasis was 38%. CONCLUSION Patients with severe psoriasis should undergo screening for lipid abnormalities. This can facilitate the early detection of lipid dysfunction and associated cardiovascular comorbidities.
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Affiliation(s)
- Miao Zhang
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Siwei Fan
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Seokgyeong Hong
- Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Xiaoying Sun
- Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Yaqiong Zhou
- Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Liu Liu
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Jiao Wang
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Chunxiao Wang
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Naixuan Lin
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Xiayi Xiao
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Xin Li
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China.
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Bellinato F, Maurelli M, Geat D, Girolomoni G, Gisondi P. Managing the Patient with Psoriasis and Metabolic Comorbidities. Am J Clin Dermatol 2024; 25:527-540. [PMID: 38748391 PMCID: PMC11193697 DOI: 10.1007/s40257-024-00857-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/14/2024] [Indexed: 06/23/2024]
Abstract
Epidemiological data demonstrate strong associations between psoriasis and metabolic comorbidities, including obesity, hypertension, diabetes mellitus, dyslipidemia, and non-alcoholic fatty liver disease. The presence of metabolic comorbidities significantly influences the selection and effectiveness of pharmacological treatments. Some drugs should be prescribed with caution in patients with metabolic comorbidities because of an increased risk of adverse events, while others could have a reduced effectiveness. The aim of this narrative review is to highlight the challenges that healthcare professionals may face regarding the management of psoriasis in patients with metabolic comorbidities. In the first part of the article, the epidemiological association between psoriasis and metabolic comorbidities and their pathogenetic mechanisms is summarized. The second part describes the efficacy and safety profile of conventional and biologic drugs in patients with selected metabolic comorbidities including obesity, non-alcoholic fatty liver disease/hepatic steatosis, and diabetes. Finally, the role of pharmacological and non-pharmacological interventions, such as diet, alcohol abstinence, physical activity, and smoking avoidance is discussed. In conclusion, the choice of the best approach to manage patients with psoriasis with metabolic comorbidities should encompass both tailored pharmacological and individualized non-pharmacological interventions.
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Affiliation(s)
- Francesco Bellinato
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, Piazzale A. Stefani 1, 37126, Verona, Italy
| | - Martina Maurelli
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, Piazzale A. Stefani 1, 37126, Verona, Italy
| | - Davide Geat
- Department of Dermatology, Spedali Civili, Brescia, Italy
| | - Giampiero Girolomoni
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, Piazzale A. Stefani 1, 37126, Verona, Italy
| | - Paolo Gisondi
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, Piazzale A. Stefani 1, 37126, Verona, Italy.
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Scala E, Mercurio L, Albanesi C, Madonna S. The Intersection of the Pathogenic Processes Underlying Psoriasis and the Comorbid Condition of Obesity. Life (Basel) 2024; 14:733. [PMID: 38929716 PMCID: PMC11204971 DOI: 10.3390/life14060733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 05/20/2024] [Accepted: 06/04/2024] [Indexed: 06/28/2024] Open
Abstract
In the past decade, our understanding of psoriasis pathogenesis has made significant steps forward, leading to the development of multiple game-changing therapies. While psoriasis primarily affects the skin, it is increasingly recognized as a systemic disease that can have effects beyond the skin. Obesity is associated with more severe forms of psoriasis and can potentially worsen the systemic inflammation and metabolic dysfunction seen in psoriatic patients. The exact mechanisms underlying the link between these two conditions are not fully understood, but it is believed that chronic inflammation and immune dysregulation play a role. In this review, we examine the existing body of knowledge regarding the intersection of pathogenic processes responsible for psoriasis and obesity. The ability of biological therapies to reduce systemic and obesity-related inflammation in patients with psoriasis will be also discussed.
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Mateu-Arrom L, Puig L. Choosing the right biologic treatment for moderate-to-severe plaque psoriasis: the impact of comorbidities. Expert Rev Clin Pharmacol 2024; 17:363-379. [PMID: 38603464 DOI: 10.1080/17512433.2024.2340552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 03/01/2024] [Indexed: 04/13/2024]
Abstract
INTRODUCTION Psoriasis is a chronic inflammatory skin disease often associated with several comorbidities, such as psoriatic arthritis, inflammatory bowel disease, obesity, diabetes mellitus or cardiovascular diseases, infections, or cancer, among others. With the progressive aging of the population, a growing number of patients with psoriasis can be expected to present multiple comorbidities. Currently, there is a wide range of biological treatments available for moderate to severe psoriasis, including tumor necrosis alpha (TNF) inhibitors, IL12/23 inhibitor, IL17 inhibitors, and IL23 inhibitors. AREAS COVERED This review aims to describe the specific characteristics of these drugs in relation to psoriasis comorbidities, in order to facilitate decision-making in clinical practice. EXPERT OPINION Some of the biological treatments can influence comorbidities, in some cases even improving them. Therefore, comorbidities are a key factor when deciding on one biological treatment over another. The development of new drugs is expanding the therapeutic arsenal for psoriasis. A high level of expertise in the field with a detailed knowledge of the characteristics of every drug is imperative to provide personalized medicine.
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Affiliation(s)
- Laura Mateu-Arrom
- Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Lluis Puig
- Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Universitat Autònoma de Barcelona, Barcelona, Spain
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Mladenić K, Lenartić M, Marinović S, Polić B, Wensveen FM. The "Domino effect" in MASLD: The inflammatory cascade of steatohepatitis. Eur J Immunol 2024; 54:e2149641. [PMID: 38314819 DOI: 10.1002/eji.202149641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 01/17/2024] [Accepted: 01/17/2024] [Indexed: 02/07/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly common complication of obesity, affecting over a quarter of the global adult population. A key event in the pathophysiology of MASLD is the development of metabolic-associated steatohepatitis (MASH), which greatly increases the chances of developing cirrhosis and hepatocellular carcinoma. The underlying cause of MASH is multifactorial, but accumulating evidence indicates that the inflammatory process in the hepatic microenvironment typically follows a pattern that can be roughly divided into three stages: (1) Detection of hepatocyte stress by tissue-resident immune cells including γδ T cells and CD4-CD8- double-negative T cells, followed by their secretion of pro-inflammatory mediators, most notably IL-17A. (2) Recruitment of pro-inflammatory cells, mostly of the myeloid lineage, and initiation of inflammation through secretion of effector-type cytokines such as TNF, TGF-β, and IL-1β. (3) Escalation of the inflammatory response by recruitment of lymphocytes including Th17, CD8 T, and B cells leading to chronic inflammation, hepatic stellate cell activation, and fibrosis. Here we will discuss these three stages and how they are consecutively linked like falling domino tiles to the pathophysiology of MASH. Moreover, we will highlight the clinical potential of inflammation as a biomarker and therapeutic target for the treatment of MASLD.
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Affiliation(s)
- Karlo Mladenić
- Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Maja Lenartić
- Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Sonja Marinović
- Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
- Division of Molecular Medicine, Laboratory for Personalized Medicine, Ruđer Bošković Institute, Zagreb, Croatia
| | - Bojan Polić
- Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Felix M Wensveen
- Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
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12
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Gordon KB, Langley RG, Warren RB, Okubo Y, Rosmarin D, Lebwohl M, Peterson L, Madden C, de Cuyper D, Davies O, Thaçi D. Bimekizumab safety in patients with moderate-to-severe plaque psoriasis: pooled data from up to 3 years of treatment in randomized phase III trials. Br J Dermatol 2024; 190:477-485. [PMID: 37950894 DOI: 10.1093/bjd/ljad429] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Revised: 10/16/2023] [Accepted: 10/29/2023] [Indexed: 11/13/2023]
Abstract
BACKGROUND Patients with psoriasis require long-term management; therefore, understanding the long-term safety of new treatments, such as bimekizumab (BKZ), is crucial. OBJECTIVES To evaluate BKZ's 3-year safety profile in patients with moderate-to-severe plaque psoriasis. METHODS Three years of safety data were pooled from three phase III trials (BE VIVID, BE READY and BE SURE) and their ongoing open-label extension (BE BRIGHT). Treatment-emergent adverse events (TEAEs) are reported using exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY). RESULTS In total, 1495 patients received at least one BKZ dose; total BKZ exposure was 3876.4 PY. The overall EAIR of TEAEs was 175.5/100 PY and decreased with longer exposure to BKZ. The most commonly reported TEAEs were nasopharyngitis, oral candidiasis and upper respiratory tract infection (EAIRs of 15.0/100 PY, 10.1/100 PY and 6.5/100 PY, respectively); 99.3% of oral candidiasis events were mild or moderate in severity, none were serious and few led to discontinuation. EAIRs of other TEAEs of interest were low, including serious infections (1.2/100 PY), adjudicated inflammatory bowel disease (0.2/100 PY) and laboratory elevations in aspartate aminotransferase or alanine aminotransferase (> 5 × upper limit of normal: 0.6/100 PY). CONCLUSIONS In these analyses pooled across 3 years, no new safety signals were observed with longer exposure to BKZ. The vast majority of oral candidiasis events were mild or moderate in severity, as reported previously.
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Affiliation(s)
| | | | - Richard B Warren
- Dermatology Centre, Northern Care Alliance NHS Foundation Trust, Manchester, UK
- NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
| | | | - David Rosmarin
- Indiana University School of Medicine, Indianapolis, IN, USA
| | - Mark Lebwohl
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | | | | | | | - Diamant Thaçi
- Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany
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Costache DO, Blejan H, Cojocaru DL, Ioniță GA, Poenaru M, Constantin MM, Costache AC, Căruntu C, Balaban DV, Costache RS. Intersecting Pathways: Nonalcoholic Fatty Liver Disease and Psoriasis Duet-A Comprehensive Review. Int J Mol Sci 2024; 25:2660. [PMID: 38473907 DOI: 10.3390/ijms25052660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 02/17/2024] [Accepted: 02/22/2024] [Indexed: 03/14/2024] Open
Abstract
Psoriasis is a chronic, immune-mediated, inflammatory disease that has a major impact on patients' quality of life. Common psoriasis-associated comorbidities include cardiovascular diseases, psoriatic arthritis, inflammatory bowel syndromes, type-2 diabetes, and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is affecting a substantial portion of the population and is closely linked with psoriasis. The interplay involves low-grade chronic inflammation, insulin resistance, and genetic factors. The review presents the pathophysiological connections between psoriasis and nonalcoholic fatty liver disease, emphasizing the role of cytokines, adipokines, and inflammatory cascades. The "hepato-dermal axis" is introduced, highlighting how psoriatic inflammation potentiates hepatic inflammation and vice versa. According to the new guidelines, the preliminary examination for individuals with psoriasis should encompass evaluations of transaminase levels and ultrasound scans as part of the initial assessment for this cohort. Considering the interplay, recent guidelines recommend screening for NAFLD in moderate-to-severe psoriasis cases. Treatment implications arise, particularly with medications impacting liver function. Understanding the intricate relationship between psoriasis and NAFLD provides valuable insights into shared pathogenetic mechanisms. This knowledge has significant clinical implications, guiding screening practices, treatment decisions, and the development of future therapeutic approaches for these chronic conditions.
