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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a broad spectrum of clinical manifestations. The proposed pathophysiological hypotheses of SLE are numerous, involving both innate and adaptive abnormal immune responses. SLE is characterized by the overproduction of different autoantibodies that form immune complexes, which cause damage in different organs. Current therapeutic modalities are anti-inflammatory and immunosuppressive. In the last decade, we have witnessed the development of many biologicals targeting different cytokines and other molecules. One of them is interleukin-17 (IL-17), a central cytokine of a proinflammatory process that is mediated by a group of helper T cells called Th17. Direct inhibitors of IL-17 are used in psoriatic arthritis, spondyloarthritis, and other diseases. Evidence about the therapeutic potential of Th17-targeted therapies in SLE is scarce, and probably the most promising is related to lupus nephritis. As SLE is a complex heterogeneous disease with different cytokines involved in its pathogenesis, it is highly unlikely that inhibition of only one molecule, such as IL-17, will be effective in the treatment of all clinical manifestations. Future studies should identify SLE patients that are eligible for Th17-targeted therapy.

Angelo Ruggiero, Gabriella Fabbrocicni, Sara Cacciapuoti, Luca Potestio, Lucia Gallo, Matteo Megna Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyCorrespondence: Angelo Ruggiero, Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, Naples, 80131, Italy, Tel +39-081-7462457, Fax +39-081-7462442, Email angeloruggiero1993@libero.itBackground: Tildrakizumab, an anti-IL-23, showed promising efficacy and safety profiles in two randomized clinical-trials (reSURFACE-1 and reSURFACE-2), comparing tildrakizumab superiority to placebo and etanercept. Due to its recent availability in clinical-practice, real-life data are still limited.Objective: To assess the efficacy and safety of tildrakizumab in a real-world-practice in patients suffering from moderate-to-severe psoriasis.Methods: A 52-week observational retrospective study enrolled patients suffering from moderate-to-severe plaque-psoriasis, starting tildrakizumab treatment.Results: A total of 42 patients were included in the study. Mean PASI showed a significant reduction at each follow-up (p< 0.001), reducing from 13.5± 5.9 at baseline, 2.8± 3.8 at week-28, resulting stable up to week-52. High rates of patients reached both PASI90 and PASI100 responses at both week 16 (PASI90: 52.4%, PASI100: 33.3%) and week 28 (PASI90: 76.1%, PASI100: 61.9%), maintaining these up to week 52 (PASI90: 73.8%, PASI100: 59.5%). The impact of treatment on patient’s quality of life has been evaluated with DLQI, which showed a significant reduction during follow-ups.Conclusion: Our data confirm tildrakizumab as an effective and generally safe treatment for the management of moderate-to-severe psoriasis, with high rates of both PASI90 and PASI100 responses, and very few reported adverse events, up to 52 weeks of follow-up.Keywords: guselkumab, risankizumab, tildrakizumab, real-world practice, psoriasis, anti-IL-23, biologics

Interleukin (IL)-23 inhibitors, guselkumab, risankizumab, and tildrakizumab, represent the latest class of biologics approved for the treatment of moderate-to-severe psoriasis. Since their approval numerous real-life studies were published on anti-IL-23 use in routine clinical practice. Indeed, real-life data are important to improve the dermatological decision-making process, including patients who are typically excluded from clinical trials, such as subjects suffering from several comorbidities, subjects on polypharmacy, as well as multifailure patients. Herein, we performed a comprehensive literature review about real-life data available on guselkumab, risankizumab, and tildrakizumab. Real-life data of anti-IL-23 seem to confirm the promising results of IL-23 shown by clinical trials, highlighting the efficacy and safety profiles of this new class of biologics also in clinical practice.

IntroductionEmerging evidence suggests psoriatic arthritis (PsA)with axial involvement (axPsA) and radiographic axial spondyloarthritis (r-axSpA) maypossibly represent distinct disorders, with some differing clinical manifestations, genetic associations, and radiographic findings. Moreover, axPsA and r-axSpA may respond differently to therapies: guselkumab (interleukin [IL]-23p19 subunit inhibitor [i]) and ustekinumab (IL-12/23p40i) demonstrated improvements in axial symptoms in patients with PsA; however, neither risankizumab (IL-23p19i) nor ustekinumab demonstrated efficacy versus placebo in patients with r-axSpA. Current analyses aim to further understand potential molecular distinctions between axPsA and r-axSpA and examine the pharmacodynamic effects of guselkumab in patients with axPsA and those with PsA without axial involvement (non-axPsA).MethodsPosthoc analyses utilized biomarker data from blood and serum samples collected from a subset of participants in phase3 studies of ustekinumab in r-axSpA and guselkumab in PsA (DISCOVER-1 and DISCOVER-2). Participants with axPsA were identified by investigator-verified sacroiliitis (imaging-confirmed)and axial symptoms. HLA mapping, serum cytokine analysis, and whole-blood RNA sequencing were conducted.ResultsRelative to r-axSpA, patients with axPsA had a lower prevalence of HLA-B27, HLA-C01, and HLA-C02 alleles and a higher prevalence of HLA-B13, HLA-B38, HLA-B57, HLA-C06, and HLA-C12 alleles. Compared with r-axSpA, patients with axPsA had elevated baseline levels of serum IL-17A and IL-17F cytokines, enrichment of IL-17 and IL-10 pathway-associated genes, and neutrophil gene markers. Across axPsA and non-axPsA cohorts, reductions in cytokine levels and normalization ofpathway-associated gene expressionwith guselkumab treatment were comparable.ConclusionThe differences in HLA genetic associations, serum cytokines, and enrichment scores support the concept that axPsA and r-axSpA may be distinct disorders. The comparable pharmacodynamic effects of guselkumab on cytokine levels and pathway-associated genes observed in patients with axPsA and non-axPsA are consistent with demonstrated clinical improvements across PsA cohorts. These findings contribute to the understanding of potential genetic and molecular distinctions between axPsA and r-axSpA.Trial registrationClinicalTrials.gov identifiers, NCT03162796, NCT0315828, NCT02437162, and NCT02438787.

Guselkumab, tildrakizumab, and risankizumab, acting on interleukin(IL)23 axis, have been recently approved for psoriasis management. However, real-life data regarding their comparison are scant.The aim of our real life study was to perform an indirect efficacy and safety comparison among anti-IL23s, particularly focusing on difficult-to-treat areas.A 2-year single-center retrospective observational study was performed enrolling moderate-to-severe psoriasis patients treated with anti-IL23. For each patient, clinical and demographical data were collected at baseline and at week4, week16, and week28. PASI, BSA, NAPSI, and specific BSA regarding difficult to treat areas were evaluated.One hundred and fifty patients were included in the study: 63 (42%) received guselkumab, 21 (14%) tildrakizumab, and 66 (44%) risankizumab. The three groups were comparable for age, sex, and disease severity, only differing for psoriasis duration, psoriatic arthritis prevalence (higher in guselkumab), and previous systemic treatment failure (lower for tildrakizumab). Mean PASI and BSA significantly reduced from baseline up to week 28 without significant differences among the 3 drugs (reduction of 95-97.3% for PASI and 94.8-96.7% for BSA). No significant differences were registered for PASI75, 90, or 100 responses, in particular, PASI100 was reached by 73.4-85% of patients. As regards difficult-to-treat areas, all the drugs displayed a high efficacy, with significant differences registered only for the rapidity of action on palmoplantar psoriasis.Our 28-weeks study demonstrated a comparable efficacy and safety profile for all anti-IL23, with guselkumab and risankizumab appearing slightly faster than tildrakizumab particularly on palmoplantar lesions in the short-term.What is already known about this topic?The interleukins (IL) 23/17 axis seems to play a key role in psoriasis management.Guselkumab, tildrakizumab, and risankizumab, selectively blocking the IL23 signaling, have been recently approved for psoriasis management.Real-world data regarding different anti-IL23 comparisons are scant.What does this study add?Our 28-weeks study showed that there were not any significant differences in terms of efficacy and safety between each anti-IL-23 apart from palmoplantar area where guselkumab and risankizumab showed higher efficacy.Globally risankizumab and guselkumab appeared slightly faster than tildrakizumab.Guselkumab, tildrakizumab, and risankizumab are valid weapons for psoriasis management, also for difficult-to-treat areas (scalp, nails, genitalia, lower limbs, and palmo-plantar area).

