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Background Dermatologists would benefit from an easy to use psoriasis severity assessment tool in the clinic. Objective To develop psoriasis assessment tools to predict PASI and Dermatology Life Quality Index (DLQI) using simple measures typically collected in clinical practice. Methods Data included 33 605 dermatology visits among plaque psoriasis patients enrolled in the CorEvitas Psoriasis Registry (4/15/15-7/11/20). Performance (adjusted coefficient of determination [R2adj], root mean square error [RMSE]) in predicting PASI and DLQI was assessed for 16 different linear regression models (specified a priori based on combinations of BSA, Investigator’s Global Assessment [IGA], itch, skin pain, patient global assessment, age, sex, BMI, comorbidity index, prior biologic use), and 2 stepwise selection models and 1 elastic net model based on 56 available variables. For each prediction model, concordance (sensitivity, specificity) of predicted PASI75, PASI90 and DLQI 0/1 with observed values was evaluated. Results Mean (SD) age, BSA, and PASI were 51 (14) years, 6 (11), and 4 (6), respectively; 46% were women, and 87% were biologic experienced. A model predicting PASI using BSA plus IGA performed best among a priori specified models (R2adj = .72, RMSE = 2.93) and only marginally worse than models including additional variables (R2adj range .64-.74, RMSE range 2.82-3.36). Models including IGA had the best concordance between predicted and observed PASI75 (sensitivity range 83-85%, specificity range 88-91%) and PASI90 (sensitivity range 76-82%, specificity range 94-98%). DLQI prediction was limited. Conclusion An assessment tool for psoriasis including BSA and IGA may be an ideal option to predict PASI in a clinic setting.

Number needed to treat (NNT) estimates are a practical metric to help identify the most effective therapies. Our objective is to compare 11 biologic drugs for moderate-to-severe psoriasis in terms of NNT.The NNT data were obtained from a Bayesian network meta-analysis of 42 double-blind, randomized, phase 3 clinical trials for 11 biologics (adalimumab, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab, and ustekinumab). We determined NNT to achieve Psoriasis Area and Severity Index (PASI) 75/90/100 responses at weeks 4, 8, 12, 16, and 48/52 and Dermatology Life Quality Index (DLQI) response 0, 1 at week 12.Highest efficacy (lowest NNT) was with brodalumab and ixekizumab for PASI 90 at weeks 4, 8, and 12; ixekizumab for PASI 90/100 at week 16; and brodalumab for PASI 100 at week 12. After 48/52 weeks, risankizumab had the highest efficacy for PASI 90/100 overlapping with guselkumab, brodalumab, and ixekizumab for PASI 90 and with brodalumab and ixekizumab for PASI 100. Ixekizumab had the highest efficacy for DLQI (0,1) at week 12.Brodalumab and ixekizumab had the lowest NNTs for achieving PASI responses at early time points and were not significantly different than risankizumab and guselkumab after 48/52 weeks.

Objective To assess treatment patterns of Ixekizumab (IXE) and evaluate the speed of onset and long-term clinical and quality-of-life outcomes among a subset of patients who switched from adalimumab (ADA) and secukinumab (SEC) to IXE in a real-world setting. Method A retrospective chart review study was conducted at a single US dermatology referral center. Result 153 patients were included in the study, 69.3% of patients were biologic-experienced. ADA was the most commonly used biologic prior to IXE initiation. 66.7% of patients remained on IXE at the study end. 47.7% of patients received concomitant methotrexate, and usage decreased consistently after 1 month. IXE treatment duration was longer among patients who were early responders (achieved sPGA (0,1) at 1 month) vs. non-early responders. 69.4% and 43.3% of patients who switched from ADA and SEC to IXE achieved sPGA (0,1) by week 4, respectively. Conclusion Patients who switched to IXE, specifically from ADA or SEC, had rapid treatment response as well as desirable long-term outcomes. IXE persistence was longer among early responders than non-early responders. Concomitant usage of methotrexate prior to switching to IXE and as a concomitant bridging treatment was reduced after IXE initiation while the proportion of patients achieving treatment targets remained high.

Background:Generalized pustular psoriasis (GPP) is a rare, severe neutrophilic skin disease with high unmet clinical need. The introduction of a GPP-specific International Classification of Diseases, 10thRevision (ICD-10), code has made it possible to generate a more accurate GPP patient profile.Objectives:To describe the characteristics and compare the patient profile and burden of disease of patients with GPP with patients with plaque psoriasis.Methods:A retrospective study was conducted using a US administrative claims database, the IBM® MarketScan® Research Database. The study took place between October 1, 2015, and September 30, 2018. Patients with at least 1 inpatient or 2 outpatient L40.1 (GPP) or L40.0 (psoriasis vulgaris) diagnostic codes were included for analysis. Outcome measures included descriptions of comorbidities, medication use, and healthcare resource utilization (HCRU) among GPP, plaque psoriasis, and general population (matched to those with GPP) cohorts.Results:Patients with GPP had more baseline comorbidities than those with plaque psoriasis and the matched cohort, including psoriatic arthritis (20.6% vs 6.4% and Conclusion:Patients with GPP generally experience more comorbidities, with higher HCRU, than patients with plaque psoriasis. Although the large dataset permitted identification of GPP patients with longitudinal follow-up, the lack of a validation algorithm for GPP is a limitation and a potential area for future research.

Introduction Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is an approved treatment for plaque psoriasis. This study aimed to use animated visualizations as a tool to simplify complex data from ixekizumab clinical trials. Methods Animated visualizations were developed to show outcomes from ixekizumab clinical trials and a Bayesian network meta-analysis of 11 approved biologics. The visualizations simultaneously highlighted both aggregate scores and the individual progression of patients over the course of treatment. Results The animations provided key messages and information from the complex data in efficient and scientific ways that were also visually pleasing and simple to understand. The animations highlighted (1) rapid reduction in disease severity from baseline; (2) sustained efficacy of ixekizumab in the treatment of skin and nail psoriasis; (3) side-by-side comparisons of treatment efficacy and clinical improvement across trials; (4) simultaneous visual presentation of individual results with summary response over time; and (5) indirect comparison of relative treatment effects with other biologics based on Bayesian network meta-analysis. Conclusion The rapid and sustained efficacy of ixekizumab in the treatment of psoriasis was demonstrated using multiple dynamic visualizations with different clinical endpoints. Animated visualizations provided a simpler and more comprehensive understanding of complex data than conventional static figures. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00548-2.