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Affiliation(s)
- Daniel Octavian Costache
- Discipline of Dermatology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Dermatology Department, Carol Davila Central Emergency Military University Hospital, 010825 Bucharest, Romania
| | - Horia Blejan
- Dermatology Department, Carol Davila Central Emergency Military University Hospital, 010825 Bucharest, Romania
| | - Damian Lucian Cojocaru
- Gastroenterology Department, Carol Davila Central Emergency Military University Hospital, 010825 Bucharest, Romania
| | - Georgiana Alexandra Ioniță
- Gastroenterology Department, Carol Davila Central Emergency Military University Hospital, 010825 Bucharest, Romania
| | - Marcela Poenaru
- Dermatology Department, Carol Davila Central Emergency Military University Hospital, 010825 Bucharest, Romania
| | - Maria Magdalena Constantin
- Discipline of Dermatology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- 2nd Dermatology Department, Colentina Clinical Hospital, 020125 Bucharest, Romania
| | - Andrei Cătălin Costache
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Constantin Căruntu
- Discipline of Internal Medicine and Gastroenterology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Daniel Vasile Balaban
- Gastroenterology Department, Carol Davila Central Emergency Military University Hospital, 010825 Bucharest, Romania
- Discipline of Physiology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Raluca Simona Costache
- Gastroenterology Department, Carol Davila Central Emergency Military University Hospital, 010825 Bucharest, Romania
- Discipline of Physiology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Academy of Romanian Scientists, 050091 Bucharest, Romania
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He T, Chang Z, Zhang Y, Lang X, Guo S, Cui H. Effects of biological agents on glycogen metabolism in psoriasis patients: A systematic review and meta-analysis. Australas J Dermatol 2024; 65:1-13. [PMID: 37876281 DOI: 10.1111/ajd.14168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 09/07/2023] [Accepted: 09/23/2023] [Indexed: 10/26/2023]
Abstract
The effectiveness and safety of biological agents for treating psoriasis have been confirmed; however, their effects on glucose metabolism biomarkers in psoriasis patients remain unclear. A systematic review and meta-analysis were performed according to PRISMA guidelines. The final analysis enrolled 12 studies, including eight randomized controlled trial (RCT) (n = 5628 patients) and four observational cohort studies (OBSs) (n = 393 patients). The meta-analysis comprising nine studies (six RCTs and three OBSs) revealed a slight reduction in the levels of HOMA-IR associated with the use of biological therapies in OBS (biological therapies vs. traditional therapies: WMD = -0.2, CI = -0.10 to 0.50, p = 0.02). Although a considerable number of studies were analysed, our review did not show a significant alteration in HOMA-IR levels among patients treated with biological therapies such as IL-17 inhibitors and IL-12/23 inhibitors at weeks 12-16 in RCTs. We also did not observe remarkable alterations in the fasting plasma glucose levels of patients in both OBS and RCT. Additional RCT on a larger scale and duration is required to provide more conclusive evidence regarding the effect of biological agents on glycogen metabolism in psoriasis.
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Affiliation(s)
- Ting He
- Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Dermatology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Zhangqian Chang
- Department of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Yingjie Zhang
- Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Dermatology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xiaoqing Lang
- Department of Dermatology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Shuping Guo
- Department of Dermatology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Hongzhou Cui
- Department of Dermatology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
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15
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Jiang Y, Huang D, Chen Q, Yu Y, Hu Y, Wang Y, Chen R, Yao L, Zhong X, Kong L, Yu Q, Lu J, Li Y, Shi Y. A novel online calculator based on clinical features and hematological parameters to predict total skin clearance in patients with moderate to severe psoriasis. J Transl Med 2024; 22:121. [PMID: 38297242 PMCID: PMC10829231 DOI: 10.1186/s12967-023-04847-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 12/29/2023] [Indexed: 02/02/2024] Open
Abstract
BACKGROUND Treatment responses to biologic agents vary between patients with moderate to severe psoriasis; while some patients achieve total skin clearance (TSC), a proportion of patients may only experience partial improvement. OBJECTIVE This study was designed to identify potential predictors for achieving TSC in psoriasis patients treated with IL-17 inhibitors. It also aimed to develop an easy-to-use calculator incorporating these factors by the nomogram to predict TSC response. METHODS A total of 381 patients with psoriasis receiving ixekizumab were included in the development cohort and 229 psoriasis patients who initiated secukinumab treatment were included in the validation cohort. The study endpoint was achieving TSC after 12 weeks of IL-17 inhibitors treatment, defined as the 100% improvement in Psoriasis Area and Severity Index (PASI 100). Multivariate Cox regression analyses and LASSO analysis were performed to identify clinical predictors and blood predictors respectively. RESULTS The following parameters were identified as predictive factors associated with TSC: previous biologic treatment, joint involvement, genital area affected, early response (PASI 60 at week 4), neutrophil counts and uric acid levels. The nomogram model incorporating these factors achieved good discrimination in the development cohort (AUC, 0.721; 95% CI 0.670-0.773) and validation cohort (AUC, 0.715; 95% CI 0.665-0.760). The calibration curves exhibited a satisfactory fit, indicating the accuracy of the model. Furthermore, the decision curve analysis confirmed the clinical utility of the nomogram, highlighting its favorable value for practical application. Web-based online calculator has been developed to enhance the efficiency of clinical applications. CONCLUSIONS This study developed a practical and clinically applicable nomogram model for the prediction of TSC in patients with moderate to severe psoriasis. The nomogram model demonstrated robust predictive performance and exhibited significant clinical utility. Trial registration A multi-center clinical study of systemic treatment strategies for psoriasis in Chinese population;ChiCTR2000036186; Registered 31 August 2020; https://www.chictr.org.cn/showproj.html?proj=58256 .
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Affiliation(s)
- Yuxiong Jiang
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, No. 1278 Bao de Road, Shanghai, 200443, China
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China
| | - Dawei Huang
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, No. 1278 Bao de Road, Shanghai, 200443, China
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China
| | - Qianyu Chen
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, No. 1278 Bao de Road, Shanghai, 200443, China
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China
| | - Yingyuan Yu
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, No. 1278 Bao de Road, Shanghai, 200443, China
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China
| | - Yifan Hu
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, No. 1278 Bao de Road, Shanghai, 200443, China
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China
| | - Yu Wang
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, No. 1278 Bao de Road, Shanghai, 200443, China
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China
| | - Rongfen Chen
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, No. 1278 Bao de Road, Shanghai, 200443, China
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China
| | - Lingling Yao
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, No. 1278 Bao de Road, Shanghai, 200443, China
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China
| | - Xiaoyuan Zhong
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, No. 1278 Bao de Road, Shanghai, 200443, China
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China
| | - Luyang Kong
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, No. 1278 Bao de Road, Shanghai, 200443, China
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China
| | - Qian Yu
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China
- Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jiajing Lu
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, No. 1278 Bao de Road, Shanghai, 200443, China.
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China.
| | - Ying Li
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, No. 1278 Bao de Road, Shanghai, 200443, China.
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China.
| | - Yuling Shi
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, No. 1278 Bao de Road, Shanghai, 200443, China.
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China.
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Guo X, Zhou J, Yu H, Cao H, Li X, Hu Q, Yu Y. Serum lipidomic study of long-chain fatty acids in psoriasis patients prior to and after anti-IL-17A monoclonal antibody treatment by quantitative GC‒MS analysis with in situ extraction. Lipids Health Dis 2024; 23:6. [PMID: 38185620 PMCID: PMC10773056 DOI: 10.1186/s12944-023-01999-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 12/28/2023] [Indexed: 01/09/2024] Open
Abstract
BACKGROUND Long-chain fatty acids (LCFAs) are involved in regulating multiple physiological processes as signalling molecules. Gas chromatography-mass spectrometry (GC-MS) is widely used to quantify LCFAs. However, current quantitative methods for LCFAs using GC-MS have demonstrated complicated issues. Psoriasis is a chronic inflammatory skin disease, and its pathogenesis may be related to the overproduction of interleukin-17A (IL-17A). Clinical efficacy of anti-IL-17A monoclonal antibody (mAb) treatment in psoriasis patients has been demonstrated. Recent studies suggest that LCFAs play varying roles in the pathogenesis of psoriasis. However, more comprehensive research is needed to illuminate the mechanism of LCFAs in psoriasis. METHODS The established in situ derivatization method for analysing LCFAs with a GC-MS platform was utilized to conduct serum lipidomics analysis of healthy volunteers and psoriasis patients receiving pretherapy and posttreatment with of anti-IL-17A mAb. Imiquimod (IMQ)-treated wild type (WT) and T-cell receptor delta chain knock-out (Tcrd-/-) mice were used to investigate the correlation between IL-17A and abnormal changes in LCFAs in psoriasis patients. RESULTS A rapid and sensitive in situ extraction derivatization method for quantifying LCFAs using GC-MS was established. Serum lipidomic results showed that psoriasis patients had higher levels of saturated fatty acids (SFAs) and ω-6 polyunsaturated fatty acids (PUFAs) but lower levels of monounsaturated fatty acids (MUFAs) and ω-3 PUFAs than healthy individuals, indicating impaired serum LCFA metabolism. Anti-IL-17A mAb treatment affected most of these LCFA changes. Analysis of LCFAs in IMQ-treated mice showed that LCFAs increased in the serum of WT mice, while there were no significant changes in the Tcrd-/- mice. SFAs increased in IMQ-treated WT mice, while MUFAs showed the opposite trend, and PUFAs did not change significantly. CONCLUSIONS This study presented a dependable method for quantifying LCFAs that enhanced sensitivity and reduced analysis time. The lipidomic analysis results showed that anti-IL-17A mAb not only ameliorated skin lesions in psoriasis patients but also affected abnormal LCFAs metabolism. Furthermore, the study indicated a potential correlation between IL-17A and abnormal LCFA metabolism in psoriasis patients, which was supported by the alterations in serum LCFAs observed in IMQ-treated WT and Tcrd-/- mice.
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Affiliation(s)
- XiaoYu Guo
- School of Pharmacy, Fudan University, Shanghai, 201203, PR China
| | - Jianglu Zhou
- School of Pharmacy, Fudan University, Shanghai, 201203, PR China
| | - Hong Yu
- NMPA Key Laboratory for Quality, Control of Traditional Chinese Medicine, Shanghai Institute for Food and Drug Control, Shanghai, 201203, PR China
| | - Han Cao
- Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200025, PR China
| | - Xia Li
- Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200025, PR China
| | - Qing Hu
- NMPA Key Laboratory for Quality, Control of Traditional Chinese Medicine, Shanghai Institute for Food and Drug Control, Shanghai, 201203, PR China.
| | - YunQiu Yu
- School of Pharmacy, Fudan University, Shanghai, 201203, PR China.
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Song Y, Yao L, Li S, Zhou J. Psoriasis comorbidity management in the COVID era: a pressing challenge. Front Microbiol 2023; 14:1294056. [PMID: 38029150 PMCID: PMC10667470 DOI: 10.3389/fmicb.2023.1294056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 10/26/2023] [Indexed: 12/01/2023] Open
Abstract
The global COVID-19 pandemic has presented a significant, ongoing challenge since its emergence in late 2019. Today, the Omicron strain, which is less lethal but more contagious than the original outbreak strain, continues to pose substantial health risks. In this background, the management of psoriatic comorbidities has become even more complex, particularly for patients with underlying inflammatory, metabolic, or cardiovascular diseases. This review aims to summarize current research on comorbid COVID-19 and psoriasis, and provide insights into the development of evidence-based management strategies. By providing appropriate patient instruction, implementing protective measures, and re-evaluating medication prescriptions based on each patient's unique situation, healthcare professionals can effectively address the challenges faced by patients with comorbid psoriasis in the COVID-19 era.
