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      Clearance of head and neck involvement in plaque psoriasis with tildrakizumab treatment in the phase 3 reSURFACE 1 study

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          Abstract

          Editor Scalp, face and neck involvement in psoriasis negatively impact patient quality of life. 1 , 2 , 3 In the phase 3 double‐blind, randomized, placebo‐controlled reSURFACE 1 trial (NCT01722331), Psoriasis Area and Severity Index (PASI) response rates in patients with moderate to severe plaque psoriasis were high and durable following treatment with interleukin (IL)‐23p19 inhibitor tildrakizumab, with acceptable safety. 4 This post hoc reSURFACE 1 analysis evaluated scalp, head and neck psoriasis over 28 weeks in adult patients with moderate to severe chronic plaque psoriasis receiving tildrakizumab 100 mg or placebo. Patients were randomized 1:2:2 to subcutaneous placebo or tildrakizumab 100 or 200 mg, respectively, at weeks 0 and 4 and every 12 weeks thereafter. At week 12, patients receiving placebo were re‐randomized to tildrakizumab 100 or 200 mg. Head involvement—including neck, scalp and face—was evaluated using PASI head component (PASIh) (range 0.0–7.2). To assess true clearance (PASIh = 0.0), values ≤0.5 were not rounded to 0. Efficacy was assessed for patients with baseline PASIh ≥ median baseline PASIh, ≥75th percentile of baseline PASIh and all patients using nonresponder imputation. In total, 309 patients receiving tildrakizumab 100 mg and 154 receiving placebo were included. For 163 patients receiving tildrakizumab 100 mg with baseline PASIh ≥ 1.4, median (interquartile range [IQR]) baseline PASIh was 2.4 (1.8, 3.5); for 94 patients with baseline PASIh ≥ 2.4, median (IQR) baseline PASIh was 3.5 (2.8, 4.0). For all 309 patients receiving tildrakizumab 100 mg, median (IQR) baseline PASIh was 1.4 (0.8, 2.4). With placebo, median (IQR) baseline PASIh was 1.2 (0.6, 2.1). Among all patients, 23 (7.4%) receiving tildrakizumab 100 mg and 12 (7.8%) receiving placebo had baseline PASIh of 0.0. For patients receiving tildrakizumab 100 mg with baseline PASIh ≥ 1.4, median (IQR) PASIh was 1.3 (0.6, 2.0) at week 4, 0.3 (0.0, 0.9) at week 12 and 0.3 (0.0, 1.2) at week 28. For patients with baseline PASIh ≥ 2.4, median (IQR) PASIh was 1.8 (1.0, 2.7) at week 4, 0.5 (0.0, 1.0) at week 12 and 0.3 (0.0, 1.2) at week 28. By week 12, 59 (36.2%) and 29 (30.9%) patients with baseline PASIh ≥ 1.4 and ≥2.4, respectively, achieved PASIh = 0.0 following tildrakizumab 100 mg treatment; 66 (40.5%) and 32 (34.0%) achieved PASIh = 0.0 by week 28 (Fig. 1). Figure 1 Distribution of PASIh scores of patients with baseline PASIh scores ≥ 1.4 at (a) week 12 and (b) week 28. Median baseline PASIh score was 1.4 for TIL 100 mg and 1.2 for PBO. TIL 100 mg, n = 163; PBO, n = 72. a n = 1. PBO‐randomized patients received PBO to week 12, followed by TIL 100 or 200 mg to week 28. PASIh, Psoriasis Area and Severity Index head component; PBO, placebo; TIL, tildrakizumab. Over 28 weeks, PASIh scores decreased rapidly for all 309 patients receiving tildrakizumab 100 mg (Fig. 2). At week 4, median (IQR) PASIh for all patients receiving tildrakizumab 100 mg was 0.5 (0.2, 1.4); by week 28, median (IQR) PASIh was 0.0 (0.0, 0.6). At weeks 12 and 28, 160 (20.8%) and 166 (21.5%) patients receiving tildrakizumab 100 mg, respectively, had PASIh = 0.0. Figure 2 Distribution of PASIh scores of all patients receiving tildrakizumab 100 mg or placebo at (a) week 0, (b) week 12 and (c) week 28. TIL 100 mg, n = 309; PBO, n = 154. PBO randomized patients received PBO to week 12, followed by TIL 100 or 200 mg to week 28. PASIh, Psoriasis Area and Severity Index head component; PBO, placebo; TIL, tildrakizumab. For patients receiving placebo, PASIh distribution at week 12 was similar to baseline (Fig. 1). Median (IQR) PASIh was 1.1 (0.3, 1.8) at week 12. The proportion of patients with PASIh = 0.0 on placebo remained steady; only 8.4%, 12.3% and 12.3% of patients had PASIh = 0.0 at week 4, 8 and 12, respectively. In total, 3 patients with baseline PASIh ≥ 1.4 receiving placebo had PASIh = 0 at week 12. Tildrakizumab 100 mg treatment through 28 weeks resulted in rapid, progressive reduction in psoriasis scalp, head and neck involvement for patients with severe disease at baseline. PASIh comprehensively assesses face, neck and scalp, capturing high impact areas. Systemic IL‐17 inhibitor ixekizumab and IL‐23 inhibitor guselkumab were effective for scalp clearance; face and neck have not been assessed. 5 , 6 Tildrakizumab efficacy for scalp, head and neck clearance was similar to IL‐17 inhibitor secukinumab and the tumour necrosis factor‐α inhibitor adalimumab. 7 , 8 , 9 A phase 3b study of tildrakizumab 100 mg for scalp psoriasis is underway. Conflicts of interest MAM has received grants and/or honoraria as a consultant, investigator and/or speaker for Abbott Labs, AbbVie, Amgen, Anacor, Boehringer Ingelheim, Celgene, Eli Lilly and Co., Janssen Biotech, LEO Pharma, Merck & Co., Novartis, Sienna, and UCB; and has been on an advisory board for AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly and Co., Janssen Biotech, LEO Pharma, and Sienna. GJM has received grants and/or honoraria as an investigator and/or speaker for Astellas Pharma US; Janssen Pharmaceuticals; Regeneron Pharmaceuticals; Merck & Co.; Eli Lilly and Co.; AbbVie; Pfizer; Demira; Bristol‐Myers Squibb; UCB; Qurient; Sun Pharmaceutical Industries, Inc.; ChemoCentryx; Galderma Research & Development; Sanofi Genzyme; and Kiniksa Pharmaceuticals; and may have stock in Valeant Pharmaceuticals North America and Astellas Pharma US. HG has received honoraria as a member of an advisory board and/or speaker from Aqua, Galderma, Ortho Dermatologics and Pfizer. AMM is an employee of Sun Pharmaceutical Industries, Inc., and has individual shares in Johnson and Johnson and as part of retirement account/mutual funds. JP has served as statistical consultant for Sun Pharmaceutical Industries, Inc., and is a statistical consultant for Kyowa Kirin Pharmaceutical Development. SJR and DD are employees of Sun Pharmaceutical Industries, Inc. AG has been an investigator for Sun Pharmaceutical Industries, Inc. Funding sources These studies were funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Analyses were funded by Sun Pharmaceutical Industries, Inc., Princeton, NJ, USA. Medical writing support was provided by Kathleen Pieper, PhD, of AlphaBioCom, LLC, and funded by Sun Pharmaceutical Industries, Inc.

