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Snehasis N, Zafar S, Herve N, Siri P, Haji Ali K. Efficacy and safety of various drug combinations in treating plaque Psoriasis: A meta-analysis. F1000Res 2025; 13:453. [PMID: 39925996 PMCID: PMC11803402 DOI: 10.12688/f1000research.149172.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/22/2025] [Indexed: 02/11/2025] Open
Abstract
Background Psoriasis, a chronic inflammatory disease affecting the skin, joints, and nails (2-3% worldwide), significantly affects quality of life. Genetic and environmental factors also play key roles. Topical corticosteroids, calcineurin inhibitors, and oral corticosteroids help to manage plaque psoriasis symptoms, but combination therapies might offer greater effectiveness and improved safety profiles. These combinations could potentially reduce medication dosages and side effects in patients. Objective To assess the efficacy and safety of various drug combinations over conventional monotherapies in the treatment of moderate to severe plaque psoriasis, which incorporates palmoplantar psoriasis and psoriasis vulgaris, by discovering and utilizing research articles comprising the same or similar variables as PASI 75 and evaluating the information using RevMan v5.4.1. Method We reviewed the efficacy and safety of combination therapy vs. monotherapy/placebo for moderate-to-severe plaque psoriasis (palmoplantar and vulgaris) using PASI 75 via RevMan v5.4.1. Risk of bias assessment and funnel plots were employed to assess the heterogeneity of each paper. Inclusion criteria - Publications < 20yrs, RCTs, plaque/palmoplantar/psoriasis vulgaris; exclusion criteria - Guttate/arthritic psoriasis, pediatric and pregnant individuals, publications > 20 yrs. Results Seventeen studies were analyzed, comprising a total of 2291 patients (n=1147 with combination regimens and n=1144 with control regimen in the analysis). A significant PASI 75- response was observed in the pioglitazone combination subgroup as compared to placebo (OR=4.92,95% CI 2.19-11.05, P = 0.0001); methotrexate combination subgroup as compared to placebo (OR=2.56, 95% CI 1.67-3.94, P< 0.0001) test of subgroup differences showed P= 0.14, I 2= 34%. Incidence rate of abnormality in levels of liver enzymes (OR=1.89,9.5% CI 6.69-5.22, P=0.22), nausea (OR=1.28,95% CI 0.77-2.14, P=0.34), headache (OR=1.28,95% CI 0.77-2.14, P=0.58), fatigue (OR=0.89, 95% CI 0.41-1.90, P=0.45).]. Conclusion This study showed that combination therapy is very effective for plaque psoriasis, with promising combinations of pioglitazone. While safety seems similar between the groups, larger studies are needed to determine the long-term effects. These findings suggest that personalized treatment plans could improve outcomes; however, confirmation through larger trials is crucial before wider use. This opens doors to research on optimal combinations for individual patients.
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Affiliation(s)
- Nayak Snehasis
- Medicine, University of Visayas Gullas college of Medicine, Banilad, Cebu, 6000, Philippines
| | - Sayed Zafar
- Medicine, University of Visayas Gullas college of Medicine, Banilad, Cebu, 6000, Philippines
| | - Ngabo Herve
- Medicine, University of Visayas Gullas college of Medicine, Banilad, Cebu, 6000, Philippines
| | - Pendyala Siri
- Medicine, University of Visayas Gullas college of Medicine, Banilad, Cebu, 6000, Philippines
| | - Karshe Haji Ali
- Medicine, University of Visayas Gullas college of Medicine, Banilad, Cebu, 6000, Philippines
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Deng G, Xu C, Mo D. Identification and mechanistic insights of cell senescence-related genes in psoriasis. PeerJ 2025; 13:e18818. [PMID: 39830966 PMCID: PMC11740738 DOI: 10.7717/peerj.18818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 12/14/2024] [Indexed: 01/22/2025] Open
Abstract
Background Psoriasis is a chronic inflammatory skin disease affecting 2-3% of the global population, characterised by red scaly patches that significantly affect patients' quality of life. Recent studies have suggested that cell senescence, a state in which cells cease to divide and secrete inflammatory mediators, plays a critical role in various chronic diseases, including psoriasis. However, the involvement and mechanisms of action of senescence-related genes in psoriasis remain unclear. Methods This study aimed to identify senescence-related genes associated with psoriasis and explore their molecular mechanisms. RNA sequencing data from psoriasis and control samples were obtained from the GEO database. Differential expression analysis was performed using DESeq2 to identify differentially expressed genes (DEGs). The intersection of DEGs with cell senescence-related genes from the CellAge database was used to identify the candidate genes. Protein-protein interaction networks, Gene Ontology, and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to explore the functions and pathways of these genes. Machine learning algorithms, including Least Absolute Shrinkage and Selection Operator (LASSO) regression and Support vector machine-recursive feature elimination (SVE-RFE), were used to select feature genes that were validated by qRT-PCR. Additionally, an immune cell infiltration analysis was performed to understand the roles of these genes in the immune response to psoriasis. Results This study identified 4,913 DEGs in psoriasis, of which 46 were related to cell senescence. Machine learning highlighted four key genes, CXCL1, ID4, CCND1, and IRF7, as significant. These genes were associated with immune cell infiltration and validated by qRT-PCR, suggesting their potential as therapeutic targets for psoriasis. Conclusions This study identified and validated key senescence-related genes involved in psoriasis, providing insights into their molecular mechanisms and potential therapeutic targets and offering a foundation for developing targeted therapies for psoriasis.
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Affiliation(s)
- Guiyan Deng
- Department of Dermatology, Nanning Second People’s Hospital, Nanning, Guangxi, China
| | - Cheng Xu
- Science and Education Department, Guangxi Zhuang Autonomous Region Jiangbin Hospital, Nanning, China
| | - Dunchang Mo
- Radiotherapy Department, Nanning Second People’s Hospital, Nanning, GuangXi, China
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Briganti S, Mosca S, Di Nardo A, Flori E, Ottaviani M. New Insights into the Role of PPARγ in Skin Physiopathology. Biomolecules 2024; 14:728. [PMID: 38927131 PMCID: PMC11201613 DOI: 10.3390/biom14060728] [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: 05/14/2024] [Revised: 06/17/2024] [Accepted: 06/18/2024] [Indexed: 06/28/2024] Open
Abstract
Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor expressed in many tissues, including skin, where it is essential for maintaining skin barrier permeability, regulating cell proliferation/differentiation, and modulating antioxidant and inflammatory responses upon ligand binding. Therefore, PPARγ activation has important implications for skin homeostasis. Over the past 20 years, with increasing interest in the role of PPARs in skin physiopathology, considerable effort has been devoted to the development of PPARγ ligands as a therapeutic option for skin inflammatory disorders. In addition, PPARγ also regulates sebocyte differentiation and lipid production, making it a potential target for inflammatory sebaceous disorders such as acne. A large number of studies suggest that PPARγ also acts as a skin tumor suppressor in both melanoma and non-melanoma skin cancers, but its role in tumorigenesis remains controversial. In this review, we have summarized the current state of research into the role of PPARγ in skin health and disease and how this may provide a starting point for the development of more potent and selective PPARγ ligands with a low toxicity profile, thereby reducing unwanted side effects.
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Affiliation(s)
| | | | | | - Enrica Flori
- Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, Italy; (S.B.); (S.M.); (A.D.N.); (M.O.)
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Erduran F, Emre S, Hayran Y, Adışen E, Polat AK, Üstüner P, Öztürkcan S, Öztürk P, Ermertcan AT, Selçuk LB, Aksu EK, Akbaş A, Kalkan G, Demirseren D, Kartal SP, Topkarcı Z, Kılıç A, Yaldız M, Aytekin S, Hızlı P, Gharehdaghi S, Borlu M, Işık L, Botsalı BR, Solak EÖ, Albayrak H, Gönülal M, Balcı DD, Polat M, Daye M, Ataseven A, Yıldız S, Özer İ, Zorlu Ö, Doğan S, Erdemir VA, Dikicier BS. Analysis of factors influencing target PASI responses and side effects of methotrexate monotherapy in plaque psoriasis: a multicenter study of 1521 patients. Arch Dermatol Res 2024; 316:278. [PMID: 38796658 DOI: 10.1007/s00403-024-03066-1] [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: 01/06/2024] [Revised: 01/06/2024] [Accepted: 04/26/2024] [Indexed: 05/28/2024]
Abstract
Methotrexate (MTX) is commonly used as first-line systemic treatment agent in psoriasis. We aimed to evaluate the clinical characteristics and treatment responses of patients with psoriasis undergoing MTX monotherapy. Data from adult patients with plaque psoriasis who received MTX monotherapy for at least 3 months between April 2012 and April 2022 were retrospectively evaluated in 19 tertiary care centers. Our study included 722 female and 799 male patients, a total of 1521 participants. The average age of the patients was 44.3 ± 15.5 years. Mode of treatment was oral in 20.4% of patients while in 79.4% it was subcutaneous. The median treatment duration was 8 months (IQR = 5-15). The median weekly dose was 15 mg (IQR = 11-15). 1448 (95.2%) patients were taking folic acid supplementation. At week 12, 16.3% of the patients achieved PASI (Psoriasis Area and Severity Index) 90 response while at week 24, 37.3% achieved it. Logistic regression analysis for week 12 identified the following independent factors affecting PASI 90 achievement positively: median weekly MTX dose ≤ 15 mg (P = 0.011), subcutaneous administration (P = 0.005), no prior systemic treatment (< 0.001) and folic acid use (0.021). In logistic regression analysis for week 24; median weekly MTX dose ≤ 15 mg (P = 0.001), baseline PASI ≥ 10 (P < 0.001), no prior systemic treatment (P < 0.004), folic acid use (P = 0.001) and absence of comorbidities (P = 0.009) were determined as independent factors affecting the achievement of PASI 90. Adverse effects were observed in 38.8% of the patients, with nausea/vomiting (23.9%) and transaminase elevation (13%) being the most common. The most common reasons for interruptions (15.3%) and discontinuations (27.1%) of the treatment were patient related individual factors. The use of MTX as the first systemic treatment agent, at doses ≤ 15 mg/week and concurrent folic acid application are positive predictive factors for achieving the target PASI response both at weeks 12 and 24. In our study, which is one of the most comprehensive studies on MTX treatment in psoriasis, we observed that MTX is an effective and safe treatment option.
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Affiliation(s)
- Funda Erduran
- Department of Dermatology TR, Ankara Bilkent City Hospital, Ankara, Türkiye.
