Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2024;14(2):e2024152 1 Long-Term Effectiveness of Brodalumab for the Treatment of Moderate-To-Severe Psoriasis: A Real-Life Multicenter Study of Up to 3 Years in a Real-Life Italian Cohort Giacomo Caldarola1,2, Marco Galluzzo3,4, Nicoletta Bernardini5, Elisabetta Botti4, Eleonora De Luca1,2, Clara De Simone1,2, Marco Mariani6, Gaia Moretta7, Sabatino Pallotta7, Elena Campione3,4, Ketty Peris1,2 1 UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy 2 Dermatologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy 3 Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy 4 Dermatology Unit, Azienda Ospedaliera Universitaria “Policlinico Tor Vergata”, Rome, Italy 5 Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University Dermatology Unit “Daniele Innocenzi”, ASL Latina, Italy 6 Section of Hygiene, University Department of Health Sciences and Public Health, Università Cattolica del Sacro Cuore, Rome, Italy 7 Dermatology Unit, Istituto Dermopatico dell’Immacolata IDI-IRCCS, Rome, Italy Key words: biologics, brodalumab, drug survival, IL-17 inhibitors, psoriasis, real-life effectiveness Citation: Caldarola G, Galluzzo M, Bernardini N, et al. Long-Term Effectiveness of Brodalumab for the Treatment of Moderate-To-Severe Psoriasis: A Real-Life Multicenter Study of Up to 3 Years in a Real-Life Italian Cohort. Dermatol Pract Concept. 2024;14(2):e2024152. DOI: https://doi.org/10.5826/dpc.1402a152 Accepted: April 15, 2024; Published: April 2024 Copyright: ©2024 Caldarola et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: G Caldarola has received consulting fees, honoraria and support for attending meetings from Abbvie, Lilly, Janssen, UCB, Novartis and Leopharma; C De Simone has received support for consulting fees, honoraria and support for attending meetings from Abbvie, Lilly, Janssen, UCB, Novartis, Leopharma, Sanofi and Almiral; K Peris has received support for consulting fees and honoraria from Abbvie, Almirall, Biogen, Celgene, Janssen Galderma, Novartis, Lilly, Novartis, Pierre Fabre, Sandoz, Sanofi and Sun Pharma. M Galluzzo declare to have acted as speakers and/or consultants for AbbVie, Almirall, Eli-Lilly, Janssen-Cilag, LeoPharma, Novartis and Sanofi, outside the submitted work. E Campione served as a consultant for Almirall, BMS, Amgen, and UCB. G Moretta has received consulting fees, honoraria and support for attending meetings from Abbvie, Leopharma, Sanofi and Lilly. All other authors declare that they have no conflicts of interest relevant to this manuscript. Authorship: G. Caldarola and M. Galluzzo contributed equally to this manuscript. All authors have contributed significantly to this publication. Corresponding Author: Eleonora De Luca, UOC di Dermatologia, Università Cattolica del Sacro Cuore, L.go F. Vito 1 00135 Roma, Italy. Phone: +39 (0)6 3015 4227 E-mail: deluca.eleonora94@gmail.com 2 Original Article | Dermatol Pract Concept. 2024;14(2):e2024152 Introduction The management of psoriasis has improved in recent years due to the expansion of available systemic therapies. Biologic drugs target specific immune system pathways involved in psoriasis, allowing for the optimization of clinical responses and the long-term management of patients. The remarkable pharmaceutical improvement in recent years has led to the development of new biologic therapies that target interleuk- ins (IL) 17 and 23, allowing to achieve higher skin clearance with a good safety profile. Brodalumab is a fully human monoclonal anti- body that specifically targets the interleukin-17 recep- tor A (IL-17RA), inhibiting the signaling pathway of several IL-17 isoforms (instead of (IL-17isoforms) in- volved in psoriasis pathogenesis [1,2]. The rapid action and high efficacy of brodalumab have already been demon- strated in three phase 3 randomized double-blind trials (RCTs): AMAGINE-1, AMAGINE-2, and AMAGINE-3 [3, 4, 5], as well as in real-life settings [6, 7, 8, 9, 10]. For the long-term management of psoriasis, evaluating brodalum- ab’s drug survival might help to assess its real-world success and patient’s adherence to the treatment, but to date data in literature are scanty. Herein we present a retrospective real-life multicenter study conducted in a real life Italian cohort, involving pa- tients with moderate to severe psoriasis who were treated with brodalumab for a period up to 3 years. Method We conducted a multicenter, retrospective, observational study in patients with psoriasis who started brodalumab therapy between May 2019 and January 2021. We included patients of age >18 years from the following dermatology units in Italy: ‘Tor Vergata’ University of Rome, Catholic University of the Sacred Heart in Rome IRCCS, ‘Daniele In- nocenzi’ of University of Rome ‘La Sapienza,’ Polo Pontino and Istituto Dermopatico dell’Immacolata – IRCCS, Rome. Exclusion criteria were generalized, palmoplantar pus- tular psoriasis, use of additional systemic therapies for psoriasis, and participation in clinical trials. Patients were treated with brodalumab at the European Medicines Agency (EMA)-approved dosage. We collected data related to the characteristics of the patients (age, sex, body mass index [BMI], comorbidities, smoking habits) and of the disease (age at onset, previous therapies, and special-site involvement). The severity of pso- riasis was measured with the Psoriasis Area and Severity In- dex (PASI) score at baseline and after 4, 12, 24, 52, 104, and 156 weeks of treatment. Patients obtaining a PASI 90 im- provement at week 4 were defined fast responders. Reasons for withdrawal of brodalumab and any adverse event that occurred during treatment were recorded. Discontinuation of therapy was defined as interruption of brodalumab ad- ministration for more than 90 days. Descriptive statistics for continuous variables were re- ported as medians/means and interquartile ranges (IR)/ standard deviations (SD), dichotomous variables were de- scribed using absolute and relative (%) frequencies. The drug survival analysis was descriptively analyzed using Introduction: Data about the long-term effectiveness of brodalumab could be valuable in assessing patient adherence to treatment and improving psoriasis management. Objective: The aim of our study was to evaluate the drug survival of brodalumab and identify any predictive factors for discontinuation. Methods: A multicenter retrospective study was conducted in patients with moderate-to-severe pso- riasis who were treated for up to 3 years. We extracted data from patient files, related to the char- acteristics of the patients and the disease. Drug survival analysis was descriptively analyzed using Kaplan–Meier survival curves. Univariable and multivariable analyses were performed to assess base- line patient characteristics that predicted clinical response. Results: The study included 90 patients. Among them, 28 (31.1%) suspended brodalumab through the observation period. At weeks 52, 104 and 156 the median PASI score were 0.0 [0.0 – 0.8], 0.0 [0.0 – 1.0] and 0.0 [0.0 – 0.0], respectively. The estimated cumulative survival rates at weeks 52 and 104 were 86.32% and 78.09%, respectively. In the multivariable survival analysis, predictor factors for overall discontinuation included body mass index (BMI) (OR 1.10, 95% CI 1.03 - 1.18), baseline PASI (OR 1.06, 95% CI 1.02 - 1.10), and psoriatic arthritis (OR 5.05, 95% CI 0.89 - 13.50). Conclusions: Brodalumab has shown long-term effectiveness for up to 3 years. Considering baseline dis- ease severity and patient characteristics could aid in optimizing the long-term management of psoriasis. ABSTRACT Original Article | Dermatol Pract Concept. 2024;14(2):e2024152 3 Kaplan–Meier survival curves. Three “events” for drug sur- vival were defined and analyzed separately. (i.e. overall discontinuation; discontinuation because of brodalumab ineffectiveness; adverse events or other type of events other than ineffectiveness). Patients were censored when lost to follow-up, discontinued due to an event other than the events of interest, or when the database was extracted, and patients were actively undergoing their treatment with the drug of interest at that moment. Univariable and multivari- able Cox regression analyses were carried out using variables considered of clinical importance. Statistical significance was set at p-value <0.05. Analyses were performed in May 2023 by using STATA 13.0 Software (StataCorp, Texas). The protocol was reviewed and approved by Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Univer- sità Cattolica del Sacro Cuore, Prot N.: 15188/23. All pa- tients signed a hospital-based informed consent. The study was performed following the principles of the Declaration of Helsinki. Results Ninety patients with moderate- to- severe plaque psoriasis treated with brodalumab were included. Mean age of pa- tients was 52.2 (SD 15.0) years, and the majority (67.8%) were males. Median PASI score at baseline was 15.0 (IR 10.0 - 22.0). Other baseline characteristics of patients are presented in Table 1. Data about the first 52 weeks of treat- ment have been already reported [11]. In particular, 29/90 (32.2%) patients achieved PASI 90 at week 4 and were con- sidered fast responders. Among 90 enrolled patients, 28 (31.1%) suspended brodalumab through the observation period. At weeks 52, 104, and 156 the median PASI score were 0.0 [0.0 – 0.8], 0.0 [0.0 – 1.0] and 0.0 [0.0 – 0.0], respectively. The reasons for discontinuation were adverse events in 8 patients (8.9%), ineffectiveness in 15 patients (16.7%) and loss to follow-up in 5 patient (5.6%). Discontinuation for adverse events were due to eczematous eruptions in 2 patients, and in singular cases to recurrent candidiasis, lower limb myalgia, myocar- dial infarction, cerebral ischemia, concomitant anemia and transaminase increase due to alcohol abuse, and to recurrent upper respiratory tract infection. Median time of observa- tion among those who discontinued brodalumab was 62.5 (IR 32.0 – 111.0) weeks after the start of the drug. The overall drug survival is reported in Figure 1A. Overall, a total of 86.32%, 78.09% of patients was under treatment at weeks 52 and 104 respectively. The drug survival rate for dis- continuation due to adverse events was 93.69% (confidence interval [CI] 85.35-97.35), and 92.04% (CI 82.93-96.39) after 52 and 104 weeks, respectively (Figure 1B). The drug survival rate for discontinuation due to ineffectiveness was Table 1. Clinical and Demographic Characteristics of the Study