Introduction Psoriasis Area Severity Index (PASI) assessment is complex and time-consuming. A simpler assessment measure more sensitive to changes in symptom severity and predictive of patients’ quality of life (Dermatology Life Quality Index, DLQI) is needed. This study aims to evaluate the Optimal Psoriasis Assessment Tool (OPAT) as an alternative to PASI. Methods This integrated analysis of three UNCOVER trials (NCT01474512, NCT01597245, and NCT01646177) randomized patients (N = 3866) with moderate-to-severe psoriasis to subcutaneously administered ixekizumab 80 mg Q2W or Q4W, or placebo or etanercept 50 mg Q2W. Pearson correlations were computed for clinical and patient-reported measures with PASI and DLQI. Results As the correlations with PASI and BSA were high and not much higher when adding severity, body surface area (BSA) was used for the clinical measure. BSA was the main measure influencing OPAT. Week 12 regression analyses results showed that PASI had a higher correlation with BSA combined with patient assessments than with BSA alone. Sensitivity analyses were also completed for PASI 75 and 90. For DLQI, correlations with the combined measures were even stronger than with BSA alone. A comprehensive model selection procedure was conducted, which illustrated that the two-term models are preferred. Conclusion The OPAT is a simple and time-saving alternative to PASI. It can be derived using BSA and patient-reported assessments having strong correlation with PASI and moderate correlation with DLQI. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00544-6.

Background SDZ-ADL (GP2017; Sandoz GmbH, Austria) is an EMA-/FDA-approved adalimumab biosimilar. The effect of SDZ-ADL on quality of life (QoL) and patient-reported outcomes (PROs) was assessed as part of two phase III studies, one in patients with moderate‐to‐severe chronic plaque psoriasis (PsO; ADACCESS) and the other in patients with rheumatoid arthritis (RA; ADMYRA). Additionally, ADACCESS included patients with psoriatic arthritis (PsA). Methods ADACCESS included 465 patients with PsO, whereas ADMYRA included 353 patients with RA. Both studies evaluated and confirmed equivalent efficacy, similar safety, and immunogenicity of SDZ-ADL with reference adalimumab (ref-ADL). A third of patients underwent multiple (four) treatment switches between study treatments starting at Week 17 (ADACCESS); all patients switched from ref-ADL to SDZ-ADL at Week 24 (ADMYRA). Assessed PROs included Dermatology Life Quality Index (DLQI) and EuroQol five-dimension health status questionnaire (EQ-5D-5L) in ADACCESS, Functional Assessment of Chronic Illness Therapy–Fatigue Scale (FACIT-Fatigue) score in ADMYRA, and Health Assessment Questionnaire–Disability Index (HAQ-DI) in both studies. Results In both studies, baseline scores for all PRO assessments were comparable between the two treatment groups. In ADACCESS, mean DLQI decreased from baseline in both groups, and the mean (standard deviation [SD]) percent reductions from baseline in DLQI were comparable between groups at Week 17 (SDZ-ADL, − 64.5 [80.3]; ref-ADL, − 70.6 [41.7]), which were sustained after the switch at Week 51 (‘continued SDZ-ADL,’ − 79.7 [36.2]; ‘continued ref-ADL,’ − 80.8 [44.6]; ‘switched to SDZ-ADL,’ − 70.7 [32.2]; ‘switched to ref-ADL,’ − 69.3 [49.6]). In ADACCESS, the proportion of patients with an EQ-5D-5L score of 1 (no problems) increased from baseline for all five dimensions in all treatment groups and was comparable between treatment groups at Week 51. In ADACCESS, in patients with PsA at baseline, mean (SD) HAQ-DI scores decreased from baseline in both treatment groups, and scores were comparable between groups at Week 17 (SDZ-ADL, 0.5 [0.6]; ref-ADL, 0.5 [0.6]) and after switching at Week 51 (‘continued SDZ-ADL,’ 0.4 [0.5]; ‘continued ref-ADL,’ 0.4 [0.6]; ‘switched to SDZ-ADL,’ 0.5 [0.8]; ‘switched to ref-ADL,’ 0.7 [0.6]). In ADMYRA, proportion of patients achieving HAQ-DI in the normal range (≤ 0.5) was comparable between treatment groups at Week 24 (SDZ-ADL, 37.8%; ref-ADL, 36.3%) and after switching at Week 48 (‘SDZ-ADL,’ 41.6%; ‘ref-ADL/switched to SDZ-ADL,’ 40.0%). In ADMYRA, mean FACIT-Fatigue scores increased from baseline in both treatment groups. At Week 24, mean (SD) percent change from baseline in the FACIT-Fatigue scores was 75.4 (135.5) in SDZ-ADL and 73.0 (96.3) in ref-ADL groups; the scores were sustained after switching at Week 48. Conclusion Treatment with SDZ-ADL and ref-ADL resulted in comparable improvements in PROs as well as QoL scores across the three diseases, PsO, PsA, and RA. Switching between SDZ-ADL and ref-ADL had no negative impact on PROs across the reported period. Clinical trials.gov identifier NCT02744755, NCT02016105. Supplementary Information The online version of this article (10.1007/s40259-021-00470-1) contains supplementary material, which is available to authorized users.

