Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2024;14(2):e2024119 1 A Real-Life 208 Week Single-Centred, Register- Based Retrospective Study Assessing Secukinumab Survival and Long-Term Efficacy and Safety Among Greek Patients with Moderate to Severe Plaque Psoriasis, Including Difficult-to-Treat Manifestations Such as Genitals and Scalp Eirini Kyrmanidou1, Christina Kemanetzi1, Chatzopoulos Stavros2, Myrto-Georgia Trakatelli1, Aikaterini Patsatsi1, Xenia Madia3, Dimitra Ignatiadi3, Evangelia Kalloniati1, Zoe Apalla1, Elizabeth Lazaridou1 1 Second Department of Dermatology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece 2 School of Statistics and Insurance Science, University of Western Macedonia, Kozani, Greece 3 Novartis, Athens, Greece Key words: psoriasis, genital psoriasis, scalp psoriasis, secukinumab, Greece Citation: Kyrmanidou E, Kemanetzi C, Stavros C, et al. A Real-Life 208 Week Single-Centred, Register-Based Retrospective Study Assessing Secukinumab Survival and Long-Term Efficacy and Safety Among Greek Patients With Moderate to Severe Plaque Psoriasis, Including Difficult-to-Treat Manifestations Such as Genitals and Scalp. Dermatol Pract Concept. 2024;14(2):e2024119. DOI: https:// doi.org/10.5826/dpc.1402a119 Accepted: December 14, 2023; Published: April 2024 Copyright: ©2024 Kyrmanidou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: Received a research fund from Novartis, Greece. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Kyrmanidou Eirini, I.Passalidi 77, 55132 Thessaloniki. Email: ekyrmanidou@gmail.com Introduction: Psoriasis is a chronic inflammatory disease with multiple skin manifestations, and in case of lesions affecting the genital area, sexual health impairment and psychological distress can fur- thermore impair the patients quality of life. Secukinumab is a fully humanized immunoglobulin G1 kappa antagonist of IL-17A and is indicated for the treatment of moderate-to-severe psoriasis, since it shows a significant efficacy in clinical outcomes, with rapid onset of remission, prolonged treatment response rate, advantageous safety profile and a valuable improvement of the patients quality of life. Objectives: This study was conducted in order to gather retrospective real-world data regarding the efficacy of secukinumab in treating patients with moderate-to-severe plaque psoriasis in Greece. To ABSTRACT 2 Original Article | Dermatol Pract Concept. 2024;14(2):e2024119 Introduction Psoriasis is a chronic inflammatory disease with multiple skin manifestations and from epidemiological studies in the United States it is estimated that 3% of adult population shows signs of psoriatic disease [1]. 90% of patients with psoriasis have chronic plaque psoriasis, whereas less common psoriasis can affect the nails (23%-27%), face (49%) palms and soles (12%-16%), or intertriginous folds (21%-30%). Quality of life is impaired in patients with psoriasis, espe- cially when sites of aesthetic significance are affected like the scalp and palms [2]. Moreover psoriasis affecting the genital area can be the cause of sexual health impairment and psy- chological distress, despite the fact that it only affects ≤ 1% of the body surface area (BSA) [3]. Although the exact pathogenetic mechanism of psori- asis has been under investigation until now, it seems that both genetic and environmental factors lead to an immune mediated hyperproliferation of the epidermal keratinocytes, an aberrant inflammatory infiltration of the dermis and an increased angiogenesis in the psoriatic lesions. Recently, the interleukin-23/T helper 17 (IL-23/Th17) pathway has been recognized as a key axis in the pathogenesis of psoriasis, which leads to the overexpression of the proinflammatory cytokine interleukin 17A (IL-17A). Secukinumab is a fully humanized immunoglobulin G1 kappa antagonist of IL-17A and is indicated for the treatment of moderate- to- severe psoriasis, moderate-to-severe paediatric plaque psoriasis, psoriatic arthritis (PsA), axial spondyloarthri- tis, juvevile idiopathic arthritis (enthesitis-related arthritis and juvenile psoriatic arthritis) and hidradenitis suppura- tiva [1-9]. Namely for the treatment of moderate-to-severe plaque psoriasis in adults, secukinumab is indicated as first line treatment. Secukinumab shows a significant