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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.

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.

Philip Hampton,1 Emma Borg,2 Jes Birger Hansen,2 Matthias Augustin3 1Department of Dermatology, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK; 2LEO Pharma A/S, Ballerup, Denmark; 3Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, GermanyCorrespondence: Philip HamptonDepartment of Dermatology, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, NE7 7DN, UKEmail philip.hampton@nhs.netPurpose: Both brodalumab and guselkumab improve skin clearance in patients with moderate-to-severe plaque psoriasis after inadequate response to ustekinumab. In the absence of a direct head-to-head comparison, the relative efficacy of brodalumab and guselkumab in non-responders to ustekinumab were compared using a matching-adjusted indirect comparison (MAIC).Patients and Methods: Individual patient data for brodalumab (n = 121) were pooled from the AMAGINE-2 and -3 trials and adjusted using a propensity score reweighting method, so that baseline and week 16 characteristics matched the aggregate published data of patients with an inadequate response to ustekinumab who switched to guselkumab (n = 135) in the NAVIGATE trial.Results: After inadequate response to ustekinumab, brodalumab resulted in significantly higher psoriasis area and severity index (PASI) 90 rates versus guselkumab at post-treatment switch week 12 (62.7% vs 48.1%, relative difference 14.6% [95% confidence interval [CI] 5.3– 23.9], p = 0.002 [number needed to treat [NNT] = 6.8]) and week 36 (63.7% vs 51.1%; relative difference 12.6% [95% CI 4.1– 21.0]; p = 0.004 [NNT = 7.9]) and PASI 100 rate at week 36 (40.3% vs 20.0%; relative difference 20.3% [95% CI 11.8– 28.7]; p < 0.001 [NNT = 4.9]).Conclusion: In this MAIC, brodalumab was associated with greater improvements than guselkumab in inadequate responders to ustekinumab. Switching to brodalumab in such patients may be a more effective strategy than switching to guselkumab.Keywords: brodalumab, guselkumab, psoriasis

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.

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.

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.

Yung Chan, Bik Sai Bessie Tong, Pui Yan Ngan, Chi Sum Au Apex Dermatology Institute, Kowloon, Hong KongCorrespondence: Yung Chan Room 1103-06, 11/F Hong Kong Pacific Centre, 28 Hankow Road, Tsim Sha Tsui, Kowloon, Hong KongTel + 852 3703 3580Fax + 852 3702 0018Email info@apexdermhk.comBackground: Interleukin-23 inhibitors are novel treatment options for psoriasis, and their efficacy and safety have been widely demonstrated in phase 3 clinical trials. Nonetheless, their real-world data remain limited, especially in Asia.Objective: To evaluate the real-world effectiveness of interleukin-23 inhibitor guselkumab in Chinese patients with psoriasis.Methods: In this retrospective single-center study, Chinese patients with psoriasis receiving a standard dose of guselkumab from November 2018 to May 2020 were included in the study cohort. Disease assessment was performed at baseline (Week 0), and at Week 4, 12, and 20 thereafter, using Psoriasis Area and Severity Index (PASI) score.Results: Data of 68 adult patients with psoriasis were retrieved for analysis. At Week 20, 72.1%/47.1% of the patients achieved PASI 90/100 response respectively, and 76.5% achieved a PASI score < 3. Baseline mean PASI score was 17.5, which significantly reduced to 2.0 at Week 20 (P=0.000). No previous use of biologics was a single significant factor associated with achieving PASI 90/100 and PASI score < 3 responses at Week 20 (all Ps< 0.05), while there were no statistically significant differences between males and females and body weight > 75 and ≤ 75 kg in achieving these responses (all Ps> 0.05). Adverse events were experienced by five patients (7.4%), and all were mild in severity.Conclusion: In this first real-world study on guselkumab among Chinese patients with psoriasis, this biologics was shown to be safe and effective in reaching an optimal clinical response up to 20 weeks.Keywords: Chinese, guselkumab, interleukin-23, psoriasis, real-world

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.

Palmoplantar pustulosis (PPP) is a chronic inflammatory disorder characterized by sterile pustules predominantly involving the palms and soles. PPP is refractory to various therapies such as topical ointment, oral medicine, and phototherapies. Pustulotic arthro-osteitis (PAO) is a major comorbidity of PPP that severely impairs patients’ quality of life. Recently, guselkumab, a monoclonal antibody against IL-23, has been available for the treatment of PPP in Japan. The purpose of the present review is to describe the characteristics of Japanese PPP patients and biologic therapy of PPP/PAO using guselkumab. Most Japanese dermatologists consider PPP as a distinct entity and co-existence of PPP and psoriasis is rare. However, outside Japan, PPP is often considered to be palmoplantar psoriasis, and extra-palmoplantar lesions associated with PPP are regarded as psoriasis. PPP develops or exacerbates either with or without arthralgia, following focal infections, such as tonsillitis, odontogenic infection, and sinusitis. Treatment of focal infection results in dramatic effects on cutaneous lesions as well as joint pain. By contrast, we sometimes see patients whose skin/joint symptoms do not improve after treatment of focal infection, whose focus of infection cannot be identified even in a detailed examination, and/or who refuse tonsillectomy even if strongly recommended. Such cases are considered to be indications of biologics. In this review, clinical features, pathophysiology and guselkumab therapy are discussed.

