Ustekinumab for the treatment of plaque psoriasis: A 6 -year real -life tertiary institution experience

Ustekinumab for the treatment of plaque psoriasis: A 6 -year real -life tertiary institution experience | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Ustekinumab for the treatment of plaque psoriasis: A 6 -year real -life tertiary institution experience Pelin HIZLI, Fatma Arzu KILIÇ, Jale Aylin AKDAŞLI This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3900794/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Since the causative mechanism of psoriasis has an immunologic basis, various novel therapeutic agents selectively targeting abnormal immune responses were developed previously. This study aimed to present the 6-year follow-up of results of patients received ustekinumab for plaque psoriasis. Methods: A 6-year real -life data of 80 patients with plaque psoriasis receiving ustekinumab were compiled from the medical archive of our tertiary institution retrospectively and presented. Results: Eighty patients with psoriasis received ustekinumab [28 (35%) females and 52(65%) males, mean age: 50.7 ±14.1 (22-80) years] were included. Overall PASI75 response rate was 72.5% on 16 th week, 82.5% on 28 th week and 86.25% on 52 nd week. The overall PASI90 response rate was 61.25% on 16 th week, 73.75% on 28 th week and 76.25% on 52 nd week Both PASI75 and PASI90 response rates did not significantly differ between naive and non-naive patients. The week of PASI75 and PASI90 achievement did not significantly differ between the patients between naive and non-naive patients, and between males and females. Both PASI75 and PASI90 achievement weeks were not significantly different between the patients with a baseline PASI of under and over 10. No severe side effect was detected. Conclusions: Our 6-year real-life clinical experience we show the effectiveness and safety of ustekinumab in plaque psoriasis even biological naive and non -naive patients. ustekinumab psoriasis real -life naive Figures Figure 1 Figure 2 Introduction Psoriasis is an inflammatory skin disease with multifactorial etiology. Various proinflammatory cytokines are overexpressed both cutaneous and systemically in patients with psoriasis. Serum Th1 cytokine levels playing an important role in the pathogenesis of psoriasis were found higher in patients with psoriasis [ 16 ]. In psoriasis lesions, Type 1 cytokines released by activated T lymphocytes including IL-1, 6, 8, 12, TNFα, IF N -γ and IL-23, IL-17, IL-20 and IL-18 were reported as increased [ 8 , 20 ]. IL-12 plays an important role in the differentiation and activity of TH1 cells and natural killer cells and stimulates the release of IFN-γ and TNF-alfa from these cells [ 10 , 12 , 14 ]. IL-23 increases the production of IL-17, IL-22 and TNF-α by inducing the differentiation of naive CD4 + T cells into Th-17 cells [ 10 ]. The IL-23 cytokine consists of IL23A (IL-23p19) and IL12B (IL-12p40) subunits. The p40 subunit is shared with IL-12 [ 28 ]. The common p40 subunit of the cytokines IL-12 and IL-23 is overexpressed in psoriasis plaques, and this subunit might be a target in the treatment of psoriasis [ 2 ]. Since the causative mechanism of psoriasis has an immunologic basis, various novel therapeutic agents selectively targeting abnormal immune responses were developed previously [ 17 , 19 ]. Ustekinumab is a human IgG1κ monoclonal antibody targeting the p40 subunit shared by IL-12 and 23, preventing the interaction of these cytokines with the receptors, and blocking the central signaling and cytokine production in inflammatory diseases [ 3 ]. The aim of this study was to present the 6-year follow- up of results of the patients received ustekinumab therapy for the treatment of plaque psoriasis. The efficacy and side effect profile of ustekinumab and treatment continuation rates of the patients were main foci of this retrospective real life experience study. Methods Subjects and study design In this retrospective archival real -life investigation, 80 adult patients with psoriasis received ustekinumab treatment in our tertiary institution between January 2016 and June 2023 were included. The study protocol was approved by institutional ethics committee of …… university (Approval number: 2023/125) Demographic features of the patients including age, gender, duration of the disease and family history, previous therapies for psoriasis (systemics and biologics), presence of coexisting psoriatic arthritis (PsA), baseline Psoriasis Area Severity Index (PASI), adverse events due to treatment, duration of treatments received, therapeutic response and the reasons for discontinuation of treatment were compiled from the medical records and noted. Psoriasis Area and Severity Index (PASI) was used to assess treatment effectiveness, PASI score at baseline, 16th, 24th, and 52nd weeks were noted as well. Therapeutic response was assessed using PASI75, and PASI90 response rates. The patients under 100 kg received 45 mg ustekinumab and the patients over 100 kg received 90 mg ustekinumab. The PASI75 and PASI90 response rates of all patients were presented as were the rates of biologically naive and non-naive patients, and as were the rates of males and females separately in 16th, 24th and 52nd weeks. Additionally, the PASI75 and PASI90 achievement weeks were compared between biologically naive and non-naive patients, between males and females and between the patients with and without PsA. Statistical Analysis Results were presented as number (percentage). The distribution pattern of the data of PASI75 and PASI90 achievement week was investigated using Kolmogorov- Smirnov test (p < 0.05). Comparisons of PASI75 and PASI90 achievement weeks were performed using Mann Whitney U test. Categorical variables were compared using Chi- square test. All statistical analysis was performed using SPSS software for Windows (SPSS Inc., Chicago, IL). A P value under 0.05 considered statistically significant. Results In total, 80 patients with psoriasis received ustekinumab [28 (35%) females and 52(65%) males, mean age: 50.7 ± 14.1 (22–80) years] were included in the study. Fourteen out of 80 (17.5%) patients were elderly patients (over 65 years). Demographics and clinical characteristics of the patients were presented in Table II. The mean weight of the patients was 84.9 ± 14.9 (56–120) kg and the mean age of disease onset was 32.3 ± 16.4 years. Nineteen out of 80 patients were over 99kg weight (≥ 100kg). A family history of psoriasis was present in 17 (21.3%) out of 80 patients. The mean baseline PASI was 11.2 ± 5.7. Thirty -one out of 80 (38.75%) patients had a baseline PASI under 10, and 49 out of 80 (61.25%) patients had a baseline PASI over 10. The rate of psoriatic arthritis was 26.3% (21 patients) and nail involvement was 32.5% (26 patients). All patients had previously received at least one conventional systemic treatment and the most commonly received agent was methotrexate (91.3%). The comparison of the PASI75 achievement weeks between males and females reached PASI75 (the patients did not reach PASI75 were not included in this comparison) revealed that the median PASI75 achievement week of males [12 (4–36) weeks] was not significantly different compared to the week of females [12 (4–40) weeks] (p = 0.32). The comparison of the PASI90 achievement weeks between males and females reached PASI90 (the patients did not reach PASI90 were not included in this comparison) revealed that the median PASI90 achievement week of males [12 (4–36) weeks] was not significantly different compared to the week of females [15 (5–28) weeks] (p = 0.75). In addition, both PASI75 and PASI90 achievement weeks were not significantly different between patients under and over 100kg (p = 0.165 and p = 0.795, respectively). Moreover, both PASI75 and PASI90 achievement weeks were not significantly different between the patients with a baseline PASI of under and over 10 (p = 0.32 and p = 0.799, respectively). The overall PASI75 response rate was 72.5% (58 patients) on 16th week, 82.5% (66 patients) on 28th week and 86.25% (69 patients) on 52nd week. The overall PASI90 response rate was 61.25% (49 patients) on 16th week, 73.75% (59 patients) on 28th week and 76.25% (61 patients) on 52nd week. Out of 80 patients, 54 (67.5%) were biologically naive and 26 (32.5%) were biologically non-naive patients. The PASI75 response rate was 79.6% (43 of 54 patients) in biologic naive patients and 57.7% (15 of 26 patients) in biologic non-naive patients on 16th week. The PASI75 response rate was 88.9% (48 of 54 patients) in biologic naive patients and 69.2% (18 of 26 patients) in biologic non-naive patients on 28th week. The PASI75 response rate was again 88.9% (48 of 54 patients) in biologic naive patients and 80.8% (21 of 26 patients) in biologic non-naive patients on 52nd week. ( Fig. 1 ) Only 6 (11.1%) patients did not reach PASI75 response in naive group and 5 (19.2%) patients did not reach PASI75 response in non-naive group. The PASI90 response