Population. Demographic or Clinical Characteristic (total n = 90) N (%); Mean (SD), Median [IQR] Sex Males 29 (32.22) Females 61 (67.78) Age 52.22 (15.03) Age of onset 29.45 (15.64) Arthritic Psoriasis Yes 21 (23.33) No 69 (76.67) BMI 26.73 [24.10 – 29.41] Scalp psoriasis Yes 44 (48.89) No 46 (51.11) Nail psoriasis Yes 23 (25.65) No 67 (74.44) Palmoplantar psoriasis Yes 12 (13.33) No 78 (86.67) Genital psoriasis Yes 25 (27.78) No 65 (72.22) Previous Biological Treatments Yes 47 (52.22) No 43 (47.78) Other anti IL17 use Yes 19 (21.11) No 71 (78.89) PASI at baseline 15.0 [10.0 – 22.0] PASI week 12 (n=90) 0.0 [0.0 – 2.0] PASI week 52 (n=85) 0.0 [0.0 – 0.8] PASI week 104 (n=73) 0.0 [0.0 – 1.0] PASI week 156 (n=24) 0.0 [0.0 – 0.0] Fast Responder* No 61 (67.78) Yes 29 (32.22) *Patients achieving PASI 90 at week 4. BMI = body mass index; IQR = interquartile range; PASI = Psoriasis Area and Severity Index; SD = standard deviation. 93.44% (IC 84.81-97.24) and 87.94% (IC 76.95-93.90) after 52 and 104 weeks, respectively (Figure 1C). Data about 156 weeks were not reported because only 24 patients reached this timepoint. 4 Original Article | Dermatol Pract Concept. 2024;14(2):e2024152 Figure 1. Kaplan–Meier curves of (A) overall drug survival; (B) discontinuation because of adverse events or other events; and (C) discontinuation because of a lack or loss of efficacy (confidence interval [CI] in light gray). An univariable logistic regression was performed and re- sults are reported in Table 2. In detail, predictive factors for overall drug discontinuation were psoriatic arthritis OR 2.93 (95% CI, 1.30 – 6.61), BMI with an OR of 1.07 (95% CI, 1.02 – 1.13) and baseline PASI OR 1.05 (95% CI, 1.02 – 1.09). At the multivariable survival analysis (Table 3), positive predictor factors for overall discontinuation resulted BMI OR 1.10 (1.03 – 1.18)), baseline PASI OR 1.06 (95% CI, 1.02 – 1.10) and psoriatic arthritis OR 5.05 (95% CI, .89 – 13.50). Factors associated with suspension for ineffectiveness were BMI OR 1.11 (95% CI, 1.01 – 1.23), baseline PASI OR 1.07 (95%CI, 1.02 – 1.13) and psoriatic arthritis OR 11.65 (95% CI, 2.92 – 46.46). No significant predictive factors emerged for discontinuation for adverse events. Detailed Report of Cases of Special Interest Patient #1: Patient with multi-drug resistance, comorbidities, and BMI ≥40. We present the case of a 56-year-old male, with class III obesity, arterial hypertension, hyperuricemia, type II diabetes, hypercholesterolemia and a history of psori- asis from the age of 32. He was in therapy from 2001 to 2002 with cyclosporine discontinued for inefficacy. Then, for more than 10 years he was treated only with topical treatments. In June 2016, ustekinumab was administered (PASI score=42), and then discontinued after 90 weeks for persistence of pso- riasis (residual PASI=15). In May 2018, therapy with secuk- inumab was started, with a lack of response, and therefore switched to guselkumab after 42 weeks of treatment (March 2019, PASI score=15). Even with this last therapy, no im- provement was observed after 108 weeks (PASI score=15). Finally, in April 2021, brodalumab treatment was started (Figure 2A), with a rapid improvement after 6 weeks (PASI score= 6, Figure 2B) and a complete remission after 12 weeks. Currently, the patient has reached the second year of treatment with brodalumab, maintaining a complete remis- sion of the disease (Figure 2C). Patient #2: A complex oncological history and multiple treatment suspensions without recurrences. A 48-year-old woman was affected by moderate-severe psoriasis for nearly 30 years and had undergone various therapies over time, in- cluding topical treatments, cyclosporine, and NB-UVB pho- totherapy, with partial benefit. Two years earlier the patient underwent a conization procedure for cervical intraepithelial neoplasia III (CIN III). However, she was in general good health. At the time of our observation, in December 2019, the patient presented a PASI score of 13 and DLQI of 12 (Figure 3A). She was prescribed brodalumab, which led to a complete remission of psoriasis (PASI 0) and pruritus after 4 weeks, along with a significant improvement in her quality of life (DLQI 4). After 9 months of therapy, the patient was diagnosed with a right fronto-temporal meningioma. Consequently, she discontinued brodalumab and underwent neurosurgery to remove the tumor. Despite discontinuing the biological ther- apy, the patient did not experience a relapse of psoriasis until 3 months after the neurosurgical intervention, when she had a recurrence localized to the scalp (Figure 3B). Subsequently, the patient resumed brodalumab after consultation with the neurosurgeon, achieving again the remission of her psoriasis. Original Article | Dermatol Pract Concept. 