| | - Selma Emre
- Department of Dermatology TR, Ankara Yıldırım Beyazıt University, Ankara, Türkiye
| | - Yıldız Hayran
- Department of Dermatology TR, Ankara Bilkent City Hospital, Ankara, Türkiye
| | - Esra Adışen
- Faculty of Medicine, Department of Dermatology TR, Gazi University, Ankara, Türkiye
| | - Asude Kara Polat
- Department of Dermatology TR, İstanbul Training and Research Hospital, İstanbul, Türkiye
| | - Pelin Üstüner
- Department of Dermatology TR, Nişantaşı University, İstanbul, Türkiye
| | - Serap Öztürkcan
- Department of Dermatology TR, Manisa Celal Bayar University, Manisa, Türkiye
| | - Perihan Öztürk
- Department of Dermatology TR, Kahramanmaraş Sütçü İmam University, Kahramanmaraş, Türkiye
| | | | - Leyla Baykal Selçuk
- Department of Dermatology TR, Karadeniz Technical University, Trabzon, Türkiye
| | - Esra Koku Aksu
- Department of Dermatology TR, İstanbul Training and Research Hospital, İstanbul, Türkiye
| | - Ayşe Akbaş
- Department of Dermatology TR, Ankara Bilkent City Hospital, Ankara, Türkiye
| | - Göknur Kalkan
- Department of Dermatology TR, Ankara Yıldırım Beyazıt University, Ankara, Türkiye
| | - Deniz Demirseren
- Department of Dermatology TR, Ankara Bilkent City Hospital, Ankara, Türkiye
| | | | - Zeynep Topkarcı
- Department of Dermatology TR, İstanbul Bakırköy Dr. Sadi Konuk Training and Reseach Hospital, İstanbul, Türkiye
| | - Arzu Kılıç
- Department of Dermatology TR, Balıkesir University, Balıkesir, Türkiye
| | - Mahizer Yaldız
- Department of Dermatology TR, Sakarya Training and Research Hospital, Sakarya, Türkiye
| | - Sema Aytekin
- Department of Dermatology TR, Tekirdağ Namık Kemal University, Tekirdağ, Türkiye
| | - Pelin Hızlı
- Department of Dermatology TR, Balıkesir University, Balıkesir, Türkiye
| | - Sheyda Gharehdaghi
- Faculty of Medicine, Department of Dermatology TR, Gazi University, Ankara, Türkiye
| | - Murat Borlu
- Department of Dermatology TR, Kayseri Erciyes University, Kayseri, Türkiye
| | - Lütfi Işık
- Department of Dermatology TR, Etlik City Hospital, Ankara, Türkiye
| | | | - Eda Öksüm Solak
- Department of Dermatology TR, Kayseri Erciyes University, Kayseri, Türkiye
| | - Hülya Albayrak
- Department of Dermatology TR, Tekirdağ Namık Kemal University, Tekirdağ, Türkiye
| | - Melis Gönülal
- Department of Dermatology TR, İzmir City Hospital, İzmir, Türkiye
| | | | - Mualla Polat
- Department of Dermatology TR, Abant İzzet Baysal University, Bolu, Türkiye
| | - Munise Daye
- Department of Dermatology TR, Necmettin Erbakan University, Konya, Türkiye
| | - Arzu Ataseven
- Department of Dermatology TR, Necmettin Erbakan University, Konya, Türkiye
| | - Sibel Yıldız
- Department of Dermatology TR, Necmettin Erbakan University, Konya, Türkiye
| | - İlkay Özer
- Department of Dermatology TR, Necmettin Erbakan University, Konya, Türkiye
| | - Özge Zorlu
- Department of Dermatology TR, Tekirdağ Namık Kemal University, Tekirdağ, Türkiye
| | - Sinan Doğan
- Department of Dermatology TR, Bakırçay University, İzmir Çiğli Training and Research Hospital, İzmir, Türkiye
| | - Vefa Aslı Erdemir
- Department of Dermatology TR, İstanbul Medeniyet University, İstanbul, Türkiye
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Vyas J, Johns JR, Ali FM, Singh RK, Ingram JR, Salek S, Finlay AY. A systematic review of 454 randomized controlled trials using the Dermatology Life Quality Index: experience in 69 diseases and 43 countries. Br J Dermatol 2024; 190:315-339. [PMID: 36971254 DOI: 10.1093/bjd/ljad079] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 01/31/2023] [Accepted: 03/14/2023] [Indexed: 02/18/2024]
Abstract
BACKGROUND Over 29 years of clinical application, the Dermatology Life Quality Index (DLQI) has remained the most used patient-reported outcome (PRO) in dermatology due to its robustness, simplicity and ease of use. OBJECTIVES To generate further evidence of the DLQI's utility in randomized controlled trials (RCTs) and to cover all diseases and interventions. METHODS The methodology followed PRISMA guidelines and included seven bibliographical databases, searching articles published from 1 January 1994 until 16 November 2021. Articles were reviewed independently by two assessors, and an adjudicator resolved any opinion differences. RESULTS Of 3220 screened publications, 454 articles meeting the eligibility criteria for inclusion, describing research on 198 190 patients, were analysed. DLQI scores were primary endpoints in 24 (5.3%) of studies. Most studies were of psoriasis (54.1%), although 69 different diseases were studied. Most study drugs were systemic (85.1%), with biologics comprising 55.9% of all pharmacological interventions. Topical treatments comprised 17.0% of total pharmacological interventions. Nonpharmacological interventions, mainly laser therapy and ultraviolet radiation treatment, comprised 12.2% of the total number of interventions. The majority of studies (63.7%) were multicentric, with trials conducted in at least 42 different countries; 40.2% were conducted in multiple countries. The minimal clinically importance difference (MCID) was reported in the analysis of 15.0% of studies, but only 1.3% considered full score meaning banding of the DLQI. Forty-seven (10.4%) of the studies investigated statistical correlation of the DLQI with clinical severity assessment or other PRO/quality of life tools; and 61-86% of studies had within-group scores differences greater than the MCID in 'active treatment arms'. The Jadad risk-of-bias scale showed that bias was generally low, as 91.8% of the studies had Jadad scores of ≥ 3; only 0.4% of studies showed a high risk of bias from randomization. Thirteen per cent had a high risk of bias from blinding and 10.1% had a high risk of bias from unknown outcomes of all participants in the studies. In 18.5% of the studies the authors declared that they followed an intention-to-treat protocol; imputation for missing DLQI data was used in 34.4% of studies. CONCLUSIONS This systematic review provides a wealth of evidence of the use of the DLQI in clinical trials to inform researchers' and -clinicians' decisions for its further use. Recommendations are also made for improving the reporting of data from future RCTs using the DLQI.
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Affiliation(s)
| | - Jeffrey R Johns
- Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK
| | - Faraz M Ali
- Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK
| | - Ravinder K Singh
- Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK
| | - John R Ingram
- Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK
| | - Sam Salek
- School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK
| | - Andrew Y Finlay
- Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK
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Sbidian E, Chaimani A, Guelimi R, Garcia-Doval I, Hua C, Hughes C, Naldi L, Kinberger M, Afach S, Le Cleach L. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev 2023; 7:CD011535. [PMID: 37436070 PMCID: PMC10337265 DOI: 10.1002/14651858.cd011535.pub6] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/13/2023]
Abstract
BACKGROUND Psoriasis is an immune-mediated disease with either skin or joints manifestations, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. The relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis. OBJECTIVES To compare the benefits and harms of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their benefits and harms. SEARCH METHODS For this update of the living systematic review, we updated our searches of the following databases monthly to October 2022: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. SELECTION CRITERIA Randomised controlled trials (RCTs) of systemic treatments in adults over 18 years with moderate-to-severe plaque psoriasis, at any stage of treatment, compared to placebo or another active agent. The primary outcomes were: proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90; proportion of participants with serious adverse events (SAEs) at induction phase (8 to 24 weeks after randomisation). DATA COLLECTION AND ANALYSIS We conducted duplicate study selection, data extraction, risk of bias assessment, and analyses. We synthesised data using pairwise and network meta-analysis (NMA) to compare treatments and rank them according to effectiveness (PASI 90 score) and acceptability (inverse of SAEs). We assessed the certainty of NMA evidence for the two primary outcomes and all comparisons using CINeMA, as very low, low, moderate, or high. We contacted study authors when data were unclear or missing. We used the surface under the cumulative ranking curve (SUCRA) to infer treatment hierarchy, from 0% (worst for effectiveness or safety) to 100% (best for effectiveness or safety). MAIN RESULTS This update includes an additional 12 studies, taking the total number of included studies to 179, and randomised participants to 62,339, 67.1% men, mainly recruited from hospitals. Average age was 44.6 years, mean PASI score at baseline was 20.4 (range: 9.5 to 39). Most studies were placebo-controlled (56%). We assessed a total of 20 treatments. Most (152) trials were multicentric (two to 231 centres). One-third of the studies (65/179) had high risk of bias, 24 unclear risk, and most (90) low risk. Most studies (138/179) declared funding by a pharmaceutical company, and 24 studies did not report a funding source. Network meta-analysis at class level showed that all interventions (non-biological systemic agents, small molecules, and biological treatments) showed a higher proportion of patients reaching PASI 90 than placebo. Anti-IL17 treatment showed a higher proportion of patients reaching PASI 90 compared to all the interventions. Biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha showed a higher proportion of patients reaching PASI 90 than the non-biological systemic agents. For reaching PASI 90, the most effective drugs when compared to placebo were (SUCRA rank order, all high-certainty evidence): infliximab (risk ratio (RR) 49.16, 95% CI 20.49 to 117.95), bimekizumab (RR 27.86, 95% CI 23.56 to 32.94), ixekizumab (RR 27.35, 95% CI 23.15 to 32.29), risankizumab (RR 26.16, 95% CI 22.03 to 31.07). Clinical effectiveness of these drugs was similar when compared against each other. Bimekizumab and ixekizumab were significantly more likely to reach PASI 90 than secukinumab. Bimekizumab, ixekizumab, and risankizumab were significantly more likely to reach PASI 90 than brodalumab and guselkumab. Infliximab, anti-IL17 drugs (bimekizumab, ixekizumab, secukinumab, and brodalumab), and anti-IL23 drugs except tildrakizumab were significantly more likely to reach PASI 90 than ustekinumab, three anti-TNF alpha agents, and deucravacitinib. Ustekinumab was superior to certolizumab. Adalimumab, tildrakizumab, and ustekinumab were superior to etanercept. No significant difference was shown between apremilast and two non-biological drugs: ciclosporin and methotrexate. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. The risk of SAEs was significantly lower for participants on methotrexate compared with most of the interventions. Nevertheless, the SAE analyses were based on a very low number of events with very low- to moderate-certainty evidence for all the comparisons. The findings therefore have to be viewed with caution. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1), the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions. AUTHORS' CONCLUSIONS Our review shows that, compared to placebo, the biologics infliximab, bimekizumab, ixekizumab, and risankizumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes measured from 8 to 24 weeks after randomisation), and is not sufficient for evaluating longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean 44.6 years) and high level of disease severity (PASI 20.4 at baseline) may not be typical of patients seen in daily clinical practice. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the safety evidence for most interventions was very low to moderate quality. More randomised trials directly comparing active agents are needed, and these should include systematic subgroup analyses (sex, age, ethnicity, comorbidities, psoriatic arthritis). To provide long-term information on the safety of treatments included in this review, an evaluation of non-randomised studies is needed. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
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Affiliation(s)
- Emilie Sbidian
- Department of Dermatology, Hôpital Henri Mondor, Créteil, France
- Clinical Investigation Centre, Hôpital Henri Mondor, Créteil, France
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE) - EA 7379, Université Paris Est Créteil (UPEC), Créteil, France
| | - Anna Chaimani
- Université de Paris, Centre of Research in Epidemiology and Statistics (CRESS), INSERM, F-75004, Paris, France
- Cochrane France, Paris, France
| | - Robin Guelimi
- Department of Dermatology, Hôpital Henri Mondor, Créteil, France
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE) - EA 7379, Université Paris Est Créteil (UPEC), Créteil, France
| | - Ignacio Garcia-Doval
- Department of Dermatology, Complexo Hospitalario Universitario de Vigo, Vigo, Spain
| | - Camille Hua
- Department of Dermatology, Hôpital Henri Mondor, Créteil, France
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE) - EA 7379, Université Paris Est Créteil (UPEC), Créteil, France
| | - Carolyn Hughes
- c/o Cochrane Skin Group, The University of Nottingham, Nottingham, UK
| | - Luigi Naldi
- Centro Studi GISED (Italian Group for Epidemiologic Research in Dermatology) - FROM (Research Foundation of Ospedale Maggiore Bergamo), Padiglione Mazzoleni - Presidio Ospedaliero Matteo Rota, Bergamo, Italy
| | - Maria Kinberger
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Sivem Afach
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE) - EA 7379, Université Paris Est Créteil (UPEC), Créteil, France
| | - Laurence Le Cleach
- Department of Dermatology, Hôpital Henri Mondor, Créteil, France
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE) - EA 7379, Université Paris Est Créteil (UPEC), Créteil, France
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Matwiejuk M, Mysliwiec H, Jakubowicz-Zalewska O, Chabowski A, Flisiak I. Effects of Hypolipidemic Drugs on Psoriasis. Metabolites 2023; 13:metabo13040493. [PMID: 37110152 PMCID: PMC10142060 DOI: 10.3390/metabo13040493] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/23/2023] [Accepted: 03/27/2023] [Indexed: 03/31/2023] Open
Abstract
Psoriasis is a chronic, systematic, inflammatory disease in which multiple metabolic and immunologic disturbances lead to lipid abnormalities, impaired glucose tolerance, metabolic syndrome, diabetes mellitus, atherosclerosis, hypertension, ischemic heart disease, and numerous metabolic disorders. In clinical practice, the most commonly used drugs in the treatment of lipid abnormalities are statins and fibrates. Statins are characterized by pleiotropic effects such as antioxidant, anti-inflammatory, anticoagulant, and antiproliferative. They work by reducing the concentrations of low-density lipoprotein (LDL), total cholesterol, and triglycerides and stabilizing atherosclerotic plaque. Fibrates are medications, which help to lower triglycerides, LDL, very low-density lipoprotein (VLDL) levels and increase lower high-density lipoprotein (HDL). In recent years, many new drugs were found to normalize the lipid profile in patients with psoriasis: glitazones (pioglitazone, troglitazone), and glucagon-like peptide-1 (GLP-1) receptor agonists. Pioglitazone improves the lipid profile, including the decrease of triglycerides, fatty acids, and LDL, as well as the increase of HDL. Glucagon-like peptide 1 (GLP-1) analogs decrease modestly low-density lipoprotein cholesterol (LDL-C), total cholesterol, and triglycerides. The purpose of this study is to assess the current state of knowledge on the effect of different hypolipidemic treatments on the course of psoriasis. The study includes literature from medical databases PubMed and Google Scholar. We were browsing PubMed and Google Scholar until the beginning of December. The systematic review includes 41 eligible original articles.
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Aryanian Z, Balighi K, Afshar ZM, Zamanian MH, Razavi Z, Hatami P. COVID vaccine recommendations in dermatologic patients on immunosuppressive agents: Lessons learned from pandemic. J Cosmet Dermatol 2022; 21:6568-6573. [PMID: 36214611 PMCID: PMC9874417 DOI: 10.1111/jocd.15448] [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: 06/06/2022] [Revised: 09/08/2022] [Accepted: 10/06/2022] [Indexed: 01/27/2023]
Abstract
BACKGROUND Since SARS-CoV2 vaccines were approved without enough long-term monitoring due to emergent situations, some issues have been raised about timing and protocol of receiving them by patients treated by different immunosuppressive agents. AIM AND METHOD Here, we present different aspects of SARS-CoV-2 vaccination in such patients in the field of dermatology. RESULT In brief, SARS-CoV-2 vaccination is recommended in all dermatologic patients, regardless of their disorders and therapeutic regimens. Nevertheless, special considerations should be given to the immunosuppressive therapy and its association with vaccination timing due to the decreased immunogenicity of vaccines in this setting. CONCLUSION Novel biologic immunotherapies are advantageous over conventional systemic therapies not only in their safety and selective functions but also in this aspect that many of them do not affect vaccines immunogenicity.