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Affiliation(s)
| | | | | | - Junfeng Zhou
- Department of Dermatology, First Hospital of Jilin University, Changchun, China
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Tamer F, Edek YC, Aksakal AB. Does biological agent treatment have an impact on serum uric acid levels in patients with psoriasis? Curr Med Res Opin 2023; 39:1297-1302. [PMID: 37725100 DOI: 10.1080/03007995.2023.2260304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Accepted: 09/14/2023] [Indexed: 09/21/2023]
Abstract
OBJECTIVE High serum uric acid levels have been associated with psoriasis as well as cardiovascular diseases and metabolic syndrome. The aim of this study was to evaluate the effect of biologic agent treatment on serum uric acid levels in patients with psoriasis. METHODS Between April 2019 and September 2022, serum uric acid levels were retrospectively evaluated in patients with psoriasis before and 3 months after biologic agent treatment. RESULTS This study included 224 patients, 100 females and 124 males, who were treated with TNF-α, IL-17, IL-12/23, and IL-23 inhibitors. Uric acid levels were significantly higher in men compared to women (p < 0.001), higher in overweight and obese patients compared to those with normal weight (p = 0.004), and higher in patients with severe versus mild psoriasis (p = 0.028). The mean serum uric acid level decreased significantly from 5.89 ± 1.53 mg/dL to 5.41 ± 1.39 mg/dL in all patients 3 months after biological agent treatment (p < 0.001). A statistically significant decrease in serum uric acid levels was detected in patients treated with adalimumab (p < 0.001), infliximab (p = 0.002), ixekizumab (p = 0.001), secukinumab (p = 0.012), and ustekinumab (p < 0.001). CONCLUSIONS Since high serum uric acid levels have been associated with increased risk for cardiovascular diseases and metabolic syndrome, treatment of psoriasis with adalimumab, infliximab, ixekizumab, secukinumab, and ustekinumab may have a positive impact on cardiometabolic comorbidities.
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Affiliation(s)
- Funda Tamer
- Department of Dermatology, School of Medicine, Gazi University, Ankara, Turkey
| | - Yusuf Can Edek
- Department of Dermatology, School of Medicine, Gazi University, Ankara, Turkey
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Zhukova OV, Artemyeva SI. The selection of the initial drug in the treatment of severe psoriasis. MEDITSINSKIY SOVET = MEDICAL COUNCIL 2023:24-34. [DOI: 10.21518/ms2023-280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Psoriasis is an immune-mediated skin disease associated with an increased risk of comorbidities and a significant negative impact on the quality of life of patients. In moderate and severe forms of psoriasis it is necessary to assign systemic therapies. The newest paradigm of treatment has become possible as a result of constant deepening of knowledge of pathophysiology of the disease. A clear mechanism is finally known down to the molecular level as to which cytokines are involved in the pathogenesis of psoriatic disease. Interleukin (IL)-23 mediates the activation of the Th17 pathway, which is hypothesised to be a major contributor to he inflammation observed in psoriasis, as proven, among other things, by the high efficacy of IL-23 inhibitor biological agents. It is obvious that great progress has been made in the field of genetically engineered biological therapy for psoriasis, both in terms of safety and efficacy. However, the issue of selecting a biologic drug individually in each patient is pressing, including in the case of initiation of the first genetically engineered biological drug in bionaive patients. The article provides an overview of the key points in the process of biological drug selection depending on the present comorbidities, and also describes a clinical case of successful therapy of a bionaive patient with concomitant depressive disorder in the anamnesis against the backdrop of a severe course of psoriasis. Successful use of IL-23 inhibitor (Guselkumab) allowed to achieve persistent remission and improve the quality of life, which in turn had a positive effect on the patient’s comorbid profile. This observation allows us to conclude that the use of guselkumab as the first biological agent is a rather effective, safe and promising option in the treatment of severe psoriasis.
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Affiliation(s)
- O. V. Zhukova
- Peoples’ Friendship University of Russia; Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology
| | - S. I. Artemyeva
- Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology
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20
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Strober B, Paul C, Blauvelt A, Thaçi D, Puig L, Lebwohl M, White K, Vanvoorden V, Deherder D, Gomez NN, Eyerich K. Bimekizumab efficacy and safety in patients with moderate to severe plaque psoriasis: Two-year interim results from the open-label extension of the randomized BE RADIANT phase 3b trial. J Am Acad Dermatol 2023; 89:486-495. [PMID: 37182701 DOI: 10.1016/j.jaad.2023.04.063] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 04/13/2023] [Accepted: 04/18/2023] [Indexed: 05/16/2023]
Abstract
BACKGROUND Bimekizumab is a monoclonal IgG1 antibody that inhibits interleukin-17A/F. Bimekizumab is more efficacious than secukinumab over 1 year in the treatment of psoriasis. OBJECTIVE Evaluate the safety and efficacy of bimekizumab through 2 years in patients with moderate to severe plaque psoriasis. METHODS The BE RADIANT phase 3b randomized controlled trial consisted of a 48-week double-blinded period, where patients received bimekizumab (320 mg every 4 or 8 weeks) or secukinumab (300 mg weekly to Week 4, then every 4 weeks), and an open-label extension (OLE). From Week 48, all patients received bimekizumab in the OLE. RESULTS At Week 48, more patients achieved complete skin clearance (PASI 100; modified non-responder imputation) with bimekizumab than secukinumab (74.8% vs 52.8%). PASI 100 responses were maintained to Week 96 in continuous bimekizumab patients (70.8%); patients who switched from secukinumab to bimekizumab had increased rates at Week 96 (76.6%). The most common adverse events were: nasopharyngitis, oral candidiasis, and urinary tract infection. Safety data were consistent with the known safety profile of bimekizumab. LIMITATIONS Limited racial diversity; overlap with the COVID-19 pandemic. CONCLUSIONS High PASI 100 responses achieved with bimekizumab over 48 weeks were sustained through Week 96; secukinumab patients who switched to bimekizumab achieved similar responses by Week 96.
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Affiliation(s)
- Bruce Strober
- Department of Dermatology, Yale University, New Haven, Connecticut; Central Connecticut Dermatology Research, Cromwell, Connecticut.
| | - Carle Paul
- Toulouse University and INSERM Infinity, Toulouse, France
| | | | - Diamant Thaçi
- Insititute and Centre for Inflammation Medicine, University of Lübeck, Lübeck, Germany
| | - Luis Puig
- Hospital de la Santa Creu I Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Mark Lebwohl
- Icahn School of Medicine at Mount Sinai, New York, New York
| | | | | | | | | | - Kilian Eyerich
- Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany
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21
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Du X, Yan C, Kong S, Che D, Peng B, Zhu L, Geng S, Guo K. Successful secukinumab therapy in plaque psoriasis is associated with altered gut microbiota and related functional changes. Front Microbiol 2023; 14:1227309. [PMID: 37621397 PMCID: PMC10445136 DOI: 10.3389/fmicb.2023.1227309] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 06/30/2023] [Indexed: 08/26/2023] Open
Abstract
Introduction The role of gut microbiome dysbiosis in the pathogenesis of psoriasis has gained increasing attention in recent years. Secukinumab, targeting interleukin (IL)-17, has a promising efficacy in psoriasis treatment. However, it remains unclear the gut microbiota alteration and related functional changes caused by successful secukinumab therapy in psoriatic patients. Methods In our study, we compared the fecal microbiome profile between psoriatic patients after secukinumab successful treatment (AT) and the other two groups, psoriatic patients without therapy (BT) and healthy people (H), respectively, by using next-generation sequencing targeting 16S ribosomal RNA. Then, shotgun metagenomic sequencing was first used to characterize bacterial gut microbial communities and related functional changes in the AT group. Results We found that the diversity and structure of the microbial community in the AT group were significantly changed compared to those in the BT group and the H group. The AT group showed a microbiota profile characterized by increased proportions of the phylum Firmicute, families Ruminococcaceae, and a reduction in the phylum Bacteroidota (elevated F/B ratio). To detect functional alteration, we discovered that secukinumab treatment may construct a more stable homeostasis of the gut microbiome with functional alteration. There were different KEGG pathways, such as the downregulated cardiovascular diseases pathway and the upregulated infectious diseases in the AT group. By metagenomic analysis, the metabolic functional pathway was changed after secukinumab therapy. Discussion It seems that gut microbiota investigation during biologic drug treatment is useful for predicting the efficacy and risks of drug treatment in disease.
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Affiliation(s)
- Xueshan Du
- Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Cong Yan
- Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Shuzhen Kong
- Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Delu Che
- Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Center for Dermatology Disease, Precision Medical Institute, Xi'an, China
| | - Bin Peng
- Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Longfei Zhu
- Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Songmei Geng
- Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Center for Dermatology Disease, Precision Medical Institute, Xi'an, China
| | - Kun Guo
- Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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22
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Douglas A, Stevens B, Lynch L. Interleukin-17 as a key player in neuroimmunometabolism. Nat Metab 2023; 5:1088-1100. [PMID: 37488456 PMCID: PMC10440016 DOI: 10.1038/s42255-023-00846-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 06/14/2023] [Indexed: 07/26/2023]
Abstract
In mammals, interleukin (IL)-17 cytokines are produced by innate and adaptive lymphocytes. However, the IL-17 family has widespread expression throughout evolution, dating as far back as cnidaria, molluscs and worms, which predate lymphocytes. The evolutionary conservation of IL-17 suggests that it is involved in innate defence strategies, but also that this cytokine family has a fundamental role beyond typical host defence. Throughout evolution, IL-17 seems to have a major function in homeostatic maintenance at barrier sites. Most recently, a pivotal role has been identified for IL-17 in regulating cellular metabolism, neuroimmunology and tissue physiology, particularly in adipose tissue. Here we review the emerging role of IL-17 signalling in regulating metabolic processes, which may shine a light on the evolutionary role of IL-17 beyond typical immune responses. We propose that IL-17 helps to coordinate the cross-talk among the nervous, endocrine and immune systems for whole-body energy homeostasis as a key player in neuroimmunometabolism.
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Affiliation(s)
- Aaron Douglas
- School of Biochemistry and Immunology, TBSI, Trinity College Dublin, Dublin, Ireland
| | - Brenneth Stevens
- School of Biochemistry and Immunology, TBSI, Trinity College Dublin, Dublin, Ireland
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Lydia Lynch
- School of Biochemistry and Immunology, TBSI, Trinity College Dublin, Dublin, Ireland.
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
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23
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Torosian K, Lal E, Kavanaugh A, Loomba R, Ajmera V, Guma M. Psoriatic disease and non-alcoholic fatty liver disease shared pathogenesis review. Semin Arthritis Rheum 2023; 59:152165. [PMID: 36716599 PMCID: PMC9992353 DOI: 10.1016/j.semarthrit.2023.152165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 12/03/2022] [Accepted: 01/04/2023] [Indexed: 01/20/2023]
Abstract
Psoriatic disease (PD) and non-alcoholic fatty liver disease (NAFLD) potentially share disease pathways given the numerous inflammatory pathways involved in both diseases and a higher prevalence of NAFLD in PD patients. Metabolic syndrome and obesity are a key link between the two diseases, but even when controlling for this, associations between both diseases are still seen. Therapeutics that impact metabolic or inflammatory pathways may be impactful in both PD and NAFLD. In this review, we describe common inflammatory pathways contributing to both PD and NAFLD and critically review the potential impact of treatments for and on both diseases.
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Affiliation(s)
- Kelly Torosian
- Department of Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA
| | - Esha Lal
- Department of Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA
| | - Arthur Kavanaugh
- Department of Rheumatology, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA
| | - Rohit Loomba
- Division of Gastroenterology and Hepatology, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA; NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, USA; Division of Epidemiology, Department of Family and Preventative Medicine, University of California at San Diego, La Jolla, USA
| | - Veeral Ajmera
- Division of Gastroenterology and Hepatology, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA; NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, USA.
| | - Monica Guma
- Department of Rheumatology, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA; Department of Medicine, Autonomous University of Barcelona, Plaça Cívica, 08193 Bellaterra, Barcelona, Spain; San Diego VA Healthcare Service, San Diego, CA, 92161, USA.
