Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2024;14(3):e2024166 1 Effectiveness of Ixekizumab in Elderly Patients for the Treatment of Moderate-to-Severe Psoriasis: Results From a Multicenter, Retrospective Real-Life Study in the Lazio Region Annunziata Dattola1, Nicoletta Bernardini2, Giacomo Caldarola3,4, Rosa Coppola5, Clara De Simone3,4, Domenico Giordano6, Alessandro Giunta7, Gaia Moretta8, Gianluca Pagnanelli8, Vincenzo Panasiti4,8, Severino Persechino6, Concetta Potenza2, Federica Trovato1, Arianna Zangrilli7, Luca Bianchi7, Giovanni Pellacani1, Ketty Peris3,4, Antonio Giovanni Richetta1 1 Dermatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Science, University of La Sapienza, Rome, Italy 2 Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome - Polo Pontino, ASL Latina , Latina, Italy 3 Section of Dermatology, Department of Translational Medicine and Surgery, Catholic University of the S. Heart; Rome, Italy 4 Dermatology Unit, Policlinico A. Gemelli, IRCCS, Rome, Italy 5 Fondazione Policlinico Universitario Campus Bio Medico, Rome, Italy 6 Department of Neurosciences, Mental Health and Sensory Organs, “Sapienza” University of Rome, Rome, Italy 7 Dermatology Unit, University of Rome “Tor Vergata”, Rome, Italy 8 Department of Dermatology, Istituto Dermopatico dell’Immacolata IDI IRCCS, Rome, Italy Key words: psoriasis, interleukin-17, ixekizumab, real-life, elderly Citation: Dattola A, Bernardini N, Caldarola G, et al. Effectiveness of Ixekizumab in Elderly Patients for the Treatment of Moderate- to-Severe Psoriasis: Results From a Multicenter, Retrospective Real-Life Study in the Lazio Region. Dermatol Pract Concept. 2024;14(3):e2024166. DOI: https://doi.org/10.5826/dpc.1403a166 Accepted: March 14, 2024; Published: July 2024 Copyright: ©2024 Dattola 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: AD: has served as a speaker, consultant or advisory board member from Abbvie, Almirall, Amgen, Eli Lilly, Leo Pharma, Janssen, Novartis, Boehringer Ingelheim and UCB Pharma. NB: served as consultant for Amgen, Abbvie, Janssen, Eli lilly, Leo-Pharma, Novartis, Bristol, Sanofi, Pfizer, Pierre Fabre, Rilastil. GC: has served as a speaker, consultant or advisory board member and has received honoraria from Abbvie, Almirall, Amgen, Eli Lilly, Leo Pharma, Janssen, Novartis, and UCB Pharma. CDS: has served as a speaker, consultant or advisory board member and has received honoraria from Abbvie, Almirall, Amgen, Eli Lilly, Leo Pharma, Janssen, Novartis, and UCB Pharma. GM consultant for Abbvie, Leo Pharma, Sanofi, Ely-Lilly. DG: consultant for Abbvie, Almirall, Amgen, Difa Cooper, Eli Lilly, Fresenius Kabi, Janssen-Cileg, Novartis, Sanofi. SP consultant for Abbvie, Almirall, Eli Lilly, Janssen-Cileg, Novartis, Sanofi. GP has served as a speaker, consultant or advisory board member from Abbvie, Almirall, Amgen, Eli Lilly, Leo Pharma, Janssen, Novartis, Boehringer Ingelheim, Loreàl, Pierre Fabbre, Eucerin and UCB Pharma. All Other authors reports no conflict of interest. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Annunziata Dattola, MD, PhD, Dermatology Clinic, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy. Email: nancydattola@gmail.com 2 Original Article | Dermatol Pract Concept. 2024;14(3):e2024166 Introduction Psoriasis is a chronic inflammatory dermatosis with a mul- tifactorial pathogenesis and a relapsing trend [1]. It is cur- rently estimated that around 120 million individuals are affected worldwide, with a prevalence around 2%-3% of the adult population and 0.5%-1% of children. Psoriasis shows a bi-modal distribution with a main onset peak around 20-30 years and a second peak after 50-60 years, with a worse prognosis if the onset occurs at a young age com- pared to a development in adulthood [2]. Skin lesions and the chronic and relapsing course