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Background: This safety analysis investigates treatment-emergent mucosal/cutaneous Candida infections in patients treated with ixekizumab (IXE), an anti-interleukin-17A monoclonal antibody, across the approved indications: psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA)., Research Design and Methods: Safety data were pooled from 25 clinical studies. Incidence rates (IRs) are expressed as per 100 patient-years (PY), using the entire duration of exposure., Results: Candida infections had an IR of 1.9 per 100 PY in patients with PsO ( N  = 6892; total PY = 18025.7), 2.0 per 100 PY in patients with PsA ( N  = 1401; total PY = 2247.7), and 1.2 per 100 PY in patients with axSpA ( N  = 932; total PY = 2097.7). The majority of treatment-emergent Candida infections were: (i) experienced only once by patients (IR = 1.3;IR = 1.6;IR = 1.0), (ii) mild/moderate in severity (IR = 0.8/0.9;IR = 1.5/0.4;IR = 0.8/0.5) as opposed to severe (IR = 0.0; IR = 0.0; IR = 0.0), (iii) oral Candida or genital Candida (IR = 0.9/0.6;IR = 1.0/0.7;IR = 0.4/0.6), (iv) marked as recovered/resolved during the studies (89.3%;93.8%;90.3%), (v) not leading to IXE discontinuation (0.0%;0.0%;0.1% discontinued), (vi) managed with topical (34.7%;22.2%;11.5%) or no anti-fungal medications (63.5%;77.8%;80.8%) as opposed to systemic therapies (1.5%;0.0%;7.7%), (vii) typically resolved before next visit., Conclusions: This integrated safety analysis shows that the risk of developing Candida infections is low with IXE, and the severity is mild-to-moderate in most instances across the approved IXE indications., Trial Registration: A comprehensive list of the clinical trials and their registration numbers is reported in Table S1 of the supplemental material.

Despite the abundance of data concerning biologic treatments for patients with psoriasis, clinicians are often challenged with discerning the optimal treatment for each patient. To inform this selection, this study explored whether a patient's baseline characteristics or disease profile could predict the likelihood of achieving complete skin clearance with biologic treatment. Machine-learning and other statistical methods were applied to the substantial data collected from patients with moderate-to-severe psoriasis in the ongoing, international, prospective, observational Psoriasis Study of Health Outcomes (PSoHO). The 3 measures of complete skin clearance were a psoriasis area and severity index (PASI)100 response at (a) week 12, (b) month 12, and (c) week 12 and maintain ed at month 6 and month 12 (PASI100 durability). From these real-world data, the absence of nail psoriasis emerged  as the most consistent feature that may be used by clinicians to predict high-level treatment responses with biologic treatment. Other significant predictors of skin clearance with biologic treatments were the absence of hypertension and a lower body surface area affected by psoriasis. Overall, this study evidences the substantial challenge of identifying reliable clinical markers of treatment response for patients with psoriasis and highlights the importance of regular screening for psoriatic nail involvement.

Purpose: Currently, in the treatment of moderate-to-severe psoriasis (PsO) there is a lack of evidence demonstrating optimal biologic treatment response with respect to disease duration. The aim of this post-hoc analysis, using real world data from the Psoriasis Study of Health Outcomes (PSoHO), is to provide evidence if early intervention with biologics is associated with better treatment outcomes and if there is any difference among drug classes or individual biologics., Materials and Methods: For this post-hoc analysis patients were categorised into two subgroups according to shorter (≤2 years) or longer (>2 years) disease duration. Analysis was performed on anti-interleukin (IL)-17A cohort vs other biologics cohort, anti-IL-17A vs other drug classes, and pairwise comparisons of ixekizumab vs individual biologics, provided that the statistical models converged. Analysis investigated the association of disease duration with the proportion of patients achieving 100% improvement in Psoriasis Area Severity Index score (PASI 100) at week 12. Adjusted comparative analyses, reported as odds ratio (OR), were performed using Frequentist Model Averaging (FMA) for each cohort or treatments within each subcategory of the subgroups., Results: At week 12, anti-IL-17A and other biologics cohorts displayed minimal differences in numerical response rate for PASI 100 with respect to disease duration. The anti-IL-17A cohort showed a higher numerical PASI 100 response rate compared to the other biologic cohort irrespective of disease duration (≤2 years: 36.7% vs 21.8%; >2 years: 35.8% vs 21.9%)., Conclusion: Overall, the results do not clearly indicate that treating patients early is critical in achieving optimal patient outcomes. Furthermore, patients treated with ixekizumab show numerically higher response rates relative to other individual biologics irrespective of disease duration.