rate was 70.4% (38 of 54 patients) in biologic naive patients and 42.3% (11 of 26 patients) in biologic non-naive patients on 16th week. The PASI90 response rate was 79.6% (43 of 54 patients) in biologic naive patients and 61.5% (16 of 26 patients) in biologic non-naive patients on 28th week. The PASI90 response rate was 81.5% (44 of 54 patients) in biologic naive patients and 65.4% (17 of 26 patients) in biologic non-naive patients on 52nd week. ( Fig. 2 . ) Ten (18.5%) patients did not reach PASI90 response in naive group and 9 (34.6%) patients did not reach PASI90 response in non-naive group. Of 54 naive patients, 48 (89%) reached PASI75, and of 26 non-naive patients, 21 (80.8%) reached PASI75. The PASI75 response rate did not significantly differ between naive and non-naive patients (89% vs. 80.8%, p = 0.32 X 2 = 0.976). The comparison of the PASI75 achievement weeks between naive and non-naive patients reached PASI75 (the patients did not reach PASI75 were not included in this comparison) revealed that the median PASI75 achievement week of naive patients [12 (4–28) weeks] was not significantly different compared to the week of non- naive patients [12 (4–40) weeks] (p = 0.43). Of 54 naive patients, 44 (81.5%) reached PASI90, and of 26 non-naive patients, 17 (65.4%) reached PASI75. The PASI90 response rate in naive group was not significantly different compared to the non-naive patients (81.5% vs. 65.4%, p = 0.16 X 2 = 2.511). The comparison of the PASI90 achievement weeks between naive and non-naive patients reached PASI90 (the patients did not reach PASI90 were not included in this comparison) revealed that the median PASI90 achievement week of naive patients [12 (4–36) weeks] was not significantly different compared to the week of non- naive patients [12 (4–36) weeks] (p = 0.62). The rate of PASI75 achievement was 80.8% (21 out of 26 patients) in patients with nail involvement, and 88.9% (48 out of 54 patients) in patients without nail involvement. The rate of PASI75 achievement did not significantly differ between the patients with and without nail involvement (p = 0.32, X 2 = 0.976). The rate of PASI90 achievement was 69.2% (18 out of 26 patients) in patients with nail involvement, and 79.6% (48 out of 54 patients) in patients without nail involvement. The rate of PASI90 achievement was greater in patients without nail involvement compared to the patients with nail involvement, however, the difference was not statistically significant (p = 0.32, X 2 = 0.976). The rate of PASI75 achievement was 90.5% (19 out of 21 patients) in patients with psoriatic arthritis, and 84.7% (50 out of 59 patients) in patients without psoriatic arthritis. The PASI75 response rate did not significantly differ between the patients with and without psoriatic arthritis (p = 0.71, X 2 = 0.429). The PASI90 response rate was 66.7% (14 out of 21 patients) in patients with psoriatic arthritis, and 79.7% (47 out of 59 patients) in patients without psoriatic arthritis. The rate of PASI90 achievement was greater in patients without psoriatic arthritis compared to the patients with psoriatic arthritis, however, the difference was not statistically significant (p = 0.245, X 2 = 1.444). Out of 80 patients, 38 (47.5%) continued their treatment, 4 (5%) patients broke the treatment up because of primary non-responsivity and 10 (12.5%) patients broke the treatment up because of secondary non-responsivity. Only 2 (2.5%) patients broke the treatment up because of adverse effect (mild increase in liver enzyme levels) (Table II) . In addition, 78 out of 80 (97.5%) patients experienced no adverse effects. Discussion In this study, we retrospectively investigated the disease characteristics of patients receiving ustekinumab treatment for moderate-to‐severe psoriasis and the real ‐life long‐term efficacy and safety profile of the treatment for more than 6 years. The effectivity and safety of ustekinumab in patients with psoriasis was examined in many prior studies [ 17 , 21 , 29 ]. However, real-life data might be different from clinical investigations because of including all patients in a specific long-term period without any inclusion or exclusion criteria, thus, real-life data might be considered more important and beneficial for assessment of a treatment modality. In the current literature, the number of studies investigating the durability and safety of ustekinumab over 5 years is quite limited [ 1 , 6 , 9 ]. In the PHOENIX 1 phase III clinical trial study, PASI 75 response rate on the 12th week was 67.1% and 66.4% in patients receiving 45 and 90 mg ustekinumab respectively, and PASI 75 response on the 28th week was 72.5% and 78.6%, respectively [ 17 ]. In the PHOENIX 2 phase III clinical trial study, PASI75 response rates on the 12th week were 66.7% and 75.7% in patients receiving 45 and 90 mg ustekinumab, respectively [ 24 ]. Elberdin et al. reported PASI75 response rates of psoriasis patients receiving ustekinumab treatment as 77.1% on the 12th week and 82.2% on the 24th week [ 6 ]. In addition, Galuzzo et al reported these rates as 70.3% on the 12th week and 82.5% on the 28th week [ 9 ]. In our study, 72.5% of the patients reached the PASI75 response on the 16th week, and 82.5% of the patients reached the PASI75 response on the 12th week. Although we reported higher PASI75 response rates compared to the results of PHOENIX 1 AND PHOENIX 2 studies, our results were consistent with the real-life experience studies by Galuzzo and Elberdin et al [ 6 , 9 ]. In our study, the comparison of the PASI75 achievement weeks between males and females revealed no difference. Contrarily, miscellaneous previous publications reported that ustekinumab was more effective and satisfactory in the treatment of psoriasis in male patients. This was attributed to lower treatment compliance and satisfaction in female patients [ 11 , 27 ]. However, there also exist studies reporting similar effectiveness in both genders, in consistent with our results [ 5 ]. Thus, we can hypothesize that gender did not affect the response to treatment in patients with treatment compliance. In our study all patients received at least one conventional systemic treatment before ustekinumab and 67.5% (54 patient) of patients were biologically naive. Various results were reported in different studies regarding the difference in the effectiveness of ustekinumab in biologically naive and non-naive patients. The therapeutic response of ustekinumab in biological naive patients was reported higher in many publications compared to non-naive patients [ 22 , 23 , 25 ]. On the other hand, there exists various studies reported no difference of treatment response rates between biologically naive and non-naive patients [ 4 , 11 , 15 ]. In our study, the rate of PASI75 achievement did not significantly differ between naive and non-naive patients, thus ustekinumab was effective in both groups. The difference of effectivity of the treatment between biologically naive and non-naive patients reported in the prior literature might be associated with the difference of disease severity between the groups [ 22 , 23 , 25 ]. According to our results, we can state that previous use of biologics did not affect response to ustekinumab, and ustekinumab might be considered as a good treatment option in non-naive patients. Ustekinumab was found to be effective in psoriatic arthritis [ 13 , 26 ]. The rate of psoriatic arthritis was 26.3% (21 patient) in our study and during the 6-year follow-up, we found that 4 of 21 patients with psoriatic arthritis discontinued their treatment because of insufficient effectivity on PsA. Our study of long-term use of ustekinumab in a real-life patient group over 6 years revealed that the safety profile of ustekinumab was quite good and no significant adverse effect was experienced, in consistent with the current literature [ 1 , 7 ]. In our study group, 38 (47.5%) patients continued their treatment. Four (5%) patients broke the treatment up because of primary non-responsivity and 10 (12.5%) patients broke the treatment up because of secondary non-responsivity. Only 2 (2.5%) patients broke the treatment up because of adverse effect (mild increase in liver enzyme levels). Again, only 2 patients experienced adverse effects (mild increase in liver enzyme levels). A study examining the adverse effects of ustekinumab on the liver reported that the liver toxicity of ustekinumab was mild and uncommon [ 18 ]. Although mild increase in liver enzyme levels of 2 patients was not proven to be due to ustekinumab because of simultaneous usage of nonsteroidal anti-inflammatory drugs, the treatment was terminated upon the patients' request. Limitations The limited number of the patients received ustekinumab (80 patients) might be considered as the only limitation of the study. Conclusion Our 6-year real-life clinical experience we show the effectiveness and safety of ustekinumab in plaque psoriasis even biological naive and non -naive patients. Declarations Competing interest statement