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Affiliation(s)
- Zeinab Aryanian
- Autoimmune Bullous Diseases Research CenterTehran University of Medical SciencesTehranIran,Department of DermatologyBabol University of Medical SciencesBabolIran
| | - Kamran Balighi
- Autoimmune Bullous Diseases Research CenterTehran University of Medical SciencesTehranIran,Department of Dermatology, School of Medicine Razi HospitalTehran University of Medical SciencesTehranIran
| | - Zeinab Mohseni Afshar
- Clinical Research Development Center, Imam Reza HospitalKermanshah University of Medical SciencesKermanshahIran,Department of Infectious Disease, School of Medicine, Imam Reza HospitalKermanshah University of Medical SciencesKermanshahIran
| | - Mohammad Hossein Zamanian
- Department of Infectious Disease, School of Medicine, Imam Reza HospitalKermanshah University of Medical SciencesKermanshahIran
| | - Zahra Razavi
- Autoimmune Bullous Diseases Research CenterTehran University of Medical SciencesTehranIran,Department of Dermatology, School of Medicine Razi HospitalTehran University of Medical SciencesTehranIran
| | - Parvaneh Hatami
- Autoimmune Bullous Diseases Research CenterTehran University of Medical SciencesTehranIran
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9
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van Huizen AM, Sikkel R, Caron AGM, Menting SP, Spuls PI. Methotrexate Dosing Regimen for Plaque-type Psoriasis: An Update of a Systematic Review. J DERMATOL TREAT 2022; 33:3104-3118. [PMID: 36043844 DOI: 10.1080/09546634.2022.2117539] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Background Methotrexate (MTX) is a systemic treatment for plaque-type psoriasis. At the time of approval, no dose-ranging studies were performed. Nowadays, a uniform dosing regimen is lacking. This might contribute to suboptimal treatment with the drug.Objective To summarize the literature involving the MTX dosing regimens in psoriasis patients.Methods In this SR, RCTs and documents with aggregated evidence (AgEv) on the MTX dosing regimen in psoriasis were summarized. All randomized controlled trials (RCTs) in which oral, subcutaneous or intramuscular MTX was used in patients with psoriasis and AgEv, were included. The MEDLINE, EMBASE and CENTRAL databases were searched up to June 20, 2022. This SR was registered in PROSPERO.Results Thirty-nine RCTs had a high risk of bias. Test dosages were given in only 3 RCTs. In the RCTs, MTX was usually prescribed in a start dose of 7.5 mg/week (n = 13). MTX was mostly given in a start dose of 15 mg/week, in the AgEv (n = 5). One guideline recommended a test dose, in other aggregated evidence a test dose was not mentioned or even discouraged.Conclusions There is a lack of high-quality evidence and available data for dosing MTX in psoriasis is heterogeneous.
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Affiliation(s)
- Astrid M van Huizen
- Amsterdam UMC, location University of Amsterdam, Department of Dermatology, Amsterdam Public Health, Infection and Immunity, Meibergdreef 9, Amsterdam, the Netherlands
| | - Rosie Sikkel
- Amsterdam UMC, location University of Amsterdam, Department of Dermatology, Amsterdam Public Health, Infection and Immunity, Meibergdreef 9, Amsterdam, the Netherlands
| | - Anouk G M Caron
- Amsterdam UMC, location University of Amsterdam, Department of Dermatology, Amsterdam Public Health, Infection and Immunity, Meibergdreef 9, Amsterdam, the Netherlands
| | - Stef P Menting
- OLVG hospital, Department of Dermatology, Amsterdam, the Netherlands
| | - Phyllis I Spuls
- Amsterdam UMC, location University of Amsterdam, Department of Dermatology, Amsterdam Public Health, Infection and Immunity, Meibergdreef 9, Amsterdam, the Netherlands
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10
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The Role of Transcription Factor PPAR-γ in the Pathogenesis of Psoriasis, Skin Cells, and Immune Cells. Int J Mol Sci 2022; 23:ijms23179708. [PMID: 36077103 PMCID: PMC9456565 DOI: 10.3390/ijms23179708] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Revised: 08/22/2022] [Accepted: 08/23/2022] [Indexed: 11/22/2022] Open
Abstract
The peroxisome proliferator-activated receptor PPAR-γ is one of three PPAR nuclear receptors that act as ligand-activated transcription factors. In immune cells, the skin, and other organs, PPAR-γ regulates lipid, glucose, and amino acid metabolism. The receptor translates nutritional, pharmacological, and metabolic stimuli into the changes in gene expression. The activation of PPAR-γ promotes cell differentiation, reduces the proliferation rate, and modulates the immune response. In the skin, PPARs also contribute to the functioning of the skin barrier. Since we know that the route from identification to the registration of drugs is long and expensive, PPAR-γ agonists already approved for other diseases may also represent a high interest for psoriasis. In this review, we discuss the role of PPAR-γ in the activation, differentiation, and proliferation of skin and immune cells affected by psoriasis and in contributing to the pathogenesis of the disease. We also evaluate whether the agonists of PPAR-γ may become one of the therapeutic options to suppress the inflammatory response in lesional psoriatic skin and decrease the influence of comorbidities associated with psoriasis.
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11
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Sbidian E, Chaimani A, Garcia-Doval I, Doney L, Dressler C, Hua C, Hughes C, Naldi L, Afach S, Le Cleach L. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev 2022; 5:CD011535. [PMID: 35603936 PMCID: PMC9125768 DOI: 10.1002/14651858.cd011535.pub5] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Psoriasis is an immune-mediated disease with either skin or joints manifestations, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. The relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis. OBJECTIVES To compare the efficacy and safety of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their efficacy and safety. SEARCH METHODS For this update of the living systematic review, we updated our searches of the following databases monthly to October 2021: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. SELECTION CRITERIA Randomised controlled trials (RCTs) of systemic treatments in adults over 18 years with moderate-to-severe plaque psoriasis, at any stage of treatment, compared to placebo or another active agent. The primary outcomes were: proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90; proportion of participants with serious adverse events (SAEs) at induction phase (8 to 24 weeks after randomisation). DATA COLLECTION AND ANALYSIS We conducted duplicate study selection, data extraction, risk of bias assessment and analyses. We synthesised data using pairwise and network meta-analysis (NMA) to compare treatments and rank them according to effectiveness (PASI 90 score) and acceptability (inverse of SAEs). We assessed the certainty of NMA evidence for the two primary outcomes and all comparisons using CINeMA, as very low, low, moderate, or high. We contacted study authors when data were unclear or missing. We used the surface under the cumulative ranking curve (SUCRA) to infer treatment hierarchy, from 0% (worst for effectiveness or safety) to 100% (best for effectiveness or safety). MAIN RESULTS This update includes an additional 19 studies, taking the total number of included studies to 167, and randomised participants to 58,912, 67.2% men, mainly recruited from hospitals. Average age was 44.5 years, mean PASI score at baseline was 20.4 (range: 9.5 to 39). Most studies were placebo-controlled (57%). We assessed a total of 20 treatments. Most (140) trials were multicentric (two to 231 centres). One-third of the studies (57/167) had high risk of bias; 23 unclear risk, and most (87) low risk. Most studies (127/167) declared funding by a pharmaceutical company, and 24 studies did not report a funding source. Network meta-analysis at class level showed that all interventions (non-biological systemic agents, small molecules, and biological treatments) showed a higher proportion of patients reaching PASI 90 than placebo. Anti-IL17 treatment showed a higher proportion of patients reaching PASI 90 compared to all the interventions, except anti-IL23. Biologic treatments anti-IL17, anti-IL12/23, anti-IL23 and anti-TNF alpha showed a higher proportion of patients reaching PASI 90 than the non-biological systemic agents. For reaching PASI 90, the most effective drugs when compared to placebo were (SUCRA rank order, all high-certainty evidence): infliximab (risk ratio (RR) 50.19, 95% CI 20.92 to 120.45), bimekizumab (RR 30.27, 95% CI 25.45 to 36.01), ixekizumab (RR 30.19, 95% CI 25.38 to 35.93), risankizumab (RR 28.75, 95% CI 24.03 to 34.39). Clinical effectiveness of these drugs was similar when compared against each other. Bimekizumab, ixekizumab and risankizumab showed a higher proportion of patients reaching PASI 90 than other anti-IL17 drugs (secukinumab and brodalumab) and guselkumab. Infliximab, anti-IL17 drugs (bimekizumab, ixekizumab, secukinumab and brodalumab) and anti-IL23 drugs (risankizumab and guselkumab) except tildrakizumab showed a higher proportion of patients reaching PASI 90 than ustekinumab and three anti-TNF alpha agents (adalimumab, certolizumab and etanercept). Ustekinumab was superior to certolizumab; adalimumab and ustekinumab were superior to etanercept. No significant difference was shown between apremilast and two non-biological drugs: ciclosporin and methotrexate. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. The risk of SAEs was significantly lower for participants on methotrexate compared with most of the interventions. Nevertheless, the SAE analyses were based on a very low number of events with low- to moderate-certainty for all the comparisons (except methotrexate versus placebo, which was high-certainty). The findings therefore have to be viewed with caution. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1), the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions. AUTHORS' CONCLUSIONS Our review shows that, compared to placebo, the biologics infliximab, bimekizumab, ixekizumab, and risankizumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes measured from 8 to 24 weeks after randomisation), and is not sufficient for evaluating longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean 44.5 years) and high level of disease severity (PASI 20.4 at baseline) may not be typical of patients seen in daily clinical practice. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the safety evidence for most interventions was low to moderate quality. More randomised trials directly comparing active agents are needed, and these should include systematic subgroup analyses (sex, age, ethnicity, comorbidities, psoriatic arthritis). To provide long-term information on the safety of treatments included in this review, an evaluation of non-randomised studies and postmarketing reports from regulatory agencies is needed. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
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Affiliation(s)
- Emilie Sbidian
- Department of Dermatology, Hôpital Henri Mondor, Créteil, France
- Clinical Investigation Centre, Hôpital Henri Mondor, Créteil, France
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE) - EA 7379, Université Paris Est Créteil (UPEC), Créteil, France
| | - Anna Chaimani
- Université de Paris, Centre of Research in Epidemiology and Statistics (CRESS), INSERM, F-75004, Paris, France
- Cochrane France, Paris, France
| | - Ignacio Garcia-Doval
- Department of Dermatology, Complexo Hospitalario Universitario de Vigo, Vigo, Spain
| | - Liz Doney
- Cochrane Skin, Centre of Evidence Based Dermatology, University of Nottingham, Nottingham, UK
| | - Corinna Dressler
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Camille Hua
- Department of Dermatology, Hôpital Henri Mondor, Créteil, France
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE) - EA 7379, Université Paris Est Créteil (UPEC), Créteil, France
| | - Carolyn Hughes
- c/o Cochrane Skin Group, The University of Nottingham, Nottingham, UK
| | - Luigi Naldi
- Centro Studi GISED (Italian Group for Epidemiologic Research in Dermatology) - FROM (Research Foundation of Ospedale Maggiore Bergamo), Padiglione Mazzoleni - Presidio Ospedaliero Matteo Rota, Bergamo, Italy
| | - Sivem Afach
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE) - EA 7379, Université Paris Est Créteil (UPEC), Créteil, France
| | - Laurence Le Cleach
- Department of Dermatology, Hôpital Henri Mondor, Créteil, France
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE) - EA 7379, Université Paris Est Créteil (UPEC), Créteil, France
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12
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Behrangi E, Sadeghzadeh‐Bazargan A, Salimi N, Shaka Z, Feyz Kazemi MH, Goodarzi A. Erythrodermic flare‐up of psoriasis with COVID‐19 infection: A report of two cases and a comprehensive review of literature focusing on the mutual effect of psoriasis and COVID‐19 on each other along with the special challenges of the pandemic. Clin Case Rep 2022; 10:e05722. [PMID: 35474976 PMCID: PMC9019895 DOI: 10.1002/ccr3.5722] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 03/12/2022] [Accepted: 03/28/2022] [Indexed: 12/11/2022] Open
Affiliation(s)
- Elham Behrangi
- Department of Dermatology Rasool Akram Medical Complex Clinical Research Development Center (RCRDC) School of Medicine Iran University of Medical Sciences (IUMS) Tehran Iran
| | - Afsaneh Sadeghzadeh‐Bazargan
- Department of Dermatology Rasool Akram Medical Complex Clinical Research Development Center (RCRDC) School of Medicine Iran University of Medical Sciences (IUMS) Tehran Iran
| | - Nastaran Salimi
- School of Medicine Iran University of Medical Sciences Tehran Iran
| | - Zoha Shaka
- School of Medicine Iran University of Medical Sciences Tehran Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA) Universal Scientific Education and Research Network (USERN) Tehran Iran
| | | | - Azadeh Goodarzi
- Department of Dermatology Rasool Akram Medical Complex Clinical Research Development Center (RCRDC) School of Medicine Iran University of Medical Sciences (IUMS) Tehran Iran
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13
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Lin X, Meng X, Song Z, Lin J. Peroxisome proliferator-activator receptor γ and psoriasis, molecular and cellular biochemistry. Mol Cell Biochem 2022; 477:1905-1920. [PMID: 35348980 DOI: 10.1007/s11010-022-04417-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 03/16/2022] [Indexed: 10/18/2022]
Abstract
The pathophysiology of psoriasis is complex and has not been completely elucidated. Better understanding of the pathogenesis may contribute to further improvement of our therapeutic strategies controlling psoriasis. Emerging evidence points to a causative relationship between altered activity of peroxisome proliferator-activated receptor γ (PPARγ) and psoriasis. The present review focuses on deeper understanding of the possible role of PPARγ in the pathogenesis of psoriasis and the potential of PPARγ agonist to improve the treatment of psoriasis. PPARγ is decreased in psoriasis. PPARγ possibly has effects on the multiple aspects of the pathogenesis of psoriasis, including abnormal lipid metabolism, insulin resistance, immune cells, pro-inflammatory cytokines, keratinocytes, angiogenesis, oxidative stress, microRNAs and nuclear factor kappa B. As defective activation of PPARγ is involved in psoriasis development, PPARγ agonists may be promising agents for treatment of psoriasis. Pioglitazone appears an effective and safe option in the treatment of patients with psoriasis, but there are still concerns about its potential side effects. Research effort has recently been undertaken to explore the PPARγ-activating potential of natural products. Among them some have been studied clinically or preclinically for treatment of psoriasis with promising results.