efficacy in clinical outcomes, with rapid onset of remission, pro- longed treatment response rate, advantageous safety profile and a valuable improvement of patients quality of life, not only from phase-III clinical trials but from real-life data as well [4,5]. Objectives This study was conducted in order to gather retrospective real-world data regarding the efficacy of secukinumab in treating patients with moderate-to-severe plaque psoriasis at the psoriasis clinic of the Second Dermatology Department of the Aristotle University of Thessaloniki, “Papageorgiou” General Hospital. fill the relevant literature gap, we included difficult-to-treat manifestations in our analysis, specifically regarding the efficacy in the genital area and on the skin folds where relevant data are missing both from the drug clinical program as well as from the real-world setting. Methods: All adult patients receiving 300 mg secukinumab and attending follow-up visits on a reg- ular basis, according to routine medical practice were included. The timeline of the study was from 2015 to 2020. Primary endpoint of the study was the percentage of patients who achieved a psoriasis area and severity index (PASI) 75 response rate at week 16 and week 52 post baseline. Secondary endpoints were the evaluation at baseline (week 0), week 4 (±1), week 16 (±1), week52 (±1), and week 104 (±1), week 156 (±1), week 208 (±1) of clinical outcomes, incidence of adverse events and potential predictive variables influencing response rate. Results: Ninety-nine patients were included in the study population, from whom sixty six patients (66.67%) were bio-naive, whereas 33 patients had never received systemic treatment. Regarding difficult-to-treat manifestations, we recorded scalp involvement in 74.74% (74/99) of our patients, genital psoriasis in 27.27% (27/99) and skin folds involvement (psoriasis inversa) in 17% (17/99). At week 16, PASI75/PASI90/PASI100 were observed in 87.5%/69.8%/49%, respectively. At week 4 lesions affecting the genital area and patients with skin fold involvement experienced a rapid re- gression and 84.1% of patients achieved sPGA 0/1 (Physician Global Assessment). Treatment with secukinumab during the 208 weeks of observation did not reveal any major adverse event or systemic infection and generally it was well tolerated. Conclusions: According to our outcomes secukinumab is an effective treatment choice for treating chronic plaque psoriasis, but, additionally, it can be efficacious in the subgroups of patients with difficult-to-treat manifestations, as our patients experienced great improvement starting even 5 weeks after treatment initiation. This real-life study offers information about clinical efficacy, retention and safety profile of secukinumab in patients from everyday clinical practice over a long-term, 4-year, follow-up period in Greece. Original Article | Dermatol Pract Concept. 2024;14(2):e2024119 3 Methods In order to fill the relevant literature gap, we included difficult-to-treat manifestations in our analysis, specifically regarding the efficacy in the genital area and on the skin folds where relevant data are missing both from the drugclinical program as well as from the real-world setting. Frequency of follow-up visits was determined by attending physicians ac- cording to routine medical practice, however data were col- lected at 4, 16, 52, 104 and 208 weeks with a time window (± 1 week) after secukinumab treatment initiation. Study Design The Psoriasis Outpatient Clinic Registry of our clinic was re- viewed and all adult patients receiving 300 mg secukinumab and attending follow-up visits on a regular basis, according to routine medical practice, were included. The timeline of the study was from 2015 to 2020. Written informed consent was obtained from each patient. Patients, aged ≥18 years, with a clinical diagnosis of chronic (≥6 months) moderate-to-severe plaque psoriasis, and candidates for systemic therapy who were receiving secukinumab (as per local label indication and according to routine medical practice) for at least for 16 weeks were included. Patients with a baseline Psoriasis Area and Severity Index (PASI) <10 were also included if the baseline Dermatology Life Quality Index (DLQI) was ≥10 or if there were symptoms in the scalp, genitals, palms, and