Guselkumab effectively treats moderate-to-severe psoriasis.To evaluate the cumulative safety experience of guselkumab using pooled data from the VOYAGE 1 and 2 studies through 5 years.Patients were randomized to guselkumab, placebo with crossover to guselkumab at week 16, or adalimumab. The studies were identical through week 24. VOYAGE 1 evaluated continuous guselkumab treatment (adalimumab-crossover-to-guselkumab at week 52), while VOYAGE 2 assessed randomized withdrawal/retreatment (weeks 28-76). Open-label guselkumab treatment was administered starting at week 52 in VOYAGE 1 and week 76 in VOYAGE 2 and continued through week 252. Pooled safety data were adjusted by exposure and analyzed in the guselkumab groups, including placebo-crossover-to-guselkumab (n = 1221) and adalimumab-crossover-to-guselkumab (n = 500), through week 264.Patients were followed for a total of 7166 patient-years (PY). Overall, 1349 of 1721 guselkumab-treated patients (78.4%) continued treatment through week 252. The rates of adverse and serious adverse events were 149/100 PY and 5.01/100 PY, respectively. Rates of adverse events of interest were low: serious infections (0.85/100 PY), nonmelanoma skin cancer (0.34/100 PY), malignancies other than nonmelanoma skin cancer (0.45/100 PY), and major adverse cardiovascular events (0.29/100 PY). Year-to-year variability was evident, but no increasing trend was observed.No direct treatment comparisons were possible after week 52.The safety profile remained consistent and favorable during 5 years of continuous guselkumab treatment of psoriasis.

OBJECTIVE Assess long-term efficacy and safety of guselkumab, an IL-23p19-subunit inhibitor, in patients with active psoriatic arthritis (PsA) from the Phase-3 DISCOVER-2 trial. METHODS In DISCOVER-2, patients with active PsA (≥5 swollen and ≥5 tender joints; CRP ≥0.6 mg/dL) despite prior nonbiologic therapy were randomized to: guselkumab 100mg every-4-weeks (Q4W); at Week0, Week4, and Q8W; or placebo➔guselkumab Q4W at Week24. Efficacy assessments included ≥20%/50%/70% improvement in ACR components (ACR20/50/70), Investigator's Global Assessment of psoriasis score=0 (IGA=0; indicating complete skin clearance), enthesitis (Leeds Enthesitis Index) and dactylitis (Dactylitis Severity Score) resolution, and changes in PsA-modified van der Heijde-Sharp (vdH-S) radiographic scores. Clinical data (imputed as no response/no change from baseline if missing) and observed radiographic data were summarized through Week100; safety assessments continued through Week112. RESULTS Of 739 randomized and treated patients, 652 (88%) completed treatment through Week100. Across groups of guselkumab-treated patients (including placebo➔Q4W) ACR20 (68%-76%), ACR50 (48%-56%), ACR70 (30%-36%), and IGA=0 (55%-67%) responses and enthesitis (62%-70%) and dactylitis (72%-83%) resolution rates at Week100 indicated amelioration of arthritis signs/symptoms and extra-articular manifestations was durable through 2years. Mean changes in PsA-modified vdH-S scores from Week52-100 (0.13-0.75) indicated the low rates of radiographic progression observed among guselkumab-treated patients at earlier timepoints extended through Week100. Through Week112, 8% (5.8/100 patient-years) and 3% (1.9/100 patient-years) of 731 guselkumab-treated patients had a serious adverse event or serious infection, respectively; one death occurred (road traffic accident). CONCLUSION In biologic-naive PsA patients, guselkumab provided durable improvements in multiple disease domains with no unexpected safety findings through 2years.

Psoriatic arthritis (PsA) is a chronic inflammatory disease of the joints, spine and enthesis from the group of spondyloarthritis that develops in patients with psoriasis. Guselkumab is a biologic disease-modifying antirheumatic drug, an inhibitor of interleukin 23, which has been shown to be effective in the treatment of plaque psoriasis and PsA.Objective: to evaluate the effectiveness of guselkumab treatment in PsA patients.Patients and methods. The study included 16 patients with PsA. All patients received 100 mg of guselkumab subcutaneously at weeks 0, 4, 12, 20. Disease activity and treatment efficacy were assessed at weeks 0, 12 and 24 using the DAS28, ASDAS, BASDAI, DAPSA activity indices, the index of the extent and severity of psoriasis PASI.Results and discussion. During treatment, patients with PsA showed a pronounced positive dynamics of the indices of disease activity and an improvement in the skin condition. Before the treatment with guselkumab, the mean value of the DAS28 index was 4.26±0.64, DAPSA – 37.94±9.45, ASDAS – 2.7±0.65, and BASDAI – 5.49±1.39, after 12 weeks of treatment these indicators decreased to 3.03±0.49; 17.06±4.58; 1.64±0.33 and 3.48±0.66, respectively, and after 24 weeks (after the 4th injection) – to 2.32±0.18; 11.31±2.18; 1.22±0.27 and 2.62±0.78, respectively (pThe treatment was well tolerated during the 24 weeks of the study, and no serious adverse events were reported.Conclusion. The data from real clinical practice indicate that guselkumab is highly effective and safe in the treatment of PsA.

Background Biologics are a good therapeutic option for severe, chronic plaque psoriasis; however, they come with significant cost to the health care system. Objective To conduct a cost-utility analysis of outpatient biologics (adalimumab, etanercept, guselkumab, ixekizumab, risankizumab, secukinumab, tildrakizumab, and ustekinumab) available to adults with severe, chronic plaque psoriasis from the perspective of the Australian health care system. Methods A Markov cohort model was constructed to estimate the quality-adjusted life years (QALYs) and costs accrued for treatment pathways commencing with different first-line biologics, over a 96-week time horizon. The model adhered to the Australian Pharmaceutical Benefits Scheme eligibility criteria and guidelines. Results A biologic treatment pathway commencing on tildrakizumab was the most cost-effective first-line treatment (Australian dollar 39,930; total utility of 1.57 QALYs over 96 weeks). First-line secukinumab and risankizumab had incremental cost-utility ratios of Australian dollar 194,524/QALY and Australian dollar 479,834/QALY, respectively, when compared with first-line tildrakizumab. Limitations The efficacy and utility input parameters were derived from international randomized control trials and patients from the United Kingdom, respectively. Findings from this study cannot be generalized beyond Australia. Conclusion Tildrakizumab may be considered as first-line treatment for adult patients with severe, chronic plaque psoriasis embarking on biologic therapy, from the economic perspective of the Australian health care system.

Introduction Guselkumab is approved for the treatment of both moderate-to-severe plaque psoriasis and active psoriatic arthritis (PsA) in the USA. However, little is known about patients initiating guselkumab in a real-world setting. The objective of this study was to describe baseline characteristics among patients with plaque psoriasis who initiated guselkumab at or after enrollment in CorEvitas’ Psoriasis Registry. Methods Adult patients who initiated guselkumab in the Psoriasis Registry between July 18, 2017 and November 6, 2018 were included. Demographics, disease characteristics, and patient-reported outcome measures (PROMs) were assessed at the time of guselkumab initiation (baseline). Patients with psoriasis were stratified according to the number of previously received biologics (0 to 4+) for comparison. A subset of patients with psoriasis and concomitant dermatologist-diagnosed PsA were stratified into biologic-naïve and biologic-experienced groups. Results Among 687 patients with psoriasis who initiated guselkumab, biologic-naïve patients and those with four or more prior biologics had the most severe disease and the worst PROM scores at baseline. Among 251 patients with concomitant dermatologist-diagnosed PsA, biologic-naïve patients had more severe disease and worse PROM scores than biologic-experienced patients. Conclusions These findings highlight important differences in baseline characteristics according to biologic experience among patients with plaque psoriasis with or without concomitant PsA initiating guselkumab in a real-world setting. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00637-2.