Background: Palmoplantar psoriasis can severely impact patient quality of life. Despite the influx of many new medications, it remains one of the most challenging psoriasis phenotypes to treat. Case Description: Herein, we present a case series of 7 patients with hyperkeratotic palmoplantar psoriasis refractory to systemic therapy who were successfully treated with tofacitinib, a Janus kinase (JAK) 1/3 inhibitor. Conclusions: Tofacitinib may be an effective therapy for the management of recalcitrant palmoplantar psoriasis. The efficacy of tofacitinib for the treatment of palmoplantar psoriasis might clarify the dependence on this subtype of psoriasis on specific cytokines that signal through JAK 1/3.

Background In practice, the goal of treatment for patients with psoriasis is to achieve almost clear or clear skin and maintain disease control, regardless of baseline disease severity. However, identifying absolute Psoriasis Area and Severity Index (PASI) values for new treatment goals is challenging, as most clinical trials report relative PASI 50, 75, 90 or 100 improvements but rarely absolute PASI values achieved. Objective Our objective was to illustrate a statistical conversion method that was developed to derive absolute PASI values from available clinical trial data on relative PASI improvements. The results of network meta‐analyses (NMAs) based on these derived data were then compared with those of NMAs based on the corresponding relative PASI improvement data for selected biologics for moderate‐to‐severe psoriasis. Methods The PASI statistical conversion method was applied to relative PASI improvement data for 11 biologic treatment regimens and placebo at 12 weeks using data from 50 published studies. The respective proportions of patients reaching absolute PASI values ≤1, 2, 3 or 5 were then calculated. Frequentist NMAs (Rücker method) were subsequently used to compare efficacy results across relative and absolute PASI data. Results The ranking of included treatment regimens for patients achieving absolute PASI 0 to 8 was aligned with results for relative PASI scores (from 100 to 60) at end of induction therapy. Across the range of PASI scores considered, the most effective treatment regimens based on both absolute and relative PASI NMAs were brodalumab 210 mg every 2 weeks and ixekizumab 80 mg every 2 weeks, followed by guselkumab 100 mg every 8 weeks and risankizumab 150 mg every 12 weeks. Conclusion Data generated using this mathematical model will be useful to inform ongoing scientific discussions on treatment goals in the absence of primary absolute PASI data for all available treatments for moderate‐to‐severe plaque psoriasis.

Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the United States population. This guideline addresses important clinical questions that arise in psoriasis management and care and provides recommendations based on the available evidence. The treatment of psoriasis with topical agents and with alternative medicine will be reviewed, emphasizing treatment recommendations and the role of dermatologists in monitoring and educating patients regarding benefits as well as risks that may be associated. This guideline will also address the severity assessment methods of psoriasis in adults.

Background Risankizumab is a humanized IgG monoclonal antibody that selectively inhibits interleukin-23 through binding the p19 subunit. In Phase 3 trials, risankizumab demonstrated superior efficacy compared with adalimumab and ustekinumab in patients with moderate-to-severe plaque psoriasis. Here, we evaluated the impact of baseline characteristics on efficacy of risankizumab compared with ustekinumab in patients with moderate-to-severe plaque psoriasis. Methods This analysis included all patients initially randomized to risankizumab or ustekinumab from the replicate, double-blinded, randomized, placebo-controlled phase 3 trials, UltIMMa-1 (NCT02684370) and UltIMMa-2 (NCT02684357). Patients received either risankizumab (150 mg) or ustekinumab (weight-based; 45 or 90 mg per label) at weeks 0, 4, 16, 28 and 40. Efficacy was assessed as the proportion of patients achieving >= 90% improvement in Psoriasis Area and Severity Index (PASI 90) at weeks 16 and 52 by baseline patient demographics, disease characteristics and prior biologic exposure. Mean per cent improvement in PASI was calculated by body weight and body mass index at week 52. Missing efficacy data were imputed as non-responders for categorical variables and last observation carried forward for continuous variables. Logistic regression analyses assessed for interactions between treatment and five independent variables (age, sex, weight, baseline PASI score and presence of psoriatic arthritis) at both weeks 16 and 52. Results Baseline patient demographics, disease characteristics and prior biologic exposure were similar between patients randomized to risankizumab (n = 598) and ustekinumab (n = 199). At weeks 16 and 52, risankizumab demonstrated superior efficacy compared with ustekinumab across these patient characteristics (P < 0.01). Logistic regression analyses demonstrated that risankizumab was superior to ustekinumab at weeks 16 and 52 in all models tested (P < 0.0001 for all). Conclusions Risankizumab demonstrated consistent and superior efficacy compared with ustekinumab regardless of patient demographics, disease characteristics or prior biologic exposure.

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 2% of the world's population. In this guideline, we focus the discussion on systemic, nonbiologic medications for the treatment of this disease. We provide detailed discussion of efficacy and safety for the most commonly used medications, including methotrexate, cyclosporine, and acitretin, and provide recommendations to assist prescribers in initiating and managing patients on these treatments. Additionally, we discuss newer therapies, including tofacitinib and apremilast, and briefly touch on a number of other medications, including fumaric acid esters (used outside the United States) and therapies that are no longer widely used for the treatment of psoriasis (ie, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus).