of the disease deeply and negatively undermine the quality of life of patients. Further- more, these patients have an increased risk of developing other serious comorbidities, such as psoriatic arthritis, meta- bolic syndrome, cardiovascular diseases, Crohn disease, psy- chiatric disorders, such as anxiety and depression [3-5]. The pathogenesis of psoriasis involves antimicrobial peptides (AMPs), dendritic cells (DCs), tumor necrosis factor (TNF)α, interleukin (IL) 23, Th17, IL17, IL22, and signal transducer and activator of transcription (STAT)3. The IL-23/TH17 im- mune axis is now thought to be central to the pathogenesis of psoriasis. The main cytokines involved in psoriasis patho- genesis, IL-23, TNF and IL-17, can be subdivided into regu- latory and effector cytokines based on their mode of action. IL-23 exerts regulatory effects on the maintenance of TH17 cells, whereas IL-17 and TNF mediate effector functions of innate (TNF) and adaptive (TNF, IL-17) immune cells. IL-23 was identified in 2000 as a heterodimer composed of the IL-12/23p40 subunit and a newly discovered p19 subunit that is exclusive to IL-23 [6] IL-23 signals through a heterod- imeric receptor complex composed of two subunits, IL-23R and IL-12Rb1. This complex predominantly activates signal transducer and activator of transcription 3 (STAT3), leading to IL-23–dependent gene expression. IL-23 is an upstream regulatory cytokine that acts early in the inflammatory cas- cade in psoriasis to maintain the TH17 cell phenotype and is critical in the production of downstream effector cytokines, such as IL-17A, IL-17F and TNF. The IL-17 cytokine fam- ily consists of six isoforms termed IL-17 A–F. IL-17A shows similarities with IL-17F and both cytokines bind to the same receptor IL-17RA. The biologically active form of IL-17A comprises either an IL-17A homodimer or an IL-17A-IL-17F heterodimer, although the first one has greater biological activity Increased expression of IL-17A, E and F in psori- atic lesions has been described [7]. TH17 (CD4+) cells are a major source of IL-17A, although this cytokine can also be produced by CD8+ T cells and cd T cells, natural killer T cells, mast cells and neutrophils. IL-17 is an effector cyto- kine downstream of IL-23 that mediates psoriatic inflamma- tion. IL-17 induces IL-17 receptor–dependent proliferation of keratinocytes and production of pro-inflammatory cy- tokines, including IL-1b, IL-6 and TNF, and antimicrobial peptides, including b-defensin and matrix metalloproteinase 9.82–85,87. Blockade of either IL-17A or the IL-17 receptor has been shown to be an effective therapy in plaque psori- asis [8]. Anti-IL17 biologics drugs (including secukinumab, ixekizumab, brodalumab and bimekizumab) are effectice in Introduction: This was an observational, retrospective, multicenter study, enrolling elderly patients (>65 years old) treated with ixekizumab with a diagnosis of psoriasis (PsO) and/or psoriatic arthritis (PsA) during the period 2020 to 2023. Objectives: Efficacy of ixekizumab in elderly patients in the treatment of moderate to severe psoriasis. Methods: We included 73 patients with psoriasis (32.9%), psoriatic arthritis (1.4%) and both of them (PsO-PsA 65.8%), attending the outpatient clinics of seven Italian referral center for psoriasis in Lazio region: Policlinico Umberto I Università Roma La Sapienza, Sant’Andrea Università di Roma La Sapienza, Polo Pontino Università Roma La Sapienza, Fondazione Policlinico Universitario A. Gemelli, Università Campus Biomedico Roma, Istituto Dermopatico dell’Immacolata – IDI and Policlinico Tor Vergata. We collected data related to the characteristics of the patients (age, sex, body mass index) and of the disease (age at onset, duration of psoriasis, previous treatments). The severity of psoriasis was measured with the Psoriasis Area