Background: Adalimumab (ADA), certolizumab pegol (CER), etanercept (ETA), guselkumab (GUS), ixekizumab (IXE), secukinumab (SEC), and ustekinumab (UST) are biologic medications approved in the USA for the treatment of moderate to severe psoriasis. We examined drug adherence and persistence of patients with moderate to severe psoriasis who initiated these seven biologic medications. Methods: Adult patients with ≥1 pharmacy/medical claim for any of the seven psoriasis medications and ≥1 diagnosis of psoriasis in the previous 6 months between July 1, 2014 and June 30, 2019 were selected from the IBM MarketScan® Commercial Claims and Encounters Database. The index date was defined as the date of the first prescription fill. Patients were required to have continuous health plan enrollment during the 6 months prior to their index date and ≥9 months after. Patients were grouped into seven study cohorts based upon their index biologic medication. Adherence was measured using the proportion of days covered (PDC) and defined by a PDC ≥80%. Adherence and persistence with index biologic medications were examined during fixed follow-up periods of 3, 6, and 9 months, with a subpopulation analysis carried out among patients with 12 months of follow-up. Results: Among psoriasis patients with ≥9 months of continuous enrollment included in the study population, the number of those who initiated each biologic medication was 10,324 for ADA, 431 for CER, 3,092 for ETA, 821 for GUS, 1,766 for IXE, 4,132 for SEC, and 5,441 for UST. The mean age at the time of initiating biologic treatment was 46.9 years. During the 9-month follow-up period, the proportions of adherent patients (i.e., PDC ≥80%) were numerically higher among those treated with UST (59.9%) and GUS (56.9%), followed by those treated with SEC (46.1%), IXE (45.5%), ADA (44.7%), ETA (33.9%), and CER (22.0%). The proportions of patients who were persistent with their index biologic medication during the 9-month follow-up period were numerically higher among those treated with UST (70.1%) and GUS (67.8%), followed by those treated with IXE (47.3%), SEC (46.9%), ADA (28.7%), CER (14.8%), and ETA (10.7%). Conclusions: In this large healthcare claims database analysis of psoriasis patients treated with seven different biologic medications, adherence was numerically higher among those treated with UST or GUS. UST and GUS were also associated with numerically greater persistence.

The article presents an analysis of literature on the efficacy and safety of a new biologic disease modifying antirheumatic drug usage, the interleukin 23 inhibitor – guselkumab (GUS) – in the treatment of patients with psoriatic arthritis (PsA). Two own clinical observations of GUS therapy are described. It has been demonstrated that in PsA of moderate activity and in severe to moderate psoriasis with nail damage, the use of GUS (100 mg at weeks 0 and 4, and then every 8 weeks), allows to achieve remission of peripheral arthritis, enthesitis and psoriasis by the 20th week of treatment as in the monotherapy regimen and in combination with methotrexate. When GUS is re-prescribed (re-treat) after a long break (10 months), its effectiveness is quickly and completely restored. The safety of GUS was confirmed in patients with comorbid pathology, in particular, Gilbert's syndrome, hyperuricemia, metabolic disorders (abdominal obesity).

Pustular psoriasis is an unusual form of psoriasis that frequently presents clinical challenges for dermatologists. The condition presents with pustules on an erythematous background and has two distinct subtypes: localized disease on the palms and soles, called palmoplantar pustulosis (PPP), and generalized pustular psoriasis (GPP). The involvement of the fingers, toes, and nails is defined as a separate localized variant, acrodermatitis continua of Hallopeau, and is now thought to be a subset of PPP. The rarity of pustular psoriasis frequently makes the correct diagnosis problematic. In addition, treatment is limited by a relative lack of evidence-based therapeutic options. Current management is often based on existing therapies for standard plaque psoriasis. However, there remains a need for treatments with high, sustained efficacy and a rapid onset of action in pustular psoriasis. Recent advances in understanding of the pathogenesis of pustular psoriasis have provided insights into potential therapies. Treatment of pustular psoriasis is generally determined by the extent and severity of disease, and recent years have seen an increasing use of newer agents, including biologic therapies. Current classes of biologic therapies with US Food and Drug Administration and European Medicines Agency approval for treatment of moderate-to-severe plaque psoriasis in the USA (and elsewhere) include tumor necrosis factor alpha inhibitors (adalimumab, certolizumab pegol, etanercept, infliximab), interleukin (IL)-17 inhibitors (brodalumab, ixekizumab, secukinumab), an IL-12/23 inhibitor (ustekinumab), and IL-23 inhibitors (guselkumab, risankizumab, tildrakizumab). Recently, specific inhibitors of the IL-36 pathway have been evaluated in GPP and PPP, including spesolimab, an IL-36 receptor inhibitor which has shown promising results in GPP. The emerging drugs for pustular psoriasis offer the possibility of rapid and effective treatment with lower toxicities than existing therapies. Further research into agents acting on the IL-36 pathway and other targeted therapies has the potential to transform the future treatment of patients with pustular psoriasis. This article reviews the clinical features of PPP and GPP, and current understanding of the genetics and immunopathology of these conditions; it also provides an update on emerging treatments. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00612-x., Plain Language Summary Pustular psoriasis is a skin condition where people develop small pus-filled blisters on their skin. Pustular psoriasis may affect certain areas of the body, such as the palms and/or the soles. This is called palmoplantar pustulosis (PPP for short). Another type of pustular psoriasis can affect most of the body called generalized pustular psoriasis (GPP for short). Not many people have PPP or GPP. Around 5–12 in every 10,000 people worldwide develop PPP. GPP is even rarer, affecting only 2–7 out of every 1 million people. In addition to being relatively uncommon, these conditions are challenging to treat. This article aims to help doctors who treat skin conditions (dermatologists) to identify and treat people with pustular psoriasis. Currently there is no standard treatment for GPP and PPP in the USA or Europe, but several medicines are approved for treatment of GPP in Japan. Doctors often use treatments that have been shown to work in plaque psoriasis, which is the most common type of psoriasis, to treat people with GPP and PPP. Traditional treatments for PPP and GPP are often not effective. Researchers are working on developing new effective treatments for pustular psoriasis that may work more rapidly and have fewer side effects. These are expected to be available in the next few years. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00612-x.

IL-23 is a key cytokine in the pathogenesis of spondyloarthritides, including PsA and axial spondyloarthritis, as well as related conditions, such as psoriasis and IBD. Genetic associations, animal models and translational studies in humans demonstrate the key role played by IL-23, especially when coupled with downstream overexpression of IL-17 via stimulation of T helper 17 (Th17) and other cells by IL-23. Whereas IL-23 inhibition has shown clear-cut benefit in psoriasis and peripheral manifestations of PsA, trials of IL-23 inhibitors have failed in the treatment of ankylosing spondylitis. More recently, exploratory data from PsA patients with axial symptoms suggests that improvement may occur, but needs confirmation in dedicated axial spondyloarthritis (axSpA) trials. Hypotheses for these apparently conflicting findings about IL-23 inhibition in various forms of spondylitis are discussed.