Introduction Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for treatment of moderate-to-severe plaque psoriasis. Our objective was to evaluate the long-term efficacy and safety of ixekizumab in moderate-to-severe plaque psoriasis through 5 years. Methods Data were integrated from the UNCOVER-1 and UNCOVER-2, randomized, double-blinded, phase-3 trials. Patients who continuously received the labeled ixekizumab dose, were static Physician’s Global Assessment (sPGA) (0,1) responders at Week 12 and completed 60 weeks of treatment could enter the long-term extension (LTE) period. Patients could escalate to every-2-week dosing per investigator opinion. Efficacy and health outcomes included proportion of patients achieving Psoriasis Area and Severity Index (PASI) 75/90/100, sPGA (0,1) and (0), absolute PASI ≤ 5/ ≤ 3/ ≤ 2/ ≤ 1 and Dermatology Life Quality Index (DLQI) (0,1). Results exclude patients who escalated to every-2-week dosing. A modified non-responder imputation method was used to account for missing data. Supplemental analyses include patients who escalated to every-2-week dosing and observed and multiple imputation results. Exposure-adjusted safety outcomes are also reported. Results Of 206 patients who entered the LTE periods, 172 completed treatment. At Week 60, PASI 75/90/100 responses were 94.7%, 85.0% and 62.1%, respectively, and at year 5 were 90.3%, 71.3% and 46.3%, respectively. Similarly, meaningful responses were achieved for the other efficacy and health measures. Among patients with PASI 100 through 5 years, 92% achieved DLQI (0,1), indicating no impact of skin disease on quality of life. During the LTE period, exposure-adjusted incidence rates were 31.4 per 100 patient-years for treatment-emergent adverse events and 6.8 per 100 patient-years for serious adverse events. No deaths were reported. No new or unexpected safety findings were noted. Conclusions The results demonstrate 80 mg ixekizumab maintains long-term efficacy and a safety profile consistent with previous data in patients with moderate-to-severe plaque psoriasis through 5 years of treatment. Trial Registration ClinicalTrials.gov identifier, UNCOVER-1: NCT01474512, UNCOVER-2: NCT01597245. Electronic Supplementary Material The online version of this article (10.1007/s13555-020-00367-x) contains supplementary material, which is available to authorized users.

Background Psoriasis severity categories have been important tools for clinicians to use in treatment decisions as well as to determine eligibility criteria for clinical studies. However, owing to the heterogeneity of severity classifications and their lack of consideration for the impact of psoriasis involvement of special areas or past treatment history, patients may be miscategorized, which can lead to undertreatment of psoriasis. Objective To develop a consensus statement on the classification of psoriasis severity. Methods A modified Delphi approach was developed by the International Psoriasis Council to define psoriasis severity. Results After completion of the exercise, 7 severity definitions were preferentially ranked. This most preferred statement rejects the mild, moderate, and severe categories in favor of a dichotomous definition: Psoriasis patients should be classified as either candidates for topical therapy or candidates for systemic therapy; the latter are patients who meet at least one of the following criteria: (1) body surface area >10%, (2) disease involving special areas, and (3) failure of topical therapy. Limitations This effort might have suffered from a lack of representation by all relevant stakeholders, including patients. Conclusion The consensus statement describes 2 categories of psoriasis severity, while accounting for special circumstances where patients may require systemic therapy.

Psoriasis is a chronic, multisystem, inflammatory disease that affects approximately 1% of children, with onset most common during adolescence. This guideline addresses important clinical questions that arise in psoriasis management and provides evidence-based recommendations. Attention will be given to pediatric patients with psoriasis, recognizing the unique physiology, pharmacokinetics, and patient-parent-provider interactions of patients younger than 18 years old. The topics reviewed here mirror those discussed in the adult guideline sections, excluding those topics that are irrelevant to, or lack sufficient information for, pediatric patients.

Brodalumab, an interleukin-17 receptor A antagonist, is approved for treatment of moderate-to-severe plaque psoriasis in adults without response or with loss of response to other systemic therapies. In the United States, there is a boxed warning for brodalumab regarding suicidal ideation and behavior; however, no causal relationship between brodalumab and suicidality was established during pivotal trials. In the 2-year pharmacovigilance data, no completed suicides or suicide attempts were reported. The most frequent adverse event (AE) was arthralgia. The safety profile of brodalumab is now being updated after 3 years of pharmacovigilance data. Here, we outline pharmacovigilance data reported to Ortho Dermatologics by patients and healthcare professionals in the United States from August 15, 2017, to August 14, 2020. Brodalumab exposure estimates were obtained by calculating the time between first and last prescription-dispensing authorization dates. Data from 1854 patients were collected, and brodalumab exposure was estimated to be 2736 patient-years. The most frequent AE was arthralgia (111 events; 0.04 events per patient-year). One episode of suicide attempt was reported in a patient with a history of depression. No completed suicides were reported. There were 81 serious infections reported, none of which were fungal. Over the 3-year period, 30 malignancies occurred in 25 patients, none of which were determined to be related to brodalumab. Three-year pharmacovigilance data are consistent with the safety profile of brodalumab previously reported in long-term analyses of clinical trials and the 2-year pharmacovigilance data.

Background Long-term efficacy, safety, and quality of life with ixekizumab (IXE) through 5 years in UNCOVER-1 and UNCOVER-2 patients with baseline scalp, nail, or palmoplantar psoriasis were assessed. Methods Patients included in this intent-to-treat subanalysis had baseline involvement in at least one of the three anatomic areas (scalp, fingernail, or palmoplantar locations) and 1) received IXE through week 60, with a 160-mg starting dose 80 mg Q2W through week 12 and Q4W thereafter, 2) achieved a static Physicianrs Global Assessment score of 0 or 1 at week 12, and 3) completed week 60 and continued treatment with IXE Q4W or were escalated to Q2W during the long-term extension. Efficacy outcomes (e.g., percent improvement in Psoriasis Scalp Severity Index [PSSI], Nail Psoriasis Severity Index [NAPSI], Palmoplantar Psoriasis Area and Severity [PPASI], and Dermatology Life Quality Index [DLQI]) were summarized by descriptive statistics through week 264. Results Patients rapidly achieved and sustained improvements in scalp, nail, and palmoplantar psoriasis for up to 5 years with IXE. Patients achieved complete clearance at year 5: observed (scalp, 82%; nail, 73%; palmoplantar, 96%) and mNRI (scalp, 77%; nail, 67%; palmoplantar, 85%). Up to 80% of patients reported DLQI 0,1 responses at week 12, which were sustained through week 264. No increases in the number of annual treatment-emergent adverse events were observed from years 1n5. Conclusion Patients receiving IXE for 5 years sustained high rates of improvement in scalp, nail, and palmoplantar psoriasis, with a long-term quality of life benefit with no unexpected safety signals. J Drugs Dermatol. 2021;20(8):880-887. doi:10.36849/JDD.6101.