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24
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Olveira A, Augustin S, Benlloch S, Ampuero J, Suárez-Pérez JA, Armesto S, Vilarrasa E, Belinchón-Romero I, Herranz P, Crespo J, Guimerá F, Gómez-Labrador L, Martín V, Carrascosa JM. The Essential Role of IL-17 as the Pathogenetic Link between Psoriasis and Metabolic-Associated Fatty Liver Disease. Life (Basel) 2023; 13:419. [PMID: 36836776 PMCID: PMC9963792 DOI: 10.3390/life13020419] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 01/19/2023] [Accepted: 01/28/2023] [Indexed: 02/05/2023] Open
Abstract
Interleukin 17 (IL-17) is an effector cytokine that plays a key role in the pathogenesis of both psoriasis and metabolic-associated fatty liver disease (MAFLD), a condition that is more prevalent and severe in patients with psoriasis. In liver inflammation, IL-17 is mainly produced by CD4+ T (TH17) and CD8+ T cells (Tc17), although numerous other cells (macrophages, natural killer cells, neutrophils and Tγδ cells) also contribute to the production of IL-17. In hepatocytes, IL-17 mediates systemic inflammation and the recruitment of inflammatory cells to the liver, and it is also implicated in the development of fibrosis and insulin resistance. IL-17 levels have been correlated with progression from MAFLD to steatohepatitis, cirrhosis, and even hepatocellular carcinoma. Clinical trials have shown that inhibiting IL-17A in patients with psoriasis could potentially contribute to the improvement of metabolic and liver parameters. A better understanding of the key factors involved in the pathogenesis of these chronic inflammatory processes could potentially lead to more efficient treatment for both psoriasis and MAFLD, and help to develop holistic strategies to improve the management of these patients.
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Affiliation(s)
- Antonio Olveira
- Department of Digestive Diseases, La Paz University Hospital, 28046 Madrid, Spain
| | - Salvador Augustin
- Liver Unit, Vall d’Hebron Hospital Universitari, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
| | - Salvador Benlloch
- Department of Digestive Diseases, Arnau de Vilanova Hospital, Centro Biomédico en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 46015 Valencia, Spain
| | - Javier Ampuero
- Department of Digestive Diseases, Virgen del Rocío University Hospital, Lab 213, Institute of Biomedicine of Sevilla (IBIS), Department of Medicine, University of Sevilla, Centro Biomédico en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 41004 Sevilla, Spain
| | | | - Susana Armesto
- Department of Dermatology, Marqués de Valdecilla University Hospital, 39008 Santander, Spain
| | - Eva Vilarrasa
- Department of Dermatology, Santa Creu i Sant Pau Hospital, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
| | - Isabel Belinchón-Romero
- Dermatology Department, Alicante University General Hospital, Institute for Health and Biomedical Research (ISABIAL), Miguel Hernández University of Elche, 03202 Alicante, Spain
| | - Pedro Herranz
- Department of Dermatology, La Paz University Hospital, 28046 Madrid, Spain
| | - Javier Crespo
- Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, IDIVAL, School Medicine, University of Cantabria, 39005 Santander, Spain
| | - Francisco Guimerá
- Dermatology and Pathology Department, Canarias University Hospital, 38320 La Laguna, Spain
| | | | - Víctor Martín
- Immunology Franchise, Novartis Farmacéutica S.A., 28033 Madrid, Spain
| | - José Manuel Carrascosa
- Department of Dermatology, Germans Trias i Pujol University Hospital, Universitat Autònoma de Barcelona, IGTP, 08193 Badalona, Spain
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25
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Tsiogka A, Gregoriou S, Stratigos A, Soulaidopoulos S, Rompoti N, Panagakis P, Papoutsaki M, Kostakis P, Kontochristopoulos G, Tsioufis K, Campanati A, Offidani A, Vlachopoulos C, Rigopoulos D. The Impact of Treatment with IL-17/IL-23 Inhibitors on Subclinical Atherosclerosis in Patients with Plaque Psoriasis and/or Psoriatic Arthritis: A Systematic Review. Biomedicines 2023; 11:biomedicines11020318. [PMID: 36830855 PMCID: PMC9953668 DOI: 10.3390/biomedicines11020318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 01/16/2023] [Accepted: 01/22/2023] [Indexed: 01/24/2023] Open
Abstract
Accumulating evidence considers psoriasis a systemic inflammatory disorder that is associated with comorbidities such as psoriatic arthritis, cardiovascular disease, and metabolic syndrome. Although the precise pathogenetic links between psoriasis and atherosclerosis warrants further investigation, it is believed that chronic systemic inflammation along with the T helper (Th)-1 and Th17 polarization are associated with endothelial dysfunction and subsequent acceleration of atherosclerosis. Considering the above, several studies have evaluated if optimal control of the inflammation in psoriasis by inhibiting interleukins targeting the Interleukin (IL)-23/Th17 axis could subsequently reduce the atherosclerotic process during anti-psoriatic treatment by using a variety of surrogate markers of subclinical atherosclerosis. This systematic review summarizes current knowledge on the pathogenetic mechanisms and diagnostic evaluation of atherosclerosis in the context of psoriasis and provides a systematic review of the literature on the impact of treatment with biologics targeting the IL-23/Th17 axis on subclinical atherosclerosis in patients with plaque psoriasis and/or psoriatic arthritis.
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Affiliation(s)
- Aikaterini Tsiogka
- First Department of Dermatology-Venereology, Faculty of Medicine, “A. Sygros” Hospital for Skin and Venereal Diseases, National and Kapodistrian University of Athens, 16121 Athens, Greece
- Correspondence: ; Tel.: +30-210-9337315; Fax: +30-2107211122
| | - Stamatios Gregoriou
- First Department of Dermatology-Venereology, Faculty of Medicine, “A. Sygros” Hospital for Skin and Venereal Diseases, National and Kapodistrian University of Athens, 16121 Athens, Greece
| | - Alexander Stratigos
- First Department of Dermatology-Venereology, Faculty of Medicine, “A. Sygros” Hospital for Skin and Venereal Diseases, National and Kapodistrian University of Athens, 16121 Athens, Greece
| | - Stergios Soulaidopoulos
- First Cardiology Department, Hippokration General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Natalia Rompoti
- First Department of Dermatology-Venereology, Faculty of Medicine, “A. Sygros” Hospital for Skin and Venereal Diseases, National and Kapodistrian University of Athens, 16121 Athens, Greece
| | - Pantelis Panagakis
- First Department of Dermatology-Venereology, Faculty of Medicine, “A. Sygros” Hospital for Skin and Venereal Diseases, National and Kapodistrian University of Athens, 16121 Athens, Greece
| | - Marina Papoutsaki
- First Department of Dermatology-Venereology, Faculty of Medicine, “A. Sygros” Hospital for Skin and Venereal Diseases, National and Kapodistrian University of Athens, 16121 Athens, Greece
| | - Panagiotis Kostakis
- First Department of Dermatology-Venereology, Faculty of Medicine, “A. Sygros” Hospital for Skin and Venereal Diseases, National and Kapodistrian University of Athens, 16121 Athens, Greece
| | - George Kontochristopoulos
- First Department of Dermatology-Venereology, Faculty of Medicine, “A. Sygros” Hospital for Skin and Venereal Diseases, National and Kapodistrian University of Athens, 16121 Athens, Greece
| | - Konstantinos Tsioufis
- First Cardiology Department, Hippokration General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Anna Campanati
- Department of Clinical and Molecular Sciences, Dermatology Clinic, Polytechnic Marche University, 60121 Ancona, Italy
| | - Annamaria Offidani
- Department of Clinical and Molecular Sciences, Dermatology Clinic, Polytechnic Marche University, 60121 Ancona, Italy
| | - Charalambos Vlachopoulos
- First Cardiology Department, Hippokration General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Dimitrios Rigopoulos
- First Department of Dermatology-Venereology, Faculty of Medicine, “A. Sygros” Hospital for Skin and Venereal Diseases, National and Kapodistrian University of Athens, 16121 Athens, Greece
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26
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Jiang Y, Chen Y, Yu Q, Shi Y. Biologic and Small-Molecule Therapies for Moderate-to-Severe Psoriasis: Focus on Psoriasis Comorbidities. BioDrugs 2023; 37:35-55. [PMID: 36592323 PMCID: PMC9837020 DOI: 10.1007/s40259-022-00569-z] [Citation(s) in RCA: 41] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/14/2022] [Indexed: 01/03/2023]
Abstract
Psoriasis is a systemic immune-mediated disease associated with an increased risk of comorbidities, such as psoriatic arthritis, cardiovascular disease, metabolic syndrome, inflammatory bowel disease, psychiatric disorders, and malignancy. In recent years, with the advent of biological agents, the efficacy and safety of psoriasis treatments have dramatically improved. Presently, tumor necrosis factor-α inhibitors, interleukin-17 inhibitors, interleukin-12/23 inhibitors, and interleukin-23 inhibitors are approved to treat moderate-to-severe psoriasis. Small-molecule inhibitors, such as apremilast and deucravacitinib, are also approved for the treatment of psoriasis. Although it is still unclear, systemic agents used to treat psoriasis also have a significant impact on its comorbidities by altering the systemic inflammatory state. Data from clinical trials and studies on the safety and efficacy of biologics and small-molecule inhibitors provide important information for the personalized care and treatment for patients with psoriasis. Notably, treatment with interleukin-17 inhibitors is associated with new-onset or exacerbations of inflammatory bowel disease. In addition, great caution needs to be taken when using tumor necrosis factor-α inhibitors in patients with psoriasis with concomitant congestive heart failure, multiple sclerosis, and malignancy. Apremilast may induce weight loss as an adverse effect, presenting also with some beneficial metabolic actions. A better understanding of the characteristics of biologics and small-molecule inhibitors in the treatment of psoriasis comorbidities can provide more definitive guidance for patients with distinct comorbidities.
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Affiliation(s)
- Yuxiong Jiang
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China
| | - Youdong Chen
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China
| | - Qian Yu
- Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China.
| | - Yuling Shi
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China.
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China.
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27
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Dong Q, Li D, Xie BB, Hu LH, Huang J, Jia XX, Tang YL, Liu GH, Shen NN, Yu XB. IL-17A and TNF-α inhibitors induce multiple molecular changes in psoriasis. Front Immunol 2022; 13:1015182. [PMID: 36483564 PMCID: PMC9723344 DOI: 10.3389/fimmu.2022.1015182] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 11/02/2022] [Indexed: 11/23/2022] Open
Abstract
Adalimumab and secukinumab are commonly used for moderate to severe psoriasis vulgaris (PV). Although distinct individual responses to and impaired effectiveness of these biological agents occur occasionally, little is known about the underlying reasons. Here, we report a proteomic analysis of psoriatic lesions from patients treated with these drugs using data-independent acquisition mass spectrometry (DIA-MS). Thousands of differentially expressed proteins (DEPs) changed over 12 weeks of treatment. Network analysis showed that DEPs could interact and induce transformation in matrix components, metabolic regulation, and immune response. The results of parallel reaction monitoring (PRM) analysis suggested that S100s, STAT1, KRT2, TYMP, SOD2, HSP90AB1, TFRC, and COL5A1 were the most significantly changed proteins in both groups. There was a positive association between the Psoriasis Area and Severity Index (PASI) score and three proteins (TFRC, IMPDH2, KRT2). Our study findings suggest that inhibition of IL-17A and TNF-α can induce changes in multiple molecules in psoriatic lesions and have an overlapping influence on the immune response and process through direct or indirect effects.