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Affiliation(s)
- Xiran Lin
- Department of Dermatology, First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Lu, Dalian, 116011, China.
| | - Xianmin Meng
- Department of Pathology and Laboratory Medicine, Axia Women's Health, 450 Cresson BLVD, Oaks, PA, 19456, USA
| | - Zhiqi Song
- Department of Dermatology, First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Lu, Dalian, 116011, China
| | - Jingrong Lin
- Department of Dermatology, First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Lu, Dalian, 116011, China
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14
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Neema S, Sandhu S, Gupta A, Jagadeesan S, Vasudevan B. Unconventional treatment options in psoriasis: A review. Indian J Dermatol Venereol Leprol 2021; 88:137-143. [PMID: 34623042 DOI: 10.25259/ijdvl_22_2021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Accepted: 05/01/2021] [Indexed: 11/04/2022]
Abstract
Psoriasis is a common skin disease that affects 1-3% of the general population. The treatment depends on body surface area involved, quality of life impairment and associated comorbidities. The treatment options include topical therapy, phototherapy, conventional systemic therapy (methotrexate, cyclosporine and acitretin), biologics and oral small molecules (apremilast and tofacitinib). Despite the availability of newer therapies such as biologics and oral small molecules, many a time, there is a paucity of treatment options due to the chronic nature of the disease, end-organ toxicity of the conventional drugs or high cost of newer drugs. In these scenarios, unconventional treatment options may be utilized as stand-alone or adjuvant therapy. In this review, we have discussed these uncommonly used treatment options in the management of psoriasis.
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Affiliation(s)
- Shekhar Neema
- Department of Dermatology, Armed Forces Medical College, Pune, Maharashtra, India
| | - Sunmeet Sandhu
- Department of Dermatology, Command Hospital Air Force, Bengaluru, Karnataka, India
| | - Ankan Gupta
- Department of Dermatology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Soumya Jagadeesan
- Department of Dermatology, Amrita Institute of Medical Sciences, Cochin, Kerala, India
| | - Biju Vasudevan
- Department of Dermatology, Armed Forces Medical College, Pune, Maharashtra, India
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15
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Moghaddasi M, Ghassemi M, Shekari Yazdi M, Habibi SAH, Mohebi N, Goodarzi A. The first case report of Haim Munk disease with neurological manifestations and literature review. Clin Case Rep 2021; 9:e04802. [PMID: 34603725 PMCID: PMC8473953 DOI: 10.1002/ccr3.4802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2021] [Revised: 08/17/2021] [Accepted: 08/25/2021] [Indexed: 11/10/2022] Open
Abstract
HMS can have neurologic MS like manifestations. It is urgent to do more research and report probable unknown associations of HMS for its better management.
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Affiliation(s)
- Mehdi Moghaddasi
- Department of NeurologyRasool Akram Medical ComplexIran University of Medial Sciences (IUMS)TehranIran
| | - Mohammadreza Ghassemi
- Department of DermatologyRasool Akram Medical ComplexIran University of Medical Sciences (IUMS)TehranIran
| | - Mohammad Shekari Yazdi
- Department of DermatologyRasool Akram Medical ComplexIran University of Medical Sciences (IUMS)TehranIran
| | - Seyed Amir Hasan Habibi
- Department of NeurologyRasool Akram Medical ComplexIran University of Medial Sciences (IUMS)TehranIran
| | - Nafiseh Mohebi
- Department of NeurologyRasool Akram Medical ComplexIran University of Medial Sciences (IUMS)TehranIran
| | - Azadeh Goodarzi
- Department of DermatologyRasool Akram Medical ComplexIran University of Medical Sciences (IUMS)TehranIran
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Zhang MX, Zheng BY, Chen HX, Chien CW. Clinical effects of antidiabetic drugs on psoriasis: The perspective of evidence-based medicine. World J Diabetes 2021; 12:1141-1145. [PMID: 34512883 PMCID: PMC8394225 DOI: 10.4239/wjd.v12.i8.1141] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 04/08/2021] [Accepted: 07/14/2021] [Indexed: 02/06/2023] Open
Abstract
Psoriasis and diabetes shared common underlying pathophysiological mechanisms. Emerging data suggested that antidiabetic medications may improve the psoriasis severity in patients with diabetes mellitus. Several hypoglycemic agents including thiazolidinediones, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and biguanides have been reported to make a remarkable reduction in the Psoriasis Area and Severity Index score from baseline. This antipsoriatic effect could be mediated not only by the glucose-lowering action of these agents but also via inhibition of keratinocyte over proliferation, increase expression of differentiation markers, suppression the immune inflammatory pathway, and blocking the calcium channels and mitogen-activated protein kinase signaling pathways. On the other hand, there was no significant increase in adverse reactions associated with the treatment of pioglitazone or metformin. However, previous studies often had the relatively short duration of the trials, and did not have enough power to assess recurrence of psoriasis. Potential bias in the study and missing data could undermine the reliability of the results. Therefore, the appropriately randomized controlled studies with large sample sizes and long-term durations in various psoriasis patients are warranted for further support.
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Affiliation(s)
- Mei-Xian Zhang
- Evidence-based Medicine Center,Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
- Public Laboratory, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
| | - Bo-Yuan Zheng
- Institute for Hospital Management, Tsing Hua University, Shenzhen Campus, Shenzhen 518055, Guangdong Province, China
| | - Hai-Xiao Chen
- Department of Orthopedics, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
| | - Ching-Wen Chien
- Institute for Hospital Management, Tsing Hua University, Shenzhen Campus, Shenzhen 518055, Guangdong Province, China
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17
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Sbidian E, Chaimani A, Garcia-Doval I, Doney L, Dressler C, Hua C, Hughes C, Naldi L, Afach S, Le Cleach L. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev 2021; 4:CD011535. [PMID: 33871055 PMCID: PMC8408312 DOI: 10.1002/14651858.cd011535.pub4] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Psoriasis is an immune-mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or joints, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. Several randomised controlled trials (RCTs) have compared the efficacy of the different systemic treatments in psoriasis against placebo. However, the relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis. OBJECTIVES To compare the efficacy and safety of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their efficacy and safety. SEARCH METHODS For this living systematic review we updated our searches of the following databases monthly to September 2020: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. We searched two trials registers to the same date. We checked the reference lists of included studies and relevant systematic reviews for further references to eligible RCTs. SELECTION CRITERIA Randomised controlled trials (RCTs) of systemic treatments in adults (over 18 years of age) with moderate-to-severe plaque psoriasis or psoriatic arthritis whose skin had been clinically diagnosed with moderate-to-severe psoriasis, at any stage of treatment, in comparison to placebo or another active agent. The primary outcomes of this review were: the proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90 at induction phase (from 8 to 24 weeks after the randomisation), and the proportion of participants with serious adverse events (SAEs) at induction phase. We did not evaluate differences in specific adverse events. DATA COLLECTION AND ANALYSIS Several groups of two review authors independently undertook study selection, data extraction, 'Risk of bias' assessment, and analyses. We synthesised the data using pair-wise and network meta-analysis (NMA) to compare the treatments of interest and rank them according to their effectiveness (as measured by the PASI 90 score) and acceptability (the inverse of serious adverse events). We assessed the certainty of the body of evidence from the NMA for the two primary outcomes and all comparisons, according to CINeMA, as either very low, low, moderate, or high. We contacted study authors when data were unclear or missing. We used the surface under the cumulative ranking curve (SUCRA) to infer on treatment hierarchy: 0% (treatment is the worst for effectiveness or safety) to 100% (treatment is the best for effectiveness or safety). MAIN RESULTS We included 158 studies (18 new studies for the update) in our review (57,831 randomised participants, 67.2% men, mainly recruited from hospitals). The overall average age was 45 years; the overall mean PASI score at baseline was 20 (range: 9.5 to 39). Most of these studies were placebo-controlled (58%), 30% were head-to-head studies, and 11% were multi-armed studies with both an active comparator and a placebo. We have assessed a total of 20 treatments. In all, 133 trials were multicentric (two to 231 centres). All but two of the outcomes included in this review were limited to the induction phase (assessment from 8 to 24 weeks after randomisation). We assessed many studies (53/158) as being at high risk of bias; 25 were at an unclear risk, and 80 at low risk. Most studies (123/158) declared funding by a pharmaceutical company, and 22 studies did not report their source of funding. Network meta-analysis at class level showed that all of the interventions (non-biological systemic agents, small molecules, and biological treatments) were significantly more effective than placebo in reaching PASI 90. At class level, in reaching PASI 90, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the non-biological systemic agents. At drug level, infliximab, ixekizumab, secukinumab, brodalumab, risankizumab and guselkumab were significantly more effective in reaching PASI 90 than ustekinumab and three anti-TNF alpha agents: adalimumab, certolizumab, and etanercept. Ustekinumab and adalimumab were significantly more effective in reaching PASI 90 than etanercept; ustekinumab was more effective than certolizumab, and the clinical effectiveness of ustekinumab and adalimumab was similar. There was no significant difference between tofacitinib or apremilast and three non-biological drugs: fumaric acid esters (FAEs), ciclosporin and methotrexate. Network meta-analysis also showed that infliximab, ixekizumab, risankizumab, bimekizumab, secukinumab, guselkumab, and brodalumab outperformed other drugs when compared to placebo in reaching PASI 90. The clinical effectiveness of these drugs was similar, except for ixekizumab which had a better chance of reaching PASI 90 compared with secukinumab, guselkumab and brodalumab. The clinical effectiveness of these seven drugs was: infliximab (versus placebo): risk ratio (RR) 50.29, 95% confidence interval (CI) 20.96 to 120.67, SUCRA = 93.6; high-certainty evidence; ixekizumab (versus placebo): RR 32.48, 95% CI 27.13 to 38.87; SUCRA = 90.5; high-certainty evidence; risankizumab (versus placebo): RR 28.76, 95% CI 23.96 to 34.54; SUCRA = 84.6; high-certainty evidence; bimekizumab (versus placebo): RR 58.64, 95% CI 3.72 to 923.86; SUCRA = 81.4; high-certainty evidence; secukinumab (versus placebo): RR 25.79, 95% CI 21.61 to 30.78; SUCRA = 76.2; high-certainty evidence; guselkumab (versus placebo): RR 25.52, 95% CI 21.25 to 30.64; SUCRA = 75; high-certainty evidence; and brodalumab (versus placebo): RR 23.55, 95% CI 19.48 to 28.48; SUCRA = 68.4; moderate-certainty evidence. Conservative interpretation is warranted for the results for bimekizumab (as well as mirikizumab, tyrosine kinase 2 inhibitor, acitretin, ciclosporin, fumaric acid esters, and methotrexate), as these drugs, in the NMA, have been evaluated in few trials. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. Nevertheless, the SAE analyses were based on a very low number of events with low to moderate certainty for all the comparisons. Thus, the results have to be viewed with caution and we cannot be sure of the ranking. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1) the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions. AUTHORS' CONCLUSIONS Our review shows that compared to placebo, the biologics infliximab, ixekizumab, risankizumab, bimekizumab, secukinumab, guselkumab and brodalumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of moderate- to high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes were measured from 8 to 24 weeks after randomisation) and is not sufficient for evaluation of longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean age of 45 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice. Another major concern is that short-term trials provide scanty and sometimes poorly-reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the evidence for all the interventions was of low to moderate quality. In order to provide long-term information on the safety of the treatments included in this review, it will also be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies. In terms of future research, randomised trials directly comparing active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between non-biological systemic agents and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve participants, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
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Affiliation(s)
- Emilie Sbidian
- Department of Dermatology, Hôpital Henri Mondor, Créteil, France
- Clinical Investigation Centre, Hôpital Henri Mondor, Créteil, France
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE) - EA 7379, Université Paris Est Créteil (UPEC), Créteil, France
| | - Anna Chaimani
- Université de Paris, Centre of Research in Epidemiology and Statistics (CRESS), INSERM, F-75004, Paris, France
- Cochrane France, Paris, France
| | - Ignacio Garcia-Doval
- Department of Dermatology, Complexo Hospitalario Universitario de Vigo, Vigo, Spain
| | - Liz Doney
- Centre of Evidence Based Dermatology, Cochrane Skin Group, The University of Nottingham, Nottingham, UK
| | - Corinna Dressler
- Division of Evidence Based Medicine, Department of Dermatology, Venerology and Allergology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Camille Hua
- Department of Dermatology, Hôpital Henri Mondor, Créteil, France
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE) - EA 7379, Université Paris Est Créteil (UPEC), Créteil, France
| | - Carolyn Hughes
- c/o Cochrane Skin Group, The University of Nottingham, Nottingham, UK
| | - Luigi Naldi
- Centro Studi GISED (Italian Group for Epidemiologic Research in Dermatology) - FROM (Research Foundation of Ospedale Maggiore Bergamo), Padiglione Mazzoleni - Presidio Ospedaliero Matteo Rota, Bergamo, Italy
| | - Sivem Afach
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE) - EA 7379, Université Paris Est Créteil (UPEC), Créteil, France
| | - Laurence Le Cleach
- Department of Dermatology, Hôpital Henri Mondor, Créteil, France
- Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE) - EA 7379, Université Paris Est Créteil (UPEC), Créteil, France
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18
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Stanescu AMA, Simionescu AA, Florea M, Diaconu CC. Is Metformin a Possible Beneficial Treatment for Psoriasis? A Scoping Review. J Pers Med 2021; 11:251. [PMID: 33808460 PMCID: PMC8065978 DOI: 10.3390/jpm11040251] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 03/24/2021] [Accepted: 03/26/2021] [Indexed: 02/06/2023] Open
Abstract
Psoriasis is a chronic inflammatory condition with genetic, immunological, and metabolic etiology. The link between psoriasis and diabetes mellitus has been shown in genetic predisposition, environmental influences, inflammatory pathways, and insulin resistance, resulting in end-organ damage in both conditions. Because comorbidities often accompany psoriasis, the therapeutic management of the disease must also take into consideration the comorbidities. Given that metformin's therapeutic role in psoriasis is not yet fully elucidated, we raised the question of whether metformin is a viable alternative for the treatment of psoriasis. We conducted this scoping review by searching for evidence in PubMed, Cochrane, and Scopus databases, and we used an extension for scoping reviews (PRISMA-ScR). Current evidence suggests that metformin is safe to use in psoriasis. Studies have shown an excellent therapeutic response to metformin in patients with psoriasis and comorbidities such as diabetes, metabolic syndrome, and obesity. There is no clear evidence supporting metformin monotherapy in patients with psoriasis without comorbidities. There is a need to further evaluate metformin in larger clinical trials, as a therapy in psoriasis.