The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript. Funding None. The authors report no involvement in the research by the sponsor that could have influenced the outcome of this work. Authors’ contributions Author PH and author FAK have given substantial contributions to the conception or the design of the manuscript, author PH and author JAA to acquisition, analysis and interpretation of the data. All authors have participated to drafting the manuscript, author FAK revised it critically. All authors read and approved the final version of the manuscript. All authors contributed equally to the manuscript and read and approved the final version of the manuscript. Data availability The data that support the findings of this study are available from the corresponding author [PH], upon reasonable request. References Babuna Kobaner G, Polat Ekinci A, Kutlay A (2021) Long-term efficacy and safety of ustekinumab for moderate-to-severe psoriasis: A 9-year real-life experience from a tertiary referral center in turkey. Dermatol Ther 34:e15042 https://doi.org/10.1111/dth.15042 Boehncke WH, Schon MP (2015) Psoriasis. Lancet 386:983–994 https://doi.org/10.1016/S0140-6736(14)61909-7 Cingoz O (2009) Ustekinumab. MAbs 1:216–221 https://doi.org/10.4161/mabs.1.3.8593 Clemmensen A, Spon M, Skov L, Zachariae C, Gniadecki R (2011) Responses to ustekinumab in the anti-tnf agent-naive vs. Anti-tnf agent-exposed patients with psoriasis vulgaris. J Eur Acad Dermatol Venereol 25:1037–1040 https://doi.org/10.1111/j.1468-3083.2010.03914.x Edson-Heredia E, Sterling KL, Alatorre CI, Cuyun Carter G, Paczkowski R, Zarotsky V, Maeda-Chubachi T (2014) Heterogeneity of response to biologic treatment: Perspective for psoriasis. J Invest Dermatol 134:18–23 https://doi.org/10.1038/jid.2013.326 Elberdin L, Fernandez-Torres R, Paradela S, Blanco E, Outeda M, Martin I, Fonseca E (2020) Ustekinumab treatment for moderate to severe psoriasis. Eight-year real-world follow-up of 61 cases in a tertiary level hospital. J Dermatolog Treat 31:698–701 https://doi.org/10.1080/09546634.2019.1605140 Elberdin L, Fernandez-Torres RM, Mateos M, Outeda M, Blanco E, Gomez-Besteiro MI, Martin-Herranz I, Fonseca E (2022) Real-world use of ustekinumab therapeutic drug monitoring in moderate to severe psoriasis. Front Med (Lausanne) 9:1017323 https://doi.org/10.3389/fmed.2022.1017323 Ergun T (2008) Etiopathogenesis of psoriasis. Turk Arch Dermatol Venereol 42:18–22 Galluzzo M, D'Adamio S, Silvaggio D, Lombardo P, Massaro A, Egan CG, Bianchi L, Talamonti M (2020) Ustekinumab treatment for moderate-to-severe plaque psoriasis: Eight-year real-life experience. Expert Opin Biol Ther 20:95–104 10.1080/14712598.2020.1684472 Goldminz AM, Gottlieb AB (2012) Ustekinumab for psoriasis and psoriatic arthritis. J Rheumatol Suppl 89:86–89 https://doi.org/10.3899/jrheum.120253 Gonulal M, Balci DD, Ozturk A, Dogan S (2023) Effectiveness and safety of ustekinumab for the treatment of psoriasis; six years of clinical experience. J Dermatolog Treat 34:2241941 https://doi.org/10.1080/09546634.2023.2241941 Gooderham MJ, Papp KA, Lynde CW (2018) Shifting the focus - the primary role of il-23 in psoriasis and other inflammatory disorders. J Eur Acad Dermatol Venereol 32:1111–1119 https://doi.org/10.1111/jdv.14868 Gottlieb A, Narang K (2013) Ustekinumab in the treatment of psoriatic arthritis: Latest findings and clinical potential. Ther Adv Musculoskelet Dis 5:277–285 https://doi.org/10.1177/1759720X13501021 Hsieh CS, Macatonia SE, Tripp CS, Wolf SF, O'Garra A, Murphy KM (1993) Development of th1 cd4 + t cells through il-12 produced by listeria-induced macrophages. Science 260:547–549 https://doi.org/10.1126/science.8097338 Hwang YJ, Youn SW, Kim BR, Yu DY, Kim Y, Pires A, Cho S, Seo SJ, Lee ES, Roh JY, Choi GS, Lee MG, investigators M (2017) Clinical factors predicting the therapeutic response to ustekinumab in patients with moderate to severe chronic plaque psoriasis. J Dermatol 44:560–566 https://doi.org/10.1111/1346-8138.13681 Kekik Çınar Ç, Karahan GE, Temurhan S, Pirmit S, Onsun N, Savran Oğuz F (2016) Investigation of cytokine gene polymorphisms in patients with psoriasis vulgaris. Turkderm-Turk Arch Dermatol Venereol 50:34–38 https://doi.org/10.4274/turkderm.68926 Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, Li S, Dooley LT, Gordon KB, investigators Ps (2008) Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (phoenix 1). Lancet 371:1665–1674 https://doi.org/10.1016/S0140-6736(08)60725-4 Llamas-Velasco M, Concha-Garzon MJ, Garcia-Diez A, Dauden E (2015) Liver injury in psoriasis patients receiving ustekinumab: A retrospective study of 44 patients treated in the clinical practice setting. Actas Dermosifiliogr 106:470–476 https://doi.org/10.1016/j.ad.2015.02.002 Nickoloff BJ, Stevens SR (2006) What have we learned in dermatology from the biologic therapies? J Am Acad Dermatol 54:S143-151 https://doi.org/10.1016/j.jaad.2005.10.059 Nickoloff BJ, Xin H, Nestle FO, Qin JZ (2007) The cytokine and chemokine network in psoriasis. Clin Dermatol 25:568–573 https://doi.org/10.1016/j.clindermatol.2007.08.011 Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, Guzzo C, Hsu MC, Wang Y, Li S, Dooley LT, Reich K, investigators Ps (2008) Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (phoenix 2). Lancet 371:1675–1684 https://doi.org/10.1016/S0140-6736(08)60726-6 Puig L, Ruiz-Salas V (2015) Long-term efficacy, safety and drug survival of ustekinumab in a spanish cohort of patients with moderate to severe plaque psoriasis. Dermatology (Basel, Switzerland) 230:46–54 https://doi.org/10.1159/000366499 Raposo I, Bettencourt A, Leite L, Selores M, Torres T (2019) Ustekinumab in real-life practice: Experience in 116 patients with moderate-to-severe psoriasis. Acta Med Port 32:214–218 https://doi.org/10.20344/amp.10728 Reich K, Schenkel B, Zhao N, Szapary P, Augustin M, Bourcier M, Guenther L, Langley RG (2011) Ustekinumab decreases work limitations, improves work productivity, and reduces work days missed in patients with moderate-to-severe psoriasis: Results from phoenix 2. J Dermatolog Treat 22:337–347 https://doi.org/10.3109/09546634.2010.499931 Ruiz Salas V, Puig L, Alomar A (2012) Ustekinumab in clinical practice: Response depends on dose and previous treatment. J Eur Acad Dermatol Venereol 26:508–513 https://doi.org/10.1111/j.1468-3083.2011.04325.x Savage LJ, Wittmann M, McGonagle D, Helliwell PS (2015) Ustekinumab in the treatment of psoriasis and psoriatic arthritis. Rheumatol Ther 2:1–16 https://doi.org/10.1007/s40744-015-0010-2 van der Schoot LS, van den Reek J, Groenewoud JMM, Otero ME, Njoo MD, Ossenkoppele PM, Mommers JM, Koetsier MIA, Berends MAM, Arnold WP, Peters B, Andriessen MPM, Den Hengst CW, Kuijpers ALA, de Jong E (2019) Female patients are less satisfied with biological treatment for psoriasis and experience more side-effects than male patients: Results from the prospective biocapture registry. J Eur Acad Dermatol Venereol 33:1913–1920 https://doi.org/10.1111/jdv.15733 Vincken NLA, Welsing PMJ, Silva-Cardoso SC, Bekker CPJ, Lopes AP, Olde Nordkamp M, Leijten EFA, Radstake T, Angiolilli C (2022) Suppression of il-12/il-23 p40 subunit in the skin and blood of psoriasis patients by tofacitinib is dependent on active interferon-gamma signaling in dendritic cells: Implications for the treatment of psoriasis and interferon-driven diseases. Exp Dermatol 31:962–969 https://doi.org/10.1111/exd.14566 Young MS, Horn EJ, Cather JC (2011) The accept study: Ustekinumab versus etanercept in moderate-to-severe psoriasis patients. Expert Rev Clin Immunol 7:9–13 https://doi.org/10.1586/eci.10.92 Tables Table 1. Demographics and clinical characteristics of the patients with psoriasis receiving ustekinumab n (%) 80 (100%) Gender Female 28 (35%) Male 52 (65%) Age (years), mean ±SD (min-max) 50.7 ±14.1 (22-80) Weight, mean ±SD (min-max) 84.9 ±14.9 (56-120) Age of onset, mean ±SD 32.3 ±16.4 Duration of psoriasis (year), mean ±SD 18.4 ±11 Family history of psoriasis, n (%) 17 (21.3%) Smoking patients, n (%) 33 (41.3%) Baseline, PASI mean ±SD (min-max) 11.2 ±5.7 (1.8-30) Psoriatic arthritis, n (%) 21 (26.3%) Nail involvement, n (%) 26 (32.5%) Previous conventional systemic treatment, n (%) Ciclosporin 22 (27.5%) Acitretin 23 (28.8%) Methotrexate 73(91.3%) Phototherapy 30 (37.5%) Previous biologic treatment, n (%) Adalimumab 7 (8.8%) Secukinumab 3 (3.8%) Infliximab 7 (8.8%) Multiple 9 (11.3%) Naive 54 (67.5%) Mean duration of ustekinumab (month), mean ±SD (min-max) 25.2 ±21.2 (1-88) Ustekinumab dose, n (%) 45mg 46 (57.5%) 90mg 29 (36.3%) Initial 45mg increased to 90mg 5 (6.2%) Table 2. Continuation of ustekinumab treatment in patients with psoriasis. n (%) Patients continuing treatment 38 (47.5%) Secondary non-responsive patients 10 (12.5%) Primary non-responsive patients 4 (5%) Patients who terminated the treatment themselves 19 (23.8%) Patients who terminated the treatment because of recovery 3 (3.8%) Patients who discontinued treatment because it had no effect on arthritis 4 (5%) Patients who broke the treatment up because of any adverse effect 2 (2.5%) Total 80 (100%) Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3900794","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":269754516,"identity":"8952e6f2-57af-41a9-aafb-ac9299333150","order_by":0,"name":"Pelin HIZLI","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3klEQVRIiWNgGAWjYFAC5oYDjA0SDHzMzAeAPAkZIrQwQrSwMbMlgLTwEKUFhBjYGHgMQFzCWszZGxsPF+6wsGdj5/n86kaNBQ8D++GjG/Bpsew52HB45hkJZjZm3m3WOceADuNJS7uBT4vBjcSGw7xtEmwgLcY5bEAtEjxm+LXcfwjWwsPGzPPMOOcfMVpuMIK1SAC1MD/ObSNCi2UPxGEGwEA2Y87tA1pHyC/m7IcPf+Ztq7Pn5z/8+HPOtzo5fvbDx/A7DInNJgEm8SlH18L8gZDqUTAKRsEoGJkAAAyGP8JPvLeWAAAAAElFTkSuQmCC","orcid":"","institution":"Balıkesir University","correspondingAuthor":true,"prefix":"","firstName":"Pelin","middleName":"","lastName":"HIZLI","suffix":""},{"id":269754517,"identity":"f973bdc4-de3d-423c-ba32-ba200f006f80","order_by":1,"name":"Fatma Arzu KILIÇ","email":"","orcid":"","institution":"Balıkesir University","correspondingAuthor":false,"prefix":"","firstName":"Fatma","middleName":"Arzu","lastName":"KILIÇ","suffix":""},{"id":269754518,"identity":"9f431249-79ca-4352-86ef-19c05eda9c9e","order_by":2,"name":"Jale Aylin AKDAŞLI","email":"","orcid":"","institution":"Balıkesir University","correspondingAuthor":false,"prefix":"","firstName":"Jale","middleName":"Aylin","lastName":"AKDAŞLI","suffix":""}],"badges":[],"createdAt":"2024-01-26 18:44:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3900794/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3900794/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":50387054,"identity":"a00d5924-de18-4e75-8f00-8d227fc15f97","added_by":"auto","created_at":"2024-01-30 17:54:12","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":141181,"visible":true,"origin":"","legend":"\u003cp\u003eThe PASI75 response rates of biologically naive and non- naive patients\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3900794/v1/bcc5aca5be70f999b01308df.jpg"},{"id":50387053,"identity":"1c401b59-01a8-44b2-b56b-bb552bd096b9","added_by":"auto","created_at":"2024-01-30 17:54:12","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":135270,"visible":true,"origin":"","legend":"\u003cp\u003eThe PASI90 response rates of biologically naive and non- naive patients\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3900794/v1/ef7495daf6c4c69c6a35a82e.jpg"},{"id":54229312,"identity":"bba4dbf3-bf5c-442f-b0b5-61942880bd3c","added_by":"auto","created_at":"2024-04-07 04:52:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":295810,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3900794/v1/e941ab71-134c-481e-b7dc-d2a5e542be16.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Ustekinumab for the treatment of plaque psoriasis: A 6 -year real -life tertiary institution experience","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePsoriasis is an inflammatory skin disease with multifactorial etiology. Various proinflammatory cytokines are overexpressed both cutaneous and systemically in patients with psoriasis. Serum Th1 cytokine levels playing an important role in the pathogenesis of psoriasis were found higher in patients with psoriasis [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In psoriasis lesions, Type 1 cytokines released by activated T lymphocytes including IL-1, 6, 8, 12, TNFα, IF N -γ and IL-23, IL-17, IL-20 and IL-18 were reported as increased [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. IL-12 plays an important role in the differentiation and activity of TH1 cells and natural killer cells and stimulates the release of IFN-γ and TNF-alfa from these cells [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. IL-23 increases the production of IL-17, IL-22 and TNF-α by inducing the differentiation of naive CD4\u0026thinsp;+\u0026thinsp;T cells into Th-17 cells [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The IL-23 cytokine consists of IL23A (IL-23p19) and IL12B (IL-12p40) subunits. The p40 subunit is shared with IL-12 [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The common p40 subunit of the cytokines IL-12 and IL-23 is overexpressed in psoriasis plaques, and this subunit might be a target in the treatment of psoriasis [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSince the causative mechanism of psoriasis has an immunologic basis, various novel therapeutic agents selectively targeting abnormal immune responses were developed previously [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Ustekinumab is a human IgG1κ monoclonal antibody targeting the p40 subunit shared by IL-12 and 23, preventing the interaction of these cytokines with the receptors, and blocking the central signaling and cytokine production in inflammatory diseases [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe aim of this study was to present the 6-year follow- up of results of the patients received ustekinumab therapy for the treatment of plaque psoriasis. The efficacy and side effect profile of ustekinumab and treatment continuation rates of the patients were main foci of this retrospective real life experience study.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSubjects and study design\u003c/h2\u003e \u003cp\u003eIn this retrospective archival real -life investigation, 80 adult patients with psoriasis received ustekinumab treatment in our tertiary institution between January 2016 and June 2023 were included. The study protocol was approved by institutional ethics committee of \u0026hellip;\u0026hellip; university (Approval number: 2023/125)\u003c/p\u003e \u003cp\u003eDemographic features of the patients including age, gender, duration of the disease and family history, previous therapies for psoriasis (systemics and biologics), presence of coexisting psoriatic arthritis (PsA), baseline Psoriasis Area Severity Index (PASI), adverse events due to treatment, duration of treatments received, therapeutic response and the reasons for discontinuation of treatment were compiled from the medical records and noted. Psoriasis Area and Severity Index (PASI) was used to assess treatment effectiveness, PASI score at baseline, 16th, 24th, and 52nd weeks were noted as well. Therapeutic response was assessed using PASI75, and PASI90 response rates. The patients under 100 kg received 45 mg ustekinumab and the patients over 100 kg received 90 mg ustekinumab. The PASI75 and PASI90 response rates of all patients were presented as were the rates of biologically naive and non-naive patients, and as were the rates of males and females separately in 16th, 24th and 52nd weeks. Additionally, the PASI75 and PASI90 achievement weeks were compared between biologically naive and non-naive patients, between males and females and between the patients with and without PsA.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eResults were presented as number (percentage). The distribution pattern of the data of PASI75 and PASI90 achievement week was investigated using Kolmogorov- Smirnov test (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Comparisons of PASI75 and PASI90 achievement weeks were performed using Mann Whitney U test. Categorical variables were compared using Chi- square test. All statistical analysis was performed using SPSS software for Windows (SPSS Inc., Chicago, IL). A P value under 0.05 considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eIn total, 80 patients with psoriasis received ustekinumab [28 (35%) females and 52(65%) males, mean age: 50.7\u0026thinsp;\u0026plusmn;\u0026thinsp;14.1 (22\u0026ndash;80) years] were included in the study. Fourteen out of 80 (17.5%) patients were elderly patients (over 65 years). Demographics and clinical characteristics of the patients were presented in \u003cb\u003eTable II.\u003c/b\u003e The mean weight of the patients was 84.9\u0026thinsp;\u0026plusmn;\u0026thinsp;14.9 (56\u0026ndash;120) kg and the mean age of disease onset was 32.3\u0026thinsp;\u0026plusmn;\u0026thinsp;16.4 years. Nineteen out of 80 patients were over 99kg weight (\u0026ge;\u0026thinsp;100kg). A family history of psoriasis was present in 17 (21.3%) out of 80 patients. The mean baseline PASI was 11.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7. Thirty -one out of 80 (38.75%) patients had a baseline PASI under 10, and 49 out of 80 (61.25%) patients had a baseline PASI over 10. The rate of psoriatic arthritis was 26.3% (21 patients) and nail involvement was 32.5% (26 patients). All patients had previously received at least one conventional systemic treatment and the most commonly received agent was methotrexate (91.3%). The comparison of the PASI75 achievement weeks between males and females reached PASI75 (the patients did not reach PASI75 were not included in this comparison) revealed that the median PASI75 achievement week of males [12 (4\u0026ndash;36) weeks] was not significantly different compared to the week of females [12 (4\u0026ndash;40) weeks] (p\u0026thinsp;=\u0026thinsp;0.32). The comparison of the PASI90 achievement weeks between males and females reached PASI90 (the patients did not reach PASI90 were not included in this comparison) revealed that the median PASI90 achievement week of males [12 (4\u0026ndash;36) weeks] was not significantly different compared to the week of females [15 (5\u0026ndash;28) weeks] (p\u0026thinsp;=\u0026thinsp;0.75). In addition, both PASI75 and PASI90 achievement weeks were not significantly different between patients under and over 100kg (p\u0026thinsp;=\u0026thinsp;0.165 and p\u0026thinsp;=\u0026thinsp;0.795, respectively). Moreover, both PASI75 and PASI90 achievement weeks were not significantly different between the patients with a baseline PASI of under and over 10 (p\u0026thinsp;=\u0026thinsp;0.32 and p\u0026thinsp;=\u0026thinsp;0.799, respectively).