and Severity Index (PASI) score at baseline and after 16, 24, 52, 104 and 156 weeks of treatment. Results: PASI90 was achieved by all the patients in week 16 and remained stable until the end of the study. PASI100 has been achieved by 55.1% of patients at weeks 16 and by 81.3% at week 104. A statistically significant difference has been showed between baseline and all the other time points (P < 0.0001) for PASI score. A similar trend was observed for Visual Analogue Scale score and Derma- tology Life Quality Index score. Conclusions: Ixekizumab was effective and with a good safety profile in psoriatic patients over 65 years. No significant adverse events were reported. ABSTRACT Original Article | Dermatol Pract Concept. 2024;14(3):e2024166 3 the treatment of psoriasis that act by neutralizing IL-17A, a key cytokine in the pathogenesis of the disease. There are three large prospective, double-blind, multicenter, phase III studies (UNCOVER-1, -2 and -3) that evaluated ixekizumab efficacy and safety [9]. Objectives Our study was designed to evaluate, in a real-world setting, the effectiveness and safety of ixekizumab in elderly patients (>65 years old) with psoriasis (PsO) and/or psoriatic arthritis (PsA) [10]. The main objective was to evaluate the effective- ness and safety of ixekizumab in a cohort of real-life psori- asis patients. Methods We performed a multicenter, retrospective, observational analysis in patients with chronic plaque psoriasis and pso- riatic arthritis in real life of elderly patients treated with ixekizumab. We included males and females attending the outpatient clinics of seven Italian referral center for psoria- sis in Lazio Region: Policlinico Umberto I Università Roma La Sapienza, Sant’Andrea Università di Roma La Sapienza, Polo Pontino Università Roma La Sapienza, Fondazione Policlinico Universitario A. Gemelli, Università Campus Bio- medico Roma; Istituto Dermopatico dell’Immacolata – IDI; Policlinico Tor Vergata. All patients were treated with ixeki- zumab at the European Medical Agency (EMA) approved dosage (80 mg x2 administered by subcutaneous injection at week 0, and 80 mg at weeks 2, 4, 8, 12, and every 4 weeks thereafter). We collected data related to the characteristics of the patients (age, sex, BMI) and of disease (age at onset, severity and duration of psoriasis, previous treatments). The severity of psoriasis was measured with the Psoriasis Area and Severity Index (PASI) score at baseline and after 16, 24, 52, 104 and 156 weeks of treatment. Study Design and Patients This was an observational, retrospective, multicenter study performed in seven centers in Italy in Lazio region, enrolling elderly patients with a diagnosis PsO and/or PsA during the period from 2020 to 2023. Inclusion Criteria Patients over 65 years old, affected by PsO and/or PsA and currently treated with ixekizumab were included in the study. Procedures Baseline clinical and demographic characteristics of the patients have been collected from hospital records. Results from the PASI and Visual Analogue Scale (VAS) have been collected for 6 time points: baseline, 16, 24, 52, 104 and 156 weeks. Results from Dermatology Life Quality Index (DLQI) have been collected at baseline and at 52 weeks. Patients have been diagnosed with PsO, PsA, or both (PsO- PsA). Concerning the body areas affected by the disease, PsO presentation has been classified in “Difficult areas” (head, nails, hands, feet, genital area) and “Widespread” (all the re- maining areas not included in the first group). Statistics The sample has been described in its clinical and demo- graphic characteristics applying descriptive statistics tech- niques. Qualitative variables have been described with absolute frequencies and percentage; quantitative variables have been summarized with mean and standard deviation. Comparisons