Objectives: To describe the results of a structured literature review of real-world outcomes with ixekizumab in patients with psoriasis (PsO) and/or psoriatic arthritis (PsA)., Methods: Literature databases, conference proceedings and additional sources were searched for relevant publications. Real-world studies of ≥25 ixekizumab-treated patients with PsO and/or PsA were included. Data on clinical effectiveness, treatment persistence/patterns, economic outcomes, patient-reported outcomes (PROs) and safety were extracted., Results: Fifty-one publications were included. Most studies focused on patients with PsO, and the number of publications with a focus on PROs was low. Studies of treatment patterns found that in general, ixekizumab had similar or better persistence versus other biologics, and rates or risk of switching similar to or less than comparator drugs. Adherence to ixekizumab was high, and patients were less likely to discontinue ixekizumab than other biologics. Ixekizumab was effective in the real world, with a safety profile consistent with that reported in clinical trials., Conclusions: Real-world use of ixekizumab in PsO and PsA is effective and safe, with generally high treatment persistence and adherence. Further work is required to determine the impact of ixekizumab on PROs in PsO, and to gather more data on real-world use of ixekizumab in PsA.

Background: Available network meta-analyses (NMAs) comparing the efficacy of biologics in nail psoriasis (NP) have not included recently approved biologics such as bimekizumab nor have they provided comparisons up to 1 year., Objective: We conducted two NMAs that update and extend results from a previous NMA comparing biologics for achieving complete resolution of NP., Methods: Bayesian NMAs were performed using a generalized linear model with a logit link to model the binary outcome of nail clearance at weeks 24-28 and 48-52., Results: For the NMA at weeks 24-28, which included seven biologics and placebo, the absolute probability of achieving complete resolution of NP was highest for ixekizumab (46.4%; 95% credibility interval [CrI] 35.2-58.0), followed by brodalumab (37.1%; 95% CrI 17.1-62.2) and bimekizumab (30.3%; 95% CrI 12.7-53.9). For the NMA at weeks 48-52, which included six biologics, the absolute probability was highest for ixekizumab (77.2%; 95% CrI 51.1-93.4), followed by adalimumab (75.6%; 95% CrI 61.5-87.3) and brodalumab (71.9%; 95% CrI 38.4-93.2)., Conclusion: Among biologics included in these two NMAs, ixekizumab has the highest absolute probability of achieving complete resolution of NP. Results may help to inform treatment decisions for patients with NP.