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Affiliation(s)
- Qiang Dong
- Department of Dermatology, Dermatology Hospital of Zhejiang Province, Huzhou, Zhejiang, China
| | - Dan Li
- Department of Dermatology, Dermatology Hospital of Zhejiang Province, Huzhou, Zhejiang, China
| | - Bi Bo Xie
- Department of Dermatology, Dermatology Hospital of Zhejiang Province, Huzhou, Zhejiang, China
| | - Li Hua Hu
- Department of Dermatology, Dermatology Hospital of Zhejiang Province, Huzhou, Zhejiang, China
| | - Jia Huang
- Department of Dermatology, Dermatology Hospital of Zhejiang Province, Huzhou, Zhejiang, China
| | - Xiao Xiao Jia
- Department of Dermatology, Dermatology Hospital of Zhejiang Province, Huzhou, Zhejiang, China
| | - Yan Li Tang
- Department of Dermatology, Dermatology Hospital of Zhejiang Province, Huzhou, Zhejiang, China
| | - Gan Hong Liu
- Department of Dermatology, Dermatology Hospital of Zhejiang Province, Huzhou, Zhejiang, China
| | - Ning Ning Shen
- Department of Dermatology, Dermatology Hospital of Zhejiang Province, Huzhou, Zhejiang, China
| | - Xiao Bing Yu
- Department of Dermatology, Dermatology Hospital of Zhejiang Province, Huzhou, Zhejiang, China
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28
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Merola JF, Kavanaugh A, Lebwohl MG, Gniadecki R, Wu JJ. Clinical Efficacy and Safety of Psoriasis Treatments in Patients with Concomitant Metabolic Syndrome: A Narrative Review. Dermatol Ther (Heidelb) 2022; 12:2201-2216. [PMID: 36008702 PMCID: PMC9515257 DOI: 10.1007/s13555-022-00790-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 08/02/2022] [Indexed: 11/26/2022] Open
Abstract
Metabolic syndrome (MetS) is well recognized as a frequent comorbidity of psoriasis with important implications for efficacy and safety of psoriasis treatment. The presence of concomitant MetS is associated with decreased efficacy response to biologic treatment for psoriasis in observational studies. In post hoc analyses of clinical trial data, the anti–IL-23p19 antibody tildrakizumab appears to maintain efficacy in patients compared to those without MetS; no published subgroup analyses by MetS status are yet available for other biologics. However, there is some evidence that obese patients have decreased psoriasis treatment efficacy with biologics with certain mechanisms of action relative to overweight patients. This confounds interpretation of the effect of MetS due to the association between MetS and body weight. Because of the association between MetS and cardiovascular risk, treatment of psoriasis in patients with concomitant MetS requires special consideration for cardiovascular safety and attention to potential for exacerbation of MetS and related conditions, including nonalcoholic fatty liver disease. Additional studies are needed to clarify the risks for treatment failure and cardiovascular safety concerns in patients with psoriasis and concomitant MetS.
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Affiliation(s)
- Joseph F Merola
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
| | | | - Mark G Lebwohl
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Robert Gniadecki
- Division of Dermatology, University of Alberta, Edmonton, AB, Canada
| | - Jashin J Wu
- Department of Dermatology, University of Miami Miller School of Medicine, Miami, FL, USA
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29
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Bellinato F, Gisondi P, Mantovani A, Girolomoni G, Targher G. Risk of non-alcoholic fatty liver disease in patients with chronic plaque psoriasis: an updated systematic review and meta-analysis of observational studies. J Endocrinol Invest 2022; 45:1277-1288. [PMID: 35147926 PMCID: PMC9184411 DOI: 10.1007/s40618-022-01755-0] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 01/25/2022] [Indexed: 11/30/2022]
Abstract
PURPOSE Chronic plaque psoriasis is associated with the presence of non-alcoholic fatty liver disease (NAFLD), but the magnitude of this association remains currently uncertain. We aimed to investigate the magnitude of the association between psoriasis and the risk of prevalent and incident NAFLD, and to assess whether psoriasis severity and/or psoriatic arthritis are associated with a greater risk of NAFLD. METHODS A systematic review and meta-analysis of observational studies evaluating the association between psoriasis and NAFLD, as diagnosed by imaging or International Classification of Diseases codes was performed. Literature search on PubMed, Scopus and Web of Science on May 3, 2021 was undertaken. Studies using liver biopsy were not available. For the meta-analysis, the random-effects modelling was adopted. RESULTS We identified 15 observational (case-control and cross-sectional) studies for a total of 249,933 patients with psoriasis (49% with NAFLD) and 1,491,402 controls (36% with NAFLD). Psoriasis was associated with prevalent NAFLD (n = 11 studies; pooled random-effects odds ratio [OR] 1.96, 95% CI 1.70-2.26; I2 = 97%, p < 0.01). Psoriatic patients with NAFLD had a higher mean psoriasis area and severity index (PASI) than their counterparts without NAFLD (n = 8 studies, pooled weighted mean difference: 3.93, 95% CI 2.01-5.84; I2 = 88%, p < 0.01). The risk of NAFLD was marginally higher in patients with psoriatic arthritis than in those with psoriasis alone (n = 5 studies, pooled random-effects OR 1.83, 95% CI 0.98-3.43; I2 = 64%, p = 0.03). Sensitivity analyses did not alter these findings. Funnel plot did not show any significant publication bias. A major limitation of the study was the high degree of heterogeneity across studies. CONCLUSION Psoriasis is associated with prevalent NAFLD and this risk parallels the severity of psoriasis.
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Affiliation(s)
- F Bellinato
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy.
| | - P Gisondi
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy
| | - A Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy
| | - G Girolomoni
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy
| | - G Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy
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30
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Effects of secukinumab and adalimumab on serum uric acid level in patients with plaque psoriasis. Chin Med J (Engl) 2022; 135:1438-1443. [PMID: 35838407 PMCID: PMC9481430 DOI: 10.1097/cm9.0000000000002130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Psoriasis is a chronic systemic inflammatory disease, and hyperuricemia is a common comorbidity in patients with psoriasis. However, there are limited reports on the relationship between serum uric acid levels and biological treatment efficacy. The purposes of this study were to compare the differences in serum uric acid levels between patients with psoriasis and healthy controls and analyze the risk of hyperuricemia. METHODS A total of 196 patients with psoriasis and 191 age- and sex-matched healthy controls were enrolled in this retrospective cohort study. One hundred and twenty-seven patients with severe psoriasis were treated with biologics. Sixty-eight patients received adalimumab, and 59 patients received secukinumab. Serum uric acid levels were measured at baseline, week 24, and week 48 of treatment. RESULTS Patients with psoriasis had higher serum uric acid levels than healthy controls (6.4 ± 1.7 mg/dL vs. 5.7 ± 1.5 mg/dL, P < 0.001). Hyperuricemia was found in 33.7% (66/196) of patients with psoriasis, which was significantly higher than that in healthy controls (13.1% [25/191], P < 0.001). Serum uric acid levels and hyperuricemia were not related to the severity of psoriasis ( P > 0.05). No significant changes in serum uric acid levels and hyperuricemia were observed following adalimumab treatment ( P > 0.05). The serum uric acid level in patients treated with secukinumab was 6.7 ± 1.6 mg/dL at week 24, which was not statistically different from that at baseline (6.6 ± 1.4 mg/dL, P = 0.885). Serum uric acid levels were significantly decreased at week 48 (6.3 ± 1.5 mg/dL vs. 6.6 ± 1.4 mg/dL, P = 0.007) in patients treated with secukinumab. Secukinumab had no significant effect on hyperuricemia either ( P > 0.05). CONCLUSIONS The serum uric acid levels and prevalence of hyperuricemia in patients with psoriasis were significantly higher than those in healthy controls. Secukinumab treatment for 48 weeks successfully decreased serum uric acid levels in patients with psoriasis, whereas adalimumab had no significant effect on serum uric acid levels.
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Actualización práctica de las recomendaciones del Grupo de Psoriasis de la Academia Española de Dermatología y Venereología (GPS) para el tratamiento de la psoriasis con terapia biológica. Parte 2 «Manejo de poblaciones especiales, pacientes con comorbilidad y gestión del riesgo». ACTAS DERMO-SIFILIOGRAFICAS 2022; 113:583-609. [DOI: 10.1016/j.ad.2022.01.024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 01/26/2022] [Indexed: 12/19/2022] Open
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Carrascosa JM, Puig L, Romero IB, Salgado-Boquete L, Del Alcázar E, Lencina JJA, Moreno D, de la Cueva P. [Translated article] Practical Update of the Guidelines Published by the Psoriasis Group of the Spanish Academy of Dermatology and Venereology (GPs) on the Treatment of Psoriasis With Biologic Agents: Part 2-Management of Special Populations, Patients With Comorbid Conditions, and Risk. ACTAS DERMO-SIFILIOGRAFICAS 2022; 113:T583-T609. [PMID: 35748004 DOI: 10.1016/j.ad.2022.01.040] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 01/26/2022] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Since its inception, the Psoriasis Group (GPs) of the Spanish Academy of Dermatology and Venereology (AEDV) has worked to continuously update recommendations for the treatment of psoriasis based on the best available evidence and incorporating proposals arising from and aimed at clinical practice. An updated GPs consensus document on the treatment of moderate to severe psoriasis was needed because of changes in the treatment paradigm and the approval in recent years of a large number of new biologic agents. METHODOLOGY The consensus document was developed using the nominal group technique complemented by a scoping review. First, a designated coordinator selected a group of GPs members for the panel based on their experience and knowledge of psoriasis. The coordinator defined the objectives and key points for the document and, with the help of a documentalist, conducted a scoping review of articles in Medline, Embase, and the Cochrane Library up to January 2021. The review included systematic reviews and meta-analyses as well as clinical trials not included in those studies and high-quality real-world studies. National and international clinical practice guidelines and consensus documents on the management of moderate to severe psoriasis were also reviewed. The coordinator then drew up a set of proposed recommendations, which were discussed and modified in a nominal group meeting. After several review processes, including external review by other GPs members, the final document was drafted. RESULTS The present guidelines include updated recommendations on assessing the severity of psoriasis and criteria for the indication of systemic treatment. They also include general principles for the treatment of patients with moderate to severe psoriasis and define treatment goals for these patients as well as criteria for the indication and selection of initial and subsequent therapies Practical issues, such as treatment failure and maintenance of response, are also addressed.