between groups of patients have been per- formed applying the Chi square test (or the Fisher Exact Test) for categorical variables; for continuous, not normally distributed, variables the Mann Whitney test have been applied. To evaluate the effectiveness of ixekizumab PASI score, VAS and DLQI have been considered. Results from the three questionnaires have been described for each time points, ap- plying the already mentioned descriptive statistics techniques. Moreover, the percentages of patients achieving PASI90 and PASI100 improvement have been calculated at each time point not considering the loss to follow-up patients. To eval- uate the changes over times a one-way repeated measures ANOVA has been performed for PASI and VAS over a to- tal of 6 time points. A Wilcoxon signed rank test has been performed for the evaluation of changes in DLQI over two timepoints (baseline and week 52). A subgroup analysis (male vs female; bio naive vs not bio naive; PsO-PsA versus PsO; BMI<25 vs BMI ≥25) for PASI, VAS (100 points score) and DLQI data, has been performed applying an ANOVA mixed model for repeated measures. Due to subgroup dimension, only PsO-PsA and PsO patients have been considered (in the sample there was only one PsA patient). Before performing the ANOVA mixed model for repeated measures, some preliminary tests were carried out to verify that groups were not significantly different at the baseline in relation to some selected variables that could in- fluence the results. Ixekizumab safety has been evaluated in- vestigating the frequency and the severity of adverse events. A P -value <0.05 has been considered as significant. All the statistical analyses were performed using R (4.3.0). Results A total of 73 patients, 56.2% males and 43.8% females, with mean age of 71.5 years (SD = 6.4), have been included in the study. The diagnosis was PsO for 24 patients (32.9%), 4 Original Article | Dermatol Pract Concept. 2024;14(3):e2024166 Similarly, with what was seen for PASI score, the one-way ANOVA model presented a significant effect of time on VAS score (P < 0.0001) and pairwise comparisons showed a sig- nificant difference between baseline and all the other time points (P < 0.0001). See Table 5 for details. DLQI Score As presented in Table 6, DLQI score decreased significantly from baseline to week 52. Mean and median changed from 15.9 and 16.0 to 0.5 and 0, respectively. The Wilcoxon signed rank test highlighted a significant difference between the two considered time points, P < 0.0001. See Figure 3 for a graphical representation of mean VAS and DLQI score. Subgroups Analyses The results of a preliminary, comparative test indicated that the proposed subgroups are not significantly different in term of age, PASI, VAS and DLQI score at baseline. There was only a statistically significant difference between mean PASI score at baseline for BMI < 25 patients and BMI ≥ 25 ones; 10.9 (SD = 6.7) and 16.1 (SD = 9.1) respectively (Table 7). Sex For PASI score, the ANOVA mixed model showed a statis- tically significant difference between sex (P = 0.037) and, as already reported, between timepoints (P < 0.0001). Pairwise comparisons showed that all timepoints are significantly dif- ferent from the baseline (P < 0.0001) but there are no signif- icant differences between the remaining pairs of timepoints. See Figure 4 for details. ANOVA mixed model also revealed a statistically sig- nificant difference in VAS scores between time points (P < 0.0001) but no significant difference in VAS score between males and females (P = 0.247). Concerning DLQI index, no statistically significant dif- ferences have been highlighted between males and females, P = 0.829. PsO Versus PsO-PsA For PASI score, the ANOVA mixed model highlighted a statistically significant difference between time points (P < 0.0001) and