2024;14(2):e2024152 5 Table 2. Univariable Drug Survival Analysis. Overall Ineffectiveness Adverse Events OR (95% CI) p-value OR (95% CI) p-value OR (95% CI) p-value Sex Female Ref Ref Ref Males 1.43 (0.60 – 3.44) 0.419 1.15 (0.39 – 3.37) 0.802 1.59 (0.32 – 7.89) 0.571 Age 1.00 (0.97 – 1.03) 0.933 1.01 (0.97 – 1.04) 0.750 0.99 (0.94 – 1.04) 0.636 Arthritic psoriasis No Ref Ref Ref Yes 2.93 (1.30 – 6.61) 0.010 5.60 (1.94 – 16.17) 0.001 1.29 (0.26 – 6.40) 0.756 BMI 1.07 (1.02 – 1.13) 0.004 1.07 (0.99 – 1.14) 0.056 1.09 (1.00 – 1.18) 0.049 Scalp psoriasis No Ref Ref Ref Yes 3.27 (1.36 – 7.86) 0.080 1.96 (0.70 – 5.53) 0.203 8.56 (1.05 – 69.76) 0.045 Nail psoriasis: No No Ref Ref Ref Yes 2.38 (0.95 – 5.96) 0.064 2.63 (0.78 – 8.80) 0.117 3.00 (0.67 – 13.57) 0.152 Palmoplantar psoriasis No Ref Ref Ref Yes 0.40 (0.06 – 2.96) 0.368 0.75 (0.10 – 5.76) 0.781 n.c. n.c. Genital psoriasis No Ref Ref Ref Yes 2.13 (0.95 – 4.81) 0.068 1.21 (0.38 – 3.87) 0.748 4.94 (1.75 – 20.75) 0.029 Other anti- IL-17 use No Ref Ref Ref Yes 0.88 (0.30 – 2.59) 0.821 1.25 (0.35 – 4.48) 0.737 0.60 (0.07 – 4.91) 0.637 Previous biological drug No Ref Ref Ref Yes 1.47 (0.65 – 3.30) 0.358 1.95 (0.65 – 5.83) 0.233 1.66 0.40 – 6.98() 0.487 Fast Responder No Ref Ref Ref Yes 1.57 (0.71 – 3.48) 0.261 1.78 (0.61 – 4.73) 0.302 1.24 (0.30 – 5.21) 0.765 PASI at baseline 1.05 (1.02 – 1.09) 0.003 1.05 (1.00 – 1.10) 0.036 1.06 (0.99 – 1.11) 0.053 BMI = body mass index; CI = confidence interval; OR = odds ratio; n.c., non computable; PASI = Psoriasis Area and Severity Index. Table 3. Multivariable Survival Analysis. Overall Ineffectiveness Adverse events OR (95% CI) p-value OR (95% CI) p-value OR (95% CI) p-value Sex Female Ref Ref Ref Males 0.70 (0.26 – 1.85) 0.466 0.46 (0.13 – 1.66) 0.237 0.87 (0.15 – 5.00) 0.878 Age 0.99 (0.95 – 1.02) 0.443 0.99 (0.94 – 1.03) 0.533 0.98 (0.93 – 1.04) 0.497 BMI 1.10 (1.03 – 1.18) 0.003 1.11 (1.01 – 1.23) 0.032 1.09(0.98 – 1.20) 0.106 Baseline PASI No 1.06 (1.02 – 1.10) 0.002 1.07 (1.02 – 1.13) 0.010 1.06 (1.00 – 1.12) 0.046 Arthritic Psoriasis No Ref Ref Ref Yes 5.05 (1.89 – 13.50) 0.001 11.65 (2.92 – 46.46) 0.001 1.71 (0.29 – 10.08) 0.554 Previous biological drug No Ref Ref Ref Yes 0.88 (0.34 – 2.23) 0.791 0.87 (0.25 – 3.04) 0.957 1.67 (0.31 – 8.94) 0.552 Fast Responder No Ref Ref Ref Yes 1.63 (0.71 – 3.74) 0.249 1.94 (0.65 – 5.78) 0.233 1.08 (0.23 – 5.06) 0.926 BMI = body mass index; CI = confidence interval; OR = odds ratio; PASI = Psoriasis Area and Severity Index. 6 Original Article | Dermatol Pract Concept. 2024;14(2):e2024152 Figure 2. Patient #1. (A) At baseline. (B) At week 6. (C) At week 108. Two years later, the patient received a diagnosis of left ovarian fibrothecoma and underwent bilateral ovariec- tomy and adnexectomy. Additionally, due to the detection of breast calcifications, multiple biopsies were performed, leading to a diagnosis of atypical ductal hyperplasia. As a result, the patient must undergo regular clinical and instru- mental follow-ups. During these assessments and surgical procedures, the patient temporarily discontinued broda- lumab therapy without experiencing a recurrence of pso- riasis. Upon advice from oncology specialists, she resumed treatment with the maintenance dosage regimen. To date, the patient remains in clinical remission for psoriasis and has not experienced a recurrence of cervical intraepithelial neoplasia or meningioma (Figure 3C). Patient #3: An obese patient with latent tuberculosis. We present the clinical case of a 52-year-old Caucasian male, a workman and habitual smoker with hypertension, dyslipid- emia, and class II obesity (BMI 37.04). The patient had a positive family history of psoriasis and was affected from plaque psoriasis since the age of 16, and psoriatic arthritis for the last 20 years. His clinical presentation was charac- terized by psoriatic plaques mainly located on the trunk and hands, with a PASI of 36 and a DLQI score of 18 (Figure 4A). Due to the high PASI score and the presence of comorbidities, Original Article | Dermatol Pract Concept. 2024;14(2):e2024152 7 Figure 3. Patient #2. (A) At baseline. (B) Recurrence of psoriasis on the scalp after neurosurgical intervention and 3 months after brodalumab discontinuation. (C) At week 160. the patient was screened to start biologic therapy. Infectious examinations revealed a positive result for Quantiferon TB Gold, indicating latent tuberculosis infection. Therefore, iso- niazid prophylaxis was initiated, but after only 15 days, it induced an increase in liver enzymes. After an infectious dis- ease consultation, the tuberculosis prophylaxis was switched to rifampicin. After 30 days of starting tuberculosis pro- phylaxis and after liver enzyme increase was resolved, the patient began treatment with brodalumab. 12 weeks later, patients achieved complete resolution of psoriasis, including the challenging lesions of the hands (Figure 4B). The patient has currently completed three years of brodalumab treat- ment, without any recurrence of psoriasis. Patient #4: Brodalumab after failure of anti-IL-17 secuk- inumab. We present the case of a 38-year-old male patient with an 11-year history of psoriasis. The patient was obese (BMI 34.7), dyslipidemic and smoker (20 cigarettes per day). Previously, he had been unsuccessfully treated with ciclospo- rin (suspended due to hypertension), etanercept (suspended due to ineffectiveness), and secukinumab (suspended due to lack of efficacy after 2 years). After a partial remission with secukinumab, the patient experienced a recurrence of the disease in November 2019, localized on the legs, trunk, and scalp. Consequently, we decided to initiate brodalumab treatment, considering its rapid action. Remarkably, after only 4 weeks, we observed a near-complete resolution of the disease, with the PASI score decreasing from 10 (at baseline) 8 Original Article | Dermatol Pract Concept. 