Background: Rapid skin improvement is a key treatment goal of patients with moderate-to-severe psoriasis (PsO)., Objectives: To compare the speed of clinical improvement of approved biologics on the symptoms and signs of psoriasis assessed by patients using the validated Psoriasis Symptoms and Signs Diary (PSSD) through 12 weeks., Methods: Psoriasis Study of Health Outcomes (PSoHO) is an international, prospective, non-interventional study that compares the effectiveness of anti-interleukin (IL)-17A biologics versus other biologics, together with pairwise comparisons of ixekizumab versus five individual biologics in patients with PsO. Using the PSSD 7-day recall period, patients assessed the symptoms (itch, skin tightness, burning, stinging and pain) and signs (dryness, cracking, scaling, shedding/flaking, redness and bleeding) of their psoriasis (0-10). Symptom and sign summary scores (0-100) are derived from the average of individual scores. Percentage change in summary scores and proportion of patients with clinically meaningful improvements (CMI) in PSSD summary and individual scores are evaluated weekly. Longitudinal PSSD data are reported as observed with treatment comparisons analysed using mixed model for repeated measures (MMRM) and generalized linear mixed models (GLMM)., Results: Across cohorts and treatments, eligible patients (n = 1654) had comparable baseline PSSD scores. From Week 1, the anti-IL-17A cohort achieved significantly larger score improvements in PSSD summary scores and a higher proportion of patients showed CMIs compared to the other biologics cohort through 12 weeks. Lower PSSD scores were associated with a greater proportion of patients reporting their psoriasis as no longer impacting their quality-of-life (DLQI 0,1) and a high level of clinical response (PASI100). Results also indicate a relationship between an early CMI in PSSD score at Week 2 and PASI100 score at Week 12., Conclusions: Treatment with anti-IL-17A biologics, particularly ixekizumab, resulted in rapid and sustained patient-reported improvements in psoriasis symptoms and signs compared with other biologics in a real-world setting., (© 2023 Eli Lilly and Co and The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Introduction: In routine clinical care, important treatment outcomes among patients with moderate-to-severe plaque psoriasis (PsO) have been shown to vary according to patient demographics and disease characteristics. This study aimed to provide direct comparative effectiveness data at week 12 between anti-interleukin (IL)-17A biologics relative to other approved biologics for the treatment of PsO across seven clinically relevant patient subgroups in the real-world setting., Methods: From the international, non-interventional Psoriasis Study of Health Outcomes (PSoHO), 1981 patients with moderate-to-severe PsO were grouped a priori according to seven clinically relevant demographic and disease variables with binary categories, which were sex (male or female), age (< 65 or ≥ 65 years), body mass index (≤ 30 or > 30 kg/m 2 ), race (White or Asian), PsO disease duration (< 15 or ≥ 15 years), psoriatic arthritis (PsA) comorbidity (present or absent), and prior biologic use (never or ≥ 1). Across these subgroups, effectiveness was compared between the anti-IL-17A cohort (ixekizumab, secukinumab) versus all other approved biologics and ixekizumab versus five individual biologics. The proportion of patients in each subgroup who achieved 90% improvement in Psoriasis Area and Severity Index (PASI90) and/or static Physician Global Assessment (sPGA) 0/1, PASI100, or PASI90 at week 12 were assessed. Comparative analyses were conducted using frequentist model averaging (FMA). Missing data were imputed using non-responder imputation., Results: Patients in each of the seven subgroups achieved similar response rates to those of the overall treatment cohort, apart from patients with PsA treated with other biologics who had 7-10% lower response rates. Consequently, patients with comorbid PsA had significantly higher odds of achieving skin clearance at week 12 with anti-IL-17A biologics compared to other biologics. Patients in all subgroups had significantly higher odds of achieving PASI90 and/or sPGA (0,1), PASI100, and PASI90 in the anti-IL-17A cohort relative to the other biologics cohort, except for the Asian subgroup. No sex- or age-specific differences in treatment effectiveness after 12 weeks were identified, neither between the treatment cohorts nor between the individual treatment comparisons., Conclusions: Despite relative consistency of comparative treatment effectiveness across subgroups, the presence of comorbid PsA may affect a patient's clinical response to some treatments., (© 2023. The Author(s).)