no significant difference between the groups (P = 0.647). Pairwise comparisons showed that all times are significantly different from the baseline (P < 0.0001) but there are no significant differences between the remaining pairs of timepoints. For VAS score, the ANOVA mixed model showed a statis- tically significant difference between time points (P = 0.011) and no significant difference between the groups (P = 0.239). For DLQI index, the ANOVA mixed model revealed a statistically significant difference between time points PsA for 1 patient (1.4%) and both of them (PsO-PsA) for 48 patients (65.8%). The mean disease duration was 25.3 years (SD = 16.0), with a minimum of 1 year and a maximum of 63 years. Most patients (N = 62; 84.9%) had undergone a tradi- tional systemic therapy and 15 patients (20.5%) were bio naive. The most frequently prescribed traditional therapy before treatment with ixekizumab was methotrexate (47 patients) and the most frequently prescribed biologic was an anti TNF-α agent. Most patients (N = 60; 82.2%) had comorbidities and the most frequent were the cardiovascu- lar diseases. See Table 1 for clinical and demographic de- tails about the sample. Concerning the safety of ixekizumab, during the study only 2 mild adverse events have been re- corded (oral candidiasis and pain at the injection site). In or- der to evaluate the effectiveness of the ixekizumab, detailed analyses of the score trend for the PASI, VAS and DLQI were performed. PASI Score At baseline the mean PASI score was 14.6 (SD=8.7), with a minimum of 1 and a maximum of 60 points. After only 16 weeks of treatment, PASI scores had improved, reaching a mean value of 1.4 (SD=2.4), with a minimum of 0 and a maximum score of 10 points. This trend remained stable until the end of the study (Table 2 and Figure 1). The one- way ANOVA model presented a significant effect of time on PASI score (P < 0.0001); pairwise comparisons highlighted a significant difference only between baseline and all the other time points (P < 0.0001). PASI90 has been achieved by all the patients in week 16 and remained stable until the end of the study. PASI100 has been achieved by 55.1% of patients on weeks 16 and by 81.3% on week 104 (Table 3 and Figure 2). The proportions of patients achieving PASI 90 and PASI 100, in the Bio-Naïve group and in the Bio-experienced group, are displayed in Table 4. PASI 90 was achieved by all the patients in both the groups in week 16 and the result was maintained until week 156. PASI 100, for all the Bio-Naïve patients, is achieved in week 24 and maintained in week 52 and 104. In week 156 the proportion of patient achiev- ing PASI 100 decreased to 83.3%. For the Bio-experienced group, the proportion of patients achieving PASI 100 is constantly increased from 52.7% of week 16 to 80.0% of week 156. VAS Score At baseline the mean pain VAS score was 16.5 points (SD=23.3), with a minimum of 0 and a maximum of 80. Mean VAS score decreased with time reaching its minimum of 1.7 points at week 52 and maintained at week 104. At week 156 mean VAS score presented a light increase (2.3). Original Article | Dermatol Pract Concept. 2024;14(3):e2024166 5 Table 1. Clinical and demographic characteristics of the sample (N = 73) Characteristics Sex (N;%) Male 41 56.2 Female 32 43.8 Diagnosis (N;%) PsO-PsA 48 65.8 PsO 24 32.9 PsA 1 1.4 Age (mean; SD) 71.5 6.4 BMI (mean; SD) 27.3 4.1 Disease duration (mean; SD) 25.3 16.0 PsO locations (N;%) Difficult areas 30 41.1 Widespread 23 31.5 missing 19 26.4 PsA subtype (N;%) Polyarticular 27 37.0 Oligoarticular 21 28.8 missing 1 2.0 Traditional therapy (N;%) Yes 62 84.9 No 11 15.1 Traditional therapy drug details (Frequency of patients that underwent a certain traditional therapy. The same patient could have undergone more than one type of traditional medicine) acitretin 10 