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Affiliation(s)
- J M Carrascosa
- Departamento de Dermatología, Hospital Universitari Germans Trias I Pujol, Badalona, Universitat Autònoma de Barcelona, IGTP, Barcelona, Spain.
| | - L Puig
- Departamento de Dermatología, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - I B Romero
- Departamento de Dermatología, Hospital General Universitario de Alicante-ISABIAL - Universidad Miguel Hernández de Elche, Alicante, Spain
| | - L Salgado-Boquete
- Departamento de Dermatología, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
| | - E Del Alcázar
- Departamento de Dermatología, Hospital Universitari Germans Trias I Pujol, Badalona, Universitat Autònoma de Barcelona, IGTP, Barcelona, Spain
| | - J J A Lencina
- Servicio de Dermatología, Hospital Universitario Vega Baja, Alicante, Spain
| | - D Moreno
- Departamento de Dermatología, Hospital Universitario Virgen Macarena, Universidad de Sevilla, Sevilla, Spain
| | - P de la Cueva
- Servicio de Dermatología, Hospital Universitario Infanta Leonor, Universidad Complutense de Madrid, Madrid, Spain
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Ion A, Dorobanțu AM, Popa LG, Mihai MM, Orzan OA. Risks of Biologic Therapy and the Importance of Multidisciplinary Approach for an Accurate Management of Patients with Moderate-Severe Psoriasis and Concomitant Diseases. BIOLOGY 2022; 11:biology11060808. [PMID: 35741329 PMCID: PMC9220356 DOI: 10.3390/biology11060808] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 05/14/2022] [Accepted: 05/23/2022] [Indexed: 11/23/2022]
Abstract
Simple Summary Psoriasis is a chronic multisystem inflammatory disease associated with a wide range of comorbidities including cardiovascular disease, hypertension, diabetes, hyperlipidemia, obesity, metabolic syndrome, anxiety, depression, chronic kidney disease, and malignancy. Currently available novel therapeutic options for moderate-severe psoriasis include tumor necrosis factor alpha inhibitors, inhibitors of the interleukin 17, and inhibitors of the interleukin 23. Apart from the concomitant diseases psoriasis patients may have, biologic therapy may cause significant complications requiring close collaboration between dermatologists and physicians of different specialties. Consequently, it was our main purpose to provide an overview of each class of biologic agents, as well as of the most frequent adverse events they may cause in psoriasis patients with concomitant diseases. Abstract Psoriasis is a chronic multisystem inflammatory disease associated with a plethora of comorbidities including metabolic syndrome, cardiovascular disease, hypertension, diabetes, hyperlipidemia, obesity, anxiety, depression, chronic kidney disease, and malignancy. Advancement in unveiling new key elements in the pathophysiology of psoriasis led to significant progress in the development of biologic agents which target different signaling pathways and cytokines involved in the inflammatory cascade responsible for the clinical manifestations found in psoriasis. Currently available novel therapeutic options for moderate-severe psoriasis include tumor necrosis factor alpha inhibitors, inhibitors of the interleukin 17, and inhibitors of the interleukin 23. Nevertheless, concerns have been raised with respect to the possible risks associated with the use of biologic therapy requiring close collaboration between dermatologists and physicians of different specialties. Our aim was to perform an in-depth literature review and discuss the potential risks associated with biologic therapy in patients with psoriasis and concurrent diseases with a focus on the influence of novel therapeutic agents on liver function in the context of hepatopathies, particularly viral hepatitis. A multidisciplinary teamwork and periodic evaluation of psoriasis patients under biologic therapy is highly encouraged to obtain an accurate management for each case.
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Affiliation(s)
- Ana Ion
- Department of Dermatology, ‘Elias’ Emergency University Hospital, 011461 Bucharest, Romania; (A.M.D.); (L.G.P.); (M.M.M.); (O.A.O.)
- Correspondence: ; Tel.: +40-74-562-2801
| | - Alexandra Maria Dorobanțu
- Department of Dermatology, ‘Elias’ Emergency University Hospital, 011461 Bucharest, Romania; (A.M.D.); (L.G.P.); (M.M.M.); (O.A.O.)
| | - Liliana Gabriela Popa
- Department of Dermatology, ‘Elias’ Emergency University Hospital, 011461 Bucharest, Romania; (A.M.D.); (L.G.P.); (M.M.M.); (O.A.O.)
- ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Mara Mădălina Mihai
- Department of Dermatology, ‘Elias’ Emergency University Hospital, 011461 Bucharest, Romania; (A.M.D.); (L.G.P.); (M.M.M.); (O.A.O.)
- ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Olguța Anca Orzan
- Department of Dermatology, ‘Elias’ Emergency University Hospital, 011461 Bucharest, Romania; (A.M.D.); (L.G.P.); (M.M.M.); (O.A.O.)
- ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
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Piaserico S, Messina F. Pharmacological management of severe plaque psoriasis in patients with cardiovascular disease. Expert Opin Pharmacother 2022; 23:853-864. [PMID: 35361040 DOI: 10.1080/14656566.2022.2060739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION There is compelling evidence about the independent association between psoriasis and an increased risk of cardiovascular diseases, in particular myocardial infarction, chronic heart failure and cardiac arrythmia. This is due to both the higher prevalence of traditional cardiovascular risk factors (including hypertension, diabetes, hyperlipidemia, obesity, and smoking) and an independent contribution of chronic systemic inflammation associated with psoriasis. Inflammation is not only important in atherosclerosis, but also is increasingly recognized as a contributing factor to heart failure and arrythmia through microvascular dysfunction and myocardial fibrosis. When treating a patient with severe psoriasis, it is recommended to take into consideration this enhanced cardiovascular risk. Moreover, the use of a systemic treatment in a patient with already existing cardiovascular comorbidities should always be considered with caution, assessing the pro and cons of these drugs. AREAS COVERED Herein, the authors review the pharmacological management of severe plaque psoriasis in patients with cardiovascular disease, providing their expert opinion and future perspectives on the subject. EXPERT OPINION Theoretically, anti-inflammatory drugs may not only dampen the systemic burden associated with psoriasis, but also potentially contribute to prevent long-term cardiovascular events in psoriasis. On the other hand, some treatments may also induce negative effects on the cardiovascular system. Whether findings from observational studies or ones evaluating surrogates of cardiovascular risk translate into reductions in cardiovascular events needs to be investigated by long-term clinical trials with clinically meaningful endpoints.
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Affiliation(s)
- Stefano Piaserico
- Department of Medicine, Dermatology Unit, University of Padua, Padua, Italy
| | - Francesco Messina
- Department of Medicine, Dermatology Unit, University of Padua, Padua, Italy
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Merola JF, McInnes IB, Deodhar AA, Dey AK, Adamstein NH, Quebe-Fehling E, Aassi M, Peine M, Mehta NN. Effect of Secukinumab on Traditional Cardiovascular Risk Factors and Inflammatory Biomarkers: Post Hoc Analyses of Pooled Data Across Three Indications. Rheumatol Ther 2022; 9:935-955. [PMID: 35305260 PMCID: PMC9127026 DOI: 10.1007/s40744-022-00434-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 02/14/2022] [Indexed: 11/29/2022] Open
Abstract
Background Psoriasis, psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) are chronic immune-mediated inflammatory diseases (IMIDs) associated with cardiovascular (CV) disease. High-sensitivity C-reactive protein (hsCRP) and, more recently, the neutrophil–lymphocyte ratio (NLR) are important inflammatory biomarkers predictive of CV disease and CV disease-associated mortality. Here, we report the effect of interleukin (IL)-17A inhibition with secukinumab on CV risk parameters in patients with psoriasis, PsA, and axSpA over 1 year of treatment. Methods This was a post hoc analysis of pooled data from phase 3/4 secukinumab studies in psoriasis, PsA, and axSpA. CV-related exclusion criteria included uncontrolled hypertension and congestive heart failure. Traditional risk factors assessed were body mass index (BMI) > 25, high fasting glucose and blood pressure (systolic and diastolic), and high cholesterol (low-density lipoproteins [LDL], total cholesterol/HDL ratio, and triglycerides). Inflammatory CV risk parameters assessed were hsCRP and NLR. Statistical analysis was descriptive. Subgroup analyses were performed in high-risk patients defined as having baseline hsCRP > 4 mg/L (patients with psoriasis) and > 10 mg/L (patients with PsA/axSpA). Results In total, 9197 patients from 19 clinical trials (8 in psoriasis, n = 4742; 5 in PsA, n = 2475; 6 in axSpA, n = 1980) were included. All traditional CV risk parameters remained stable in secukinumab-treated patients through 1 year. Secukinumab rapidly reduced both hsCRP and the NLR compared with placebo at week 12 (psoriasis) or week 16 (PsA/axSpA) in the overall population and in high-risk patients (all P < 0.01). This reduction was maintained for at least 1 year of secukinumab therapy in all indications. Conclusions Secukinumab led to a rapid and sustained reduction in hsCRP and the NLR in patients with IMIDs with a high systemic inflammatory burden. Traditional CV risk factors remained stable for at least 1 year in patients with psoriasis, PsA, and axSpA. Taken together, secukinumab had a favorable effect on systemic inflammation without impact on traditional CV risk factors. Trials Registration ClinicalTrials.gov, NCT01365455, NCT01358578, NCT01406938, NCT01555125, NCT01636687, NCT02752776, NCT02074982, NCT02826603, NCT01752634, NCT01989468, NCT02294227, NCT02404350, NCT02745080, NCT01863732, NCT01649375, NCT02008916, NCT02159053, NCT02896127, NCT02696031. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-022-00434-z.
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Affiliation(s)
- Joseph F Merola
- Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | | | | | - Amit K Dey
- Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA
| | | | | | | | | | - Nehal N Mehta
- Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
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Gialouri CG, Evangelatos G, Fragoulis GE. Choosing the Appropriate Target for the Treatment of Psoriatic Arthritis: TNFα, IL-17, IL-23 or JAK Inhibitors? Mediterr J Rheumatol 2022; 33:150-161. [PMID: 36127928 PMCID: PMC9450184 DOI: 10.31138/mjr.33.1.150] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 10/25/2021] [Accepted: 11/15/2021] [Indexed: 02/05/2023] Open
Abstract
Psoriatic arthritis (PsA) is a highly heterogenous disease. Apart from arthritis and psoriasis, other manifestations can also occur, including enthesitis, dactylitis, axial-, nail-, eye- and bowel- involvement. Comorbidities are also frequent in the setting of PsA, with cardiovascular disease and mental-health disorders being the most frequent. The Rheumatologist's arsenal has many different treatment options for treating PsA. Despite their effectiveness, there are some differences in terms of efficacy and safety that might affect clinician's decision for one or the other drug. Comparing biologic DMARDs and JAK-inhibitors, one could say that they have similar effectiveness in terms of musculoskeletal manifestations. However, anti-IL-17 and anti-IL-23 drugs seem to be more effective for skin manifestations. In contrast, JAK-inhibitors and etanercept might be less effective for these manifestations. Inflammatory bowel disease and uveitis are non-responsive to etanercept and anti-IL-17 drugs. As regards to comorbidities, data are scarce, but future studies will shed light on possible differential effect of bDMARDs or JAK-inhibitors. Safety is always an important drive for choosing the appropriate treatment. Infections are the most common adverse event of these drugs. Etanercept and anti-IL-17 drugs are safer for patients having latent tuberculosis, while herpes zoster is more common in individuals receiving JAK-inhibitors. Finally, venous thromboembolism risk, should be taken into account when JAK-inhibitors are used. In this review, we comparatively present, as outlined above, the various aspects that could affect the choice of the appropriate bDMARD or JAK-inhibitor for the treatment of a PsA patient.
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Affiliation(s)
- Chrysoula G. Gialouri
- First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens,“Laiko” General Hospital, Athens, Greece
| | - Gerasimos Evangelatos
- First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens,“Laiko” General Hospital, Athens, Greece
| | - George E. Fragoulis
- First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens,“Laiko” General Hospital, Athens, Greece
- Corresponding Author: George E. Fragoulis, MD, PhD Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens Laiko General Hospital, Mikras Asias 75 Str, 11527 Athens, Greece, Tel.: +30 210 746 2636, E-mail:
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Patel S, Kumthekar A. Psoriatic Arthritis: The Influence of Co-morbidities on Drug Choice. Rheumatol Ther 2022; 9:49-71. [PMID: 34797530 PMCID: PMC8814223 DOI: 10.1007/s40744-021-00397-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 09/28/2021] [Indexed: 12/20/2022] Open
Abstract
Psoriatic arthritis (PsA) is associated with a higher burden of co-morbidities such as obesity, cardiovascular disease, non-alcoholic fatty liver disease, inflammatory eye disease, inflammatory bowel disease, skin cancer and depression compared to the general population. In the last 20 years, the therapeutic options for PsA have increased exponentially with the availability of tumor necrosis factor-alpha (TNF) inhibitors, interleukin (IL)-17 inhibitors, IL-12/23 inhibitors and Janus kinases/signal transducer and activator of transcription proteins (JAK/STAT) inhibitors. The articular and extra-articular manifestations of PsA usually dictate the treatment choice but important consideration must be given to the corresponding co-morbidities while deciding the drug therapy due to associated safety profile, effect on disease activity, etc. This review provides a comprehensive review of common co-morbidities in PsA and how they can influence treatment choices.