feet or if onycholysis of at least 3 fingernails was characterized as persistent manifestation according to local and global guide- lines. Use of concomitant anti-psoriatic agents (systemic or topical) was permitted as per everyday clinical practice. Patients were excluded if the medical file data of interest was incomplete for eligibility evaluation and if there were any contradictions to IL-17/secukinumab intake as per label. Primary endpoint of the study was the percentage of pa- tients who achieved a PASI75 response rate at week 16 and week 52 post baseline. Secondary endpoints were the evalua- tion at baseline (week 0), week 4 (±1), week 16 (±1), week52 (±1), and week 104 (±1), week 156(±1), week 208 (±1) of: a. absolute PASI; percentage of patients who achieved PASI75, PASI90, PASI100 response rates, b. percentage of patients achieving scalp PGA 0/1 (sPGA) c. percentage of patients achieving full/almost full genitals clearing; d. percentage of patients achieving full/almost full folds clearing; e. incidence of adverse events (AE) and serious adverse events (SAEs) and identification of AE leading to drug discontinuation; f. potential predictive clinical variables influencing re- sponse at week 52, and 104. Assessments were collected only when available in rou- tine clinical practice, and they were not prerequisites for study participation. Statistical Analysis Frequencies and percentages are given for qualitative vari- ables, while means and standard deviations, as well as me- dians and interquartile ranges, are given for quantitative variables. Since there were limited cases of loss to follow-up (<5% of the study sample), effectiveness data were analyzed using an ‘as observed analysis’. Descriptive statistics were performed using relevant Descriptive statistics tests (for ex- ample Shapiro–Wilk/Shapiro–Francia test). For the compar- ison of categorical variables, Chi-Squared and Fisher Exact tests were used, while, depending on the distribution of con- tinuous variables, unpaired t-test and Mann–Whitney U-test were applied. The Chi-Square test was applied to analyze differences in PASI Scores between subgroups of patients, such as PsA and bio-naïve patients. Univariable logistic re- gression analysis considering all variables collected was also performed in order to identify potential links and clinical factors of interest associated with the efficacy as per other similar RWE studies. Multivariable analysis could not be performed due to the high number of independent variables, along with the sample size of present study. All statistical analyses were done with IBM SPSS 27.0 (IBM).  Alpha level of significance was set at 0.05. Results Ninety-nine patients were included in the study population and their demographic and baseline characteristics are sum- marized in Table 1. More precisely, 74 (74.75%) patients had scalp involvement, genitals and skin folds were affected in 27 (27.27%) and 17 (17.17%) respectively, and 32 (32.32%) of the studied population had psoriatic arthritis. Sixty-six patients (66.67%) were bio-naive, whereas 33 patients had never received systemic treatment. In the bio-experienced group, 12 patients had received one biologic agent, 12 pa- tients had received two biologic agents and 5 patients had experienced treatment failure of any reason in 3 or more biologic agents. Moreover out of all the studied popula- tion 17.17% (17/99), 11.11% (11/99), 12 (12/99), 10.10% (10/99), 2.02% (2/99) had received adalimumab, etanercept, infliximab, ustekinumab and golimumab respectively. PDE4 inhibitors had been prescribed in 14.14% (14/99) of them. Mean BMI index in our study population was 29.3. Regarding comorbidities 15 patients (15.15%) were obese (BMI>30), 42 patients (42.42%) had Hashimoto dis- ease, 19 patients (19.19%) were diagnosed with depression or anxiety disorder and 8 patients (8.08%) had diabetes mel- litus. Overall 53 patients (53.54%) had no comorbidities, 4 Original Article | Dermatol Pract Concept. 