\u003c/p\u003e \u003cp\u003eThe overall PASI75 response rate was 72.5% (58 patients) on 16th week, 82.5% (66 patients) on 28th week and 86.25% (69 patients) on 52nd week. The overall PASI90 response rate was 61.25% (49 patients) on 16th week, 73.75% (59 patients) on 28th week and 76.25% (61 patients) on 52nd week.\u003c/p\u003e \u003cp\u003eOut of 80 patients, 54 (67.5%) were biologically naive and 26 (32.5%) were biologically non-naive patients. The PASI75 response rate was 79.6% (43 of 54 patients) in biologic naive patients and 57.7% (15 of 26 patients) in biologic non-naive patients on 16th week. The PASI75 response rate was 88.9% (48 of 54 patients) in biologic naive patients and 69.2% (18 of 26 patients) in biologic non-naive patients on 28th week. The PASI75 response rate was again 88.9% (48 of 54 patients) in biologic naive patients and 80.8% (21 of 26 patients) in biologic non-naive patients on 52nd week. \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e Only 6 (11.1%) patients did not reach PASI75 response in naive group and 5 (19.2%) patients did not reach PASI75 response in non-naive group.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe PASI90 response rate was 70.4% (38 of 54 patients) in biologic naive patients and 42.3% (11 of 26 patients) in biologic non-naive patients on 16th week. The PASI90 response rate was 79.6% (43 of 54 patients) in biologic naive patients and 61.5% (16 of 26 patients) in biologic non-naive patients on 28th week. The PASI90 response rate was 81.5% (44 of 54 patients) in biologic naive patients and 65.4% (17 of 26 patients) in biologic non-naive patients on 52nd week. \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003cb\u003e)\u003c/b\u003e Ten (18.5%) patients did not reach PASI90 response in naive group and 9 (34.6%) patients did not reach PASI90 response in non-naive group.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOf 54 naive patients, 48 (89%) reached PASI75, and of 26 non-naive patients, 21 (80.8%) reached PASI75. The PASI75 response rate did not significantly differ between naive and non-naive patients (89% vs. 80.8%, p\u0026thinsp;=\u0026thinsp;0.32 X\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.976). The comparison of the PASI75 achievement weeks between naive and non-naive patients reached PASI75 (the patients did not reach PASI75 were not included in this comparison) revealed that the median PASI75 achievement week of naive patients [12 (4\u0026ndash;28) weeks] was not significantly different compared to the week of non- naive patients [12 (4\u0026ndash;40) weeks] (p\u0026thinsp;=\u0026thinsp;0.43).\u003c/p\u003e \u003cp\u003eOf 54 naive patients, 44 (81.5%) reached PASI90, and of 26 non-naive patients, 17 (65.4%) reached PASI75. The PASI90 response rate in naive group was not significantly different compared to the non-naive patients (81.5% vs. 65.4%, p\u0026thinsp;=\u0026thinsp;0.16 X\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;2.511). The comparison of the PASI90 achievement weeks between naive and non-naive patients reached PASI90 (the patients did not reach PASI90 were not included in this comparison) revealed that the median PASI90 achievement week of naive patients [12 (4\u0026ndash;36) weeks] was not significantly different compared to the week of non- naive patients [12 (4\u0026ndash;36) weeks] (p\u0026thinsp;=\u0026thinsp;0.62).\u003c/p\u003e \u003cp\u003eThe rate of PASI75 achievement was 80.8% (21 out of 26 patients) in patients with nail involvement, and 88.9% (48 out of 54 patients) in patients without nail involvement. The rate of PASI75 achievement did not significantly differ between the patients with and without nail involvement (p\u0026thinsp;=\u0026thinsp;0.32, X\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.976). The rate of PASI90 achievement was 69.2% (18 out of 26 patients) in patients with nail involvement, and 79.6% (48 out of 54 patients) in patients without nail involvement. The rate of PASI90 achievement was greater in patients without nail involvement compared to the patients with nail involvement, however, the difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.32, X\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.976).\u003c/p\u003e \u003cp\u003eThe rate of PASI75 achievement was 90.5% (19 out of 21 patients) in patients with psoriatic arthritis, and 84.7% (50 out of 59 patients) in patients without psoriatic arthritis. The PASI75 response rate did not significantly differ between the patients with and without psoriatic arthritis (p\u0026thinsp;=\u0026thinsp;0.71, X\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.429). The PASI90 response rate was 66.7% (14 out of 21 patients) in patients with psoriatic arthritis, and 79.7% (47 out of 59 patients) in patients without psoriatic arthritis. The rate of PASI90 achievement was greater in patients without psoriatic arthritis compared to the patients with psoriatic arthritis, however, the difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.245, X\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;1.444).\u003c/p\u003e \u003cp\u003eOut of 80 patients, 38 (47.5%) continued their treatment, 4 (5%) patients broke the treatment up because of primary non-responsivity and 10 (12.5%) patients broke the treatment up because of secondary non-responsivity. Only 2 (2.5%) patients broke the treatment up because of adverse effect (mild increase in liver enzyme levels) \u003cb\u003e(Table II)\u003c/b\u003e. In addition, 78 out of 80 (97.5%) patients experienced no adverse effects.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we retrospectively investigated the disease characteristics of patients receiving ustekinumab treatment for moderate-to‐severe psoriasis and the real ‐life long‐term efficacy and safety profile of the treatment for more than 6 years.\u003c/p\u003e \u003cp\u003eThe effectivity and safety of ustekinumab in patients with psoriasis was examined in many prior studies [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. However, real-life data might be different from clinical investigations because of including all patients in a specific long-term period without any inclusion or exclusion criteria, thus, real-life data might be considered more important and beneficial for assessment of a treatment modality. In the current literature, the number of studies investigating the durability and safety of ustekinumab over 5 years is quite limited [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the PHOENIX 1 phase III clinical trial study, PASI 75 response rate on the 12th week was 67.1% and 66.4% in patients receiving 45 and 90 mg ustekinumab respectively, and PASI 75 response on the 28th week was 72.5% and 78.6%, respectively [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In the PHOENIX 2 phase III clinical trial study, PASI75 response rates on the 12th week were 66.7% and 75.7% in patients receiving 45 and 90 mg ustekinumab, respectively [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eElberdin et al. reported PASI75 response rates of psoriasis patients receiving ustekinumab treatment as 77.1% on the 12th week and 82.2% on the 24th week [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In addition, Galuzzo et al reported these rates as 70.3% on the 12th week and 82.5% on the 28th week [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In our study, 72.5% of the patients reached the PASI75 response on the 16th week, and 82.5% of the patients reached the PASI75 response on the 12th week. Although we reported higher PASI75 response rates compared to the results of PHOENIX 1 AND PHOENIX 2 studies, our results were consistent with the real-life experience studies by Galuzzo and Elberdin et al [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, the comparison of the PASI75 achievement weeks between males and females revealed no difference. Contrarily, miscellaneous previous publications reported that ustekinumab was more effective and satisfactory in the treatment of psoriasis in male patients. This was attributed to lower treatment compliance and satisfaction in female patients [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. However, there also exist studies reporting similar effectiveness in both genders, in consistent with our results [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Thus, we can hypothesize that gender did not affect the response to treatment in patients with treatment compliance.