cyclosporine 25 oral steroids 5 phototherapy 7 methotrexate 47 salazopyrine 3 Bio-Naive (N;%) No 58 79.5 Yes 15 20.5 Bio-experienced (N %) anti TNF-Alpha 43 58.9 anti TNF-Alpha, anti IL-17 4 5.5 anti TNF-Alpha, anti IL-17, anti IL-23 3 4.1 anti TNF-Alpha, anti IL-23 3 4.1 anti IL-23 2 2.7 APREMILAST 2 2.7 anti IL-17 1 1.4 Comorbidities (N;%) Yes ( 60 82.2 No 13 17.8 Comorbidities details (Frequency of patients that presents the same comorbidity. The same patient could have more than one comorbidity) Cardiovascular 42 Other 18 Diabetes 11 Dyslipidemia 10 Thyroid gland disorders 7 Depression 3 Obesity 3 Fibromyalgia 2 Bipolar disorder 1 Tuberculosis 1 BMI = body mass index; PsA = psoriatic arthritis; PsO = psoriasis; SD standard deviation. 6 Original Article | Dermatol Pract Concept. 2024;14(3):e2024166 Table 2. Descriptive statistics for PASI score at each timepoints and pairwise comparisons P-value. Baseline Week 16 Week 24 Week 52 Week 104 Week 156 N 72 69 68 64 48 40 Mean 14.58 1.43 0.55 0.59 0.47 0.81 Std. Dev. 8.71 2.39 1.23 1.54 1.15 1.82 Median 15 0 0 0 0 0 Min 1 0 0 0 0 0 Max 60 10 6 8 5 7 Pairwise comparisons (timepoints) Baseline versus other timepoints (P-value) <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 Figure 1. Trend in mean Psoriasis Area and Severity Index (PASI) score at each time point. Table 3. Proportion of patients achieving Psoriasis Area and Severity Index (PASI) 90 and PASI 100 at each time point Week 16 Week 24 Week 52 Week 104 Week 156 Patients achieving PASI 90 69/69 68/68 64/64 48/48 40/40 PASI 90 100% 100% 100% 100% 100% Patients achieving PASI 100 38/69 51/68 50/64 39/48 33/41 PASI 100 55.1% 75.0% 78.1% 81.3% 80.5% Figure 2. Proportion of patients achieving Psoriasis Area and Sever- ity Index (PASI )90 and PASI 100 at each time point. Table 4. Proportions of patients achieving Psoriasis Area and Severity Index (PASI) 90 and PASI 100 at each time point. Bio-Naive vs Not Bio-Naive Week 16 Week 24 Week 52 Week 104 Week 156 Bio-Naïve patients achieving PASI 90 14/14 13/13 12/12 7/7 5/5 PASI 90 (Bio-Naïve) 100.0% 100.0% 100.0% 100.0% 100.0% Bio-Naïve patients achieving PASI 100 9/14 13/13 12/12 7/7 5/6 PASI 100 (Bio-Naïve) 64.3% 100.0% 100.0% 100.0% 83.3% Bio-experienced patients achieving PASI 90 55/55 55/55 52/52 41/41 35/35 PASI 90 (Bio-experienced) 100.0% 100.0% 100.0% 100.0% 100.0% Bio-experienced patients achieving PASI 100 29/55 38/55 38/52 32/41 28/35 PASI 100 (Bio-experienced) 52.7% 69.1% 73.1% 78.0% 80.0% Original Article | Dermatol Pract Concept. 2024;14(3):e2024166 7 Table 5. Descriptive statistics for Visual Analogue Scale score at each timepoints and pairwise comparisons P-value Baseline Week 16 Week 24 Week 52 Week 104 Week 156 N 56 53 53 50 43 38 Mean 16.5 4.8 2.9 1.7 1.7 2.3 Standard deviation 23.3 9.8 6.2 4.4 5.0 4.4 Median 7.5 0.0 0.0 0.0 0.0 0.0 Min 0 0 0 0 0 0 Max 80 50 30 20 30 20 Pairwise comparisons (timepoints) Baseline versus other timepoints (P-value) <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 Table 6. Descriptive statistics for Dermatology Life Quality Index (DLQI) at each time point DLQI_ BASALE DLQI_ WEEK52 P-value N 73 65 Mean 15.9 0.5 <0.0001 SD 6.2 1.6 Median 16.0 0.0 Min 1 0 Max 29 10 SD = standard deviation. Figure 3. Mean Visual Analogue Scale (VAS) and Dermatology Life Quality Index (DLQI) score at each timepoints. (P < 0.0001) and no significant difference between the groups (P = 0.291). Bio-naive Versus Bio-experienced For PASI score, the ANOVA mixed model highlighted a statis- tically significant difference between time points (P < 0.0001) and no significant difference between the groups (P = 0.99). Pairwise comparisons showed that all times are significantly different from the baseline (P < 0.0001) but there are no sig- nificant differences between the remaining pairs of times. For VAS score, the