2024;14(2):e2024119 efficacy of secukinumab at week 16, PASI75 was achieved by 84/96 (87.5%) patients, PASI90 by 67/96 (69.8%) and PASI100 by 47/96 (49%) (Table2). By week 52 PASI75/ PASI90/PASI100 was achieved by 86.4%/77.8%/43.2%, by week 104 PASI75/PASI90/PASI100 was achieved by 94.5%/78.2%/47.3% and in 9 patients having completed 208 weeks of therapy PASI100/PASI90 was achieved in a percentage of 88.9%/100% respectively (Table 2). Aiming to identify potential predictive factors influenc- ing response, univariable analyses were performed at weeks 52 and 104 taking into consideration various parameters, namely age, height, weight, BMI, BSA, disease/therapy du- ration, previous treatments (conventional/ biologic), special manifestations of psoriasis (scalp, nails, genitals, folds) and comorbidities (PsA, obesity, coronary disease, depression, 5 patients (5.05%) had one comorbidity, 30 patients (30.30%) had two comorbidities and 11 (11.11%) patients had 3 or more comorbidities. 17.17% of the patients were active smokers (> 10 cigarettes/day). All patients started receiving secukinumab as monother- apy together with topical steroids and vitamin D analogues. Topical treatment was discontinued by almost all patients (92/99, 93%) by the first follow up visit at week 4. Cyclo- sporine was added as additional therapy for two patients, for 12 weeks (week 4-week 16) and for 24 weeks (week 60-week 84) respectively. Four patients received methotrexate addi- tionally, two at week 8, one at week 84 and one at week 116 respectively. Baseline mean PASI, BSA, sPGA and DLQI scores are 12.7, 27.14, 2.2 and 11.68 respectively. Addressing the Table 1. Epidemiological and clinical characteristics at baseline (N = 99). Characteristics N N % Age (yr, median, range) 99 50 (23-76) Sex male 99 53 53.5 Weight (kg, mean [SD]) 99 87.78 [17.98] BMI (mean, [SD]) 99 29.3 [4.88] BSA (mean [SD]) 99 27.14 [12.01] PASI baseline (mean [SD]) 99 12.7 [3.94] DLQI baseline (mean [SD]) 99 11.68 [2.95] Psoriatic arthritis (N, %) 99 32 32.32 Previous systemic treatment 99 66 66.67 Conventional treatment 61/99 61 61.61 Previous Biological therapy 33 Biologic naive 99 66 66.67 Psoriasis genital involvement 99 27 27.27 Psoriasis scalp 99 74 74.74 Psoriasis involving folds 99 17 17.17 Psoriasis nails 99 49 49.49 Comorbidity N n % Hashimoto disease 99 42 42.42 Obesity (BMI>30) 99 15 15.15 Depression 99 12 12.12 Diabetes mellitus 99 8 8.08 Anxiety disorder 99 7 7.07 Hypertension 99 6 6.06 Coronary disease 99 3 3.03 Dyslipidemia 99 3 3.03 Smoking 99 17 17.17 Patients comorbidities None 99 53 53.53 1-2 99 35 35.05 >3 99 11 11.11 BMI = Body Mass Index; BSA = Body Surface Area; DLQI = Dermatology Quality of Life Index; SD = standard deviation. Original Article | Dermatol Pract Concept. 2024;14(2):e2024119 5 16 due to lack of efficacy. Lastly, one patient was diagnosed with ulcerative colitis at week 108 and the treatment was discontinued. Up until the 208 weeks of the observation pe- riod no major adverse events were recorded. During the observation period after week 16 and up until week 208, 11 patients discontinued the treatment due to lack of efficacy and this was observed mainly after 104 weeks of therapy, in bio-experienced patients and patients with multi- ple comorbidities (Table 3). In three patients a quantiferon tuberculosis conversion was recorded, but a systematic infection was not confirmed. For safety reasons those patients underwent prophylactic an- tibiotic therapy. Conclusions Our study provides retrospective data of patients with chronic plaque psoriasis and their treatment outcomes after receiving secukinumab in real-life clinical practice in Greece. Additionally, we focused on difficult-to-treat areas, namely psoriasis affecting the skin folds and the genital area, mainly because data of the effect of secukinumab on these manifes- tations are limited. The studied population that was selected were patients with moderate to severe chronic plaque psoria- sis that were treated with secukinumab at the recommended dose. Bio-naïve, as well as bio-experienced patients were included. Increased rates of comorbidities were recorded, with almost half of the patients reporting at least one; a fac- tor that generally levels up the difficulty in managing the disease. Secukinumab accomplished to improve the disease burden in an impressively fast manner, with over half of the patients (55.6%) achieving PASI75 and one out of four pa- tients (25.3%) achieving PASI90 at week 4. This improve- ment continued to increase to reach at week 16 PASI75/ PASI90/PASI100 in 87.5%/69.8%/49% respectively. In accordance