Background: Clinical trials study treatment outcomes under stringent conditions, capturing incompletely the heterogeneity of patient populations and treatment complexities encountered in real-world practice., Objectives: To compare the effectiveness of anti-interleukin (IL)-17A biologics relative to other approved biologics in patients with moderate-to-severe psoriasis., Methods: The Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year observational cohort study in adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. Primary study endpoint is the proportion of patients achieving 90% improvement in Psoriasis Area and Severity Index (PASI 90) and/or static Physician Global Assessment (sPGA) 0/1 at Week 12 (W12) in the anti-IL-17A cohort (ixekizumab [IXE], secukinumab) vs. all other approved biologics. Secondary outcomes include the proportion of patients who achieve PASI 75/90/100, absolute PASI scores ≤5, ≤2 and ≤1, Dermatology Life Quality Index (DLQI) score of 0/1 at W12 between the two cohorts and among the individual biologics. Comparative effectiveness analyses were conducted using Frequentist Model Averaging (FMA), a novel causal inference machine learning approach. Missing data for binary outcomes were imputed as non-response., Results: Patient profiles in the anti-IL-17A cohort and other biologics cohort were similar, with more frequent comorbid psoriatic arthritis and less frequent exposure to conventional treatments in the patients receiving anti-IL-17A biologics. At W12, 71.4% of patients who received an anti-IL-17A biologic achieved PASI 90 and/or sPGA 0/1 compared to 58.6% of patients who received other biologics (odds ratios [OR], 1.9; 95% confidence intervals [CI], [1.6, 2.4]). Similar findings were observed for secondary outcomes., Conclusions: These results reflect the high efficacy and early onset of skin clearance of IL-17A inhibitors observed in randomized clinical trials and confirm the effectiveness of anti-IL-17A biologics in the real-world setting., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Nail psoriasis is a chronic, difficult-to-treat condition affecting almost half of patients with psoriasis. It is associated with considerable social stigma and impairment of patients' quality of life. The aim of this study was to assess improvements in objective measures of nail psoriasis among patients from the long-term extension of the UNCOVER-3 study who received the interleukin-17A inhibitor ixekizumab and had either any degree of nail psoriasis (Nail Psoriasis Severity Index (NAPSI) >=1) or significant nail psoriasis (fingernail NAPSI ≥ 16 and ≥ 4 fingernails involved) at baseline. Efficacy outcomes reported through week 264 included the mean percentage improvements from baseline in NAPSI score and the proportion of patients achieving nail psoriasis resolution (NAPSI=0). In UNCOVER-3, 56.9% (219/385) of patients had nail psoriasis at baseline; of those, 61.2% (134/219) had significant nail psoriasis. At week 60, a total of 66.9% and 59.1% of patients with baseline nail psoriasis and significant baseline nail psoriasis, respectively, reported complete clearance of nail psoriasis, an effect which was sustained through week 264. This analysis demonstrates that continuous treatment with ixekizumab in adult patients with moderate-to-severe-psoriasis through 264 weeks was associated with improvements and clearance of fingernail psoriasis, irrespective of the severity of nail psoriasis at baseline.

Background: Nail psoriasis (NP) is common and of high importance in patients with psoriasis. Complete resolution of NP at week 24‒26 is an unambiguous nail outcome accessible for indirect treatment comparison of biologics., Objective: To evaluate the comparative efficacy of approved biologics in achieving complete resolution of NP at week 24‒26., Methods: A network meta-analysis (NMA) was conducted to indirectly compare the efficacy of six biologics in achieving complete resolution of NP at week 24‒26 in patients with moderate-to-severe psoriasis and concomitant NP. Complete resolution of NP was defined as a score of zero on the Nail Psoriasis Severity Index (NAPSI), modified NAPSI (mNAPSI) or Physician's Global Assessment of Fingernails (PGA-F)., Results: The probability of achieving complete resolution of NP was highest for ixekizumab (46.5%; 95% credibility interval [CrI] 35.1‒58.0; Surface Under the Cumulative RAnking curve [SUCRA] 97%), followed by brodalumab (37.0%; 17.0‒61.0; 79%), adalimumab (28.3%; 24.4‒32.4; 62%), guselkumab (27.7%; 21.1‒35.1; 58%), ustekinumab (20.8%; 10.2‒35.2; 37%), and infliximab (0.8%; 0.0‒8.9; 17%)., Conclusion: In patients with moderate-to-severe psoriasis and concomitant NP, ixekizumab has the greatest likelihood among approved biologics of achieving complete resolution of NP at week 24‒26. Findings should be interpreted carefully because of inherent study limitations.