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Affiliation(s)
| | - Anca Angela Simionescu
- Department of Obstetrics and Gynecology, Filantropia Clinical Hospital, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Mira Florea
- Community Medicine Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania
| | - Camelia Cristina Diaconu
- Department of Internal Medicine, Clinical Emergency Hospital of Bucharest, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
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19
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Ghassemi M, Hosseinchi S, Seirafianpour F, Dodangeh M, Goodarzi A. Non-alcoholic fatty liver and lipid profile status in patients with melasma: A case-control study. J Cosmet Dermatol 2021; 20:3656-3660. [PMID: 33609335 DOI: 10.1111/jocd.14014] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 01/13/2021] [Accepted: 02/16/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND There are pieces of evidence regarding the association between melasma and metabolic syndrome. To assess the prevalence and grade of nonalcoholic fatty liver and lipid profile status in patients with melasma, we designed this case-control study. METHODS This study was performed on 30 consecutive women with melasma who referred to the dermatology clinic of the hospital as the case group and 34 healthy women. For all participants, serum lipid profiles and liver enzymes were checked. Also, the existence of fatty liver was assessed by ultrasonography. RESULTS Except for serum level of LDL (low-density lipoprotein) that was significantly higher in the melasma group than in the healthy group (104.23 ± 25.00 mg/dl versus 89.85 ± 23.00 mg/dl, p = 0.020), the level of other parameters including other lipid profiles, blood sugar, or liver enzymes was similar in both groups. In ultrasonography, the overall prevalence of fatty liver was 23.3% in the melasma group and 20.6% in the control group, and no difference was found between the two groups in grade of fatty liver (p = 0.791). CONCLUSION The study showed a higher serum LDL level in patients with melasma compared to women without melasma, but there was no difference between the groups in prevalence or grade of fatty liver.
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Affiliation(s)
- Mohammadreza Ghassemi
- Dermatology Department, Rasool Akram Medical Complex, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | | | - Farnoosh Seirafianpour
- Student Research Committee, School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Milad Dodangeh
- Student Research Committee, School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Azadeh Goodarzi
- Dermatology Department, Rasool Akram Medical Complex, Iran University of Medical Sciences (IUMS), Tehran, Iran
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20
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Chi CC, Lee CY, Liu CY, Wang SH, Tien O'Donnell F, Tung TH. Effects of antidiabetic drugs on psoriasis: A meta-analysis. Eur J Clin Invest 2021; 51:e13377. [PMID: 32914429 DOI: 10.1111/eci.13377] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 07/31/2020] [Accepted: 08/05/2020] [Indexed: 01/10/2023]
Abstract
BACKGROUND Psoriasis, a chronic inflammatory skin disease, poses an elevated risk of developing diabetes mellitus. PURPOSE To investigate the effects of antidiabetic medications on psoriasis. DATA SOURCES, STUDY SELECTION AND DATA EXTRACTION We conducted a systemic review and meta-analysis and searched MEDLINE, EMBASE and CENTRAL for relevant randomized controlled trials. Our outcomes included 75% improvement in the psoriasis area and severity index from baseline (PASI 75), change in the psoriasis area and severity index (PASI) score, or change in the Dermatology Life Quality Index score under antidiabetic agents. Cochrane Collaboration's tool was used to evaluate the risk of bias of included studies. Subgroup analysis of different dosages of the antidiabetic agents was also performed. DATA SYNTHESIS We included 10 randomized controlled studies examining the effect of antidiabetic agents. Eight studies were rated high risk of bias. Pioglitazone demonstrated significant increase in PASI 75 (risk difference = 0.42; 95% CI: 0.18-0.65) and decrease in mean PASI (mean difference = -3.82; 95% CI: -6.05-1.ㄍ59). In subgroup analysis, 30 mg pioglitazone group demonstrated a significantly higher portion of PASI 75 than 15 mg pioglitazone group (P = .003). LIMITATIONS Some biases are reported high risk in involved articles. The main limitation of the study is in the inclusion of only glitazones. The lack of effect was seen for rosiglitazone and metformin. In the case of metformin, there was only one study available, which is also an important issue. CONCLUSIONS The current evidence demonstrates therapeutic efficacy of pioglitazone, which may be a treatment option in patients with psoriasis and diabetes mellitus.
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Affiliation(s)
- Ching-Chi Chi
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chin-Yu Lee
- Chang Gung Memorial Hospital, Linkou, Taiwan
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan
| | - Chia-Yu Liu
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan
| | - Shu-Hui Wang
- Department of Dermatology, Far Easten Memorial Hospital, New Taipei, Taiwan
| | | | - Tao-Hsin Tung
- Hechi Third People's Hospital, Guangxi, China
- Enze Medical Research Center, Affiliated Taizhou Hospital of Wenzhou Medical College, Taizhou, China
- Department of Medical Research and Education, Cheng-Hsin General Hospital, Taipei, Taiwan
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21
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Chang G, Wang J, Song J, Zhang Z, Zhang L. Efficacy and safety of pioglitazone for treatment of plaque psoriasis: a systematic review and meta-analysis of randomized controlled trials. J DERMATOL TREAT 2020; 31:680-686. [PMID: 31116619 DOI: 10.1080/09546634.2019.1610552] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 04/10/2019] [Indexed: 02/07/2023]
Abstract
Background: A growing number of studies have shown that thiazolidinediones (TZD) can be antipsoriatic. Pioglitazone is a representative of the class of antidiabetic drugs known as TZD. TZD can activate nuclear peroxisome proliferator-activated receptors (PPAR)-c. PPARs are expressed on epidermal keratinocytes and exert their effects by promoting the terminal differentiation of keratinocytes, inhibiting epidermal growth, and reducing inflammatory responses. These observations suggest that TZD have potential benefits in the treatment of cutaneous and metabolic pathologies associated with psoriasis.Objective: A systematic review and meta-analysis was carried out to evaluate the efficacy of combined pioglitazone treatment. We point out three controversial side effects from administration of pioglitazone in psoriasis: elevated liver enzymes, weight gain, and nausea.Study selection: Randomized, single blind, or double blind, published studies of pioglitazone compared with placebo given to patients with plaque psoriasis for 10 weeks or 12 weeks were considered for inclusion in this review. The primary outcomes were 75% or greater improvement in the Psoriasis Area and Severity Index score from baseline (PASI 75) with pioglitazone.Data collection and analysis: The systematic literature search was conducted in the PubMed, Embase, Google Scholar, and Cochrane databases from inception up to December 20 2018. Data analysis was done using Revman 5.3 Haymarket, London, United Kingdom.Main results: We included six studies (three publications of pioglitazone only; three publications of pioglitazone combination therapy) comprising a total of 294 patients (n = 149 with pioglitazone only and n = 145 with pioglitazone combination therapy) in the analysis. There was a significant PASI 75 response, in the pioglitazone only subgroup as compared to placebo (OR = 8.74, 95% CI 3.76-20.31, p < .00001), and the pioglitazone combination subgroup as compared to placebo (OR = 4.64, 95% CI 2.03-10.60, p < .00001), others, the total of pioglitazone as compared to placebo (OR = 6.37, 95% CI 3.55-11.43, p < .00001), and tests of subgroup differences show: p = .29, I2 = 9.5%. The incidence rate of elevated liver enzymes (OR = 3.70, 95% CI 0.56-24.31, p = .99), weight gain (OR = 1.44, 95% CI 0.60-3.47, p = .41), and nausea (OR = 0.76, 95% CI 0.23-2.49, p = .65) were not significantly different compared with the control group.Conclusion: Pioglitazone has efficacy for the treatment of plaque psoriasis. There is no significant difference between patients treated with pioglitazone only or in combination with other therapies. The incidence rate of side effects associated with pioglitazone treatment such as elevated liver enzymes, weight gain, and nausea were not significantly different compared with the control group.
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Affiliation(s)
- Guizhen Chang
- Dermatology and Venereology, Graduate School of Tianjin Medical University, Tianjin, China
| | - Jin Wang
- Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine of Affiliated Hospital, Tianjin, China
| | - Jingxin Song
- Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine of Affiliated Hospital, Tianjin, China
| | - Zhilong Zhang
- Department of Dermatology, Binhai Hospital of Tianjin Medical University General Hospital, Tianjin, China
| | - Litao Zhang
- Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine of Affiliated Hospital, Tianjin, China
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22
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Chen P, Chen X, Lei L, Zhang Y, Xiang J, Zhou J, Lv J. The efficacy and safety of pioglitazone in psoriasis vulgaris: A meta-analysis of randomized controlled trials. Medicine (Baltimore) 2020; 99:e21549. [PMID: 32769894 PMCID: PMC7593001 DOI: 10.1097/md.0000000000021549] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Pioglitazone may have potential benefits in the treatment of cutaneous and metabolic derangements of psoriasis, but its role in the treatment of psoriasis remains in debate. We therefore conducted a meta-analysis to evaluate the clinical efficacy and safety of pioglitazone in psoriasis vulgaris (PsV).We performed a comprehensive search in database of PubMed, Web of Science, Cochrane library, Embase and China National Knowledge Infrastructure (CNKI), and Wan fang database through March 2019 to identify eligible studies. Randomized controlled trials that have evaluated the effect and safety of pioglitazone in PsV were included. Treatment success was defined as ≥75% reduction in psoriasis area and severity index (PASI) score after treatment. Weighted mean differences (WMD), relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were pooled to compare the clinical efficacy and safety between different groups.Six randomized controlled trials (n = 270) were included. Meta-analysis showed that pioglitazone was associated with a remarkable reduction in PASI score in patients with PsV (weight mean difference: 2.68, 95% CI 1.41-3.94, P < .001). The treatment success rate in the pioglitazone group was higher than in the control group (RR 3.60, 95 CI 1.61-8.01, P < .001). Compared with control group, pioglitazone was not related to a pronounced increase in total adverse events (RR 1.180, 95 CI 0.85-1.63, P = .33). Moreover, the risk of common adverse events in the 2 groups were similar, such as elevated liver enzyme, fatigue, nausea, weight gain.This meta-analysis suggested pioglitazone is an effective and safe drug in the treatment of patients with PsV.