2024;14(2):e2024152 Figure 4. Patient #3. (A) At baseline. (B) At week 12. Figure 5. Patient #4, at baseline and after 4 weeks and 3 years of treatment with brodalumab. The hyperchromic patches can be attributed to post-inflammatory hyperpigmented outcomes. to 1 (Figure 5). After 3 years, the patient continues to re- ceive brodalumab treatment with complete clearance of pso- riasis and no impact on his quality of life (PASI 0; DLQI 0) (Figure 5). Drug survival is a real-life indicator of treatment success over the long-term, encompassing factors such as drug effi- cacy, safety and patient adherence. Considering the diverse range of systemic therapies available for psoriasis, drug sur- vival plays a crucial role in guiding us in the selection of the most suitable treatment option for patients [12]. In this study we assessed the drug survival of broda- lumab, a monoclonal antibody targeting the interleukin-17 receptor A (IL-17RA), in patients with moderate to severe psoriasis. The data collected over a 3-year period provided valuable insights into the long-term effectiveness of the drug. In detail, after 52 and 104 weeks, 86.32% and 78.09% of patients, respectively, were still receiving brodalumab. These results demonstrated a favorable drug survival rate, with a significant proportion of patients remaining on the treat- ment throughout the observation period. There are currently limited studies available that report the long-term survival rate of brodalumab and they report conflicting data and differences between various anti IL- 17 agents [7, 13, 14, 15, 16]. Elgaard et al. reported a low brodalumab survival rate, in detail 65.7% and 57.2% after 1 and 2 years respectively. However, this datum may be ex- plained by the very high percentage of bio-experienced pa- tients (>90%) and by the low number of patients followed Original Article | Dermatol Pract Concept. 2024;14(2):e2024152 9 The optimal safety profile of brodalumab has been also confirmed by its successful use in our reported patients with a complex medical history, such as those with latent tuber- culosis and multiple neoplasms (cases 2 and 3, respectively). Moreover, we analyzed predictive factors for drug survival. Psoriatic arthritis and PASI at baseline were identified as positive predictive factors for overall discontinuation and suspension due to ineffectiveness. Psoriatic arthritis affects approximately 30% of patients with psoriasis [25] and there- fore the ability of a drug to manage the articular component is important when choosing among the available therapeutic options. Brodalumab showed good results in clinical trials for psoriatic arthritis [26], but evidence in real-world is cur- rently limited [17]. In contrast to our result, in the study of Kojanova et al and of Gkanti et al, psoriatic arthritis resulted associated to a longer drug survival [18, 27]. PASI at baseline can have an impact on the efficacy of treatments for psoriasis [28]. Patients with higher baseline PASI may experience a reduced responsiveness or a loss of efficacy to biological treatments. In fact, although it has not yet been reported in drug survival analyses specific on broda- lumab, higher baseline PASI was identified as a predictor of drug discontinuation in the drug survival analysis of Il 17 and Il 23 inhibitors by Torres et al [19]. This finding aligns with our result and confirms that patients with a more severe disease at baseline may have a lower drug survival. Moreover, although two of the reported cases showed a high effective- ness of brodalumab in very obese patients, at the multivari- able analysis BMI resulted associated with a mild increase risk (OR 1.10) of discontinuation for all reasons and for in- effectiveness [29]. Although in the post hoc analysis of AM- AGINE 2/3 trials BMI was not associated to a lower efficacy of brodalumab [30], in the real-world setting this finding is not always confirmed and obesity in some studies seems to be related to lower efficacy and drug survival [14, 17, 18]. For this reason, a trial is currently ongoing to investigate the administration of a higher dosage of brodalumab in patients with an increased BMI (NCT04306315). Finally, we did not find significant difference in effective- ness between biologic-naive and bio-experienced patients. This datum is worthy of note since, in the real-world setting, bio-experienced patients represent a therapeutic challenge because they may have developed resistance or inefficacy to prior biologic treatments. In fact, therapies for psoriasis of- ten have a faster, greater efficacy and longer drug survival in patients who are naive to biologics [31, 32, 33]. The effi- cacy of brodalumab in bio-experienced patients may be ex- plained with its unique mechanism of action that inhibits the IL17-receptor. This is in line with our cases 1 and 4, pivotal trials and real-world studies showing that brodalumab re- sulted effective also in patients previously treated with other biologics anti IL-17A. (amagine1-2-3) [34, 35]. up for the whole period of the study. Moreover, Gaudet et al. reported similar results and, in particular, a 1-year