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Affiliation(s)
- Sneha Patel
- Rheumatology, Acclaim Physicians/JPS Hospital, Fort Worth, TX, USA
| | - Anand Kumthekar
- Division of Rheumatology, Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, New York, NY, USA.
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Lee TL, Tsai TF. Non-immune functions of inflammatory cytokines targeted by anti-psoriatic biologics: a review. Inflamm Res 2022; 71:157-168. [PMID: 34981130 DOI: 10.1007/s00011-021-01528-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 11/25/2021] [Accepted: 11/25/2021] [Indexed: 12/01/2022] Open
Abstract
PURPOSE Psoriasis is an inflammatory disease characterized by skin thickening with silvery white desquamation due to dysregulated inflammatory pathways and elevated levels of inflammatory cytokines. Biologic agents targeting these inflammatory cytokines have brought about significant improvement in clearing psoriatic lesions in patients with moderate-to-severe psoriasis. Moreover, biologics exert both beneficial and detrimental effects on comorbidities in psoriasis, which include increased risk of cardiovascular events, metabolic syndrome, among other conditions. However, non-immune functions of cytokines targeted by biologics, and, hence, the potential risks and benefits of biologics for psoriasis to different organs/systems and comorbidities, have not been well elucidated. RESULTS This review summarizes current understanding of the pathogenesis of psoriasis-related comorbidities and emerging discoveries of roles of cytokines targeted in psoriasis treatment, including tumor necrosis factor α and interleukins 12, 23, and 17, aiming to complete the safety profile of each biologics and provide therapeutic implications on psoriasis-related comorbidities, and on diseases involving other organs or systems.
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Affiliation(s)
- Tung-Lin Lee
- Department of Medical Education, National Taiwan University Hospital, Taipei, Taiwan
| | - Tsen-Fang Tsai
- Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, 7 Chung-Shan S. Rd., Taipei, 100, Taiwan.
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Balak DMW, Piaserico S, Kasujee I. Non-Alcoholic Fatty Liver Disease (NAFLD) in Patients with Psoriasis: A Review of the Hepatic Effects of Systemic Therapies. PSORIASIS (AUCKLAND, N.Z.) 2021; 11:151-168. [PMID: 34909410 PMCID: PMC8665778 DOI: 10.2147/ptt.s342911] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 11/09/2021] [Indexed: 12/12/2022]
Abstract
There is increasing interest in the association between psoriasis and non-alcoholic fatty liver disease (NAFLD), which is a prevalent liver disease characterized by excessive fat storage and inflammation that can progress to fibrosis and cancer. Patients with psoriasis have a two-fold higher risk to develop NAFLD and a higher risk to progress to more severe liver disease. Psoriasis and NAFLD share common risk factors such as smoking, alcohol consumption, and the presence of metabolic syndrome and its component disorders. In addition, both psoriasis and NAFLD hinge upon a systemic low-grade inflammation that can lead to a vicious cycle of progressive liver damage in NAFLD as well as worsening of the underlying psoriasis. Other important shared pathophysiological pathways include peripheral insulin resistance and oxidative stress. NAFLD should receive clinical awareness as important comorbidity in psoriasis. In this review, we assess the recent literature on the epidemiological and pathophysiological relationship of psoriasis and NAFLD, discuss the clinical implications of NAFLD in psoriasis patients, and summarize the hepatotoxic and hepatoprotective potential of systemic psoriasis therapies.
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Affiliation(s)
- Deepak M W Balak
- Department of Dermatology, LangeLand Ziekenhuis, Zoetermeer, the Netherlands.,Department of Dermatology, Ghent University Hospital, Ghent, Belgium
| | - Stefano Piaserico
- Dermatology Unit, Department of Medicine, University of Padova, Padova, Italy
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Tripolino C, Ciaffi J, Ruscitti P, Giacomelli R, Meliconi R, Ursini F. Hyperuricemia in Psoriatic Arthritis: Epidemiology, Pathophysiology, and Clinical Implications. Front Med (Lausanne) 2021; 8:737573. [PMID: 34631755 PMCID: PMC8492931 DOI: 10.3389/fmed.2021.737573] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 08/27/2021] [Indexed: 01/02/2023] Open
Abstract
Psoriatic arthritis (PsA) represents the articular component of the systemic psoriatic disease and the extra-cutaneous disorder most frequently found in patients with psoriasis. Besides the articular involvement, PsA is associated with several metabolic abnormalities such as insulin resistance, hypertension, diabetes and hyperuricemia. Uric acid is the final product of purine metabolism and the etiological substrate of gout. Accumulating evidence highlights the emerging role of hyperuricemia as a major cardiovascular risk factor. Moreover, different studies evaluated the interplay between hyperuricemia and psoriatic disease, suggesting that individuals affected by psoriasis or PsA might present higher serum levels of uric acid and that hyperuricemia might affect severity of clinical manifestations and degree of inflammation in PsA patients. In this review, we focus on the bidirectional relationship between uric acid and PsA, analyzing how uric acid may be involved in the pathogenesis of psoriasis/PsA and how clinical manifestations of PsA and inflammatory mediators are affected by uric acid concentrations. Finally, the effects of anti-rheumatic drugs on uric acid levels and the potential benefit of urate-lowering therapies on psoriasis and PsA were summarized.
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Affiliation(s)
- Cesare Tripolino
- Geriatric Medicine Unit, Department of Medical Functional Area, "San Giovanni di Dio" Hospital, Crotone, Italy
| | - Jacopo Ciaffi
- Medicine and Rheumatology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Ortopedico Rizzoli (IOR), Bologna, Italy
| | - Piero Ruscitti
- Rheumatology Unit, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Roberto Giacomelli
- Unit of Allergology, Immunology, Rheumatology, Department of Medicine, Università Campus Bio-Medico Di Roma, Rome, Italy
| | - Riccardo Meliconi
- Medicine and Rheumatology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Ortopedico Rizzoli (IOR), Bologna, Italy.,Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Francesco Ursini
- Medicine and Rheumatology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Ortopedico Rizzoli (IOR), Bologna, Italy.,Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, Bologna, Italy
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Biologic Treatment in Combination with Lifestyle Intervention in Moderate to Severe Plaque Psoriasis and Concomitant Metabolic Syndrome: Rationale and Methodology of the METABOLyx Randomized Controlled Clinical Trial. Nutrients 2021; 13:nu13093015. [PMID: 34578893 PMCID: PMC8471656 DOI: 10.3390/nu13093015] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 08/19/2021] [Accepted: 08/27/2021] [Indexed: 01/04/2023] Open
Abstract
Inflammatory diseases including psoriasis are associated with metabolic and cardiovascular comorbidities, including obesity and metabolic syndrome. Obesity is associated with greater psoriasis disease severity and reduced response to treatment. Therefore, targeting metabolic comorbidities could improve patients’ health status and psoriasis-specific outcomes. METABOLyx is a randomized controlled trial evaluating the combination of a lifestyle intervention program with secukinumab treatment in psoriasis. Here, the rationale, methodology and baseline patient characteristics of METABOLyx are presented. A total of 768 patients with concomitant moderate to severe plaque psoriasis and metabolic syndrome were randomized to secukinumab 300 mg, or secukinumab 300 mg plus a tailored lifestyle intervention program, over 24 weeks. A substudy of immunologic and metabolic biomarkers is ongoing. The primary endpoint of METABOLyx is PASI90 response at week 24. Other endpoints include patient-reported outcomes and safety. METABOLyx represents the first large scale clinical trial of an immunomodulatory biologic in combination with a standardized lifestyle intervention.
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Magdaleno-Tapial J, López-Martí C, Ortiz-Salvador JM, Hernández-Bel P, Tamarit-García JJ, Diago-Madrid M, Sánchez-Carazo JL, Pérez-Ferriols A. Can secukinumab improve liver fibrosis? A pilot prospective study of 10 psoriatic patients. Dermatol Ther 2021; 34:e15065. [PMID: 34289229 DOI: 10.1111/dth.15065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 06/30/2021] [Accepted: 07/14/2021] [Indexed: 11/30/2022]
Affiliation(s)
| | - Cristina López-Martí
- Department of Dermatology, Hospital General Universitario de Valencia, Valencia, Spain
| | | | - Pablo Hernández-Bel
- Department of Dermatology, Hospital General Universitario de Valencia, Valencia, Spain
| | | | - Moisés Diago-Madrid
- Department of Gastroenterology and Hepatology, Hospital General Universitario de Valencia, Valencia, Spain
| | | | - Amparo Pérez-Ferriols
- Department of Dermatology, Hospital General Universitario de Valencia, Valencia, Spain
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Nowowiejska J, Baran A, Flisiak I. Aberrations in Lipid Expression and Metabolism in Psoriasis. Int J Mol Sci 2021; 22:6561. [PMID: 34207318 PMCID: PMC8234564 DOI: 10.3390/ijms22126561] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 06/15/2021] [Accepted: 06/16/2021] [Indexed: 12/11/2022] Open
Abstract
Psoriasis (PSO) is a common skin disease that affects about 1%-3% of the general population. It is a great medical, social and economic burden since PSO is associated with many comorbidities, of which the most common are cardiometabolic disorders. Psoriatic patients suffer more frequently from obesity, dyslipidemia, atherosclerosis, and nonalcoholic fatty liver disease. Research shows that lipid expression and metabolism disorders are present more often in such patients. This review focuses on a variety of aberrations in lipids in the skin, blood, and adipose tissue in psoriatic patients and their multifactorial impact on the pathogenesis of psoriasis.
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Affiliation(s)
| | - Anna Baran
- Department of Dermatology and Venereology, Medical University of Bialystok, Zurawia 14 St, 15-540 Bialystok, Poland; (J.N.); (I.F.)
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Piros ÉA, Szabó Á, Rencz F, Brodszky V, Wikonkál N, Miheller P, Horváth M, Holló P. Anti-Interleukin-17 Therapy of Severe Psoriatic Patients Results in an Improvement of Serum Lipid and Inflammatory Parameters' Levels, but Has No Effect on Body Composition Parameters. Life (Basel) 2021; 11:life11060535. [PMID: 34207504 PMCID: PMC8228146 DOI: 10.3390/life11060535] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 05/27/2021] [Accepted: 06/07/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND: Psoriasis is frequently accompanied by metabolic syndrome. Effect of anti-tumor necrosis factor therapies on increases in body weight is well-known. Data on the effects of interleukin-17 inhibitors are limited. Authors determined the effect of anti-interleukin-17 therapies on the body composition and serum lipid and inflammatory parameters among severe psoriatic patients. METHODS: Thirty-five severe psoriatic patients were enrolled. Twenty-two received secukinumab and 13 received ixekizumab as their 2nd-or 3rd-line biological treatment. Before treatment initiation and 6 months later, laboratory examinations measuring metabolic and inflammatory panels and body composition analyses were performed. RESULTS: After 6 months, a significant reduction was observed in psoriasis area severity index (p < 0.001) from 18 to 0, in c-reactive protein (p < 0.001) from 6.6 to 4.00 mg/L, in low-density lipoprotein-cholesterol (p = 0.004) from 3.69 to 3.19 mmol/L, and an improvement in high-density lipoprotein-cholesterol (p = 0.022) from 1.31 to 1.40 mmol/L. Median baseline body mass index was 32.80 kg/m2. The body composition parameters did not show any significant changes. CONCLUSIONS: Anti-interleukin-17 therapy of severe psoriatic patients does not cause significant changes in body composition parameters. Improvements in the lipid and inflammatory parameters might have a beneficial effect on patients’ cardiometabolic status. This effect might be detectable in high-risk obese psoriatic patients.