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Affiliation(s)
- Pengfei Chen
- Department of Gastroenterology, The Central Hospital of Enshi Autonomous Prefecture, Enshi
| | - Xiubing Chen
- Department of Gastroenterology, The First People's Hospital of Qinzhou, Qinzhou
| | - Lei Lei
- Department of Gastroenterology, The Central Hospital of Enshi Autonomous Prefecture, Enshi
| | | | - Jianjun Xiang
- Department of Medical Section, The Central Hospital of Enshi Autonomous Prefecture, Enshi
| | - Jinxia Zhou
- Department of Neurology, Puren Hospital, Wuhan University of Science and Technology, Wuhan, China
| | - Jun Lv
- Department of Dermatology
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23
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Schaap MJ, van Winden ME, Seyger MM, de Jong EM, Lubeek SF. Representation of older adults in randomized controlled trials on systemic treatment in plaque psoriasis: A systematic review. J Am Acad Dermatol 2020; 83:412-424. [DOI: 10.1016/j.jaad.2019.07.079] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 07/15/2019] [Accepted: 07/19/2019] [Indexed: 12/17/2022]
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24
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Chen M, Chen W, Liu P, Yan K, Lv C, Zhang M, Lu Y, Qin Q, Kuang Y, Zhu W, Chen X. The impacts of gene polymorphisms on methotrexate in Chinese psoriatic patients. J Eur Acad Dermatol Venereol 2020; 34:2059-2065. [PMID: 32271961 DOI: 10.1111/jdv.16440] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Accepted: 03/24/2020] [Indexed: 01/05/2023]
Abstract
BACKGROUND Methotrexate (MTX) is the first-line treatment for psoriasis in China. The metabolic processes of MTX include various proteins and genes. Previous studies have shown that gene polymorphisms had significant impacts on the efficacy of MTX. However, the influence of gene polymorphisms has not been reported in the Chinese psoriatic patients. OBJECTIVE The aim of this study was to verify the impacts of candidate genes polymorphisms on the effectiveness of MTX in a Chinese psoriatic population. METHODS In this study, we enrolled 259 psoriasis patients from two clinical centres. Each of them received MTX treatment at 7.5-15 mg/week for at least 8 weeks. Patients were stratified as responders and non-responders according to whether the Psoriasis Area and Severity Index score declined more than 75% (PASI75). According to previous reports, 16 single nucleotide polymorphisms (SNPs) were selected and genotyped for each patient using the Sequenom platform. Fisher's exact test, the chi-square test, Mann-Whitney tests and ANOVA analyses were used for statistical analysis. RESULTS Among 259 patients, there were 182 males and 77 females, 63 patients with psoriatic arthritis and 196 patients without arthritis phenotype, and the age of all patients ranged from 19 to 70 years (49.7 ± 13.6). The baseline PASI value of patients was 13.8 ± 8.5, and 33.2% of patients achieved a PASI75 response after MTX treatment. Patients carrying the ATP-binding cassette subfamily B member 1 gene (ABCB1) rs1045642 TT genotype were associated with more severe psoriasis skin lesion (P = 0.032). Furthermore, the ABCB1 rs1045642 TT genotype was found to be more frequent in non-responders (P = 0.017), especially in moderate-to-severe patients (P = 0.002) and patients without psoriatic arthritis (P = 0.026) after MTX treatment. CONCLUSION We have demonstrated for the first time that polymorphism of the ABCB1 rs1045642 TT genotype is predictive of a worse clinical response of skin lesions to MTX therapy in a Chinese psoriatic population.
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Affiliation(s)
- M Chen
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, Hunan, China.,Hunan Engineering Research Center of Skin Health and Disease, Changsha, Hunan, China.,Department of Dermatology, Hua Shan Hospital, Fu dan University, Shanghai, China
| | - W Chen
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, Hunan, China.,Hunan Engineering Research Center of Skin Health and Disease, Changsha, Hunan, China.,Department of Dermatology, Hua Shan Hospital, Fu dan University, Shanghai, China
| | - P Liu
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, Hunan, China.,Hunan Engineering Research Center of Skin Health and Disease, Changsha, Hunan, China.,Department of Dermatology, Hua Shan Hospital, Fu dan University, Shanghai, China
| | - K Yan
- Department of Dermatology, Dalian Dermatosis Hospital, Dalian, Liaoning, China
| | - C Lv
- Gerontology Center of Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - M Zhang
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, Hunan, China.,Hunan Engineering Research Center of Skin Health and Disease, Changsha, Hunan, China.,Department of Dermatology, Hua Shan Hospital, Fu dan University, Shanghai, China
| | - Y Lu
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, Hunan, China.,Hunan Engineering Research Center of Skin Health and Disease, Changsha, Hunan, China.,Department of Dermatology, Hua Shan Hospital, Fu dan University, Shanghai, China
| | - Q Qin
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, Hunan, China.,Hunan Engineering Research Center of Skin Health and Disease, Changsha, Hunan, China.,Department of Dermatology, Hua Shan Hospital, Fu dan University, Shanghai, China
| | - Y Kuang
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, Hunan, China.,Hunan Engineering Research Center of Skin Health and Disease, Changsha, Hunan, China.,Department of Dermatology, Hua Shan Hospital, Fu dan University, Shanghai, China
| | - W Zhu
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, Hunan, China.,Hunan Engineering Research Center of Skin Health and Disease, Changsha, Hunan, China.,Department of Dermatology, Hua Shan Hospital, Fu dan University, Shanghai, China
| | - X Chen
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, Hunan, China.,Hunan Engineering Research Center of Skin Health and Disease, Changsha, Hunan, China.,Department of Dermatology, Hua Shan Hospital, Fu dan University, Shanghai, China
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25
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Lajevardi V, Kashiri A, Ghiasi M, Khosravi D, Fazlolahi S, Etesami I. Evaluating the efficacy of ursodeoxycholic acid plus methotrexate vs methotrexate alone in the treatment of moderate to severe plaque-type psoriasis: A randomized clinical trial. Dermatol Ther 2020; 33:e13455. [PMID: 32323429 DOI: 10.1111/dth.13455] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 04/04/2020] [Accepted: 04/20/2020] [Indexed: 11/29/2022]
Affiliation(s)
- Vahideh Lajevardi
- Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Amine Kashiri
- Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Ghiasi
- Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Darya Khosravi
- Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Samaneh Fazlolahi
- Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Ifa Etesami
- Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran
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Abidi A, Rizvi DA, Saxena K, Chaudhary S, Ahmad A. The evaluation of efficacy and safety of methotrexate and pioglitazone in psoriasis patients: A randomized, open-labeled, active-controlled clinical trial. Indian J Pharmacol 2020; 52:16-22. [PMID: 32201442 PMCID: PMC7074427 DOI: 10.4103/ijp.ijp_88_19] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 05/16/2019] [Accepted: 01/30/2020] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVES Psoriasis is a chronic inflammatory disease showing co-existence with metabolic syndrome (MS), as has been confirmed by numerous epidemiologic studies in recent times. In this study, the aim was to ascertain the beneficial effects of pioglitazone in psoriasis, simultaneously targeting the improvement of MS parameters. MATERIALS AND METHODS We conducted a prospective randomized open-labeled parallel-group interventional study in patients of moderate-to-severe chronic plaque psoriasis. A total of 90 patients were inducted in study and divided into three groups of standard treatment (methotrexate 7.5 mg/week for 12 weeks), active treatment (pioglitazone 15 mg tablets once daily for 12 weeks), and their combination. Primary outcome was taken as percentage Psoriasis Area and Severity Index (PASI) improvement from baseline; secondary outcomes were PASI-75, safety profile, and MS parameters. RESULTS Intergroup evaluation of PASI score showed that standard treatment methotrexate and active treatment pioglitazone were comparable. Combination of methotrexate and pioglitazone proved superior in efficacy from both standard and active treatment in 8 and 12 weeks. Adverse drug reactions were mild and treated symptomatically. Pioglitazone and combination group also demonstrated beneficial efficacy in parameter of MS hence establishing it as a potential therapy in psoriasis with MS. CONCLUSIONS Pioglitazone alone or in combination with standard treatment may be a safe alternative drug for psoriasis coexisting with MS proving beneficial for both.
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Affiliation(s)
- Afroz Abidi
- Department of Pharmacology, Era's Lucknow Medical College, Lucknow, Uttar Pradesh, India
| | - Dilshad Ali Rizvi
- Department of Pharmacology, Era's Lucknow Medical College, Lucknow, Uttar Pradesh, India
| | - Kshitij Saxena
- Department of Dermatology, Era's Lucknow Medical College, Lucknow, Uttar Pradesh, India
| | - Savita Chaudhary
- Department of Dermatology, Era's Lucknow Medical College, Lucknow, Uttar Pradesh, India
| | - Ali Ahmad
- Department of Pharmacology, Era's Lucknow Medical College, Lucknow, Uttar Pradesh, India
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Zhang JZ, Ding Y, Xiang F, Yu SR, Zhang DZ, Guan MM, Kang XJ. Effectiveness and safety of different doses of pioglitazone in psoriasis: a meta-analysis of randomized controlled trials. Chin Med J (Engl) 2020; 133:444-451. [PMID: 31977550 PMCID: PMC7046258 DOI: 10.1097/cm9.0000000000000642] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Pioglitazone may be beneficial in the treatment of psoriasis. However, based on the effectiveness and safety considerations, it has not been widely used. To fully evaluate the strength of evidence supporting psoriasis treatment with pioglitazone, we conducted a meta-analysis of existing published studies. METHODS PubMed, Ovid, Cochrane Library, Google Scholar, and Web of Science databases were systematically searched before February 2019. Randomized controlled trials (RCTs) of pioglitazone administration compared with placebo, administered to patients with psoriasis for at least 10 weeks, and published in English were included. Quality of the included RCTs was identified by the modified Jadad scale. The quality of evidence for each outcome was evaluated using the GRADEpro Guideline Development Tool online software. Primary outcomes were proportion of patients showing psoriasis area and severity index (PASI) score improvement (>75%) and the mean percent change in PASI score from baseline to the end of treatment. Dichotomous data were analyzed using odds ratios (ORs) corresponding to the 95% confidence interval (CI), whereas continuous variables, expressed as mean and standard deviation, were analyzed using the mean differences (MD) with the 95% CI. RESULTS Six RCTs were analyzed. Meta-analysis showed that pioglitazone reduced the PASI scores in patients with psoriasis compared with the control group when administered at 30 mg per day (P < 0.001, MD = -3.82, 95% CI = -5.70, -1.93) and at 15 mg per day (P = 0.04, MD = -3.53, 95% CI = -6.86, -0.20). The PASI-75 of the pioglitazone group was significantly higher than that of the control group at 30 mg per day (P < 0.001, OR = 8.30, 95% CI = 3.99, 17.27) and at 15 mg per day (P = 0.03, OR = 2.96, 95% CI = 1.08, 8.06). No statistically significant differences in total adverse events were observed between the groups. There were no significant differences in common adverse reactions such as weight gain and elevated liver enzymes between the two pioglitazone groups. CONCLUSIONS Use of pioglitazone in the current treatment of psoriasis is beneficial. The therapeutic effect of the daily 30 mg dose may be greater than that of the 15 mg dose per day with no significant change in the frequency of adverse reactions.