\u003c/p\u003e \u003cp\u003eIn our study all patients received at least one conventional systemic treatment before ustekinumab and 67.5% (54 patient) of patients were biologically naive. Various results were reported in different studies regarding the difference in the effectiveness of ustekinumab in biologically naive and non-naive patients.\u003c/p\u003e \u003cp\u003eThe therapeutic response of ustekinumab in biological naive patients was reported higher in many publications compared to non-naive patients [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. On the other hand, there exists various studies reported no difference of treatment response rates between biologically naive and non-naive patients [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, the rate of PASI75 achievement did not significantly differ between naive and non-naive patients, thus ustekinumab was effective in both groups. The difference of effectivity of the treatment between biologically naive and non-naive patients reported in the prior literature might be associated with the difference of disease severity between the groups [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. According to our results, we can state that previous use of biologics did not affect response to ustekinumab, and ustekinumab might be considered as a good treatment option in non-naive patients.\u003c/p\u003e \u003cp\u003eUstekinumab was found to be effective in psoriatic arthritis [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The rate of psoriatic arthritis was 26.3% (21 patient) in our study and during the 6-year follow-up, we found that 4 of 21 patients with psoriatic arthritis discontinued their treatment because of insufficient effectivity on PsA.\u003c/p\u003e \u003cp\u003eOur study of long-term use of ustekinumab in a real-life patient group over 6 years revealed that the safety profile of ustekinumab was quite good and no significant adverse effect was experienced, in consistent with the current literature [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study group, 38 (47.5%) patients continued their treatment. Four (5%) patients broke the treatment up because of primary non-responsivity and 10 (12.5%) patients broke the treatment up because of secondary non-responsivity. Only 2 (2.5%) patients broke the treatment up because of adverse effect (mild increase in liver enzyme levels). Again, only 2 patients experienced adverse effects (mild increase in liver enzyme levels). A study examining the adverse effects of ustekinumab on the liver reported that the liver toxicity of ustekinumab was mild and uncommon [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Although mild increase in liver enzyme levels of 2 patients was not proven to be due to ustekinumab because of simultaneous usage of nonsteroidal anti-inflammatory drugs, the treatment was terminated upon the patients' request.\u003c/p\u003e\n\u003ch3\u003eLimitations\u003c/h3\u003e\n\u003cp\u003eThe limited number of the patients received ustekinumab (80 patients) might be considered as the only limitation of the study.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur 6-year real-life clinical experience we show the effectiveness and safety of ustekinumab in plaque psoriasis even biological naive and non -naive patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting interest statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone. The authors report no involvement in the research by the sponsor that could have influenced the outcome of this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthor PH and author FAK have given substantial contributions to the conception or the design of the manuscript, author PH and author JAA to acquisition, analysis and interpretation of the data. All authors have participated to drafting the manuscript, author FAK revised it critically. All authors read and approved the final version of the manuscript. All authors contributed equally to the manuscript and read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author [PH], upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBabuna Kobaner G, Polat Ekinci A, Kutlay A (2021) Long-term efficacy and safety of ustekinumab for moderate-to-severe psoriasis: A 9-year real-life experience from a tertiary referral center in turkey. Dermatol Ther 34:e15042 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/dth.15042\u003c/span\u003e\u003cspan address=\"10.1111/dth.15042\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoehncke WH, Schon MP (2015) Psoriasis. Lancet 386:983\u0026ndash;994 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S0140-6736(14)61909-7\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(14)61909-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCingoz O (2009) Ustekinumab. MAbs 1:216\u0026ndash;221 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.4161/mabs.1.3.8593\u003c/span\u003e\u003cspan address=\"10.4161/mabs.1.3.8593\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClemmensen A, Spon M, Skov L, Zachariae C, Gniadecki R (2011) Responses to ustekinumab in the anti-tnf agent-naive vs. Anti-tnf agent-exposed patients with psoriasis vulgaris. J Eur Acad Dermatol Venereol 25:1037\u0026ndash;1040 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1468-3083.2010.03914.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1468-3083.2010.03914.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEdson-Heredia E, Sterling KL, Alatorre CI, Cuyun Carter G, Paczkowski R, Zarotsky V, Maeda-Chubachi T (2014) Heterogeneity of response to biologic treatment: Perspective for psoriasis. J Invest Dermatol 134:18\u0026ndash;23 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/jid.2013.326\u003c/span\u003e\u003cspan address=\"10.1038/jid.2013.326\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eElberdin L, Fernandez-Torres R, Paradela S, Blanco E, Outeda M, Martin I, Fonseca E (2020) Ustekinumab treatment for moderate to severe psoriasis. Eight-year real-world follow-up of 61 cases in a tertiary level hospital. J Dermatolog Treat 31:698\u0026ndash;701 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1080/09546634.2019.1605140\u003c/span\u003e\u003cspan address=\"10.1080/09546634.2019.1605140\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eElberdin L, Fernandez-Torres RM, Mateos M, Outeda M, Blanco E, Gomez-Besteiro MI, Martin-Herranz I, Fonseca E (2022) Real-world use of ustekinumab therapeutic drug monitoring in moderate to severe psoriasis. Front Med (Lausanne) 9:1017323 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fmed.2022.1017323\u003c/span\u003e\u003cspan address=\"10.3389/fmed.2022.1017323\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eErgun T (2008) Etiopathogenesis of psoriasis. Turk Arch Dermatol Venereol 42:18\u0026ndash;22\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGalluzzo M, D'Adamio S, Silvaggio D, Lombardo P, Massaro A, Egan CG, Bianchi L, Talamonti M (2020) Ustekinumab treatment for moderate-to-severe plaque psoriasis: Eight-year real-life experience. Expert Opin Biol Ther 20:95\u0026ndash;104 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/14712598.2020.1684472\u003c/span\u003e\u003cspan address=\"10.1080/14712598.2020.1684472\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoldminz AM, Gottlieb AB (2012) Ustekinumab for psoriasis and psoriatic arthritis. J Rheumatol Suppl 89:86\u0026ndash;89 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3899/jrheum.120253\u003c/span\u003e\u003cspan address=\"10.3899/jrheum.120253\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGonulal M, Balci DD, Ozturk A, Dogan S (2023) Effectiveness and safety of ustekinumab for the treatment of psoriasis; six years of clinical experience. J Dermatolog Treat 34:2241941 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1080/09546634.2023.2241941\u003c/span\u003e\u003cspan address=\"10.1080/09546634.2023.2241941\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGooderham MJ, Papp KA, Lynde CW (2018) Shifting the focus - the primary role of il-23 in psoriasis and other inflammatory disorders. J Eur Acad Dermatol Venereol 32:1111\u0026ndash;1119 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/jdv.14868\u003c/span\u003e\u003cspan address=\"10.1111/jdv.14868\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGottlieb A, Narang K (2013) Ustekinumab in the treatment of psoriatic arthritis: Latest findings and clinical potential. Ther Adv Musculoskelet Dis 5:277\u0026ndash;285 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1177/1759720X13501021\u003c/span\u003e\u003cspan address=\"10.1177/1759720X13501021\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHsieh CS, Macatonia SE, Tripp CS, Wolf SF, O'Garra A, Murphy KM (1993) Development of th1 