Introduction Many targeted, systemic therapies have been developed for treatment of moderate-to-severe psoriasis (PsO). A network meta-analysis (NMA) allows for comparison between treatments not directly compared in randomized controlled trials (RCT). This study’s objective was to compare the short-term (10–16 weeks) clinical efficacy according to the Psoriasis Area and Severity Index (PASI) among approved biologic treatments for moderate-to-severe PsO using a novel (enhanced) NMA model. Methods A systematic literature review (SLR) of RCTs for patients with moderate-to-severe PsO was conducted. English publications in MEDLINE, Embase, and The Cochrane Library up to March 2019 were searched. An enhanced multinomial Bayesian NMA was performed to simultaneously adjust for baseline risk and utilize the conditional nature of the PASI (50, 75, 90, and 100) levels. The model relaxes typical constraints that all treatments must have the same ranks across PASI levels. Results The SLR resulted in 319 relevant publications, of which 72 publications from 73 RCTs reporting 10- to 16-week data for at least one PASI response level (30,314 total patients) were included. Interleukin (IL) inhibitors (risankizumab, ixekizumab, brodalumab, secukinumab, and guselkumab) were the best performing treatments for achieving all PASI levels. Etanercept was outperformed by the other subcutaneous tumor necrosis factor α inhibitors. Application of an enhanced NMA model that allowed treatment rankings to differ by PASI level tested the robustness of results of previous NMAs in PsO. Conclusion The results of this model confirmed that IL inhibitors are likely the best short-term treatment choices for improving all PASI levels. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00602-z.

Background The comparative safety and benefit-risk profiles of moderate-to-severe psoriasis treatment have not been well studied. Objective To compare the short-term (12-16 weeks) and long-term (48-56 weeks) safety and benefit-risk profiles of moderate-to-severe psoriasis treatments. Methods A systematic literature review of phase II-IV randomized controlled trials of moderate-to-severe psoriasis treatments was conducted (cutoff: July 1, 2020). Any adverse events (AEs), any serious AEs, and AEs leading to treatment discontinuation were compared using Bayesian network meta-analyses (NMAs). Results Fifty-two and 7, respectively, randomized controlled trials were included in the short- and long-term NMAs, respectively. In the short-term NMA, the rates of any AEs were the lowest for tildrakizumab (posterior median: 46.0%), certolizumab (46.2%), and etanercept (49.1%). The rates of any serious AE were the lowest for certolizumab (0.8%), risankizumab (1.2%), and etanercept (1.6%). The rates of AEs leading to treatment discontinuation were the lowest for risankizumab (0.5%), tildrakizumab (1.0%), and guselkumab (1.5%). In the long-term NMA, risankizumab had the lowest rates of all 3 outcomes (67.5%, 4.4%, and 1.0%, respectively) and the most favorable benefit-risk profile. Limitations The results may not be generalizable to real-world populations. Conclusions Anti–interleukin 23 agents were associated with low rates of safety events. Risankizumab had the most favorable benefit-risk profile in the long term.

Psoriasis (PSO) is an inflammatory disease that emerges as a dysregulation of the interleukin 23 (IL23)/Th17 axis. There are many biologic alternatives to treat PSO that are administered monthly, every 2 months and every 3 months. Guselkumab (GUS) is a fully human monoclonal antibody, that selectively blocks IL-23 through binding to its p19 subunit. There is scarce evidence on dose optimization of GUS in psoriatic patients. Retrospective, observational case series review which includes patients with moderate-to-severe PSO who switched from ustekinumab to GUS as standard dosing or every 12 weeks, regarding daily clinical practice of every dermatology unit. Clinical and demographic data from patients were included from February 2019 to October 2021. Analyses were performed "as observed" using GraphPad Prism version 8.3.0 for Windows (GraphPad Software, San Diego, CA, USA, www.graphpad.com). A total of 30 patients were included in this study: 20 receiving GUS as standard of care (SC) and 10 receiving an optimized dosing (Q12W) (GUS every 12 weeks without induction). The Q12W group presented greater percentage of comorbidities and was less refractory to previous biologic treatments. After receiving GUS as SC or Q12W, psoriasis area severity index and dermatology life quality index improved dramatically in both groups up to 52 weeks. Survival was 87.2% and 100% for the SC and Q12W, respectively, and there were not safety signals. Our case series of 10 patients receiving GUS every 12 weeks without induction showed a good effectiveness and safety profile accompanied by an excellent treatment survival. However, more studies are needed to provide strong evidence of dosing alternatives different than SC.

Guselkumab is a monoclonal antibody that selectively blocks the p19 subunit of interleukin 23 and has been approved for the treatment of moderate to severe psoriasis and active psoriatic arthritis in adult patients due to its efficacy in different clinical trials. Therefore, itis important to know the performance of guselkumab in this setting of patients in clinical practice given that a high percentage of them are not represented in these clinical trials. Our objective was to evaluate the effectiveness and tolerability of guselkumab in clinical practice in the first patients with psoriasis and psoriatic arthritis treated since the date of its approval for psoriasis in Spain, in joint dermatology-rheumatology clinics. A multicenter retrospective data collection was carried out, in which 14 hospitals participated, including a total of 90 patients with psoriatic arthritis confirmed by a rheumatologist. Data collection was recorded at baseline and at weeks 12, 24, and 52 for both the articular and cutaneous domains. Ninety PsA patients started treatment with guselkumab and therefore were included in this study. The vast majority had already failed to at least to one biologic therapyprior guselkumab prescription. The median age was 55 years, 61% were female and 46% had a BMI >= 30 kg/m(2). Sixty-nine percent suffered from peripheral arthritis, and in 34% an axial involvement was also detected; dactylitis or enthesitis was present in 24% and 29% of patients, respectively. Guselkumab was effective in controlling both articular and skin manifestations of PsA patients. Absolute PASI significantly decreased from 10.5 to 4.8, 1.9 and 1.3 at weeks 12, 24, and 52, respectively. In 29 out of 61 (48%) of cases, DAPSA was moderate or high, and patients showed a significant reduction in DAPSA at 12, 24, and 52 weeks of treatment (mean DAPSA values at baseline and follow up were 29, 20, 16, and 14, respectively). Patients with DAPSA in low activity or in remission at the time of initiation of guselkumab maintained response at the end of the study period. No new safety concerns were detected. Seventy-eight out of 90 patients (84.4%) persisted on treatment after 2 years follow-up. Our experience suggests that guselkumab isan effective drug for PsA and PsO patients in clinical practice with good tolerability and no additional safety signals, making it a new therapeutic alternative for the treatment of PsA and PsO patients.

Background Axial involvement constitutes a specific domain of psoriatic arthritis (PsA). Interleukin (IL)-23 inhibitors have demonstrated improvement in axial PsA (axPsA) symptoms, but have not shown efficacy in treating ankylosing spondylitis (AS), suggesting differences in axPsA processes and treatments. In a post hoc, pooled analysis of patients with investigator- and imaging-confirmed sacroiliitis in two phase 3, randomized, placebo-controlled studies (DISCOVER-1 and DISCOVER-2), patients treated with guselkumab, an IL-23p19 inhibitor, had greater axial symptom improvements compared with placebo. Confirmatory imaging at baseline was restricted to the sacroiliac (SI) joints, occurred prior to/at screening, and was locally read. Methods The STAR study will prospectively assess efficacy outcomes in PsA patients with magnetic resonance imaging (MRI)-confirmed axial inflammation. Eligible, biologic-naïve patients with PsA (N = 405) for ≥ 6 months and active disease (≥ 3 swollen and ≥ 3 tender joints, C-reactive protein [CRP] ≥ 0.3 mg/dL) despite prior non-biologic disease-modifying antirheumatic drugs, apremilast, and/or nonsteroidal anti-inflammatory drugs will be randomized (1:1:1) to guselkumab every 4 weeks (Q4W); guselkumab at week (W) 0, W4, then every 8 weeks (Q8W); or placebo with crossover to guselkumab at W24, W28, then Q8W. Patients will have Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4, spinal pain component score (0–10 visual analog scale) ≥ 4, and screening MRI-confirmed axial involvement (positive spine and/or SI joints according to centrally read Spondyloarthritis Research Consortium of Canada [SPARCC] score ≥ 3 in ≥ 1 region). The primary endpoint is mean change from baseline in BASDAI at W24; multiplicity controlled secondary endpoints at W24 include AS Disease Activity Score employing CRP (ASDAS), Disease Activity Index for PsA (DAPSA), Health Assessment Questionnaire – Disability Index (HAQ-DI), Investigator’s Global Assessment of skin disease (IGA), and mean changes from baseline in MRI SI joint SPARCC scores. Centrally read MRIs of spine and SI joints (scored using SPARCC) will be obtained at W0, W24, and W52, with readers blinded to treatment group and timepoint. Treatment group comparisons will be performed using a Cochran-Mantel-Haenszel or chi-square test for binary endpoints and analysis of covariance, mixed model for repeated measures, or constrained longitudinal data analysis for continuous endpoints. Discussion This study will evaluate the ability of guselkumab to reduce both axial symptoms and inflammation in patients with active PsA. Trial registration This trial was registered at ClinicalTrials.gov, NCT04929210, on 18 June 2021. Protocol version: Version 1.0 dated 14 April 2021.