Introduction Biologics used to treat moderate-to-severe plaque psoriasis may cause injection site reactions (ISRs) characterized by erythema, edema, itch, and sometimes pain. The Federal Adverse Event Reporting System (FAERS) is a repository of spontaneous post-marketing reports of adverse events (AEs) that are reported to the US Food and Drug Administration (FDA). Our objective was to perform a pharmacovigilance analysis of FAERS reports of ISRs associated with the use of subcutaneously administered biologic products approved to treat moderate-to-severe plaque psoriasis. Methods The products included in our assessment were adalimumab, etanercept, ixekizumab, secukinumab, and ustekinumab. Reports from the date of US approval for each biologic as treatment for plaque psoriasis through 2 years were included using the search term “injection site.” Results The results show that the FAERS database contained reports of ISRs for all of the included biologics during the 2 years following FDA approval. The most common reports on ISRs were on pain, irritation, and erythema for adalimumab; reaction, pain, and erythema for etanercept; erythema, pain, and reaction for ixekizumab; bruising, pain, hemorrhage for secukinumab; and pain, induration, and swelling for ustekinumab. FAERS does not include data on total patient exposure; therefore, ISR rates could not be calculated. Conclusions Specific ISRs varied among the biologic therapies assessed. The findings presented could be helpful when patients consider switching therapies due to ISRs. Funding Eli Lilly and Company.

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 3.2% of the world's population. In this section of the guidelines of care for psoriasis, we will focus the discussion on ultraviolet (UV) light-based therapies, which include narrowband and broadband UVB, UVA in conjunction with photosensitizing agents, targeted UVB treatments such as with an excimer laser, and several other modalities and variations of these core phototherapies, including newer applications of pulsed dye lasers, intense pulse light, and light-emitting electrodes. We will provide an in-depth, evidence-based discussion of efficacy and safety for each treatment modality and provide recommendations and guidance for the use of these therapies alone or in conjunction with other topical and/or systemic psoriasis treatments.

Introduction Psoriasis Longitudinal Assessment and Registry (PSOLAR) was designed in 2007 as the first disease-based registry for patients with psoriasis. Objective The aim of this study was to discuss methodological limitations and post hoc analyses in long-term safety registries using learnings from analyses of a potential safety risk for major adverse cardiovascular events (MACE) in PSOLAR. Methods PSOLAR is an international observational study of over 12,000 psoriasis patients that was conducted to meet postmarketing safety commitments for infliximab and ustekinumab. A recent annual review of registry data indicated a potential MACE risk for ustekinumab vs. non-biologics based on prespecified COX model regression analyses, which yielded an adjusted hazard ratio (HR) of 1.533 (95% confidence interval [CI] 1.103–2.131). Therefore, we conducted a comprehensive review of key statistical methodology and implemented post hoc analytical methods to address specific limitations. Results The following limiting factors were identified: (1) inclusion of both prevalent and incident (new) users of biologics; (2) unanticipated imbalances in patient characteristics between treatment cohorts at baseline; (3) limited availability of relevant clinical data after enrollment; and (4) divergence of characteristics associated with outcomes among comparator groups over time. The analysis was modified to include only incident users, propensity scores were used to weight HRs, and adalimumab was deemed a more clinically appropriate comparator. The revised HR was 0.820 (95% CI 0.532–1.265), indicating no meaningful increase in MACE risk for ustekinumab. Conclusion Our results, which do not support a causal association between ustekinumab exposure and MACE risk, underscore the need for ongoing assessment of analytical methods in long-term observational studies.

Introduction Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. In the United States, brodalumab carries a boxed warning about suicidal ideation and behavior; however, no causal association was established between brodalumab and suicides reported during pivotal trials. We have previously reported results from an analysis of 1-year pharmacovigilance data in patients in the United States who took brodalumab, in which the most commonly reported adverse event was psoriasis flare. There were no completed suicides, suicide attempts, or serious fungal infections. Here, we provide a 2-year US pharmacovigilance report. Methods This analysis summarizes pharmacovigilance data reported to Ortho Dermatologics by US patients and healthcare providers from August 15, 2017, through August 14, 2019. The most common adverse events listed in the brodalumab package insert (incidence ≥ 1%; arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection-site reactions, influenza, neutropenia, and tinea infections) and adverse events of special interest are reported. Results Data were collected from 2677 patients in the United States who took brodalumab, with an estimated exposure of 1656 patient-years. Arthralgia was the most commonly reported adverse event (73 events; 0.04 events per patient-year). No suicide attempts or completed suicides were reported; there were 25 reports of depression. There were 46 serious infections and no serious fungal infections. One event of Crohn’s disease was reported, which led to discontinuation. There were 13 malignancies, with none deemed related to brodalumab. Conclusions This pharmacovigilance report supports the safety profile of brodalumab previously reported from long-term analyses of clinical trials and 1-year pharmacovigilance data.