cd4\u0026thinsp;+\u0026thinsp;t cells through il-12 produced by listeria-induced macrophages. Science 260:547\u0026ndash;549 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1126/science.8097338\u003c/span\u003e\u003cspan address=\"10.1126/science.8097338\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHwang YJ, Youn SW, Kim BR, Yu DY, Kim Y, Pires A, Cho S, Seo SJ, Lee ES, Roh JY, Choi GS, Lee MG, investigators M (2017) Clinical factors predicting the therapeutic response to ustekinumab in patients with moderate to severe chronic plaque psoriasis. J Dermatol 44:560\u0026ndash;566 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/1346-8138.13681\u003c/span\u003e\u003cspan address=\"10.1111/1346-8138.13681\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKekik \u0026Ccedil;ınar \u0026Ccedil;, Karahan GE, Temurhan S, Pirmit S, Onsun N, Savran Oğuz F (2016) Investigation of cytokine gene polymorphisms in patients with psoriasis vulgaris. Turkderm-Turk Arch Dermatol Venereol 50:34\u0026ndash;38 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.4274/turkderm.68926\u003c/span\u003e\u003cspan address=\"10.4274/turkderm.68926\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, Li S, Dooley LT, Gordon KB, investigators Ps (2008) Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (phoenix 1). Lancet 371:1665\u0026ndash;1674 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S0140-6736(08)60725-4\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(08)60725-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLlamas-Velasco M, Concha-Garzon MJ, Garcia-Diez A, Dauden E (2015) Liver injury in psoriasis patients receiving ustekinumab: A retrospective study of 44 patients treated in the clinical practice setting. Actas Dermosifiliogr 106:470\u0026ndash;476 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ad.2015.02.002\u003c/span\u003e\u003cspan address=\"10.1016/j.ad.2015.02.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNickoloff BJ, Stevens SR (2006) What have we learned in dermatology from the biologic therapies? J Am Acad Dermatol 54:S143-151 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jaad.2005.10.059\u003c/span\u003e\u003cspan address=\"10.1016/j.jaad.2005.10.059\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNickoloff BJ, Xin H, Nestle FO, Qin JZ (2007) The cytokine and chemokine network in psoriasis. Clin Dermatol 25:568\u0026ndash;573 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.clindermatol.2007.08.011\u003c/span\u003e\u003cspan address=\"10.1016/j.clindermatol.2007.08.011\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePapp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, Guzzo C, Hsu MC, Wang Y, Li S, Dooley LT, Reich K, investigators Ps (2008) Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (phoenix 2). Lancet 371:1675\u0026ndash;1684 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S0140-6736(08)60726-6\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(08)60726-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePuig L, Ruiz-Salas V (2015) Long-term efficacy, safety and drug survival of ustekinumab in a spanish cohort of patients with moderate to severe plaque psoriasis. Dermatology (Basel, Switzerland) 230:46\u0026ndash;54 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1159/000366499\u003c/span\u003e\u003cspan address=\"10.1159/000366499\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRaposo I, Bettencourt A, Leite L, Selores M, Torres T (2019) Ustekinumab in real-life practice: Experience in 116 patients with moderate-to-severe psoriasis. Acta Med Port 32:214\u0026ndash;218 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.20344/amp.10728\u003c/span\u003e\u003cspan address=\"10.20344/amp.10728\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReich K, Schenkel B, Zhao N, Szapary P, Augustin M, Bourcier M, Guenther L, Langley RG (2011) Ustekinumab decreases work limitations, improves work productivity, and reduces work days missed in patients with moderate-to-severe psoriasis: Results from phoenix 2. J Dermatolog Treat 22:337\u0026ndash;347 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3109/09546634.2010.499931\u003c/span\u003e\u003cspan address=\"10.3109/09546634.2010.499931\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRuiz Salas V, Puig L, Alomar A (2012) Ustekinumab in clinical practice: Response depends on dose and previous treatment. J Eur Acad Dermatol Venereol 26:508\u0026ndash;513 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1468-3083.2011.04325.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1468-3083.2011.04325.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSavage LJ, Wittmann M, McGonagle D, Helliwell PS (2015) Ustekinumab in the treatment of psoriasis and psoriatic arthritis. Rheumatol Ther 2:1\u0026ndash;16 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s40744-015-0010-2\u003c/span\u003e\u003cspan address=\"10.1007/s40744-015-0010-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan der Schoot LS, van den Reek J, Groenewoud JMM, Otero ME, Njoo MD, Ossenkoppele PM, Mommers JM, Koetsier MIA, Berends MAM, Arnold WP, Peters B, Andriessen MPM, Den Hengst CW, Kuijpers ALA, de Jong E (2019) Female patients are less satisfied with biological treatment for psoriasis and experience more side-effects than male patients: Results from the prospective biocapture registry. J Eur Acad Dermatol Venereol 33:1913\u0026ndash;1920 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/jdv.15733\u003c/span\u003e\u003cspan address=\"10.1111/jdv.15733\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVincken NLA, Welsing PMJ, Silva-Cardoso SC, Bekker CPJ, Lopes AP, Olde Nordkamp M, Leijten EFA, Radstake T, Angiolilli C (2022) Suppression of il-12/il-23 p40 subunit in the skin and blood of psoriasis patients by tofacitinib is dependent on active interferon-gamma signaling in dendritic cells: Implications for the treatment of psoriasis and interferon-driven diseases. Exp Dermatol 31:962\u0026ndash;969 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/exd.14566\u003c/span\u003e\u003cspan address=\"10.1111/exd.14566\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoung MS, Horn EJ, Cather JC (2011) The accept study: Ustekinumab versus etanercept in moderate-to-severe psoriasis patients. Expert Rev Clin Immunol 7:9\u0026ndash;13 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1586/eci.10.92\u003c/span\u003e\u003cspan address=\"10.1586/eci.10.92\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eDemographics and clinical characteristics of the patients with psoriasis receiving ustekinumab\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.23045267489712%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.76954732510288%\" valign=\"top\"\u003e\n \u003cp\u003e80 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.256673511293634%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eGender \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.059548254620125%\" valign=\"top\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.68377823408624%\" valign=\"top\"\u003e\n \u003cp\u003e28 (35%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"55.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e52 (65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.23045267489712%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAge (years), mean \u0026plusmn;SD (min-max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.76954732510288%\" valign=\"top\"\u003e\n \u003cp\u003e50.7 \u0026plusmn;14.1 (22-80)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.23045267489712%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eWeight, mean \u0026plusmn;SD (min-max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.76954732510288%\" valign=\"top\"\u003e\n \u003cp\u003e84.9 \u0026plusmn;14.9 (56-120)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.23045267489712%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAge of onset, mean \u0026plusmn;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.76954732510288%\" valign=\"top\"\u003e\n \u003cp\u003e32.3 \u0026plusmn;16.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.23045267489712%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eDuration of psoriasis (year), mean \u0026plusmn;SD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.76954732510288%\" valign=\"top\"\u003e\n \u003cp\u003e18.4 \u0026plusmn;11\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.23045267489712%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eFamily history of psoriasis, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.76954732510288%\" valign=\"top\"\u003e\n \u003cp\u003e17 (21.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.23045267489712%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eSmoking patients, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.76954732510288%\" valign=\"top\"\u003e\n \u003cp\u003e33 (41.