with the treatment outcomes of this study, secukinumab has shown high efficacy in managing psoriasis quickly. In fact in ERASURE, FEATURE and JUNCTURE clinical trials there was a PASI75/PASI90/PASI100 reduc- tion rate at week 16 in 86.1%/69.8%/41.6% [5]. Simi- lar were the results from Rompoti et al in Greece where, at week 16, a PASI75/PASI90/PASI100 reduction rate in 83.3%/70%/46.3% of the patients was recorded [6]. Our study population shares some characteristics with the above- mentioned study in Greece. Namely both include over- weight patients (mean BMI: 29.3; range: 18.4-45.2 versus 29.1; range: 17.3-50.2) and almost half of the studied pop- ulation in both trials have at least one comorbidity (46% versus 49.4%). We report 32.3% patients with PsA whereas Rompoti et al report 43.2% (versus 20% in clinical trials). Bai et al conducted a systematic review with a network meta- analysis (NMA) of all randomized trials in order to deter- mine the differences in efficacy and safety profiles of Il-17, diabetes mellitus, dyslipidemia, hypertension, Hashimoto disease, anxiety disorder, smoking). In a univariate analysis, no medical, sociodemographic and the assessed clinical bio- marker was significantly associated with PASI responses. Regarding difficult-to-treat manifestations, we recorded scalp involvement in 74.74% (74/99) of our patients, geni- tal psoriasis in 27.27% (27/99) and skin folds involvement (psoriasis inversa) in 17% (17/99). After secukinumab initia- tion (week 4) lesions in the genital area and patients with skin fold involvement experienced a rapid regression which was evident in 37/44 (84.1%) of patients. Skin folds and genitals were remarkably cleared at week 5 (mean week of clearing 5.29 [SD 1.49], median week of clearing: 5, [IQR:2]), and sPGA 0/1 at week 4. Regarding drug retention, we report 11 patients that had to discontinue treatment throughout the observation period. 7 patients lost PASI75 within more than 2 years of the treatment and lost its effectiveness. 3 patients had to switch to other therapies because they did not re- spond to the drug by week 16 (Table 3). Safety Most of the adverse events (AE) recorded was characterized as low grade and did not require a treatment discontinua- tion. Actually 3 patients reported AE: two patients reported fatigue grade 1 CTCAE possibly drug-related and one re- ported headache grade 1 CTCAE probably not-drug related. Four patients had to discontinue the treatment up until week Table 2. Clinical efficacy of secukinumab. PASI outcomes AS OBSERVED WEEK N N (%) PASI 75 4 99 55/99 (55.6%) 16 96 84/96 (87.5%) 52 81 70/81 (86.4%) 104 55 52/55 (94.5%) 156 30 29/30 (96.7%) 208 9 9/9 (100%) PASI 90 4 99 25/99 (25.3%) 16 96 67/96 (69.8%) 52 81 70/81 (77.8%) 104 55 43/55 (78.2%) 156 30 24/30 (80.0%) 208 9 9/9 (100%) PASI 100 4 99 14/99 (14.1%) 16 96 47/96 (49.0%) 52 81 35/81 (43.2%) 104 55 26/55 (47.3%) 156 30 15/30 (50.0%) 208 9 8/9 (88.9%) PASI = Psoriasis Area and Severity Index. 6 Original Article | Dermatol Pract Concept. 2024;14(2):e2024119 sustained until the end of the observation period (week 208). These findings are in agreement with clinical trials reporting 5-year data, as well as other long-term real-life studies for Secukinumab [8-10]. Addressing the difficult-to-treat psoriatic manifesta- tions, in particular scalp psoriasis, nail psoriasis and pal- moplantar psoriasis, secukinumab has shown a rapid and sustained response in improving psoriatic lesions and asso- ciated symptoms [11-15]. Likewise treatment response in our studied population showed significant improvement in difficult-to-treat specific locations. We recorded scalp involve- ment in 74,74% (74/99) of our patients, genital psoriasis in 27.27% (27/99) and skin folds involvement (psoriasis in- versa) in 17% (17/99). After secukinumab initiation lesions in the genital area and patients with skin fold involvement experienced a rapid regression which was evident in 37/44 (84.1%) of patients. Skin folds and genitals were remarkably cleared at week 5 (mean 5.29 [SD 1.49], median: 5, [IQR:2]), and sPGA 0/1 at week 4. Data regarding secukinumab effi- cacy on areas with fold involvement as well as genital psori- asis are lacking from the drug clinical program, as well as the real-world setting. To our knowledge this is the