Risankizumab selectively inhibits interleukin 23, a cytokine that contributes to psoriatic inflammation.To evaluate the efficacy and safety of risankizumab vs placebo and continuous treatment vs withdrawal in adults with moderate to severe plaque psoriasis.Multinational, phase 3, randomized, double-blind, placebo-controlled trial conducted from March 6, 2016, to July 26, 2018. A total of 507 eligible patients had stable moderate to severe chronic plaque psoriasis for 6 months or longer, body surface area involvement greater than or equal to 10%, Psoriasis Area and Severity Index (PASI) greater than or equal to 12, and a static Physician's Global Assessment (sPGA) score greater than or equal to 3. Intention-to-treat analysis was conducted.Patients were randomized (4:1, interactive response technology) to risankizumab, 150 mg, subcutaneously, or placebo at weeks 0 and 4 (part A1). All patients received risankizumab at week 16. At week 28, patients randomized to risankizumab who achieved an sPGA score of 0/1 were rerandomized 1:2 to risankizumab or placebo every 12 weeks (part B).Co-primary end points for the part A1 phase included proportions of patients achieving greater than or equal to 90% improvement in PASI (PASI 90) and sPGA score of 0/1 at week 16. The PASI measures severity of erythema, infiltration, and desquamation weighted by area of skin involvement over the head, trunk, upper extremities, and lower extremities; scores range from 0 (no disease) to 72 (maximal disease activity). The sPGA assesses average thickness, erythema, and scaling of all psoriatic lesions; scores range from 0 (clear) to 4 (severe), with 0/1 indicating clear or almost clear. Primary and secondary end points in part B included proportion of rerandomized patients achieving an sPGA score of 0/1 at week 52 (primary) and week 104 (secondary).Of 563 patients screened, 507 were randomized to risankizumab (n = 407) or placebo (n = 100). Most patients were men (356 [70.2%]); median age was 51 years (interquartile range, 38-60 years). At week 16, 298 patients (73.2%) in the treatment group vs 2 patients (2.0%) receiving placebo achieved a PASI 90 response, and 340 patients (83.5%) receiving risankizumab vs 7 patients (7.0%) receiving placebo achieved sPGA 0/1 scores (placebo-adjusted differences: PASI 90: 70.8%; 95% CI, 65.7%-76.0%; sPGA 0/1: 76.5%; 95% CI, 70.4%-82.5%; P .001 for both). At week 28, 336 responders were rerandomized to risankizumab (n = 111) or treatment withdrawal (n = 225). At week 52, the sPGA 0/1 score was achieved by 97 patients (87.4%) receiving risankizumab vs 138 patients (61.3%) receiving placebo. At week 104, the sPGA 0/1 score was achieved by 90 patients (81.1%) receiving risankizumab vs 16 patients (7.1%) receiving placebo (placebo-adjusted differences: week 52: 25.9%; 95% CI, 17.3%-34.6%; week 104: 73.9%; 95% CI, 66.0%-81.9%; P .001 for both). Rates of treatment-emergent adverse events were similar between risankizumab (186 [45.7%]) and placebo (49 [49.0%]) in part A1 and remained stable over time.Risankizumab showed superior efficacy compared with placebo through 16 weeks and treatment withdrawal through 2 years. Risankizumab was well tolerated, with no unexpected safety findings during the 2-year trial.ClinicalTrials.gov Identifier: NCT02672852.

Background Data for the effect of metabolic syndrome (MetS) on the efficacy and safety of biologic agents for psoriasis treatment are limited. Objective To evaluate long-term tildrakizumab efficacy, drug survival, and safety in patients with psoriasis by baseline MetS status. Methods Post hoc analyses of up to 3 years of efficacy data and 5 years of safety data from the phase 3, double-blind, randomized controlled reSURFACE 1 and 2 trial ( NCT01722331 and NCT01729754 ) base and extension studies were conducted for patients receiving continuous tildrakizumab 100 or 200 mg. Results Of 338 (n = 124/214 in reSURFACE 1/2) and 307 (n = 147/160 in reSURFACE 1/2) patients continuously receiving tildrakizumab 100 and 200 mg, respectively, throughout the studies, 26/44 (21%/21%) and 34/30 (23%/19%) met MetS criteria. Proportions of patients who achieved a 75% improvement in the Psoriasis Area and Severity Index (PASI) in reSURFACE 1/2 were generally comparable among those with versus without MetS at week 52 (tildrakizumab 100 mg, 85%/86% vs 86%/94%; tildrakizumab 200 mg, 76%/87% vs 76%/87%) and through week 148. Results were similar for responders with 90% and 100% improvement in the PASI. Tildrakizumab's safety profile did not vary by MetS status. Limitations Small sample size and post hoc analysis limit interpretation. Conclusion Long-term tildrakizumab efficacy and safety were comparable between patients with and without MetS.

Engaging global key opinion leaders, the International Psoriasis Council (IPC) held a day-long roundtable discussion with the primary purpose to discuss the treatment goals of psoriasis patients and worldwide barriers to optimal care. Setting clear expectations might ultimately encourage undertreated psoriasis patients to seek care in an era in which great gains in therapeutic efficacy have been achieved. Here, we discuss the option for early treatment of all categories of psoriasis to alleviate disease impact while emphasizing the need for more focused attention for psoriasis patients with mild and moderate forms of this autoimmune disease. In addition, we encourage policy changes to keep pace with the innovative therapies and clinical science and highlight the demand for greater understanding of treatment barriers in resource-poor countries.

BACKGROUND The recently updated dosing recommendation for adalimumab for moderate to severe plaque psoriasis states that patients with inadequate response to adalimumab every other week (EOW) after 16 weeks may benefit from an increase in dosing frequency to 40 mg every week (EW). OBJECTIVE To determine the long-term efficacy of adalimumab in patients with psoriasis with flexibility to escalate and de-escalate between EOW and EW dosing. METHODS Data from an open-label study in patients with psoriasis who had received adalimumab in phase 2/3 studies and their extensions were included. Patients initially received 40 mg adalimumab EOW for 24 weeks. From weeks 24-252, patients whose Psoriasis Area and Severity Index response was

BACKGROUND: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A, is approved for the treatment of moderate-to-severe psoriasis.OBJECTIVES: This analysis represents an overview of the efficacy outcomes from three Phase 3 psoriasis studies.METHODS: Data were integrated from the 12-week induction period of three studies in which patients received ixekizumab 80 mg every 2 (IXE Q2W; N=1169) or 4 weeks (IXE Q4W; N=1165) after an initial 160-mg dose for both, etanercept (ETN) (50 mg biweekly; N=740; two studies), or placebo (PBO) (N=792). The co-primary endpoints were the percentages of patients with response of sPGA (0,1) and a 75% improvement in baseline psoriasis area severity index (PASI 75) at Week 12. Response rates were compared between treatments using the Cochran-Mantel-Haenszel test stratified by study. Treatment comparisons with placebo included data from three studies, whereas etanercept comparisons were based on two studies.RESULTS: Ixekizumab treatment was superior to placebo (pCONCLUSIONS: Ixekizumab therapy at both dosing regimens demonstrated rapid onset and superior efficacy compared with placebo and etanercept, with IXE Q2W providing better outcomes than IXE Q4W during the first 12 weeks of treatment. This article is protected by copyright. All rights reserved.