sur- vival rate of 70%, analyzing data collected through the brodalumab patient support program in Canada [11, 17]. Our results are in line with the studies by other authors that reported survival rates at 1 year ranging from 85 to 89.9% and at 2 years from 77.32 to 80.0%. In addition, Torres et al analyzed the drug survival of different IL-17 and IL-23 in- hibitors, and brodalumab resulted the IL-17 inhibitor with the highest drug survival at 24 months (overall probability of drug survival of 0.80 compared to 0.79 for ixekizumab, and 0.75 for secukinumab). The higher drug survival of broda- lumab compared to other IL-17 inhibitors, although with no statistical significance, appeared also in the recent real-world analysis conducted in the Czech Republic [18, 19]. Finally, Gargiulo et al. recently published an Italian study that involved 606 patients treated with brodalumab, out of which 115 completed a 3-year follow-up. The study con- firmed the high persistence in treatment even at 36 months, with a notable survival rate of 85.64% [20]. Discontinuation of brodalumab in our study primarily occurred due to adverse events. The most frequent in our patients was the onset of an eczematous eruption, occurring in 2/90 patients (2.22%). This is a well-known adverse event which can occur during anti IL-17 treatments. Although the exact underlying pathogenetic mechanism is not yet fully understood, it has been hypothesized that the incidence of eczematous eruptions is mainly linked to the overexpression of IL-17 C. Brodalumab, acting on IL-17RA and blocking IL17A, IL-17 F, and IL-17 C, does not result in an increase of IL-17 C and this may explain the lower prevalence of this side effect in our population respect to what is reported for other anti IL17 agents (2.2% vs 5.8%) [21]. Several cases have been described that support this hypothesis. For in- stance, a patient with an eczematous eruption induced by ixekizumab was treated with brodalumab with success, and a patient with concurrent atopic dermatitis and psoriasis was managed with brodalumab achieving a complete clinical re- sponse [22, 23]. Otherwise, brodalumab was well tolerated in our population and only one patient (1/90) experienced another well-known IL17 agent side effect, such as recurrent candidiasis. This is in line with the role of IL-17 in host de- fence against mucocutaneous candidiasis [24]. Predictive factors associated with suspension due to adverse events in the univariable logistic regression were BMI, scalp psoriasis, and genital psoriasis. It’s now well- established that a higher BMI is associated with increased comorbidities and adverse events, even not directly related to psoriatic therapy, while we do not clinically correlate scalp psoriasis and genital psoriasis with adverse events. These predictive factors were not confirmed in the multivariable analysis. 10 Original Article | Dermatol Pract Concept. 2024;14(2):e2024152 7. Bettencourt MS. Real-World Clinical Experience With the IL-17 Receptor A Antagonist Brodalumab. J Drugs Dermatol. 2020 Feb 1;19(2):132–136. doi: 10.36849/JDD.2020.4774. PMID: 32129956. 8. Fargnoli MC, Esposito M, Dapavo P, Parodi A, Rossi M, Tiberio R, Dastoli S, Offidani AM, Argenziano G, Gisondi P, Lo Schiavo A, Loconsole F, Pella P, Bardazzi F, Cusano F, Gattoni M, Nacca M, Cannavò SP, Pellegrini C, Costanzo A; BRILLIANT Working Group. Brodalumab for the treatment of moderate-to-severe plaque-type psoriasis: a real-life, retrospective 24-week experi- ence. J Eur Acad Dermatol Venereol. 2021 Mar;35(3):693–700. doi: 10.1111/jdv.16931. Epub 2020 Oct 13. PMID: 32916767. 9. Megna M, Potestio L, Camela E, Fabbrocini G, Ruggiero A. Ixekizumab and brodalumab indirect comparison in the treat- ment of moderate to severe psoriasis: Results from an Italian single-center retrospective study in a real-life setting. Dermatol Ther. 2022 Sep;35(9):e15667. doi: 10.1111/dth.15667. Epub 2022 Jul 11. PMID: 35762107; PMCID: PMC9540270. 10. Gaudet V, Yap B, Hassan S, Barbeau M. Brodalumab for Plaque Psoriasis: A Canadian Real-World Experience at 2-Years Post- Launch. J Cutan Med Surg. 2023 May-Jun;27(3):226–235. doi: 10.1177/12034754231168851. Epub 2023 Apr 21. PMID: 37083148. 11. Galluzzo M, Caldarola G, De Simone C, Bernardini N, Moretta G, Pallotta S, Botti E, Campione E, Pirro F, Potenza C, Bianchi L, Peris K. Use of brodalumab for the treatment of chronic plaque psoriasis: a one-year real-life study in the Lazio region, It- aly. Expert Opin Biol Ther. 2021 Sep;21(9):1299–1310. doi: 10.1080/14712598.2021.1941862. Epub 2021 Jun 28. PMID: 34114515. 12. No DJ, Inkeles MS, Amin M, Wu JJ. Drug survival of biologic treat- ments in psoriasis: a systematic review. J Dermatolog Treat. 2018 Aug;29(5):460–466. doi: 10.1080/09546634.2017.1398393. Epub 2017 Nov 10. PMID: 29076754. 13. Rompoti N, Politou M, Stefanaki I, Vavouli C, Papoutsaki M, Neofotistou A, Rigopoulos D, Stratigos A, Nicolaidou E. Broda- lumab in plaque psoriasis: Real-world data on effectiveness, safety and clinical predictive factors of initial response and drug survival over a period of 104 weeks. J Eur Acad Dermatol Ve- nereol. 2023 Apr;37(4):689–697. doi: 10.1111/jdv.18825. Epub 2023 Jan 4. PMID: 36562663. 