The safety and efficacy of guselkumab for palmoplantar pustulosis (PPP) have been established through week (W)52; however, no sufficient information is available beyond 1 year. This study was conducted to assess the efficacy and safety of guselkumab through W84, and to explore factors associated with the sustainability of its efficacy in Japanese PPP patients. Patients received guselkumab 100 or 200 mg at W0, W4, W12, and every 8 weeks (q8w) until W60, or placebo at W0, W4, and W12. At W16, patients receiving placebo were re-randomized to receive guselkumab 100/200 mg at W16, W20, and q8w until W60. Efficacy end-points included PPP Area and Severity Index (PPPASI), PPP Severity Index (PPSI), Physician's Global Assessment scores, and patient reported outcomes (PRO) (Dermatology Life Quality Index, EuroQoL-5 Dimensions, and 36-item Short Form Health Survey). Post-hoc comparison of patient characteristics was performed between PPPASI-75/90 responders and non-responders at W60, and sustained responders and non-responders at W84. Safety was evaluated through W84. A total of 45, 43, 21, and 24 patients from the guselkumab 100 mg, guselkumab 200 mg, placebo→guselkumab 100 mg, and placebo→guselkumab 200 mg groups, respectively, completed the study through W84. Overall, the mean improvement in the guselkumab groups from baseline in the PPPASI and PPSI total scores at W84 was ~79% and ~66%, respectively. All PRO improved through W84. The proportion of responders through W60 was higher in patients who had not received prior phototherapy and non-biologic systemic therapy for PPP. Non-smokers and patients with no prior non-biologic systemic treatment tended numerically towards sustained efficacy through W84. The majority of treatment-emergent adverse events (TEAE) were mild to moderate (~88%) with low incidence of serious TEAE (7.6%). Overall, guselkumab showed sustained efficacy and safety with improvement in the health-related quality of life through W84 in Japanese PPP patients.

Background: Biologic switching is not uncommon in the treatment of psoriasis and is most often due to inadequate response of adverse events. Staying within or switching out of the class is still based on expert opinion but there are published data on intra-class switching with TNF-alpha and IL-17 inhibitors. Less is known about the IL-23 inhibitors because of their limited time in the market. We would like to present our experience with inadequate responders to tildrakizumab, a selective IL23 inhibitor, who were switched to an alternative IL-23 inhibitor. Case Description: This is a case series of 6 patients at a single institution considered inadequate responders to tildrakizumab, which included primary failures, secondary failures, and intermediate responders, who were subsequently switched to another IL-23 inhibitor. Conclusion: All 6 patients who were inadequate responders to tildrakizumab showed significant improvement after switching to another IL-23 inhibitor, with 5/6 reaching IGA 0/1 after 16 weeks of treatment.

Purpose Guselkumab, an interleukin (IL)-23 inhibitor, effectively treats moderate-to-severe plaque psoriasis. Materials and methods ECLIPSE, was a Phase 3, multicenter, 56-week, double-blinded, active-comparator study of guselkumab vs. secukinumab (IL-17A inhibitor) in patients with moderate-to-severe psoriasis. Patients were treated with guselkumab 100 mg (n = 534) or secukinumab 300 mg (n = 514) through week 44. Efficacy (at least a 90% and 100% improvement from baseline in Psoriasis Area and Severity Index [PASI 90 and PASI 100], Investigator's Global Assessment [IGA] 0/1, and IGA 0) was analyzed across subpopulations defined by baseline: age ( Results Overall, 1048 patients were randomized. At week 48, numerically greater proportions of patients achieved PASI 90, PASI 100, IGA 0/1, and IGA 0 with guselkumab vs. secukinumab regardless of baseline age, body weight, BMI, disease severity, body region, and prior medication. The largest differences were in patients ≥65 years old and patients weighing >100 kg. Conclusions Guselkumab treatment provided greater efficacy vs. secukinumab at week 48 in most subpopulations of patients with psoriasis.

There is substantial evidence regarding the association between psoriasis and the elevated risk of cardiovascular (CV) disease. Many patients with psoriasis may also be concerned that their treatments may be associated with a further increase in the risk of CV disease. In this article, we summarize the data regarding the biological role of interleukin (IL)-12/23 in atherogenesis. We performed a literature search for currently known CV safety data from trials and observational studies of treatments targeting IL-12/23 in psoriasis, i.e. the p40 inhibitors ustekinumab and briakinumab, and the p19 inhibitors guselkumab, risankizumab, and tildrakizumab. On balance, extensive evidence supports the CV safety of ustekinumab, with over 14 years of follow-up data in multiple cohort studies and randomized controlled trials (RCTs). One self-controlled study concluded ustekinumab may precipitate short-term raised CV risk, but the study had limitations hindering interpretation. The safety evidence from RCTs on the p19 inhibitors are reassuring thus far, but these studies may not detect rare CV events in real-world patients. We concluded that the overall evidence does not show that ustekinumab is associated with an increase in the risk of CV disease in patients with psoriasis, but further data are awaited to assess the CV safety of p19 inhibitors for the treatment of psoriasis.

Guselkumab (TREMFYA®), a fully human immunoglobulin G1λ (IgG1λ) monoclonal antibody that selectively targets interleukin (IL)-23, is an effective and generally well-tolerated treatment option for active psoriatic arthritis. Guselkumab is administered subcutaneously and can be used alone or in combination with methotrexate. In randomized, double-blind, placebo-controlled phase 3 trials in adults with active psoriatic arthritis and an inadequate response to or intolerance of standard treatment, guselkumab was effective in reducing disease activity and structural damage progression. Guselkumab conferred improvements in arthritis, enthesitis, dactylitis, psoriasis, axial symptoms, physical function and health-related quality of life. The clinical benefits of guselkumab for the diverse signs and symptoms of psoriatic arthritis increased or were maintained through two years of treatment, with no new safety signals emerging. Psoriatic arthritis is an inflammatory joint disease that commonly occurs in patients with psoriasis. While several drugs are now available for the treatment of psoriatic arthritis, patients often need to switch treatments due to inadequate efficacy or tolerability concerns. Guselkumab (TREMFYA®) treats psoriatic arthritis via a novel mechanism of action. In well-designed clinical trials, guselkumab provided durable improvements in the various signs and symptoms of psoriatic arthritis (including arthritis, joint inflammation and structural damage, skin disease and spinal manifestations). Guselkumab recipients reported gains in physical function and health-related quality of life. Guselkumab is an effective option for the treatment of active psoriatic arthritis and is generally well tolerated, with no new safety concerns identified during longer-term use.

Objective To determine the relative effectiveness and safety of doses of secukinumab and guselkumab in patients with active psoriatic arthritis (PsA). Materials and methods A Bayesian network meta-analysis was performed incorporating data from randomized controlled trials (RCTs) to evaluate the effectiveness and safety of secukinumab 150 mg, secukinumab 300 mg, and guselkumab 100 mg every 4 weeks (Q4W) and guselkumab every 8 weeks (Q8W). Results Six RCTs, including 2,385 patients, fulfilled the inclusion criteria. The surface under the cumulative ranking curve (SUCRA) revealed that secukinumab 300 mg had the highest probability of reaching a 20% American College of Rheumatology (ACR20) response rate, followed by secukinumab 150 mg, guselkumab 100 mg Q4W, guselkumab 100 mg Q8W, and placebo. The ACR50 response rate revealed the same distribution pattern as the ACR20 response rate. The SUCRA rating, dependent on the psoriasis area and severity index of at least 75% (PASI75) response rate, showed that guselkumab 100 mg Q4W had the highest possibility of achieving the PASi75 response, followed by guselkumab 100 mg Q8W, secukinumab 300 mg, secukinumab 150 mg, and placebo. Safety analyses focused on serious adverse events (SAEs), adverse events (AEs), and withdrawals attributable to AEs that did not have statistically relevant variation in the respective intervention categories. Conclusion Based on the ACR20 and ACR50 response rates, secukinumab 300 mg had the strongest response effectiveness, whereas guselkumab 100 mg Q4W was the most effective treatment strategy for PsA based on PASI75. However, there was little disparity between the treatment options with regard to SAEs.