Background Adalimumab is approved for the treatment of hidradenitis suppurativa (HS), plaque psoriasis, and other inflammatory conditions. Objective Our objective was to examine the safety of adalimumab administered every other week (EOW) and every week (EW) in patients with HS and psoriasis and to investigate informative data from non-dermatologic indications. Methods The safety of adalimumab 40-mg EOW versus EW dosing was examined during placebo-controlled and open-label study periods in patients with HS (three studies), psoriasis (two studies), Crohn’s disease (six studies), ulcerative colitis (three studies), and rheumatoid arthritis (one study). Results No new safety risks or increased rates of particular adverse events (AEs) were identified with EW dosing. In patients with HS or psoriasis, the overall safety of adalimumab 40-mg EOW and EW was generally comparable. In studies of adalimumab for non-dermatologic indications, including Crohn’s disease, ulcerative colitis, and rheumatoid arthritis, the overall AE rates were similar for EW and EOW dosing. Conclusion In patients with HS or psoriasis, the safety of adalimumab EW and EOW was comparable and consistent with the expected adalimumab AE profile. The safety of adalimumab EW dosing in patients with dermatologic conditions is supported by data comparing adalimumab EW and EOW dosing for Crohn’s disease, ulcerative colitis, and rheumatoid arthritis. Trial registration ClinicalTrials.gov NCT00918255, NCT01468207, NCT01468233, NCT00645814, NCT00077779, NCT00055497, NCT01070303, NCT00195715, NCT00348283, NCT00385736, NCT00408629, and NCT00573794.

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Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the US population. This guideline addresses important clinical questions that arise in psoriasis management and care, providing recommendations on the basis of available evidence.

Background Adalimumab is used to treat several inflammatory diseases, including plaque psoriasis. GP2017 is a proposed adalimumab biosimilar. Objectives To assess the impact of multiple switches between GP2017 and reference adalimumab (ref-ADMB) following the demonstration of equivalent efficacy and similar safety and immunogenicity, in adult patients with active, clinically stable, moderate-to-severe plaque psoriasis. Methods This 51-week double-blinded, phase III study randomly assigned patients to GP2017 (n = 231) or ref-ADMB (n = 234) 80 mg subcutaneously at week 0, then 40 mg biweekly from week 1. At week 17, patients were rerandomized to switch (n = 126) or continue (n = 253) treatment. The primary end point was patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 16, with equivalence confirmed if the 95% confidence interval (CI) for the difference in PASI 75 between treatments was ± 18%. The key secondary end point was the change from baseline to week 16 in continuous PASI. Other end points were PASI over time; PASI 50, 75, 90 and100; pharmacokinetics; safety; tolerability and immunogenicity for the switched and continued treatment groups. Results Equivalent efficacy between GP2017 and ref-ADMB was confirmed for the primary (66·8% and 65·0%, respectively; 95% CI -7·46 to 11·15) and key secondary end points (-60·7% and -61·5%, respectively; 95% CI -3·15 to 4·84). PASI improved over time and was similar between treatment groups at week 16, and the switched and continued groups from weeks 17 to 51. There were no relevant safety or immunogenicity differences between GP2017 and ref-ADMB at week 16, or the switched and continued groups from weeks 17 to 51. No hypersensitivity to adalimumab was reported upon switching. Conclusions Following the demonstration of GP2017 biosimilarity to ref-ADMB, switching up to four times between GP2017 and ref-ADMB had no detectable impact on efficacy, safety or immunogenicity.

BackgroundApremilast works intracellularly to regulate inflammatory mediators.ObjectiveESTEEM 1 evaluated efficacy/safety of apremilast at 30 mg twice a day for moderate to severe plaque psoriasis.MethodsThis phase III, multicenter, double-blind, placebo-controlled study randomized adults (2:1) to apremilast or placebo. At week 16, the placebo group switched to apremilast through week 32, followed by a randomized treatment withdrawal phase to week 52. Binary end points were analyzed using χ2 test; continuous end points used analysis of covariance.ResultsIn all, 844 patients were randomized (n = 282, placebo; n = 562, apremilast). At week 16, significantly more patients taking apremilast achieved 75% or greater reduction from baseline Psoriasis Area and Severity Index score (PASI-75) (33.1%) versus placebo (5.3%, P < .0001; primary end point). Most (61.0%) patients rerandomized to apremilast at week 32 achieved PASI-75 at week 52 versus 11.7% rerandomized to placebo. Of patients rerandomized to apremilast at week 32, mean percentage change from baseline PASI score was −88% to −81% (weeks 32-52). During the placebo-controlled period, 55.7% and 69.3% of patients randomized to placebo and apremilast, respectively, had 1 or more adverse events. Most adverse events were mild/moderate in severity. No new significant adverse events emerged with continued apremilast exposure versus the placebo-controlled period.LimitationsData were limited to 52 weeks and may not generalize to nonplaque psoriasis.ConclusionsApremilast was effective in moderate to severe plaque psoriasis.

This review delivers a commentary on the first decade of biologics’ use in psoriasis and provides a glimpse of the pipeline of therapies currently in development for psoriasis that will enhance the therapeutic armamentarium available to the dermatologist. In addition, the authors revisit the rationale for the development of biological therapies, inventory the available therapies of today, and retrospectively assess their impact on the dermatology practice as it relates to the management of patients with psoriasis.