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Affiliation(s)
- Jing-Zhan Zhang
- Department of Dermatology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang 830000, China
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Sbidian E, Chaimani A, Afach S, Doney L, Dressler C, Hua C, Mazaud C, Phan C, Hughes C, Riddle D, Naldi L, Garcia-Doval I, Le Cleach L. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev 2020; 1:CD011535. [PMID: 31917873 PMCID: PMC6956468 DOI: 10.1002/14651858.cd011535.pub3] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Psoriasis is an immune-mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or joints, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. Several randomised controlled trials (RCTs) have compared the efficacy of the different systemic treatments in psoriasis against placebo. However, the relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis. This is the baseline update of a Cochrane Review first published in 2017, in preparation for this Cochrane Review becoming a living systematic review. OBJECTIVES To compare the efficacy and safety of conventional systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis, and to provide a ranking of these treatments according to their efficacy and safety. SEARCH METHODS We updated our research using the following databases to January 2019: the Cochrane Skin Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS and the conference proceedings of a number of dermatology meetings. We also searched five trials registers and the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) reports (until June 2019). We checked the reference lists of included and excluded studies for further references to relevant RCTs. SELECTION CRITERIA Randomised controlled trials (RCTs) of systemic treatments in adults (over 18 years of age) with moderate-to-severe plaque psoriasis or psoriatic arthritis whose skin had been clinically diagnosed with moderate-to-severe psoriasis, at any stage of treatment, in comparison to placebo or another active agent. The primary outcomes of this review were: the proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90 at induction phase (from 8 to 24 weeks after the randomisation), and the proportion of participants with serious adverse effects (SAEs) at induction phase. We did not evaluate differences in specific adverse effects. DATA COLLECTION AND ANALYSIS Several groups of two review authors independently undertook study selection, data extraction, 'Risk of bias' assessment, and analyses. We synthesised the data using pair-wise and network meta-analysis (NMA) to compare the treatments of interest and rank them according to their effectiveness (as measured by the PASI 90 score) and acceptability (the inverse of serious adverse effects). We assessed the certainty of the body of evidence from the NMA for the two primary outcomes, according to GRADE, as either very low, low, moderate, or high. We contacted study authors when data were unclear or missing. MAIN RESULTS We included 140 studies (31 new studies for the update) in our review (51,749 randomised participants, 68% men, mainly recruited from hospitals). The overall average age was 45 years; the overall mean PASI score at baseline was 20 (range: 9.5 to 39). Most of these studies were placebo-controlled (59%), 30% were head-to-head studies, and 11% were multi-armed studies with both an active comparator and a placebo. We have assessed a total of 19 treatments. In all, 117 trials were multicentric (two to 231 centres). All but two of the outcomes included in this review were limited to the induction phase (assessment from 8 to 24 weeks after randomisation). We assessed many studies (57/140) as being at high risk of bias; 42 were at an unclear risk, and 41 at low risk. Most studies (107/140) declared funding by a pharmaceutical company, and 22 studies did not report the source of funding. Network meta-analysis at class level showed that all of the interventions (conventional systemic agents, small molecules, and biological treatments) were significantly more effective than placebo in terms of reaching PASI 90. At class level, in terms of reaching PASI 90, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents. At drug level, in terms of reaching PASI 90, infliximab, all of the anti-IL17 drugs (ixekizumab, secukinumab, bimekizumab and brodalumab) and the anti-IL23 drugs (risankizumab and guselkumab, but not tildrakizumab) were significantly more effective in reaching PASI 90 than ustekinumab and 3 anti-TNF alpha agents: adalimumab, certolizumab and etanercept. Adalimumab and ustekinumab were significantly more effective in reaching PASI 90 than certolizumab and etanercept. There was no significant difference between tofacitinib or apremilast and between two conventional drugs: ciclosporin and methotrexate. Network meta-analysis also showed that infliximab, ixekizumab, risankizumab, bimekizumab, guselkumab, secukinumab and brodalumab outperformed other drugs when compared to placebo in reaching PASI 90. The clinical effectiveness for these seven drugs was similar: infliximab (versus placebo): risk ratio (RR) 29.52, 95% confidence interval (CI) 19.94 to 43.70, Surface Under the Cumulative Ranking (SUCRA) = 88.5; moderate-certainty evidence; ixekizumab (versus placebo): RR 28.12, 95% CI 23.17 to 34.12, SUCRA = 88.3, moderate-certainty evidence; risankizumab (versus placebo): RR 27.67, 95% CI 22.86 to 33.49, SUCRA = 87.5, high-certainty evidence; bimekizumab (versus placebo): RR 58.64, 95% CI 3.72 to 923.86, SUCRA = 83.5, low-certainty evidence; guselkumab (versus placebo): RR 25.84, 95% CI 20.90 to 31.95; SUCRA = 81; moderate-certainty evidence; secukinumab (versus placebo): RR 23.97, 95% CI 20.03 to 28.70, SUCRA = 75.4; high-certainty evidence; and brodalumab (versus placebo): RR 21.96, 95% CI 18.17 to 26.53, SUCRA = 68.7; moderate-certainty evidence. Conservative interpretation is warranted for the results for bimekizumab (as well as tyrosine kinase 2 inhibitor, acitretin, ciclosporin, fumaric acid esters, and methotrexate), as these drugs, in the NMA, have been evaluated in few trials. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. Nevertheless, the SAE analyses were based on a very low number of events with low to very low certainty for just under half of the treatment estimates in total, and moderate for the others. Thus, the results have to be viewed with caution and we cannot be sure of the ranking. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1) the results were very similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions. AUTHORS' CONCLUSIONS Our review shows that compared to placebo, the biologics infliximab, ixekizumab, risankizumab, bimekizumab, guselkumab, secukinumab and brodalumab were the best choices for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of moderate- to high-certainty evidence (low-certainty evidence for bimekizumab). This NMA evidence is limited to induction therapy (outcomes were measured from 8 to 24 weeks after randomisation) and is not sufficient for evaluation of longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean age of 45 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice. Another major concern is that short-term trials provide scanty and sometimes poorly-reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. Indeed, we found no significant difference in the assessed interventions and placebo in terms of SAEs, but the evidence for all the interventions was of very low to moderate quality. In order to provide long-term information on the safety of the treatments included in this review, it will also be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies. In terms of future research, randomised trials comparing directly active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between conventional systemic and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve participants, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
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Affiliation(s)
- Emilie Sbidian
- Hôpital Henri Mondor, Department of Dermatology, 51 Avenue du Maréchal de Lattre de Tassigny, Créteil, France, 94000
- Hôpital Henri Mondor, Clinical Investigation Centre, Créteil, France, 94010
- Université Paris Est Créteil (UPEC), Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE) - EA 7379, Créteil, France
| | - Anna Chaimani
- Université de Paris, Research Center in Epidemiology and Statistics Sorbonne Paris Cité (CRESS-UMR1153), Inserm, Inra, F-75004, Paris, France
- Cochrane France, Paris, France
| | - Sivem Afach
- Université Paris Est Créteil (UPEC), Epidemiology in dermatology and evaluation of therapeutics (EpiDermE) - EA 7379, Créteil, France
| | - Liz Doney
- Cochrane Skin Group, The University of Nottingham, Centre of Evidence Based Dermatology, A103, King's Meadow Campus, Lenton Lane, Nottingham, UK, NG7 2NR
| | - Corinna Dressler
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Division of Evidence Based Medicine, Department of Dermatology, Venerology and Allergology, Charitéplatz 1, Berlin, Germany, 10117
| | - Camille Hua
- Hôpital Henri Mondor, Department of Dermatology, 51 Avenue du Maréchal de Lattre de Tassigny, Créteil, France, 94000
| | - Canelle Mazaud
- Hôpital Henri Mondor, Department of Dermatology, 51 Avenue du Maréchal de Lattre de Tassigny, Créteil, France, 94000
| | - Céline Phan
- Centre Hospitalier Victor Dupouy, Department of Dermatology, Argenteuil, France
| | - Carolyn Hughes
- The University of Nottingham, c/o Cochrane Skin Group, A103, King's Meadow Campus, Lenton Lane, Nottingham, UK, NG7 2NR
| | - Dru Riddle
- Texas Christian University (TCU), School of Nurse Anesthesia, Fort Worth, Texas, USA
| | - Luigi Naldi
- Padiglione Mazzoleni - Presidio Ospedaliero Matteo Rota, Centro Studi GISED (Italian Group for Epidemiologic Research in Dermatology) - FROM (Research Foundation of Ospedale Maggiore Bergamo), Via Garibaldi 13/15, Bergamo, Italy, 24122
| | - Ignacio Garcia-Doval
- Complexo Hospitalario Universitario de Vigo, Department of Dermatology, Meixoeiro sn, Vigo, Spain, 36214
| | - Laurence Le Cleach
- Hôpital Henri Mondor, Department of Dermatology, 51 Avenue du Maréchal de Lattre de Tassigny, Créteil, France, 94000
- Université Paris Est Créteil (UPEC), Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE) - EA 7379, Créteil, France
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Serum homocysteine level, vitamin B12 levels, and erythrocyte folate in psoriasis: A case-control study. Int J Womens Dermatol 2019; 5:171-174. [PMID: 31360751 PMCID: PMC6637066 DOI: 10.1016/j.ijwd.2018.12.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Revised: 12/09/2018] [Accepted: 12/24/2018] [Indexed: 12/20/2022] Open
Abstract
Background One of the most important organ involvements in psoriasis is atherosclerotic cardiovascular disease. Homocysteine is known to have atherogenic properties, but some inconsistency exists in the literature about its probable role as a risk factor of cardiovascular disorder in patients with psoriasis. Objective Because of some controversies, we compared homocysteine levels and related parameters of metabolic cycles in patients with psoriasis and healthy individuals. Methods This case-control study was conducted on 50 patients with psoriasis and 50 healthy individuals as the controls. Serum homocysteine, vitamin B12 levels, and erythrocyte folate concentrations were checked in all participants. Results Mean serum homocysteine, erythrocyte folate, and vitamin B12 levels did not show any significant difference between the two groups (p > .05), but interestingly, in patients with psoriasis, men had a significantly higher incidence of hyperhomocysteinemia and lower levels of erythrocyte folate (p = .14). Overall, there is no significant difference in serum levels of homocysteine and metabolic-related parameters between the case and control group. There was no significant relationship between the severity of psoriasis and the body mass index of patients (p > .05). Conclusion Patients with psoriasis had a higher body mass index and higher levels of homocysteine in men. Hyperhomocysteinemia could be a predisposing factor of cardiovascular events, but more evaluations as a part of metabolic syndrome in patients with psoriasis are needed.
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Ghiasi M, Ebrahimi S, Lajevardi V, Taraz M, Azizpour A. Efficacy and safety of pioglitazone plus phototherapy versus phototherapy in patients with plaque type psoriasis: a Double Blinded Randomized Controlled Trial. J DERMATOL TREAT 2018; 30:664-667. [PMID: 30394148 DOI: 10.1080/09546634.2018.1544702] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Introduction: Thiazolidinediones have shown a good therapeutic effect in psoriasis treatment with no major adverse effects. The purpose of this study was to evaluate and compare the therapeutic effects of the combination of phototherapy and Pioglitazone with the phototherapy alone on plaque psoriasis patients. Methods and Materials: About 60 adults with plaque type psoriasis entered the study. They were randomly divided into two groups; one with pioglitazone and one with placebo and both underwent 30 sessions of phototherapy during 10 weeks. Before and after the treatment Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) were assessed. Side effects of the treatment were also investigated. Results: The average PASI of the pioglitazone group was reduced from 20.9 ± 9.8 to 1.8 ± 1.4 (p < .001) versus the placebo group in which the PASI was reduced from 22 ± 8.5 to 4.4 ± 4. In other words, PASI was reduced in the pioglitazone and placebo group by 83.5% and 56.7% respectively (p < .05). The two groups didn't have a significant difference in reducing the DLQI (p = .315). Conclusion: Pioglitazone can vastly enhance the effectiveness of phototherapy in plaque psoriasis patients without causing any important adverse effect and with no success in improving the score of DLQI.
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Affiliation(s)
- Maryam Ghiasi
- a Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences , Tehran , Iran
| | - Sahar Ebrahimi
- a Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences , Tehran , Iran
| | - Vahide Lajevardi
- a Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences , Tehran , Iran
| | - Mohammad Taraz
- b College of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran
| | - Arghavan Azizpour
- a Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences , Tehran , Iran
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Pongparit K, Chularojanamontri L, Limphoka P, Silpa-Archa N, Wongpraparat C. Effectiveness of and factors associated with clinical response to methotrexate under daily life conditions in Asian patients with psoriasis: A retrospective cohort study. J Dermatol 2018; 45:540-545. [PMID: 29512181 DOI: 10.1111/1346-8138.14270] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Accepted: 01/29/2018] [Indexed: 01/09/2023]
Abstract
Given the relative scarcity of data concerning the efficacy of methotrexate under daily life conditions in psoriasis, this study aimed to investigate the effectiveness of methotrexate in Asian psoriatic patients and to identify factors associated with clinical response. This observational retrospective cohort study included adult psoriatic patients who had been treated with or were going to start methotrexate. Psoriasis Area and Severity Index (PASI) scores at baseline and at 3, 6 and 12 months were recorded. At 3 months, patients achieving 50% or more reduction from baseline PASI score were defined as responders. One hundred, 74 and 61 patients were followed for 3, 6 and 12 months, respectively. Mean follow-up time was 15.3 ± 10.2 months. A reduction in PASI score of at least 75% was achieved in 26%, 32.5% and 45.2% at 3, 6 and 12 months, respectively. At 12 and 24 months, Kaplan-Meier analysis showed 68.7% and 52.1% probability of drug survival, respectively. Male sex, body mass index (BMI) of less than 25 kg/m2 and absence of abdominal obesity were factors associated with response to treatment in univariate analysis. Male sex was the only significant factor in multivariate analysis. The effectiveness of methotrexate in clinical practise seemed to be lower than in clinical trials, but effectiveness increased with longer duration of treatment. Problems associated with methotrexate use in clinical practise may be due to medication adherence rather than lack of medication effectiveness. Female sex, abdominal obesity and BMI of 25 kg/m2 or more might decrease response to methotrexate.