Guselkumab is an IL-23 inhibitor that has been demonstrated to be effective and safe for the treatment of moderate-to-severe plaque psoriasis in clinical trials. The data pool relating to the use of guselkumab in a real-life setting is still lacking. To evaluate the efficacy and safety of guselkumab in a real-life setting, focusing on predictors of early clinical response, a single-center prospective study was conducted enrolling patients with moderate-to-severe psoriasis. The clinical data relating to the efficacy and safety of the drug were acquired at initiation of treatment and at all subsequent clinical follow-ups: the primary endpoint was PASI90 and PASI100 response at week 12, 24, and 48. Out of the total cohort of 74 patients, 62 (83.8) reached a 48-week follow-up 64 (87.8%) reached a 24-week follow-up, while 72 (97.3%) a 12-week follow-up. Treatment with guselkumab reduced the mean PASI from the initial 11 ± 6.3 to 2.5 ± 3.1 at 12 weeks, to 1.2 ± 1.8 at 24 weeks, and to 0.8 ± 1.6 at 48 weeks. At week 12, a PASI 90 and PASI 100 response was achieved by 44.4% and 23.6% of patients, respectively. After 24 weeks, 63% of patients reported a PASI 90 while 46.1% achieved PASI 100. Previous treatment with one or more other biologics did not impact significantly on the achievement of the PASI 90 and 100 at any endpoints analyzed. We reported no difference between bio-naïve and non-naïve patients in the response to guselkumab, high safety, and efficacy was showed in both populations.

Introduction The clinical benefits of biologic and oral treatments for moderate-to-severe plaque psoriasis are well-established, but efficacy outcomes can vary across therapies. Comparative efficacy analysis can be highly informative in clinical settings with multiple therapeutic options. This study assessed the short-term and long-term comparative efficacy of biologic and oral treatments for moderate-to-severe psoriasis. Methods A systematic literature review identified phase 2/3/4 randomized controlled trials (RCTs) through to 1 July 2020 for Food and Drug Administration- or European Medicines Agency-licensed treatments for moderate-to-severe psoriasis. Psoriasis Area and Severity Index (PASI) 75/90/100 response rates at the end of the primary response (short-term: 10–16 weeks from baseline) and maintenance periods (long-term: 48–52 weeks from baseline) were estimated using Bayesian network meta-analysis. Surfaces under the cumulative ranking curves (SUCRA) were estimated to present the relative ranking of treatments. Results In the short term (N = 71 RCTs), the PASI 90 response rates were highest for ixekizumab (72.9%, SUCRA 0.951), risankizumab (72.5%, 0.940), and brodalumab (72.0%, 0.930), which were significantly higher than those for guselkumab (65.0%, 0.795), secukinumab (65.0%, 0.794), infliximab (56.8%, 0.702), certolizumab (400 mg: 49.6%, 0.607; 200 mg: 42.2%, 0.389), ustekinumab (90 mg: 47.9%, 0.568; weight-based: 45.7%, 0.505; 45 mg: 44.6%, 0.460), adalimumab (43.0%, 0.410), tildrakizumab (200 mg: 39.7%, 0.327; 100 mg: 37.2%, 0.268), etanercept (18.0%, 0.171), apremilast (12.4%, 0.090), and dimethyl fumarate (12.2%, 0.092). The PASI 100 response rates were highest for ixekizumab (41.4%), risankizumab (40.8%), and brodalumab (40.3%). In the long term (N = 11 RCTs), the PASI 90 rate was highest for risankizumab (85.3%, SUCRA: 0.998), which were significantly higher than those for brodalumab (78.8%, 0.786), guselkumab (78.1%, 0.760), ixekizumab (72.1%, 0.577), secukinumab (67.0%, 0.450), ustekinumab (weight-based: 55.0%, 0.252), adalimumab (51.6%, 0.176), and etanercept (37.9%, 0.001). Risankizumab had the highest PASI 100 response rate (65.4%), followed by brodalumab (55.7%) and guselkumab (54.8%). Conclusions Ixekizumab, risankizumab, and brodalumab had the highest short-term efficacy, and risankizumab had the highest long-term efficacy. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00511-1.

The three monoclonal antibodies ustekinumab, guselkumab and risankizumab targeting the p 40 or the 19 subunit of interleukin -23 have now been approved for the indication psoriasis and the former two also for psoriatic arthritis (PsA). Ustekinumab and risankizumab have appeared ineffective in randomised controlled trials with patients with axial spondyloarthritis (axSpA), but post-hoc analyses of PsA trials have now suggested that they may improve back pain symptoms potentially induced by axial inflammation based on PsA. Here we argue that, based on the absence of efficacy in axSpA, this is unlikely and more probably due to generic, non-specific effects, which are not adequately covered by the tools developed for the assessment of inflammation in axSpA.

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.

In Japan, the Japanese Society for Psoriasis Research (JSPR) has been conducting annual epidemiological surveys of patients with psoriasis since 1982. The aim of this study was to conduct a recent epidemiological analysis of the psoriasis patients who were enrolled in the JSPR from 2013 to 2018. A total of 15 287 cases were enrolled from 132 medical institutions, out of which 65.3% (9989 cases) were male and 34.7% (5298 cases) were female. Approximately 50.0% of the cases had past history and comorbidities, such as hypertension (42.0%), dyslipidemia (30.0%), diabetes mellitus (23.7%), hyperuricemia (15.1%), cardiovascular disease (6.0%), and cerebral vascular disorders (6.0%). There was a yearly increase in the use of corticosteroid/vitamin D3 combinations and apremilast for treating psoriasis. In contrast, the use of phototherapy gradually decreased. From 2013 to 2018, approximately 18.6% of the cases were treated with biologics, such as infliximab (17.6%), adalimumab (23.3%), ustekinumab (21.4%), secukinumab (11.6%), ixekizumab (7.6%), brodalumab (6.3%), and guselkumab (4.3%). In the past decade, the biologics have changed the treatment and management of psoriasis. This survey includes significant information regarding the recent perspective of psoriasis in the Japanese Society, especially focusing on the treatment trends after the introduction of biologics.