Objectives: This study aimed to elicit preferences for psoriasis treatment features and to test for preference heterogeneity across groups of respondents., Materials and Methods: A discrete-choice experiment was employed to elicit preferences of patients with plaque psoriasis in multiple countries. The survey instrument included a series of choice questions between three hypothetical treatments, each characterized by varying levels of six attributes (namely, lesion reduction, risk of impairing side effects, time to reach results, mode and frequency of administration, itching reduction, and side effects). Random parameters logit was used to model the data. Results were compared across a total of 18 subgroup sets., Results: The data analysis from 1,123 respondents showed that, on average, respondents receive more utility gain from higher levels of lesion reduction and lower risks of impairing side effects than changes in other attributes included in the study. Systematic differences were detected for 13 sets; the most pronounced differences were observed based on disease severity, nail psoriasis, biologic experience, and quality-of-life scores., Conclusion: These many sources of preference heterogeneity identified by our analysis suggest that to improve patient satisfaction and, probably, adherence and persistence, clinicians should discuss options with patients when prescribing their treatment.

In clinical practice, interruption of treatment may not result in immediate cessation of disease control, and some patients even experience sustained treatment response following treatment interruption. This post hoc analysis of UNCOVER-1 and -2 Phase 3 clinical trials characterized the time to loss of treatment response in patients with psoriasis who responded to ixekizumab through a 12-week treatment period, and who were then re-randomized to placebo for the following 48 weeks. For those with static Physician Global Assessment [sPGA]0/1 and Psoriasis Area and Severity Index [PASI]90 at Week 12, the median time to loss of PASI90 was 16.1 weeks (95% confidence interval 12.7-16.4). For those with PASI100 at Week 12, the median time to loss of PASI100 was 12.1 weeks (95% confidence interval 9.0-13.0). A small subset of patients maintained high levels of disease control through Week 60. This study adds to the growing body of evidence on sustained treatment response following treatment interruption.

Background: It is challenging to select the most appropriate biologic treatment for patients with moderate-to-severe plaque psoriasis., Objective: To compare speed of onset and level of skin improvement between the interleukin (IL)-17A antagonist ixekizumab and the IL-23 p19 inhibitors guselkumab, tildrakizumab, and risankizumab in patients with moderate-to-severe plaque psoriasis., Methods: Using data from controlled clinical trials, both adjusted indirect comparisons (AICs) and matching adjusted indirect comparisons (MAICs) were performed to determine the risk difference (RD) between ixekizumab and each IL-23 p19 inhibitor for the proportion of patients with ≥75%/90%/100% improvement compared with baseline in Psoriasis Area and Severity Index (PASI 75/90/100) up to week 12. Placebo, etanercept, or ustekinumab were used as the comparator bridge., Results: In all (M)AICs, RDs generally significantly favored ixekizumab over guselkumab (placebo bridge), tildrakizumab (placebo or etanercept bridge), and risankizumab (placebo or ustekinumab bridge) from the earliest assessment time (≥ week 2) to week 12 when considering PASI 75/90/100 responses., Conclusion: Ixekizumab provides a faster onset of effect and earlier clinical benefits than guselkumab, tildrakizumab, or risankizumab in patients with moderate-to-severe psoriasis, as reflected by higher levels of skin improvement than with these IL-23 p19 inhibitors up to week 12.