first study that included skin fold improvement as a treatment endpoint for investigating the treatment efficacy of secukinumab in this difficult-to-treat area. However, patients of this study who had chronic plaque psoriasis and lesions affecting the skin folds and the genital area could be characterized as IL12/23 and IL23 inhibitors used in treating moderate to severe plaque psoriasis. Regarding the short-term achieve- ments amongst 19840 patients from 28 trials secukinumab ranked first in achieving sPGA 0/1 or IGA 0/1 or PGA 0/1, and second in achieving PASI75 at week 12 or 16 [7]. In agreement with that, and according to the results of our study, secukinumab is highly efficacious in managing the dis- ease burden of chronic plaque psoriasis in a fast manner in real life clinical practice too. In phase II/III, clinical trials pa- tients are selected according to specific inclusion criteria. It is reasonable to hypothesize that in a real-world setting, where patients differ at least in disease severity and comorbidities, treatment efficacy can vary vastly. Augustin et al designed a review of all available published studies of real-world evi- dence using secukinumab in treating plaque psoriasis from 1 January 2015 to 31 May 2019. This meta-analysis included 43 studies and the effectiveness results for PASI75/PASI90/ PASI100 at 12 weeks were 72%/50%/36% respectively. The endpoint of clinical improvement of psoriasis in our real-life population complies with this data, supporting additionally the consistency secukinumab offers in fast treatment efficacy. With regard to the durability of response, secukinumab presented long-lasting and went as far as to improve the ef- ficacy at subsequent timepoints in this study, with almost 100% of patients maintaining PASI 75 response, 78.2% achieving PASI 90 response and 47.3% achieving PASI 100 response at week 104, whilst these efficacy rates were further Table 3. Previous treatment, Adjuvant therapy, reason for discontinuation. Patient (gender, age) Previous treatment Adjuvant therapy Week of treatment Reason for discontinuation Discontinuation time Female, 76y acitretin Week 52 Loss of effectiveness Week 80 Male, 49y Ustekinumab Topical steroids Week 24 Loss of effectiveness Week 52 Male, 55y Infliximab, Ustekinumab Topical steroids Week 48 Loss of effectiveness Week 112 Male, 52y Topical steroids Week 108 Loss of effectiveness Week 160 Male, 31y Cyclosporine Topical steroids Week 52 Loss of effectiveness Week 108 Female, 59y Cyclosporine, Infliximab Methotrexate, Apremilast Loss of effectiveness Week 70 Female, 53y Cyclosporine, Acitretin Topical steroids Week 52 Loss of effectiveness Week 120 Male, 55y No response Week 16 Female, 47 Ustekinumab, Adalimumab No response Week 16 Male, 52y Cyclosporine, Infliximab, Adalimumab, Methotrexate Methotrexate Week 0 No response Week 20 Male, 42y Ulcerative colitis Week 152 Original Article | Dermatol Pract Concept. 2024;14(2):e2024119 7 According to our outcomes, secukinumab is an effective treatment choice for treating chronic plaque psoriasis, but, additionally, it can be efficacious in the subgroups of patients with difficult-to-treat manifestations. Especially, regarding lesions at the genital area, as well as psoriasis inversa, pa- tients in our study experienced a great improvement and this occurred rapidly at a mean time of 5 weeks after therapy ini- tiation. In addition, the already well described advantageous safety profile of secukinumab is confirmed by the results of this study, since we did not report any serious adverse events during the 208 weeks observational period. Consequently, this real-life study offers information about clinical efficacy, retention and safety profile of secukinumab in patients from everyday clinical practice over a long-term, 4-year, follow-up period in Greece. Acknowledgement: This study was conducted in collabora- tion with Novartis, Greece. References 1. Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis preva- lence among adults in the United States. J Am Acad Dermatol. 2014;70(3):512-516. DOI: 10.1016/j.jaad.2013.11.013. PMID: 24388724. 2. Dopytalska K, Sobolewski P, Błaszczak A, Szymańska E, Walecka I. Psoriasis in special localizations. Reumatologia. 2018;56(6):392-398. DOI: 10.5114/reum.2018.80718. PMID: 30647487. PMCID: PMC6330687. 