14. Dapavo P, Siliquini N, Mastorino L, Avallone G, Merli M, Agostini A, Cariti C, Viola R, Stroppiana E, Verrone A, Ortoncelli M, Quaglino P, Ribero S. Efficacy, safety, and drug survival of IL-23, IL-17, and TNF-alpha inhibitors for psoriasis treatment: a retro- spective study. J Dermatolog Treat. 2022 Jun;33(4):2352–2357. doi: 10.1080/09546634.2021.1961998. Epub 2021 Aug 13. PMID: 34315331. 15. Galan-Gutierrez M, Font-Ugalde P, Padilla L, Hernandez-Montoya C, Godoy D, Armario-Hita JC, Ruiz-Villaverde R. Brodalumab: Efficacy, safety, and survival in mid-term (52 weeks) on real clinical practice in Andalucia, Spain. Int J Dermatol. 2023 May;62(5):700–706. doi: 10.1111/ijd.16527. Epub 2022 Dec 10. PMID: 36495585. 16. Caldarola G, Mariani M, Pirro F, Nicolotti N, Burlando M, Calabrese L, Parodi A, Peris K, De Simone C. Comparison of short- and long-term effectiveness of ixekizumab and secuk- inumab in real-world practice. Expert Opin Biol Ther. 2021 Feb;21(2):279–286. doi: 10.1080/14712598.2021.1849133. Epub 2021 Jan 20. PMID: 33170052. Limitations The limitations of our study are the retrospective study design and the size of the study population. However, the long observation period provide important evidence in a real-world setting. Conclusions Brodalumab has shown promising long-term efficacy in the management of moderate to severe plaque psoriasis, in a period up to 3 years. The data presented in our study con- tribute to the better understanding of brodalumab’s success in real world. Consideration of baseline disease severity, co- morbidities, and BMI can help in predicting patient adher- ence and optimizing the long-term management of moderate to severe plaque psoriasis with brodalumab. References 1. Blair HA. Brodalumab: a review in moderate to severe plaque psoriasis. Drugs. 2018;78(4):495–504. 2. Russell CB, Rand H. Gene expression profiles normal- ized in psoriatic skin by treatment with brodalumab, a hu- man anti-IL-17 receptor monoclonal antibody. J Immunol. 2014;192(8):3828–3836. 3. Papp KA, Reich K, Paul C, Blauvelt A, Baran W, Bolduc C, Toth D, Langley RG, Cather J, Gottlieb AB, Thaçi D, Krueger JG, Russell CB, Milmont CE, Li J, Klekotka PA, Kricorian G, Nirula A. A pro- spective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol. 2016 Aug;175(2):273–86. doi: 10.1111 /bjd.14493. Epub 2016 Jun 23. PMID: 26914406. 4. Lebwohl M, Strober B, Menter A, Gordon K, Weglowska J, Puig L, Papp K, Spelman L, Toth D, Kerdel F, Armstrong AW, Stingl G, Kimball AB, Bachelez H, Wu JJ, Crowley J, Langley RG, Blicharski T, Paul C, Lacour JP, Tyring S, Kircik L, Chimenti S, Callis Duffin K, Bagel J, Koo J, Aras G, Li J, Song W, Milmont CE, Shi Y, Erondu N, Klekotka P, Kotzin B, Nirula A. Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis. N Engl J Med. 2015 Oct;373(14):1318–28. doi: 10.1056/NEJMoa1503824. PMID: 26422722. 5. Puig L, Lebwohl M, Bachelez H, Sobell J, Jacobson AA. Long-term efficacy and safety of brodalumab in the treatment of psoriasis: 120-week results from the randomized, double-blind, placebo- and active comparator-controlled phase 3 AMAGINE-2 trial. J Am Acad Dermatol. 2020 Feb;82(2):352–359. doi: 10.1016 /j.jaad.2019.05.095. Epub 2019 Jun 5. PMID: 31175909. 6. Papadavid E, Zafeiriou E, Georgiou S, Roussaki-Schulze AV, Spiliopoulos T, Vryzaki E, Oikonomou C, Drongoula O, Boziou M, Goudouras G, Sfaelos K, Apalla Z, Lazaridou E. Real-world clinical outcomes of treatment with brodalumab in patients with moderate-to-severe psoriasis: a retrospective, 24-month experience from four academic dermatology centers in Greece. J Dermatolog Treat. 2022 Nov;33(7):3053–3059. doi: 10.1080/09546634.2022.2110836. Epub 2022 Aug 23. PMID: 36000186. Original Article | Dermatol Pract Concept. 2024;14(2):e2024152 11 Arthritis in Patients With Psoriasis: A Prospective Cohort Study. Arthritis Rheumatol. 2016 Apr;68(4):915–23. doi: 10.1002/art .39494. PMID: 26555117. 26. Mease PJ, Helliwell PS, Hjuler KF, et al. Brodalumab in psoriatic arthritis: results from the randomised phase III AMVISION-1 and AMVISION-2 trials. Ann Rheum Dis. 2021;80(2):185–93. 27. Gkanti V, Dalamaga M, Papadavid E. Drug survival of broda- lumab is greater in patients with psoriasis and psoriatic arthritis in a real-world setting. Int J Dermatol. 2023 Jan;62(1):e31-e34. doi: 10.1111/ijd.16408. Epub 2022 Sep 10. PMID: 36087047. 28. Reich K, Mrowietz U, Menter A, Griffiths CEM, Bagel J, Strober B, Nunez Gomez N, Shi R, Guerette B, Lebwohl M. Effect of base- line disease severity on achievement of treatment target with apremilast: results from a pooled analysis. J Eur Acad Dermatol Venereol. 2021 Dec;35(12):2409–2414. doi: 10.1111/jdv.17520. Epub 2021 Aug 23. PMID: 34255891. 29. Merola JF, Kavanaugh A, Lebwohl MG, et al. Clinical efcacy and safety of psoriasis treatments in patients with concomitant meta- bolic syndrome: a narrative review. Dermatol Ther (Heidelb). 2022. 30. Hsu S, Green LJ, Lebwohl MG, Wu JJ, Blauvelt A, Jacobson AA. Comparable efficacy and safety of brodalumab in obese and nonobese patients with psoriasis: analysis of two randomized controlled trials. Br J Dermatol. 2020 Apr;182(4):880–888. doi: 10.1111/bjd.18327. Epub 2019 Oct 16. PMID: 31276189. 