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          PASI90 response: the new standard in therapeutic efficacy for psoriasis.

          In a non-life-threatening disease such as psoriasis, treatment goals should be referred to the improvement in severity and extent of the disease and their impact on patients' perceived health-related quality of life (HRQoL), usually measured by the Dermatology Life Quality Index (DLQI). The ultimate goal of therapy is blanching, and an improvement of 90% or better (PASI90 response) with respect to baseline Psoriasis Area and Severity Index (PASI) is considered as treatment success by the European Medicines Agency. PASI75 response has become accepted as a less stringent reasonable therapeutic goal, but absolute PASI values might provide a better benchmark, irrespective of baseline PASI. Anyway, objective measures of psoriasis involvement are clinically meaningful only if they correlate with significant improvements in DLQI, and especially with the achievement of a DLQI = 0-1 status, corresponding to lack of effect of the disease on patient's HRQoL. Even though PASI75 response meets therapeutic expectations in most patients, PASI90 response or better has a significantly higher impact on DLQI improvement and is associated with significantly higher DLQI = 0-1 response rates. The introduction of anti-IL17 drugs in clinical practice bears the promise of achieving PASI90 response or better in the majority of patients, and initial data suggest that the PASI90 benchmark provides better discriminatory value as regards achievement of DLQI = 0-1 response. Further research is required to confirm the value of absolute PASI cut-offs as a measure of therapeutic success independent of baseline and duration of treatment, and to develop newer, more practical and more accurate measures of psoriasis severity.
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            Long‐term efficacy and safety of tildrakizumab for moderate‐to‐severe psoriasis: pooled analyses of two randomized phase III clinical trials (re SURFACE 1 and re SURFACE 2) through 148 weeks †