3. Hong JJ, Mosca ML, Hadeler EK, Brownstone ND, Bhutani T, Liao WJ. Genital and Inverse/Intertriginous Psoriasis: An Up- dated Review of Therapies and Recommendations for Practical Management. Dermatol Ther (Heidelb). 2021;11(3):833-844. DOI: 10.1007/s13555-021-00536-6. PMID: 33914293. PMCID: PMC8163914. 4. Blauvelt A, Prinz JC, Gottlieb AB, et al. Secukinumab adminis- tration by pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol. 2015;172(2):484-493. DOI: 10.1111/bjd.13348. PMID: 25132411. 5. Lee JH, Morita A, Tsai TF, et al. Secukinumab efficacy and safety in Asian subjects with moderate to severe plaque psori- asis: Pooled analysis from the FIXTURE and ERASURE phase III clinical studies. Journal of the American Academy of Derma- tology. PSORIASIS AND OTHER PAPULOSQUAMOUS DIS- ORDERS; 2015;72(5): SUPPLEMENT 1, AB249. DOI: 10.1016 /j.jaad.2015.02.994. 6. RRompoti N, Katsimbri P, Kokkalis G, et al. Real world data from the use of secukinumab in the treatment of moderate-to- severe psoriasis, including scalp and palmoplantar psoriasis: A 104-week clinical study. Dermatol Ther. 2019;32(5):e13006. DOI: 10.1111/dth.13006. PMID: 31228319. 7. B Bai F, Li GG, Liu Q, Niu X, Li R, Ma H. Short-Term Effi- cacy and Safety of IL-17, IL-12/23, and IL-23 Inhibitors Broda- lumab, Secukinumab, Ixekizumab, Ustekinumab, Guselkumab, Tildrakizumab, and Risankizumab for the Treatment of Moder- ate to Severe Plaque Psoriasis: A Systematic Review and Network secondary involvement. Burlando et al recently presented the superiority of anti-IL17 antibodies, in comparison to anti-IL12/23 and anti-TNFα drugs, in improving genital pso- riasis in a small group of female patients [16]. With regard to drug retention, we report only 11 pa- tients that had to discontinue the treatment. Seven patients lost PASI75 within more than 2 years of treatment and lost its effectiveness. Three patients had to switch to other ther- apies because they did not respond to the drug by week 16 (Table 3). These results adhere to what has been presented in other real-world studies assessing psoriasis patients treated with Secukinumab [6,10,17].Additionally, it needs to be men- tioned that, in our study, almost half of the patients who dis- continued secukinumab (5/11, 45%) were bio- experienced with at least one biologic drug that failed in the management of the disease. Previous biologic experience has been already identified as a factor influencing drug survival [18]. Another key point to be mentioned is the fact that in January 2022, the local label of Secukinumab was updated to include an intensified dosing scheme (300 mg every 2 weeks, as maintenance dose) for adult patients with moderate to se- vere plaque psoriasis and body weight 90 kg or higher, based on clinical response. Since the observation period of this study started before this update, it is not known, whether the effi- cacy outcomes in patients who belong to this sub- population and show a sub-optimal response could have responded bet- ter, had this option been available at the time [19]. Treatment with secukinumab during the 208 weeks of observation did not reveal any major adverse events or sys- temic infections and it was generally well-tolerated. Only three patients reported AEs of low grade, which at no point was an adequate enough reason to discontinue secukinumab. These were characterized as self-limited without requiring any additional treatment. One 42-year-old male patient was diagnosed with ulcer- ative colitis at week 152 of treatment. Personal and family history were negative of any inflammatory bowel disease, and he was a smoker. This is characterized as a paradoxical gastrointestinal effect of IL-17 inhibitors with a still unclear pathogenetic mechanism. It is believed that type I interferon might be involved and may be the reason for a hyperactive innate inflammatory pathway [20]. Furthermore, three of our patients had a quantiferon tuberculosis conversion and as per the guidelines they underwent prophylactic antibi- otic therapy without clinical or radiographic evidence of TB infection. We acknowledge the fact that this is a retrospective monocentric observational study and the data extracted were obtained from a small number of patients. 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