31. Chiricozzi A, Balato A, Conrad C, Conti A, Dapavo P, Ferreira P, Gaiani FM, Leite L, Malagoli P, Mendes-Bastos P, Megna M, Messina F, Nidegger A, Odorici G, Panduri S, Piaserico S, Piscitelli L, Prignano F, Ribero S, Valerio J, Torres T. Secukinumab demon- strates improvements in absolute and relative psoriasis area severity indices in moderate-to-severe plaque psoriasis: re- sults from a European, multicentric, retrospective, real-world study. J Dermatolog Treat. 2020 Aug;31(5):476–483. doi: 10.1080/09546634.2019.1671577. Epub 2019 Oct 2. PMID: 31557063. 32. Thein D, Rosenø NAL, Maul JT, Wu JJ, Skov L, Bryld LE, Rasmussen MK, Ajgeiy KK, Thomsen SF, Thyssen JP, Egeberg A. Drug survival of adalimumab, secukinumab, and ustekinumab in psoriasis as determined by either dose escalation or drug discontinuation during the first 3 years of treatment - a na- tionwide cohort study. J Invest Dermatol. 2023 Apr 27:S0022– 202X(23)02041-9. doi: 10.1016/j.jid.2023.04.009. Epub ahead of print. PMID: 37119965. 33. Mastorino L, Castelli F, Stroppiana E, Verrone A, Ortoncelli M, Susca S, Boskovic S, Passerini SG, Macagno N, Cariti C, Licciardello M, Solaroli C, Pertusi G, Aragone MG, Baggini G, Addese C, Leporati C, Peila R, Giura MT, Rossotto G, Pella P, Mocci L, Merlo G, Tiberio R, Graziola F, Quaglino P, Dapavo P, Ribero S. Risankizumab shows faster response in bio naïve than in bio-experienced psoriatic patients. J Eur Acad Dermatol Vene- reol. 2022 Oct;36(10):e838-e841. doi: 10.1111/jdv.18314. Epub 2022 Jun 22. PMID: 35686942. 34. Kimmel G, Chima M, Kim HJ, et al. Brodalumab in the treat- ment of moderate to severe psoriasis in patients when previous anti-interleukin 17A therapies have failed. J Am Acad Dermatol. 2019;81(3):857–859. 35. Kromer C, Wilsmann-Theis D, Gerdes S, et al. Changing within the same class: efficacy of brodalumab in plaque psoriasis after treatment with an IL-17A blocker - a retrospective multicenter study. J Dermatolog Treat. 2020. p. 1–5. 17. Elgaard CDB, Iversen L, Hjuler KF. Single-Centre Real-World Study on Drug Survival and Effectiveness of Brodalumab for Treatment of Psoriasis and Psoriatic Arthritis. Drugs R D. 2023 May 8. doi: 10.1007/s40268-023-00422-w. Epub ahead of print. PMID: 37155121. 18. Kojanova M, Hugo J, Velackova B, Cetkovska P, Fialova J, Dolezal T, Tichy M, Gkalpakiotis S; BIOREP study group. Effi- cacy, safety, and drug survival of patients with psoriasis treated with IL-17 inhibitors - brodalumab, ixekizumab, and secuk- inumab: real-world data from the Czech Republic BIOREP registry. J Dermatolog Treat. 2022 Sep;33(6):2827–2837. doi: 10.1080/09546634.2022.2082354. Epub 2022 May 29. PMID: 35635185. 19. Torres T, Puig L, Vender R, Yeung J, Carrascosa JM, Piaserico S, Gisondi P, Lynde C, Ferreira P, Bastos PM, Dauden E, Leite L, Valerio J, Del Alcázar-Viladomiu E, Rull EV, Llamas-Velasco M, Pirro F, Messina F, Bruni M, Licata G, Ricceri F, Nidegger A, Hugo J, Mufti A, Daponte AI, Teixeira L, Balato A, Romanelli M, Prignano F, Gkalpakiotis S, Conrad C, Lazaridou E, Rompoti N, Papoutsaki M, Nogueira M, Chiricozzi A. Drug Survival of Inter- leukin (IL) 17 and IL 23 Inhibitors for the Treatment of Psoriasis: A Retrospective Multi country, Multicentric Cohort Study. Am J Clin Dermatol. 2022 Nov;23(6):891–904. doi: 10.1007/s40257 -022-00722-y. Epub 2022 Aug 17. PMID: 35976568. 20. Gargiulo L, Ibba L, Malagoli P, Amoruso F, Argenziano G, Balato A, Bardazzi F, Burlando M, Carrera CG, Damiani G, Dapavo P, Dini V, Fabbrocini G, Franchi C, Gaiani FM, Girolomoni G, Guarneri C, Lasagni C, Loconsole F, Marzano AV, Megna M, Sampogna F, Travaglini M, Costanzo A, Narcisi A. Brodalumab for the treatment of plaque psoriasis in a real-life setting: a 3  years multicenter retrospective study-IL PSO (Italian land- scape psoriasis). Front Med (Lausanne). 2023 Jul 3;10:1196966. doi: 10.3389/fmed.2023.1196966. PMID: 37469659; PMCID: PMC10352451. 21. Caldarola G, Pirro F, Di Stefani A, Talamonti M, Galluzzo M, D’Adamio S, Magnano M, Bernardini N, Malagoli P, Bardazzi F, Potenza C, Bianchi L, Peris K, De Simone C. Clinical and histo- pathological characterization of eczematous eruptions occurring in course of anti IL-17 treatment: a case series and review of the literature. Expert Opin Biol Ther. 2020 Jun;20(6):665–672. doi: 10.1080/14712598.2020.1727439. Epub 2020 Feb 17. PMID: 32045273. 22. Kimura R, Sugita K, Yamamoto O. Successful switching to brodalumab in a patient with severe psoriasis developing ixekizumab-induced eczema. Eur J Dermatol. 2020 Dec 1;30(6): 732–734. doi: 10.1684/ejd.2020.3904. PMID: 33237034. 23. Gambardella A, Licata G, De Rosa A, Pagliuca F, Calabrese G, Alfano R, Argenziano G. Concurrent Atopic Dermatitis and Pso- riasis Successfully Treated With Brodalumab. Dermatitis. 2021 Oct 1;32(1S):e86-e88. doi: 10.1097/DER.0000000000000645. PMID: 33208631. 24. Davidson L, van den Reek JMPA, Bruno M, van Hunsel F, Herings RMC, Matzaraki V, Boahen CK, Kumar V, Groenewoud HMM, van de Veerdonk FL, Netea MG, de Jong EMGJ, Kullberg BJ. Risk of candidiasis associated with interleukin-17 inhibitors: A real-world observational study of multiple independent sources. Lancet Reg Health Eur. 2021 Nov 22;13:100266. doi: 10.1016/j.lanepe.2021.100266. PMID: 34950923; PMCID: PMC8671639. 25. Eder L, Haddad A, Rosen CF, Lee KA, Chandran V, Cook R, Gladman DD. The Incidence and Risk Factors for Psoriatic