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.

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.

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.

Psoriasis is a chronic immune-mediated disease involving complex interaction of T cells and keratinocytes. The comprehensive pathogenesis of psoriasis is not fully understood but the IL-23/Th17 axis is a central pathway in driving disease development. Guselkumab is the first treatment of moderate-to-severe psoriasis that specifically targets the p19 subunit of IL-23. The benefit of guselkumab has been established by a number of clinical trials including demonstration of greater long-term efficacy in recent comparator trials. This review addresses the results of head-to-head trials (ECLIPSE, IXORA-R, and POLARIS) that compared guselkumab to secukinumab, ixekizumab, and fumaric acid esters. The previously demonstrated long-term efficacy of guselkumab has been corroborated by many recently published studies. The effective and safe profile, convenient dosing, and improved quality of life in patients make gulselkumab a viable first-line treatment option for moderate-to-severe psoriasis.

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 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.

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.

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.

Psoriasis is one of the most frequent chronic inflammatory skin diseases and it has been of interest to many scientists for ages. The review presents data on all systemic treatment options, that are to date officially registered in Russian Federation for moderate-to-severe psoriasis. Aspects of the mechanism of action, efficacy and tolerability of both basic drugs (methotrexate, cyclosporine, acitretin) and biologics (infliximab, adalimumab, etanercept, certolizumab pegol, ustekinumab, guselkumab, secukinumab, ixekizumab, netakimab) and small molecules (tofacitinib, apremilast) are considered in detail. Special emphasis is placed on the important nuances of biological therapy: immunogenicity, drugs' survival and switch due to lack of efficacy. Invention of biologics signified a new era of moderate-to-severe psoriasis treatment. It became possible to achieve complete clinical remission more safely, which significantly improved the quality of life of patients. However, due to the unknown etiology of psoriasis, there is still no universal remedy that would allow to cure every patient, this fact makes scientists from all over the world keep conducting numerous clinical trials to find even more effective and safe therapeutic options.

Guselkumab appears to be safe and effective in the treatment of patients with HS, who do not respond to adalimumab and other systemic therapies. Guselkumab can be used in patients with comorbid Crohn's disease.

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:** Psoriasis is a chronic inflammatory skin condition that impacts quality of life and requires long-term treatment and effective symptom management. Interleukin-23 (IL-23) has emerged as a key player in the pathogenesis of psoriasis and tildrakizumab and guselkumab are both immunomodulatory agents that inhibit the p19 subunit of IL-23. In its pivotal Phase III trial, tildrakizumab demonstrated greater efficacy than etanercept in moderate-to-severe psoriasis. However, there are no head-to-head trials comparing tildrakizumab with guselkumab. **Methods:** We conducted a systematic literature review and Bucher indirect comparison of tildrakizumab and guselkumab, using placebo as a common comparator. We searched MEDLINE, MEDLINE In-Process, MEDLINE(R) Daily Epub Ahead of Print, and Cochrane Central Register of Controlled Trials for Phase III randomized controlled trials between 1946 and November 2018. Inclusion criteria were adult patients ≥18 years with moderate-to-severe chronic plaque psoriasis, and intervention with tildrakizumab or guselkumab compared to placebo or best supportive care. Outcomes included were severity of psoriasis as defined by the Psoriasis Area and Severity Index (PASI) 75 and PASI 90, frequency of serious adverse events (SAEs), and treatment discontinuations. Outcomes were evaluated at Weeks 12 to 16 and 24 to 28. Analysis was based on the intent-to-treat population and, for all outcomes, the number of events reported were analyzed as a proportion of the number of patients randomized to ensure consistency across trials. **Results:** Overall, 154 unique records were identified. Five studies met the eligibility criteria and were included in the analysis; two tildrakizumab trials (reSURFACE 1 and reSURFACE 2) and three guselkumab trials (VOYAGE 1, VOYAGE 2, and a Japanese study). There was no statistically significant difference between guselkumab and tildrakizumab for PASI 75, PASI 90, SAEs, and rate of discontinuations at either timepoint. **Conclusion:** This study assessed the comparative efficacy of tildrakizumab and guselkumab for the treatment of moderate-to-severe psoriasis. Limitations included the limited number of publications, imputation of placebo arm values for Weeks 24 to 28, and limited relevance of the Japanese study. This indirect comparison does not provide evidence that one treatment is superior to the other.