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Affiliation(s)
- Éva Anna Piros
- Department of Dermatology, Venereology and Dermato-Oncology, Semmelweis University, 1085 Budapest, Hungary; (N.W.); (P.H.)
- Rácz Károly Doctoral School of Clinical Medicine, Semmelweis University, 1085 Budapest, Hungary;
- Correspondence:
| | - Ákos Szabó
- Rácz Károly Doctoral School of Clinical Medicine, Semmelweis University, 1085 Budapest, Hungary;
- Department of Health Economics, Corvinus University, 1093 Budapest, Hungary; (F.R.); (V.B.)
| | - Fanni Rencz
- Department of Health Economics, Corvinus University, 1093 Budapest, Hungary; (F.R.); (V.B.)
| | - Valentin Brodszky
- Department of Health Economics, Corvinus University, 1093 Budapest, Hungary; (F.R.); (V.B.)
| | - Norbert Wikonkál
- Department of Dermatology, Venereology and Dermato-Oncology, Semmelweis University, 1085 Budapest, Hungary; (N.W.); (P.H.)
- Military Hospital-State Health Centre, 1134 Budapest, Hungary
| | - Pál Miheller
- 1st Department of Surgery and Interventional Gastroenterology, Semmelweis University, 1082 Budapest, Hungary; (P.M.); (M.H.)
| | - Miklós Horváth
- 1st Department of Surgery and Interventional Gastroenterology, Semmelweis University, 1082 Budapest, Hungary; (P.M.); (M.H.)
| | - Péter Holló
- Department of Dermatology, Venereology and Dermato-Oncology, Semmelweis University, 1085 Budapest, Hungary; (N.W.); (P.H.)
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The Association of Psoriasis and Obesity: Focusing on IL-17A-Related Immunological Mechanisms. INTERNATIONAL JOURNAL OF DERMATOLOGY AND VENEREOLOGY 2021. [DOI: 10.1097/jd9.0000000000000155] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Pannu S, Rosmarin D. Psoriasis in Patients with Metabolic Syndrome or Type 2 Diabetes Mellitus: Treatment Challenges. Am J Clin Dermatol 2021; 22:293-300. [PMID: 33586126 DOI: 10.1007/s40257-021-00590-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/23/2021] [Indexed: 12/14/2022]
Abstract
Psoriasis is a chronic inflammatory disease that affects 2-3% of the population worldwide. It is associated with plaques, psoriatic arthritis, and metabolic syndrome and its components, including obesity, diabetes, dyslipidemia, nonalcoholic fatty liver disease, and cardiovascular disease. In this review, we highlight the shared pathogenic pathways leading to the comorbid existence of both diseases and the impact of drugs used for psoriasis on metabolic syndrome and vice versa. Persistent inflammation is common to both diseases. They share increased inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin-6. Biologics have revolutionized the treatment of plaque psoriasis and also have a positive impact on metabolic syndrome. There is some evidence that TNFα inhibitors decrease insulin resistance and improve glycemic indices. Some psoriasis treatments may result in decreased body weight. Lifestyle measures used in the management of metabolic syndrome, such as weight loss, exercise, and healthy diet, are beneficial in patients with psoriasis. Considering the association between metabolic syndrome and psoriasis, we recommend screening patients with psoriasis for metabolic syndrome with clinical examinations and laboratory tests. Patients with a co-diagnosis of these diseases deserve special attention for optimal treatment.
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Affiliation(s)
- Sukhmani Pannu
- The Department of Dermatology, Tufts Medical Center, Boston, MA, USA
| | - David Rosmarin
- The Department of Dermatology, Tufts Medical Center, Boston, MA, USA.
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Wang CR, Tsai HW. Anti- and non-tumor necrosis factor-α-targeted therapies effects on insulin resistance in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. World J Diabetes 2021; 12:238-260. [PMID: 33758645 PMCID: PMC7958474 DOI: 10.4239/wjd.v12.i3.238] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/07/2021] [Accepted: 01/22/2021] [Indexed: 02/06/2023] Open
Abstract
In addition to β-cell failure with inadequate insulin secretion, the crucial mechanism leading to establishment of diabetes mellitus (DM) is the resistance of target cells to insulin, i.e. insulin resistance (IR), indicating a requirement of beyond-normal insulin concentrations to maintain euglycemic status and an ineffective strength of transduction signaling from the receptor, downstream to the substrates of insulin action. IR is a common feature of most metabolic disorders, particularly type II DM as well as some cases of type I DM. A variety of human inflammatory disorders with increased levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β, have been reported to be associated with an increased risk of IR. Autoimmune-mediated arthritis conditions, including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), with the involvement of proinflammatory cytokines as their central pathogenesis, have been demonstrated to be associated with IR, especially during the active disease state. There is an increasing trend towards using biologic agents and small molecule-targeted drugs to treat such disorders. In this review, we focus on the effects of anti-TNF-α- and non-TNF-α-targeted therapies on IR in patients with RA, PsA and AS. Anti-TNF-α therapy, IL-1 blockade, IL-6 antagonist, Janus kinase inhibitor and phospho-diesterase type 4 blocker can reduce IR and improve diabetic hyper-glycemia in autoimmune-mediated arthritis.
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Affiliation(s)
- Chrong-Reen Wang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan
| | - Hung-Wen Tsai
- Department of Pathology, National Cheng Kung University Hospital, Tainan 70403, Taiwan
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Nast A, Smith C, Spuls P, Avila Valle G, Bata‐Csörgö Z, Boonen H, De Jong E, Garcia‐Doval I, Gisondi P, Kaur‐Knudsen D, Mahil S, Mälkönen T, Maul J, Mburu S, Mrowietz U, Reich K, Remenyik E, Rønholt K, Sator P, Schmitt‐Egenolf M, Sikora M, Strömer K, Sundnes O, Trigos D, Van Der Kraaij G, Yawalkar N, Dressler C. EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris – Part 2: specific clinical and comorbid situations. J Eur Acad Dermatol Venereol 2021; 35:281-317. [DOI: 10.1111/jdv.16926] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 08/13/2020] [Indexed: 12/15/2022]
Affiliation(s)
- A. Nast
- Charité – Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin Department of Dermatology, Venereology and Allergology Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin Germany
| | - C. Smith
- St John’s Institute of Dermatology London UK
| | - P.I. Spuls
- Academic Medical Centre Amsterdam Amsterdam Netherlands
| | - G. Avila Valle
- Charité – Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin Department of Dermatology, Venereology and Allergology Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin Germany
| | | | - H. Boonen
- Office‐Based Dermatology Practice Geel Belgium
| | - E. De Jong
- Radboud University Medical Centre Nijmegen Nijmegen Netherlands
| | - I. Garcia‐Doval
- Unidad de Investigación. Fundación Piel Sana AEDV Madrid Spain
| | | | | | - S. Mahil
- Guy's and St Thomas' NHS Foundation Trust London UK
| | - T. Mälkönen
- Helsinki University Central Hospital Helsinki Finland
| | - J.T. Maul
- Department of Dermatology University Hospital of Zürich Zürich Switzerland
| | - S. Mburu
- International Federation of Psoriasis Associations (IFPA)
| | - U. Mrowietz
- Universitätsklinikum Schleswig‐Holstein Kiel Germany
| | - K. Reich
- Translational Research in Inflammatory Skin Diseases Institute for Health Services Research in Dermatology and Nursing University Medical Center Hamburg‐Eppendorf Hamburg Germany
| | | | | | - P.G. Sator
- Municipal Hospital Hietzing Vienna Austria
| | - M. Schmitt‐Egenolf
- Dermatology Department of Public Health & Clinical Medicine Umeå University Umeå Sweden
| | - M. Sikora
- Department of Dermatology Medical University of Warsaw Warsaw Poland
| | - K. Strömer
- Office‐Based Dermatology Practice Mönchengladbach Germany
| | | | - D. Trigos
- International Federation of Psoriasis Associations (IFPA)
| | | | - N. Yawalkar
- Department of Dermatology, Inselspital Bern University HospitalUniversity of Bern Bern Switzerland
| | - C. Dressler
- Charité – Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin Department of Dermatology, Venereology and Allergology Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin Germany
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Gisondi P, Bellinato F, Bruni M, De Angelis G, Girolomoni G. Methotrexate vs secukinumab safety in psoriasis patients with metabolic syndrome. Dermatol Ther 2020; 33:e14281. [DOI: 10.1111/dth.14281] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 08/28/2020] [Accepted: 08/30/2020] [Indexed: 12/30/2022]
Affiliation(s)
- Paolo Gisondi
- Section of Dermatology and Venereology, Department of Medicine University of Verona Verona Italy
| | - Francesco Bellinato
- Section of Dermatology and Venereology, Department of Medicine University of Verona Verona Italy
| | - Manfredo Bruni
- Section of Dermatology and Venereology, Department of Medicine University of Verona Verona Italy
| | - Giulia De Angelis
- Section of Dermatology and Venereology, Department of Medicine University of Verona Verona Italy
| | - Giampiero Girolomoni
- Section of Dermatology and Venereology, Department of Medicine University of Verona Verona Italy
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50
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Wang HN, Huang YH. Changes in metabolic parameters in psoriatic patients treated with secukinumab. Ther Adv Chronic Dis 2020; 11:2040622320944777. [PMID: 32821362 PMCID: PMC7412909 DOI: 10.1177/2040622320944777] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 06/26/2020] [Indexed: 12/18/2022] Open
Abstract
Background: Psoriasis is associated with cardiovascular disease and metabolic syndrome but the effects of interleukin (IL)-17A inhibitor treatment on metabolic parameters are unknown. This study aimed to determine the effects of secukinumab on metabolic parameters based on the disease activity and treatment response in patients with psoriasis. Methods: In this retrospective study, we included 99 patients with moderate to severe psoriasis, who received IL-17 inhibitor (secukinumab) treatment for 24 weeks between January 2016 and February 2020. The disease activity [Psoriasis Area and Severity Index (PASI)] and metabolic parameters at baseline and after 12 or 24 weeks of treatment were collected. Results: The PASI improved with a significant reduction of high-sensitivity C-reactive protein (hs-CRP) at weeks 12 and 24 respectively. However, body weight and body mass index were significantly increased at week 12 and 24 of treatment. Triglycerides level and atherogenic index of plasma were significantly higher in week 24 in PASI-90 non-responders. The baseline hs-CRP level and PASI-90 non-response correlated with elevated triglyceride levels. Conclusion: Our results suggest that obesity and hypertriglyceridemia still existed in patients despite the improved disease activity after secukinumab treatment. Higher baseline hs-CRP level and PASI-90 non-response were predictors for elevated triglyceride levels after treatment. Therefore, patient education, regular screening of the lipid profile, and weight control are recommended during the treatment of secukinumab.
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Affiliation(s)
- Hsuan Ning Wang
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou Branch, College of Medicine, Chang Gung University, Taiwan
| | - Yu Huei Huang
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou Branch, College of Medicine, Chang Gung University No.5, Fuxing St., Guishan Dist., Taoyuan City 333, Taiwan
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