BACKGROUND: Measuring cumulative clinical treatment benefit over time captures speed and magnitude of effects. Assessing the cost of biologics relative to their cumulative clinical benefits versus a single time point represents an alternative to evaluate the value of a given biologic used to treat psoriasis. OBJECTIVE: To compare cumulative benefit and cost per cumulative benefit of biologics in treatment of moderate to severe psoriasis from a network meta-analysis (NMA). METHODS: Biologics included in the analysis were ixekizumab, adalimumab, guselkumab, ustekinumab, secukinumab, risankizumab, and certolizumab pegol. Psoriasis Area and Severity Index (PASI) responses over the initial 16-week treatment period were obtained from 31 articles. Cumulative benefits for PASI 75, PASI 90, and PASI 100 responses were measured as area under the curve (AUC) using the trapezoidal method. Bayesian-based NMA modeled percent maximum AUC through week 16 (%Max_AUCW16). The AUC estimates over 16 weeks were converted to total skin clearance threshold days achieved for PASI 75, PASI 90, and PASI 100 with each biologic. Cost per cumulative benefit was estimated by multiplying number of doses (per FDA label) by nationally representative discounted wholesale acquisition costs (WACs) for 16 weeks of treatment divided by %Max_AUCW16. The primary cost analysis used WACs, including week 16 doses. Co-primary cost analysis used discounted WACs, including week 16 doses. Sensitivity analysis was conducted using WACs and discounted WACs, excluding doses administered at week 16. RESULTS: Among biologics with available week 16 AUC data for PASI 90 and PASI 100, cumulative benefits over the initial 16-week treatment period ranged from 20.2% (certolizumab pegol) to 47.0% (ixekizumab) for PASI 90 and from 7.4% (adalimumab) to 22.2% (ixekizumab) for PASI 100. The total number of estimated PASI 90 and PASI 100 days achieved over the first 16 weeks of treatment was highest with ixekizumab (53 days and 25 days, respectively). In the primary analysis, guselkumab had the lowest cost per cumulative benefit (95% credible interval [CrI]; $99,742 [$89,941-$111,653]), followed by ixekizumab ($108,906 [$95,928-$126,093]) and adalimumab ($111,233 [$97,549-$129,022]) for PASI 90, and ixekizumab had the lowest cost per cumulative benefit ($230,884 [$191,611-$291,115]), followed by secukinumab ($238,945 [$204,029-$288,072]) and risankizumab ($279,968 [$250,683-$316,872]) for PASI 100 responses. In the co-primary analysis, ixekizumab had the lowest discounted cost per AUC (95% CrI; $60,988 [$53,719-$70,612]), followed by guselkumab ($66,827 [$60,260-$74,807]) and secukinumab ($69,622 [$61,783-$79,786]) for PASI 90, and ixekizumab had the lowest cost per cumulative benefit ($129,295 [$107,302-$163,024]), followed by secukinumab ($148,146 [$126,498-$178,605]) and guselkumab ($188,190 [$166,791-$215,969]) for PASI 100 responses. Conclusions: Among biologics studied, ixekizumab demonstrated the greatest cumulative clinical benefit, maintaining the lowest cost per cumulative benefit for PASI 100 responses and lowest discounted cost per cumulative benefit for PASI 90 and PASI 100 responses for moderate to severe psoriasis over the initial 16-week treatment period. DISCLOSURES: This study was funded by Eli Lilly and Company (Indianapolis, IN). Blauvelt has served as a scientific adviser and/or clinical study investigator for AbbVie, Aclaris, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dermira, Eli Lilly and Company, Forte, Galderma, Incyte, Janssen, Leo, Novartis, Ortho, Pfizer, Rapt, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB Pharma and as a paid speaker for AbbVie. Burge, Zhu, Malatestinic, Brnabic, Guo, and Janardhanan are employees and shareholder of Eli Lilly and Company.

Objective To compare the efficacy and safety of biologics for patients with moderate to severe plaque psoriasis. Methods We systematically reviewed 60 randomized controlled trials (34,020 participants), which compared 14 biological drugs for treatment of moderate to severe plaque psoriasis. The main assessment criteria were ≥ 90 % reductions in Psoriasis Area and Severity Index (PASI 90) and the number of patients who reported treatment-emergent adverse events (AEs). Secondary criteria were ≥ 75 % reductions in Psoriasis Area and Severity Index (PASI 75), Physician's Global Assessment 0/1 (PGA 0/1) and infections. Results This network meta-analysis showed that biologics were significantly more effective than placebo. Ixekizumab, risankizumab, and bimekizumab were among the most effective treatments, and tildrakizumab, guselkumab and risankizumab were better than the other drugs with respect to safety. Risankizumab and guselkumab performed relatively stable with respect to both efficacy and safety. At the class level, blockers of interleukin (IL)-17A showed favorable efficacy while inhibitors of the p19 subunit of IL-23 were best tolerated of all efficient biologics. Conclusions Ixekizumab was the most effective biologic in PASI 90, while IL-23p19 inhibitors, risankizumab and guselkumab performed relatively stable with respect to efficacy and safety.

INTRODUCTION Guselkumab is a subcutaneously administered human monoclonal antibody, selectively blocking IL-23 through binding to its p19 subunit. It was initially approved for the treatment of patients with moderate-to-severe plaque-psoriasis who are candidates for systemic therapy or phototherapy. Pubmed and Embase databases were searched for publications, using the following search terms: psoriasis, psoriatic arthritis, guselkumab, risankizumab, tildrakizumab, p19, interleukin 23, guidelines, treatment recommendations, DISCOVER, ECLIPSE, and VOYAGE. AREAS COVERED Accumulating evidence suggests that the IL-23/Th17 pathway is important in the pathogenesis of both psoriasis and psoriatic arthritis. Following a successful development program in psoriasis, guselkumab was evaluated for its efficacy and safety in psoriatic arthritis in a comprehensive clinical trial program, comprising one phase-2 study and two phase-3 studies (DISCOVER-1 and -2). Complementary data on pharmacokinetics and safety exist from pre-clinical experiments and pooled analyses from two long-term studies in psoriasis (VOYAGE-1 and -2). Based on the DISCOVER-1 and -2 data, guselkumab was approved by the FDA for the treatment of active psoriatic arthritis in 2020. EXPERT OPINION Guselkumab is the first selective IL-23 inhibitor approved to treat adults with active psoriatic arthritis, broadening therapeutic options in the field through a novel mode of action.

Introduction: Despite advances in the medical management of ulcerative colitis (UC), a subgroup of patients does not respond to currently available therapies. A number of novel drugs are in late stages of clinical development or have recently received regulatory approval for UC. Areas covered: This review focuses on three drug classes that have recently been approved or are awaiting approval for UC: antibodies against interleukin (IL)-23, sphingosine-1-phosphate receptor (S1PR) modulators, and selective inhibitors of Janus kinases (JAK). We provide an overview of their mechanism of action and summarize available evidence for their efficacy and safety. Finally, we discuss expected future challenges in UC management. Expert opinion: The evaluated drugs have demonstrated efficacy with an acceptable safety profile. IL-23 antagonists appear to be safest with very few (serious) adverse events, while the use of S1PR modulators or JAK inhibitors has been associated with infectious and cardiovascular/thromboembolic events, albeit in low numbers. Although advances in drug development are promising, there is an urgent need for (validated) biomarkers to guide rational treatment selection. The scarcity of head-to-head trials also complicates comparisons between available drugs. Breaking the therapeutic ceiling of efficacy in UC will require marked advances in management extending well beyond drug development.

Nowadays, the biological equipment available for the treatment of moderate-to-severe psoriasis is plenty. Anti-interleukin-23 represents the latest class of biologic approved for the management of moderate-to-severe psoriasis. Their efficacy and safety have been assessed through two major sources: clinical trials (CTs) and real-world experiences data (RWE). Notably, the two sources differ from one another, but together, they complement information and current knowledge on both efficacy and safety of biological therapy. We carry out a review on CTs and RWE reports on the latest group of biological approved for moderate-to-severe psoriasis: anti-IL23 (guselkumab, risankizumab, and tildrakizumab).

Objective Treatment of recalcitrant moderate-to-severe psoriasis can be challenging. Combination therapy of biologics and immunosuppressive agents can be a new strategy for treating therapy-resistant cases with comorbidities, where many systemic medications are contraindicated. Case presentation We report a case of a 62-year-old diabetic man with a 30-year history of severe plaque psoriasis and psoriatic arthritis with cirrhosis and diabetic nephropathy that was treated successfully in combination with apremilast and etanercept after multiple previous unsuccessful treatment attempts. Conclusion There are no data supporting the combination of apremilast and etanercept in the management of recalcitrant cases of moderate-to-severe psoriasis and multiple comorbidities including psoriatic arthritis, diabetic nephropathy, and cirrhosis. In patients who do not respond to multiple approaches for the treatment of psoriasis, combination therapy with biologic agents and new systemic medications may lead to dramatic disease control.