ANOVA mixed model showed a statistically significant difference between time points (P < 0.0001) and no significant difference between the groups (P = 0.259). Pairwise comparisons showed that all times are significantly different from the baseline but there are no sig- nificant differences between the remaining pairs of times. For DLQI index, the ANOVA mixed model revealed a statistically significant difference between time points (P < 0.0001) and no significant difference between the groups (P = 0.265). BMI < 25 Versus BMI ≥ 25 As seen in Table 5, there was a statistically significant dif- ference between mean PASI score at baseline for BMI < 25 patients and BMI ≥ 25 ones; 10.9 (SD=6.7) and 16.1 (SD=9.1) respectively. For PASI score, the ANOVA mixed model highlighted a statistically significant difference be- tween time points (P < 0.0001) and no significant differ- ence between the groups (P = 0.374). Pairwise comparisons showed that all times are significantly different from the baseline (P < 0.0001) but there are no significant differences between the remaining pairs of times. For VAS score, the ANOVA mixed model showed a statistically significant difference between time points (P < 0.0001). No significant difference between the groups (P = 0.970) was observed. Pairwise comparisons showed that all times are significantly different from the baseline but there are no significant differences between the remaining pairs of times. For DLQI index, the ANOVA mixed model highlighted a statistically significant difference between time points (P < 0.0001) and no significant difference between the groups (P = 0.668). For a fully detailed description of subgroups comparison see Table 8. 8 Original Article | Dermatol Pract Concept. 2024;14(3):e2024166 Conclusions As we know, psoriasis is a chronic and relapsing dermatosis. Approximately 15-20% of affected patients are over 65 years of age and are affected by many comorbidities (cardiovascu- lar, metabolic, renal, intestinal, etc) [11-12]. Therefore, in this category of patients, when considering treatment of psori- asis, it is very important to take into account not only the clinical presentation and severity of skin disease but also all the associated pathologies. Data on the efficacy and safety of other biological drugs in the treatment of patients with psori- asis treated with biological drugs have been presented in the literature. In particular, for example, in the work presented by Ruggiero and collaborators, the authors focus their atten- tion on the elderly patient being treated with guselkumab, ri- sankizumab and tildrakizumab over the age of 65, but there are no data in clinical practice on the efficacy of ixekizumab in the elderly patients [13]. However, most of the reported relevant clinical studies on biologics in elderly patients have focused on the efficacy and safety of anti-TNFα drugs, ow- ing to their longer market availability [11,12-14]. Regarding anti-IL-17 inhibitors, a recent study including 114 elderly patients showed that these drugs were an effective and safe therapeutic option for patients with psoriasis aged ≥ 65 years, with low rates of only mild adverse events; however, the dis- continuation rate was 28.9%, mostly related to psoriasis re- lapses. A post hoc analysis of three phase III secukinumab trials (ERASURE, FIXTURE and CLEAR) showed compa- rable efficacy profiles between elderly and younger patients; however, the rates of serious AEs and discontinuation were higher in older participants [15,16]. For ixekizumab, a ret- rospective observational study showed optimal efficacy and safety in elderly patients throughout a 1-year treatment pe- riod, confirming the results highlighted in the drug product information, reporting that the response in elderly patients seems to be higher than that in younger patients [17]. We performed a multicenter, retrospective, observational analy- sis in real life in patients with chronic plaque psoriasis and psoriatic arthritis of elderly patients (>65 years) treated with ixekizumab. We included male and female patients attending the outpatient clinics of seven Italian referral center for psori- asis in Lazio Region: Policlinico Umberto I Università Roma La Sapienza, Sant’Andrea Università di Roma La Sapienza, Polo Pontino Università Roma La Sapienza, Fondazione Policlinico Universitario A. Gemelli, Università Campus Bio- medico Roma; Istituto Dermopatico dell’Immacolata – IDI; Policlinico Tor Vergata. Our results show that ixekizumab was found to be effective and safe in the whole sample of en- rolled patients, every parameter taken into consideration has already significantly improved at week 16, maintaining the results. Subgroup analyzes confirmed that time is significant Figure 4. Trend in mean Psoriasis Area and Severity Index (PASI) score by sex at each time point. Table 7. Subgroups comparison on a selected list of variables Female Male Pmean SD mean SD PASI (baseline) 12.2 6.5 16.5 9.8 0.07 VAS (baseline) 17.0 25.2 16.2 22.3 0.54 DLQI (baseline) 15.7 6.8 16.1 5.9 0.79 Age 72.0 5.9 71.2 6.7 0.45 PsO PsO-PsA Pmean SD mean SD PASI (baseline) 15.4 6.5 14.2 9.7 0.47 VAS (baseline) 6.0 1.4 16.8 23.1 0.07 DLQI (baseline) 18.3 3.8 14.6 6.9 0.07 Age 71.0 6.4 71.4 6.0 0.21 Bio-naive Not Bio-naive Pmean SD mean SD PASI (baseline) 14.2 8.9 16.0 8.1 0.55 VAS (baseline) 16.3 23.5 18.6 23.2 0.19 DLQI (baseline) 15.3 6.6 18.0 4.1 0.23 Age 71.2 6.1 72.9 7.2 0.51 BMI <25 BMI≥25 Pmean SD mean SD PASI (baseline) 10.9 6.7 16.1 9.1 0.02 VAS (baseline) 21.1 28.3 14.6 20.8 0.65 DLQI (baseline) 15.1 6.7 16.2 6.1 0.41 Age, years 71.8 7.4 71.4 5.9 0.89 BMI = body mass index; DLQI = Dermatology Life Quality Index PsA = psoriatic arthritis; PsO = psoriasis; SD standard deviation. PASI = Psoriasis Area and Severity Index; SD = standard deviation; VAS = Visual Analogue Scale. Original Article | Dermatol Pract Concept. 2024;14(3):e2024166 9 Table 8. Subgroups comparisons Sex PASI score P-value PASI score P-value M vs F 0.037 Naive, Bio-experienced Naive vs Bio-experienced 0.99 BL vs week 16 <0.0001 BL vs week 16 <0.0001 BL vs week 24 <0.0001 BL vs week 24 <0.0001 BL vs week 52 <.,0001 BL vs week 52 <0.0001 BL vs week 104 <0.0001 BL vs week 104 <0.0001 BL vs week 156 <0.0001 BL vs week 156 <0.0001 VAS score P-value VAS score P-value M vs F 0.247 Naive vs Bio-experienced 0.259 BL vs week 16 0.004 BL vs week 16 <0.0001 BL vs week 24 0.005 BL vs week 24 <0.0001 BL vs week 52 0.006 BL vs week 52 <0.0001 BL vs week 104 0 BL vs week 104 <0.0001 BL vs week 156 0.015 BL vs week 156 <0.0001 DLQI score P-value DLQI score P-value M vs F 0.829 Naive vs Bio-experienced 0.265 BL vs week 52 <0.0001 BL vs week 52 <0.0001 BMI<25, BMI≥25 PASI score P-value PsO, Pso-PsA PASI score P-value BMI<25 vs BMI≥25 0.374 PsO vs PsO-PsA 0.647 BL vs week 16 <0,0001 BL vs week 16 <0.0001 BL vs week 24 <0.0001 BL vs week 24 <0.0001 BL vs week 52 <0.0001 BL vs week 52 <0.0001 BL vs week 104 <0.0001 BL vs week 104 <0.0001 BL vs week 156 <0.0001 BL vs week 156 <0.0001 VAS score P-value VAS score P-value BMI<25 vs BMI≥25 0.97 PsO vs PsO-PsA 0.239 BL vs week 16 <0.0001 BL vs week 16 <0.0001 BL vs week 24 <0.0001 DLQI score p-value BL vs week 52 <0.0001 PsO vs PsO-PsA 0.291 BL vs week 104 <0.0001 BL vs week 52 <0.0001 BL vs week 156 <0.0001 DLQI score P-value BMI<25 vs BMI≥25 0.668 BL vs week 52 <0.0001 BL = Baseline ;BMI = body mass index; DLQI = Dermatology Life Quality Index; PsO = Psoriasis PsA = Psoriatic Arthritis ; PASI Psoriasis Area and Severity Index; VAS =Visual Analogue Scale; vs = versus. but that, among subgroups, only gender for PASI is signif- icant. 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