            Summary Background Tildrakizumab is a specific anti‐interleukin‐23p19 monoclonal antibody approved for the treatment of plaque psoriasis. Objectives To evaluate the long‐term efficacy and safety of tildrakizumab treatment for patients with moderate‐to‐severe psoriasis for up to 148 weeks. Methods Pooled analysis from two double‐blind, randomized controlled trials: reSURFACE 1 and reSURFACE 2. Efficacy was assessed for responders (≥ 75% improvement in Psoriasis Area and Severity Index; PASI 75) and partial responders (PASI 50–75) to tildrakizumab 100 mg and 200 mg at week 28 who were maintained on the same dose (administered every 12 weeks), and for partial responders or nonresponders (PASI < 50) to etanercept 50 mg at week 28 who, after a 4‐week washout, were switched to tildrakizumab 200 mg (administered at weeks 32 and 36, and every 12 weeks thereafter). Safety was assessed in the all‐patients‐as‐treated population. Three different methods of imputing missing data were used: nonresponder imputation (NRI), multiple imputation and observed cases. The Clinicaltrials.gov numbers are NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2). Results At week 148 (NRI), 72·6%, 53·8% and 28·9% of tildrakizumab 100‐mg responders and 80·2%, 59·9% and 32·6% of tildrakizumab 200‐mg responders had PASI 75, 90 and 100 responses, respectively. For partial responders to tildrakizumab 100 mg and 200 mg, the proportions of patients achieving PASI 75, 90 and 100 responses were 32·5%, 25·0% and 10·0%; and 47·1%, 27·5% and 12·8%, respectively. For patients who were partial responders or nonresponders to etanercept, the proportions of patients achieving PASI 75, 90 and 100 responses were 66·9%, 43·8% and 14·9% at week 148. Rates of discontinuations due to adverse events [tildrakizumab 100 mg: 1·7 per 100 patient‐years (PYs); tildrakizumab 200 mg: 1·2 per 100 PYs] and exposure‐adjusted rates of serious adverse events (5·9 per 100 PYs; 5·5 per 100 PYs), severe infections (1·1 per 100 PYs; 1·1 per 100 PYs), malignancies (0·6 per 100 PYs; 0·4 per 100 PYs) and major adverse cardiovascular events (0·4 per 100 PYs; 0·5 per 100 PYs) were low. Conclusions Tildrakizumab was well tolerated and efficacy was well maintained in week 28 responders who continued tildrakizumab treatment through 3 years, or improved among etanercept partial responders or nonresponders who switched to tildrakizumab. What's already known about this topic? Tildrakizumab 100 mg and 200 mg are efficacious and well tolerated with short‐term use in the treatment of patients with moderate‐to‐severe plaque psoriasis. What does this study add? High levels of efficacy are maintained for up to 3 years of psoriasis treatment with tildrakizumab. There is a favourable long‐term safety profile with both tildrakizumab 100 mg and 200 mg, with a low incidence of adverse events of special interest through 3 years.
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              Underdiagnosed and undertreated psoriasis: Nuances of treating psoriasis affecting the scalp, face, intertriginous areas, genitals, hands, feet, and nails

              Abstract Psoriasis of the scalp, face, intertriginous areas, genitals, hands, feet, and nails is often underdiagnosed, and disease management can be challenging. Despite the small surface area commonly affected by psoriasis in these locations, patients have disproportionate levels of physical impairment and emotional distress. Limitations in current disease severity indices do not fully capture the impact of disease on a patient's quality of life, and, combined with limitations in current therapies, many patients do not receive proper or adequate care. In this review, we discuss the clinical manifestations of psoriasis in these less commonly diagnosed areas and its impact on patient quality of life. We also examine clinical studies evaluating the effectiveness of therapies on psoriasis in these regions. This article highlights the need to individualize treatment strategies for psoriasis based on the area of the body that is affected and the emerging role of biologic therapy in this regard.
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                Author and article information

                Contributors
                amderm@gmail.com
                Journal
                J Eur Acad Dermatol Venereol
                J Eur Acad Dermatol Venereol
                10.1111/(ISSN)1468-3083
                JDV
                Journal of the European Academy of Dermatology and Venereology
                John Wiley and Sons Inc. (Hoboken )
                0926-9959
                1468-3083
                03 August 2020
                December 2020
                : 34
                : 12 ( doiID: 10.1111/jdv.v34.12 )
                : e803-e805
                Affiliations
                [ 1 ] Division of Dermatology Baylor Scott & White, and Texas A&M College of Medicine Dallas TX USA
                [ 2 ] Somerset Skin Centre Troy MI USA
                [ 3 ] Dermatology and Skin Cancer Surgery Center McKinney TX USA
                [ 4 ] Sun Pharmaceutical Industries, Inc Princeton NJ USA
                [ 5 ] Division of Dermatology Department of Medicine University of Toronto School of Medicine Toronto ON Canada
                [ 6 ] Mediprobe Research, Inc London ON Canada
                Author notes
                [*] [* ] Correspondence: M.A. Menter. E-mail: amderm@ 123456gmail.com

                Author information
                https://orcid.org/0000-0002-8664-7723
                Article
                JDV16648
                10.1111/jdv.16648
                7953895
                32432798
                13327c73-51aa-408d-a6bd-f2b89bfd2538
                © 2020 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 01 April 2020
                : 04 May 2020
                : 11 May 2020
                Page count
                Figures: 2, Tables: 0, Pages: 3, Words: 1400
                Funding
                Funded by: Sun Pharmaceutical Industries, Inc.
                Funded by: Merck Sharp & Dohme , open-funder-registry 10.13039/100009947;
                Categories
                Letter to the Editor
                Letters to the Editor
                Custom metadata
                2.0
                December 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.9 mode:remove_FC converted:12.03.2021

                Dermatology
                Dermatology

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