The article presents the results of clinical studies of the efficacy and safety of the use of a new drug of genetically engineered biological therapy guselkumab. Guselkumab is the first representative of the interleukin-23 (IL-23) inhibitor class and has a number of advantages over existing therapy. According to direct comparative randomized clinical trials, guselkumab is superior in the short-term and, most importantly, in the long-term to most genetically engineered biologic drugs, including TNF- inhibitors, secukinumab and ustekinumab. In phase 3 studies (VOYAGE 1 and VOYAGE 2), the ECLIPSE study shows that guselkumab can achieve complete (PASI 100) and almost complete (PASI 90) skin cleansing by 16 weeks from the start of therapy in 37.4 and 73.3% of patients, respectively, with a subsequent increase in the proportion of patients with clean and almost clean skin by 24 weeks to 44.4 and 80.2%, respectively, and maintaining the achieved performance indicators for 4 years at the level of 51.7 and 84.0% respectively. One of the potential advantages of IL-23 inhibitors is also the long-term maintenance of the achieved effect after treatment cessation. Guselkumab therapy is characterized by a favorable safety profile comparable to ustekinumab. During the follow-up period of patients in the course of randomized controlled trials of phase 3, data were obtained on the high safety of the drug and the absence of significant risks for serious infections, cardiovascular events, malignancies or suicidal tendencies. The drug is effective for insufficient response to adalimumab and ustekinumab. The article presents 3 clinical cases of guselkumab use in patients with severe, including "problematic" psoriasis, comorbid pathology, with inefficiency or intolerance to systemic therapy, with secondary inefficiency of adalimumab. All patients managed to achieve a PASI of 90/100. No adverse events were observed.

Objective To assess performance of psoriatic arthritis (PsA) composite indices and evaluate guselkumab’s effect on achieving low disease activity or remission. Methods In this phase II trial, patients with active PsA (≥3 tender and ≥3 swollen joints, C‐reactive protein level ≥0.3 mg/dl, ≥3% body surface‐area with psoriasis involvement) were randomized 2:1 to subcutaneous guselkumab 100 mg (n = 100) or placebo (n = 49) at week 0, week 4, and every 8 weeks through week 44. At week 16, patients with

Guselkumab effectively treats moderate-to-severe psoriasis. Results of continuous guselkumab treatment through 4 years from VOYAGE 2 are presented. At baseline, 992 patients were randomized to receive guselkumab 100 mg every 8 weeks, placebo, or adalimumab 40 mg every 2 weeks. Placebo-treated patients crossed over to guselkumab at week 16. Weeks 28–76 incorporated randomized withdrawal, and all patients received open-label guselkumab through to week 204. Efficacy was analyzed using pre-specified treatment failure rules (patients were considered nonresponders after discontinuing due to lack of efficacy, worsening of psoriasis, or use of a prohibited treatment). There was no missing data imputation after treatment failure rules. Safety was analyzed through 4 years. The proportions of guselkumab-treated patients who achieved and maintained designated clinical responses at weeks 100 and 204, respectively, were as follows: at least a 75% improvement in Psoriasis Area and Severity Index from baseline (PASI 75): 94.1% and 92.3%; PASI 90: 79.1% and 79.7%; PASI 100: 48.4% and 51.0%; Investigator’s Global Assessment (IGA) score of 0/1: 83.1% and 81.9%; IGA score of 0: 52.7% and 52.7%; Dermatology Life Quality Index score of 0/1: 70.2% and 69.1%; Psoriasis Symptoms and Signs Diary (PSSD) symptom score of 0: 35.7% and 39.7%; PSSD sign score of 0: 22.0% and 27.2%; ≥ 5% improvement in Short Form-36 (SF-36) physical component score: 48.8% and 45.0%; ≥ 5% improvement in SF-36 mental component score: 45.1% and 43.2%; Hospital Anxiety and Depression Score (HADS)-anxiety score ≥ 8: 22.9% and 21.7%; and HADS-depression score ≥ 8: 16.6% and 21.0%. Similar findings were reported for the adalimumab → guselkumab group. No new safety signals were identified. High efficacy levels were maintained from week 100 through to week 204 with continuous guselkumab treatment, across multiple endpoints, in VOYAGE 2. Guselkumab was well tolerated. NCT02207244.

Objectives: We aimed to evaluate the effectiveness, safety and tolerability of guselkumab in a real-life setting.Methods: A prospective, observational, single-center, real-life study including patients under guselkumab treatment from October 2018 to January 2020 was conducted.Results: Twenty-three patients with moderate-to-severe psoriasis were enrolled and twenty-two continued the treatment until week 44. One patient discontinued for increase in liver enzymes. At baseline, mean PASI score was 15.1 ± 6.1, which reduced up to 3.2 ± 1.9 at week 12 (p < 0.001) and 0.8 ± 0.7 at week 44 (p < 0.001). BSA reduced from 36.4 ± 13.6 at baseline, to 8.3 ± 7.4 at week 12 (p < 0.001), up to 2.2 ± 1.4 at week 44 (p < 0.001). A total of 4 patients (17.4%) experienced mild blood tests alterations and 6 subjects (26%) experienced potential adverse events (AEs). No AEs required guselkumab discontinuation. No cases of serious AEs, injection site reaction, candida, malignancy, cardiovascular events were reported.Conclusions: Patients under guselkumab therapy reach an optimal clinical response, even in a real-life and long-term setting.

Background Biologic medications for plaque psoriasis have been used to treat erythrodermic psoriasis (EP). Since the guidelines for management of EP were published, new biologic medications have been approved for the treatment of plaque psoriasis. Objective To analyze the evidence of biologic medications in the treatment of EP based on response and tolerability. Methods A comprehensive search was conducted with the PubMed, Cochrane Library, Embase, and Scopus databases through December 31, 2018. Studies reporting 1 or more cases of EP, defined as >75% body surface area involvement, in patients aged ≥18 years treated with biologics were included. Baseline Psoriasis Area and Severity Index score, score improvement, and adverse events were documented. Adequate response to treatment was defined as Psoriasis Area and Severity Index ≥50. Results Included were 43 articles, yielding a total of 179 patients. Most patients responded at some point during treatment, with a higher level of evidence for infliximab, ustekinumab, ixekizumab, and guselkumab. Infection was the most common adverse event (n = 35). Limitations Data are limited to case reports, case series, and uncontrolled studies. Conclusion Patients with EP treated with biologics demonstrated positive responses and treatment was well-tolerated, with a weak recommendation and limited quality of evidence in favor of infliximab, ustekinumab, ixekizumab, and guselkumab.

Background: The phase 3 studies, VOYAGE 1 and 2, were conducted to assess guselkumab in the treatment of patients with moderate-to-severe psoriasis.Objectives: To investigate the efficacy and safety of guselkumab in Korean patients.Methods: The Korean sub-population of VOYAGE 1 and 2 study patients were included in this analysis. Efficacy and safety were evaluated through Weeks 24 and 28, respectively.Results: Of 126 randomized Korean patients, 30, 63, and 33 received placebo, guselkumab, and adalimumab, respectively. At Week 16, guselkumab was superior to placebo in achieving an Investigator's Global Assessment (IGA) score of 0 or 1 (cleared or minimal; 90.5 vs. 20.0%, p

Palmoplantar pustulosis, or pustulosis palmaris et plantaris (PPP), is a chronic, recurrent inflammatory skin disease that is sometimes unresponsive to conventional therapy. The anti-interleukin 23 antibody guselkumab is effective for treating PPP.This review details the current understanding of PPP and discusses why guselkumab may be effective. Guselkumab is only approved for the treatment of PPP in Japan. In the United States, Canada, the European Union, and several other countries, it is approved for the treatment of moderate-to-severe plaque psoriasis, but not for PPP. Furthermore, guselkumab was approved only 1 year ago; its efficacy will be proven only by phase 2 and 3 clinical trials.The first double-blinded randomized placebo-controlled trial (RCT) of guselkumab for PPP has been completed. The drug was effective, and guselkumab could be used as a new agent for PPP treatment, in addition to several conventional therapeutics. However, several issues remain. For example, there is no mouse model of PPP, so careful observation of human PPP patients and establishment of a good experimental PPP model are essential.