The sphingolipid sphingosine-1-phosphate (S1P) fulfills distinct functions in immune cell biology via binding to five G protein-coupled receptors. The immune cell-specific sphingosine-1-phosphate receptor 4 (S1pr4) was connected to the generation of IL-17-producing T cells through regulation of cytokine production in innate immune cells. Therefore, we explored whether S1pr4 affected imiquimod-induced murine psoriasis via regulation of IL-17 production. We did not observe altered IL-17 production, although psoriasis severity was reduced in S1pr4-deficient mice. Instead, ablation of S1pr4 attenuated the production of CCL2, IL-6, and CXCL1 and subsequently reduced the number of infiltrating monocytes and granulocytes. A connection between S1pr4, CCL2, and Mϕ infiltration was also observed in Zymosan-A induced peritonitis. Boyden chamber migration assays functionally linked reduced CCL2 production in murine skin and attenuated monocyte migration when S1pr4 was lacking. Mechanistically, S1pr4 signaling synergized with TLR signaling in resident Mϕs to produce CCL2, likely via the NF-κB pathway. We propose that S1pr4 activation enhances TLR response of resident Mϕs to increase CCL2 production, which attracts further Mϕs. Thus, S1pr4 may be a target to reduce perpetuating inflammatory responses., (© 2020 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Massimo Travaglini,1 Julia-Tatjana Maul,2,3 Christian Kors,4 Shirin Zaheri,5 Jens Gerwien,6 Michaela Müller,6 Alan Brnabic,6 Silvia Sabatino,6 Christopher Schuster,6,7 Tsen-Fang Tsai8 1Centre for the Treatment of Psoriasis, Di Summa-Perrino Hospital, Brindisi, Italy; 2Department of Dermatology and Venereology, University Hospital of Zurich, Zurich, Switzerland; 3Faculty of Medicine, University of Zurich, Zurich, Switzerland; 4Private Practice Dermatology, Berlin, Germany; 5Department of Dermatology, The Harley Street Clinic, HCA Healthcare UK, London, UK; 6Eli Lilly and Company, Indianapolis, IN, USA; 7Department of Dermatology, Medical University of Vienna, Vienna, Austria; 8Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei City, TaiwanCorrespondence: Tsen-Fang Tsai, Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, 7, Chung-Shan South Road, Taipei City, 100225, Taiwan, Tel +886 223123456&num;65734, Email tftsai@yahoo.comPurpose: Since skin is highly accessible, clinical photography is a useful tool to visually substantiate the real-world effectiveness outcomes of biologic-treated adults with moderate-to-severe psoriasis (PsO). We report the effectiveness and patient-reported outcomes at Week 12 between anti-interleukin (IL)-17A biologics and other biologics as well as ixekizumab and guselkumab in patients with available clinical photography at baseline and Week 12.Patients and Methods: The Psoriasis Study of Health Outcomes (PSoHO) is an international, non-interventional, cohort study investigating the effectiveness of biologics in adults with moderate-to-severe psoriasis at Week 12. Outcomes included the proportion of patients who achieved 90% improvement in Psoriasis Area and Severity Index (PASI90) and/or static Physician Global Assessment (sPGA) 0/1 (primary endpoint), PASI100, PASI90, Dermatology Life Quality Index (DLQI), and Itch Numeric Rating Scale (NRS) (secondary endpoints) at Week 12. Data are reported descriptively.Results: This analysis included 59 biologic-treated (23 anti-IL-17A; 36 other biologics) patients with available clinical photographs from the overall PSoHO study (n=1981). At baseline, the mean (standard deviation [SD]) age was 45.7 (11.1) years, 71.2% were male, 52.5% were bio-experienced and the median (interquartile range) duration of disease was 10.5 (12.4) years. Mean (SD) PASI was 16.9 (9.3) and sPGA was 3.5 (0.8). At Week 12, 65.2%/47.2% of the anti-IL-17A/other biologics cohort achieved the primary outcome. Response rates for PASI90/100 were numerically higher with anti-IL-17A than with other biologics. Patients receiving anti-IL-17A had numerically better outcomes for DLQI 0/1 and Itch NRS than those receiving other biologics at Week 12. Clinical photographs confirmed skin improvements in ixekizumab- and guselkumab-treated patients.Conclusion: This subgroup analysis showed that anti-IL-17A biologics are effective at rapidly improving signs and symptoms of PsO and improving quality of life. Additionally, serial photography provided visual evidence of biologic treatment response over time.Keywords: psoriasis, ixekizumab, guselkumab, real-world, clinical photography

PSY48 DO CLINICAL AND DEMOGRAPHIC CHARACTERISTICS AFFECT PATIENT PREFERENCE HETEROGENEITY FOR PSORIASIS TREATMENTS? This study aimed to elicit patients' preferences for psoriasis treatments and to test whether patients with different characteristics have systematically different preferences. We identified systematic differences in preferences across multiple subgroups indicating that determining the appropriate psoriasis treatment may be informed by patient characteristics and their preferences. [Extracted from the article]