Background Certolizumab pegol, the only Fc-free, PEGylated anti–tumor necrosis factor biologic, demonstrated clinically meaningful improvements suggestive of a positive risk-benefit balance in phase 2 studies in adults with moderate-to-severe chronic plaque psoriasis. Objective Assess certolizumab efficacy and safety versus placebo in phase 3 studies. Methods Patients with moderate-to-severe chronic plaque psoriasis were randomized 2:2:1 to certolizumab 400 mg, certolizumab 200 mg, or placebo every 2 weeks. At week 16, certolizumab-treated patients achieving a 50% reduction in Psoriasis Area and Severity Index continued treatment through week 48. Coprimary endpoints were week 16 responder rates, defined as a 75% reduction in Psoriasis Area and Severity Index and Physician's Global Assessment 0/1 (clear/almost clear) and ≥2-point improvement. Safety was assessed by treatment-emergent adverse events. Results Week-16 endpoints were significantly greater for both doses of certolizumab versus placebo, and the responses were maintained through week 48. For most measures, improvement was numerically greater for certolizumab 400 mg. No unexpected safety signals were identified. Limitation There was no active comparator. Conclusion Treatment with either certolizumab 400 mg or 200 mg every 2 weeks was associated with significant and clinically meaningful improvements in moderate-to-severe psoriasis. The 400-mg dose could provide additional clinical benefit. The safety profile was consistent with the therapeutic class.

Evidence of the cost-efficacy of ixekizumab for the treatment of moderate-to-severe plaque psoriasis (PsO) in the US is limited.To estimate the number needed to treat (NNT) and monthly cost of achieving one additional Psoriasis Area and Severity Index (PASI) 75, 90, and 100 responder for ixekizumab and other Food and Drug Administration (FDA)-approved biologics in PsO.A network meta-analysis estimated the probability of achieving PASI 75, 90, or 100 response during induction for each biologic. NNTs were calculated using response difference of each respective biologic vs placebo at the end of induction. Monthly costs per additional PASI responder were based on FDA-approved doses, wholesale acquisition costs, and induction NNTs.Induction NNTs for ixekizumab 80 mg once every 2 weeks (Q2W) relative to placebo were consistently lower across all levels of clearance compared with the other biologics. Monthly cost per additional responder was lowest for ustekinumab 45 mg at PASI 75 and for secukinumab 300 mg and ixekizumab 80 mg Q2W at PASI 90. Ixekizumab 80 mg Q2W had the lowest cost for PASI 100.In this analysis, ixekizumab is the most cost-efficient biologic in the US when targeting complete resolution, as measured by PASI 100 in PsO.

New therapies, recent pathophysiological findings, and updated guidelines combined to create compelling presentations at the Skin Disease Education Foundation's 41st Annual Hawaii Dermatology Seminar™. This educational supplement summarizes the highlights of clinical sessions presented during this CME/CE conference. A growing understanding of the biology of psoriasis has facilitated the development of increasingly efficacious medications. Skin clearance used to be regarded as an impractical goal for psoriasis therapy. Now, some clinical trials of newer medications report more than half of participants attaining Psoriasis Area and Severity Index (PASI) scores of 90. Two leading investigators review the latest findings about the treatment of this condition. Recent evidence demonstrates that psoriasis and psoriatic arthritis share multiple pathological underpinnings. A T helper type 17 (Th17) lymphocyte-based pathogenesis, genes, and microbiome changes have been identified in both conditions. Many therapeutics used in psoriasis care are efficacious in psoriatic arthritis. An expert in psoriatic arthritis updates readers about this condition. Cutaneous fungal infections, including onychomycosis, pose diagnostic and treatment challenges. New topical therapies and an investigational oral agent offer expanded options for management. The American Academy of Dermatology has issued new guidelines for the treatment of acne. Appropriate antibiotic use is a prominent theme. The US Food and Drug Administration has issued a communication about the risk of unintentional injection of soft tissue fillers into facial blood vessels-including blindness. The lead author of a recent review about this topic discusses how to prevent this serious outcome. The volume of new information about pathophysiology, diagnosis, therapy, and safety challenges our ability to keep current while enabling us to improve patient care. We hope that the highlights of this seminar offer you information that can be applied to your busy practices.

Background Phase 3 studies showed some patients maintained response for ≥6 months post-ustekinumab discontinuation. Objectives To assess clinical responses with extended ustekinumab maintenance dosing intervals. Methods Adults with moderate-to-severe plaque psoriasis received ustekinumab (45mg/90mg for weight ≤100 kg/>100 kg) at Week0, Week4, Week16 during open-label treatment. Patients achieving a Week 28 Physician's Global Assessment score of cleared/minimal (PGA=0/1) were randomized 1:4 to Group1 (approved every-12-weeks [q12wk] maintenance) or Group2 (q12-24wk response-based dosing determined by time–to-loss-of-PGA=0/1). Key endpoints included number of visits with PGA=0/1 (primary endpoint) and ≥75% improvement in Psoriasis Area and Severity Index (PASI75) between Weeks88-112, and PGA/PASI responses between Weeks28-112. Results 378 patients achieved PGA=0/1 at Week28 and were randomized to Group1 (n=76) or Group2 (n=302). Group1 patients had numerically greater mean numbers of visits with PGA=0/1 than Group2 (4.5 and 4.1, respectively; mean-difference [95%CI]: -0.46 [-1.20; 0.29]) and PASI75 (5.8 and 5.4, respectively; -0.32 [-0.96;0.33]) from Week88-112. A higher proportion of patients in Group1 (55.3%) than Group2 (38.7%) had PGA=0/1 at all seven Week88-112 visits. Maintenance of response was observed with dose-interval extension beyond q12wk (q16wk, q20wk, q24wk) in a subset of patients (28% of patients randomized to Group 2 extended maintenance dosing to q24wks and maintained high levels of response). Extending dosing interval did not affect antibody development or safety. Conclusions Efficacy was better maintained among Week28 PGA-responders randomized to continue q12wk ustekinumab versus extending maintenance dosing based on clinical response, although some patients maintained high levels of efficacy with up to q24wk dosing. This article is protected by copyright. All rights reserved.