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Affiliation(s)
- Kamolwan Pongparit
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Leena Chularojanamontri
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Pichaya Limphoka
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Narumol Silpa-Archa
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Chanisada Wongpraparat
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Sbidian E, Chaimani A, Garcia‐Doval I, Do G, Hua C, Mazaud C, Droitcourt C, Hughes C, Ingram JR, Naldi L, Chosidow O, Le Cleach L. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev 2017; 12:CD011535. [PMID: 29271481 PMCID: PMC6486272 DOI: 10.1002/14651858.cd011535.pub2] [Citation(s) in RCA: 104] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Psoriasis is an immune-mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or joints, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. Several randomised controlled trials (RCTs) have compared the efficacy of the different systemic treatments in psoriasis against placebo. However, the relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head to head, which is why we chose to conduct a network meta-analysis. OBJECTIVES To compare the efficacy and safety of conventional systemic agents (acitretin, ciclosporin, fumaric acid esters, methotrexate), small molecules (apremilast, tofacitinib, ponesimod), anti-TNF alpha (etanercept, infliximab, adalimumab, certolizumab), anti-IL12/23 (ustekinumab), anti-IL17 (secukinumab, ixekizumab, brodalumab), anti-IL23 (guselkumab, tildrakizumab), and other biologics (alefacept, itolizumab) for patients with moderate to severe psoriasis and to provide a ranking of these treatments according to their efficacy and safety. SEARCH METHODS We searched the following databases to December 2016: the Cochrane Skin Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS. We also searched five trials registers and the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) reports. We checked the reference lists of included and excluded studies for further references to relevant RCTs. We searched the trial results databases of a number of pharmaceutical companies and handsearched the conference proceedings of a number of dermatology meetings. SELECTION CRITERIA Randomised controlled trials (RCTs) of systemic and biological treatments in adults (over 18 years of age) with moderate to severe plaque psoriasis or psoriatic arthritis whose skin had been clinically diagnosed with moderate to severe psoriasis, at any stage of treatment, in comparison to placebo or another active agent. DATA COLLECTION AND ANALYSIS Three groups of two review authors independently undertook study selection, data extraction, 'Risk of bias' assessment, and analyses. We synthesised the data using pair-wise and network meta-analysis (NMA) to compare the treatments of interest and rank them according to their effectiveness (as measured by the Psoriasis Area and Severity Index score (PASI) 90) and acceptability (the inverse of serious adverse effects). We assessed the certainty of the body of evidence from the NMA for the two primary outcomes, according to GRADE; we evaluated evidence as either very low, low, moderate, or high. We contacted study authors when data were unclear or missing. MAIN RESULTS We included 109 studies in our review (39,882 randomised participants, 68% men, all recruited from a hospital). The overall average age was 44 years; the overall mean PASI score at baseline was 20 (range: 9.5 to 39). Most of these studies were placebo controlled (67%), 23% were head-to-head studies, and 10% were multi-armed studies with both an active comparator and placebo. We have assessed all treatments listed in the objectives (19 in total). In all, 86 trials were multicentric trials (two to 231 centres). All of the trials included in this review were limited to the induction phase (assessment at less than 24 weeks after randomisation); in fact, all trials included in the network meta-analysis were measured between 12 and 16 weeks after randomisation. We assessed the majority of studies (48/109) as being at high risk of bias; 38 were assessed as at an unclear risk, and 23, low risk.Network meta-analysis at class level showed that all of the interventions (conventional systemic agents, small molecules, and biological treatments) were significantly more effective than placebo in terms of reaching PASI 90.In terms of reaching PASI 90, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents. Small molecules were associated with a higher chance of reaching PASI 90 compared to conventional systemic agents.At drug level, in terms of reaching PASI 90, all of the anti-IL17 agents and guselkumab (an anti-IL23 drug) were significantly more effective than the anti-TNF alpha agents infliximab, adalimumab, and etanercept, but not certolizumab. Ustekinumab was superior to etanercept. No clear difference was shown between infliximab, adalimumab, and etanercept. Only one trial assessed the efficacy of infliximab in this network; thus, these results have to be interpreted with caution. Tofacitinib was significantly superior to methotrexate, and no clear difference was shown between any of the other small molecules versus conventional treatments.Network meta-analysis also showed that ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab outperformed other drugs when compared to placebo in terms of reaching PASI 90: the most effective drug was ixekizumab (risk ratio (RR) 32.45, 95% confidence interval (CI) 23.61 to 44.60; Surface Under the Cumulative Ranking (SUCRA) = 94.3; high-certainty evidence), followed by secukinumab (RR 26.55, 95% CI 20.32 to 34.69; SUCRA = 86.5; high-certainty evidence), brodalumab (RR 25.45, 95% CI 18.74 to 34.57; SUCRA = 84.3; moderate-certainty evidence), guselkumab (RR 21.03, 95% CI 14.56 to 30.38; SUCRA = 77; moderate-certainty evidence), certolizumab (RR 24.58, 95% CI 3.46 to 174.73; SUCRA = 75.7; moderate-certainty evidence), and ustekinumab (RR 19.91, 95% CI 15.11 to 26.23; SUCRA = 72.6; high-certainty evidence).We found no significant difference between all of the interventions and the placebo regarding the risk of serious adverse effects (SAEs): the relative ranking strongly suggested that methotrexate was associated with the best safety profile regarding all of the SAEs (RR 0.23, 95% CI 0.05 to 0.99; SUCRA = 90.7; moderate-certainty evidence), followed by ciclosporin (RR 0.23, 95% CI 0.01 to 5.10; SUCRA = 78.2; very low-certainty evidence), certolizumab (RR 0.49, 95% CI 0.10 to 2.36; SUCRA = 70.9; moderate-certainty evidence), infliximab (RR 0.56, 95% CI 0.10 to 3.00; SUCRA = 64.4; very low-certainty evidence), alefacept (RR 0.72, 95% CI 0.34 to 1.55; SUCRA = 62.6; low-certainty evidence), and fumaric acid esters (RR 0.77, 95% CI 0.30 to 1.99; SUCRA = 57.7; very low-certainty evidence). Major adverse cardiac events, serious infections, or malignancies were reported in both the placebo and intervention groups. Nevertheless, the SAEs analyses were based on a very low number of events with low to very low certainty for just over half of the treatment estimates in total, moderate for the others. Thus, the results have to be considered with caution.Considering both efficacy (PASI 90 outcome) and acceptability (SAEs outcome), highly effective treatments also had more SAEs compared to the other treatments, and ustekinumab, infliximab, and certolizumab appeared to have the better trade-off between efficacy and acceptability.Regarding the other efficacy outcomes, PASI 75 and Physician Global Assessment (PGA) 0/1, the results were very similar to the results for PASI 90.Information on quality of life was often poorly reported and was absent for a third of the interventions. AUTHORS' CONCLUSIONS Our review shows that compared to placebo, the biologics ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab are the best choices for achieving PASI 90 in people with moderate to severe psoriasis on the basis of moderate- to high-certainty evidence. At class level, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents, too. This NMA evidence is limited to induction therapy (outcomes were measured between 12 to 16 weeks after randomisation) and is not sufficiently relevant for a chronic disease. Moreover, low numbers of studies were found for some of the interventions, and the young age (mean age of 44 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice.Another major concern is that short-term trials provide scanty and sometimes poorly reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. Indeed, we found no significant difference in the assessed interventions and placebo in terms of SAEs. Methotrexate appeared to have the best safety profile, but as the evidence was of very low to moderate quality, we cannot be sure of the ranking. In order to provide long-term information on the safety of the treatments included in this review, it will be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies as well.In terms of future research, randomised trials comparing directly active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between conventional systemic and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve patients, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents.
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Affiliation(s)
| | | | - Ignacio Garcia‐Doval
- Complexo Hospitalario Universitario de VigoDepartment of DermatologyTorrecedeira 10, 2º AVigoSpain36202
| | - Giao Do
- Hôpital Henri MondorDepartment of Dermatology51 Avenue du Maréchal de Lattre de TassignyCréteilFrance94000
| | - Camille Hua
- Hôpital Henri MondorDepartment of Dermatology51 Avenue du Maréchal de Lattre de TassignyCréteilFrance94000
| | - Canelle Mazaud
- Hôpital Henri MondorDepartment of Dermatology51 Avenue du Maréchal de Lattre de TassignyCréteilFrance94000
| | - Catherine Droitcourt
- Université de Rennes 1Department of Dermatology2 rue Henri le GuillouxRennesFrance35000
| | - Carolyn Hughes
- The University of Nottinghamc/o Cochrane Skin GroupA103, King's Meadow CampusLenton LaneNottinghamUKNG7 2NR
| | - John R Ingram
- Cardiff UniversityDepartment of Dermatology & Wound Healing, Cardiff Institute of Infection & Immunity3rd Floor Glamorgan HouseHeath ParkCardiffUKCF14 4XN
| | - Luigi Naldi
- Padiglione Mazzoleni ‐ Presidio Ospedaliero Matteo RotaCentro Studi GISED (Italian Group for Epidemiologic Research in Dermatology) ‐ FROM (Research Foundation of Ospedale Maggiore Bergamo)Via Garibaldi 13/15BergamoItaly24122
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West J, Ogston S, Foerster J. Safety and Efficacy of Methotrexate in Psoriasis: A Meta-Analysis of Published Trials. PLoS One 2016; 11:e0153740. [PMID: 27168193 PMCID: PMC4864230 DOI: 10.1371/journal.pone.0153740] [Citation(s) in RCA: 75] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Accepted: 04/04/2016] [Indexed: 01/19/2023] Open
Abstract
Background Methotrexate (MTX) has been used to treat psoriasis for over half a century. Even so, clinical data characterising its efficacy and safety are sparse. Objective In order to enhance the available evidence, we conducted two meta-analyses, one for efficacy and one for safety outcomes, respectively, according to PRISMA checklist. (Data sources, study criteria, and study synthesis methods are detailed in Methods). Results In terms of efficacy, only eleven studies met criteria for study design and passed a Cochrane risk of bias analysis. Based on this limited dataset, 45.2% [95% confidence interval 34.1–60.0] of patients achieve PASI75 at primary endpoint (12 or 16 weeks, respectively, n = 705 patients across all studies), compared to a calculated PASI75 of 4.4 [3.5–5.6] for placebo, yielding a relative risk of 10.2 [95% C.I. 7.1–14.7]. For safety outcomes, we extended the meta-analysis to include studies employing the same dose range of MTX for other chronic inflammatory conditions, e.g. rheumatoid arthritis, in order not to maximise capture of relevant safety data. Based on 2763 patient safety years, adverse events (AEs) were found treatment limiting in 6.9 ± 1.4% (mean ± s.e.) of patients treated for six months, with an adverse effect profile largely in line with that encountered in clinical practice. Finally, in order to facilitate prospective clinical audit and to help generate long-term treatment outcomes under real world conditions, we also developed an easy to use documentation form to be completed by patients without requirement for additional staff time. Limitations Meta-analyses for efficacy and safety, respectively, employed non-identical selection criteria. Conclusions These meta-analyses summarise currently available evidence on MTX in psoriasis and should be of use to gauge whether local results broadly fall within outcomes.
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Affiliation(s)
- Jonathan West
- University of Dundee, College of Medicine, Dentistry, and Nursing, Dundee, Scotland
| | - Simon Ogston
- University of Dundee, College of Medicine, Dentistry, and Nursing, Dundee, Scotland
| | - John Foerster
- University of Dundee, College of Medicine, Dentistry, and Nursing, Dundee, Scotland
- Department of Dermatology and Photobiology, NHS Tayside, Dundee, Scotland
- * E-mail:
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Feldman SR, Mathias SD, Schenkel B, Colwell HH, McQuarrie K, Randazzo B, Han C. Development of a patient-reported outcome questionnaire for use in adults with moderate-to-severe plaque psoriasis: The Psoriasis Symptoms and Signs Diary. JOURNAL OF DERMATOLOGY & DERMATOLOGIC SURGERY 2016. [DOI: 10.1016/j.jdds.2015.07.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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Mahajan VK. Psoriasis treatment: Unconventional and non-standard modalities in the era of biologics. World J Dermatol 2016; 5:17. [DOI: 10.5314/wjd.v5.i1.17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Revised: 10/25/2015] [Accepted: 12/18/2015] [Indexed: 02/06/2023] Open
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Gupta M, Mahajan VK, Mehta KS, Chauhan PS, Rawat R. Peroxisome proliferator-activated receptors (PPARs) and PPAR agonists: the 'future' in dermatology therapeutics? Arch Dermatol Res 2015; 307:767-780. [PMID: 25986745 DOI: 10.1007/s00403-015-1571-1] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Revised: 04/11/2015] [Accepted: 05/05/2015] [Indexed: 01/10/2023]
Abstract
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors and comprise three different isoforms namely PPARα, PPARγ, and PPARβ/δ with PPARβ/δ being the predominant subtype in human keratinocytes. After binding with specific ligands, PPARs regulate gene expression, cell growth and differentiation, apoptosis, inflammatory responses, and tumorogenesis. PPARs also modulate a wide variety of skin functions including keratinocyte proliferation, epidermal barrier formation, wound healing, melanocyte proliferation, and sebum production. Recent studies have shown the importance of PPARs in the pathogenesis of many dermatological disorders. Clinical trials have suggested possible role of PPAR agonists in the management of various dermatoses ranging from acne vulgaris, psoriasis, hirsutism, and lipodystrophy to cutaneous malignancies including melanoma. This article is intended to be a primer for dermatologists in their understanding of clinical relevance of PPARs and PPAR agonists in dermatology therapeutics.
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Affiliation(s)
- Mrinal Gupta
- Department of Dermatology, Venereology and Leprosy, Dr. R. P. Govt. Medical College, Kangra, Tanda, 176001, Himachal Pradesh, India
| | - Vikram K Mahajan
- Department of Dermatology, Venereology and Leprosy, Dr. R. P. Govt. Medical College, Kangra, Tanda, 176001, Himachal Pradesh, India.
| | - Karaninder S Mehta
- Department of Dermatology, Venereology and Leprosy, Dr. R. P. Govt. Medical College, Kangra, Tanda, 176001, Himachal Pradesh, India
| | - Pushpinder S Chauhan
- Department of Dermatology, Venereology and Leprosy, Dr. R. P. Govt. Medical College, Kangra, Tanda, 176001, Himachal Pradesh, India
| | - Ritu Rawat
- Department of Dermatology, Venereology and Leprosy, Dr. R. P. Govt. Medical College, Kangra, Tanda, 176001, Himachal Pradesh, India
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Pioglitazone ameliorates methotrexate-induced renal endothelial dysfunction via amending detrimental changes in some antioxidant parameters, systemic cytokines and Fas production. Vascul Pharmacol 2015; 74:139-150. [DOI: 10.1016/j.vph.2015.07.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2015] [Revised: 06/29/2015] [Accepted: 07/04/2015] [Indexed: 02/07/2023]
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Abstract
In the era of biologic therapies, methotrexate (MTX), a classic immunomodulator, is still the cornerstone of systemic treatment of psoriasis. MTX has been used for many years, achieving good responses with a good safety profile. However, only a few randomized clinical trials have been performed involving MTX, and most of the current evidence comes from pivotal studies of biologic drugs. The aim of this article is to make an extensive review of the MTX mechanism of action, pharmacokinetics, efficacy, safety and tolerability, especially focusing on the future perspective of this old drug and recent advances in the field of pharmacogenetics.
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Affiliation(s)
- Oriol Yélamos
- Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, C/Sant Antoni Maria Claret 167, 08025 Barcelona, Spain
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