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.23045267489712%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eBaseline, PASI mean \u0026plusmn;SD (min-max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.76954732510288%\" valign=\"top\"\u003e\n \u003cp\u003e11.2 \u0026plusmn;5.7 (1.8-30)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.23045267489712%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ePsoriatic arthritis, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.76954732510288%\" valign=\"top\"\u003e\n \u003cp\u003e21 (26.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.23045267489712%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eNail involvement, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.76954732510288%\" valign=\"top\"\u003e\n \u003cp\u003e26 (32.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.256673511293634%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003ePrevious conventional systemic treatment, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.059548254620125%\" valign=\"top\"\u003e\n \u003cp\u003eCiclosporin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.68377823408624%\" valign=\"top\"\u003e\n \u003cp\u003e22 (27.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003eAcitretin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"55.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e23 (28.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003eMethotrexate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"55.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e73(91.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003ePhototherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"55.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e30 (37.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.256673511293634%\" rowspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003ePrevious biologic treatment, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.059548254620125%\" valign=\"top\"\u003e\n \u003cp\u003eAdalimumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.68377823408624%\" valign=\"top\"\u003e\n \u003cp\u003e7 (8.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003eSecukinumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"55.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e3 (3.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003eInfliximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"55.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e7 (8.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003eMultiple\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"55.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e9 (11.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003eNaive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"55.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e54 (67.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"58.23045267489712%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eMean duration of ustekinumab (month), mean \u0026plusmn;SD (min-max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.76954732510288%\" valign=\"top\"\u003e\n \u003cp\u003e25.2 \u0026plusmn;21.2 (1-88)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.256673511293634%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eUstekinumab dose, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.059548254620125%\" valign=\"top\"\u003e\n \u003cp\u003e45mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.68377823408624%\" valign=\"top\"\u003e\n \u003cp\u003e46 (57.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e90mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"55.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e29 (36.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003eInitial 45mg increased to 90mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"55.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e5 (6.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eContinuation of ustekinumab treatment in patients with psoriasis.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"501\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.86027944111777%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.139720558882235%\" valign=\"bottom\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.86027944111777%\" valign=\"top\"\u003e\n \u003cp\u003ePatients continuing treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.139720558882235%\" valign=\"top\"\u003e\n \u003cp\u003e38 (47.5%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.86027944111777%\" valign=\"top\"\u003e\n \u003cp\u003eSecondary non-responsive patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.139720558882235%\" valign=\"top\"\u003e\n \u003cp\u003e10 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.86027944111777%\" valign=\"top\"\u003e\n \u003cp\u003ePrimary non-responsive patients\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.139720558882235%\" valign=\"top\"\u003e\n \u003cp\u003e4 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.86027944111777%\" valign=\"top\"\u003e\n \u003cp\u003ePatients who terminated the treatment themselves\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.139720558882235%\" valign=\"top\"\u003e\n \u003cp\u003e19 (23.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.86027944111777%\" valign=\"top\"\u003e\n \u003cp\u003ePatients who terminated the treatment because of recovery\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.139720558882235%\" valign=\"top\"\u003e\n \u003cp\u003e3 (3.8%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.86027944111777%\" valign=\"top\"\u003e\n \u003cp\u003ePatients who discontinued treatment because it had no effect on arthritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.139720558882235%\" valign=\"top\"\u003e\n \u003cp\u003e4 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.86027944111777%\" valign=\"top\"\u003e\n \u003cp\u003ePatients who broke the treatment up because of any adverse effect\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.139720558882235%\" valign=\"top\"\u003e\n \u003cp\u003e2 (2.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.86027944111777%\" valign=\"top\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.139720558882235%\" valign=\"top\"\u003e\n \u003cp\u003e80 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"ustekinumab, psoriasis, real -life, naive","lastPublishedDoi":"10.21203/rs.3.rs-3900794/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3900794/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eSince the causative mechanism of psoriasis has an immunologic basis, various novel therapeutic agents selectively targeting abnormal immune responses were developed previously.\u003cstrong\u003e \u003c/strong\u003eThis study aimed to present the 6-year follow-up of results of patients received ustekinumab for plaque psoriasis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA 6-year real -life data of 80 patients with plaque psoriasis receiving ustekinumab were compiled from the medical archive of our tertiary institution retrospectively and presented.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eEighty patients with psoriasis received ustekinumab [28 (35%) females and 52(65%) males, mean age: 50.7 ±14.1 (22-80) years] were included. Overall PASI75 response rate was 72.5% on 16\u003csup\u003eth\u003c/sup\u003e week, 82.5% on 28\u003csup\u003eth\u003c/sup\u003e week and 86.25% on 52\u003csup\u003end\u003c/sup\u003e week. The overall PASI90 response rate was 61.25% on 16\u003csup\u003eth\u003c/sup\u003e week, 73.75% on 28\u003csup\u003eth\u003c/sup\u003e week and 76.25% on 52\u003csup\u003end\u003c/sup\u003e week\u003c/p\u003e\n\u003cp\u003eBoth PASI75 and PASI90 response rates did not significantly differ between naive and non-naive patients. The week of PASI75 and PASI90 achievement did not significantly differ between the patients between naive and non-naive patients, and between males and females. Both PASI75 and PASI90 achievement weeks were not significantly different between the patients with a baseline PASI of under and over 10. No severe side effect was detected.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eOur 6-year real-life clinical experience we show the effectiveness and safety of ustekinumab in plaque psoriasis even biological naive and non -naive patients.\u003c/p\u003e","manuscriptTitle":"Ustekinumab for the treatment of plaque psoriasis: A 6 -year real -life tertiary institution experience","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-30 17:54:07","doi":"10.21203/rs.3.rs-3900794/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"135cd67b-c48b-49a4-8fbc-030e814b08cd","owner":[],"postedDate":"January 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-07T04:44:48+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-30 17:54:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3900794","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3900794","identity":"rs-3900794","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}