Publications by authors named "Mark Lebwohl"

381 Publications

Biosimilars in Dermatology.

Authors:
Mark Lebwohl

JAMA Dermatol 2021 Apr 7. Epub 2021 Apr 7.

Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamadermatol.2021.0219DOI Listing
April 2021

Study protocol of the global Effisayil 1 Phase II, multicentre, randomised, double-blind, placebo-controlled trial of spesolimab in patients with generalized pustular psoriasis presenting with an acute flare.

BMJ Open 2021 Mar 30;11(3):e043666. Epub 2021 Mar 30.

Service de Dermatologie, Assistance Publique-Hôpitaux de Paris Hôpital Saint-Louis, Paris, France

Introduction: Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening disease characterised by recurrent flares of widespread neutrophilic aseptic skin pustular eruption. Despite the availability of approved biologics for GPP in Japan, Taiwan and Thailand, associated evidence is largely based on uncontrolled studies in which acute flares were not directly assessed. Therefore, there is a high unmet need to investigate new rapid-acting effective treatments that resolve symptoms associated with acute GPP flares. A prior Phase I proof-of-concept study showed rapid improvements in skin and pustule clearance with a single intravenous dose of spesolimab, a novel anti-interleukin-36 receptor antibody, in patients presenting with an acute GPP flare. Here, we present the design and rationale of Effisayil 1, a global, Phase II, placebo-controlled study to evaluate the efficacy, safety and tolerability of spesolimab in patients presenting with an acute GPP flare.

Methods And Analysis: At least 51 patients with an acute GPP flare will be randomised 2:1 to receive a single 900 mg intravenous dose of spesolimab or placebo and followed for up to 28 weeks. The primary endpoint is a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (pustule clearance) at Week 1. The key secondary endpoint is a GPPGA score of 0 or 1 (clear or almost clear) at Week 1. Safety will be assessed over the study duration by the occurrence of treatment-emergent adverse events. Blood and skin biopsies will be collected to assess biomarkers. Superiority of spesolimab over placebo in the proportion of patients achieving the primary and key secondary endpoints will be evaluated.

Ethics And Dissemination: The study complies with the ethical principles of the Declaration of Helsinki, the International Council for Harmonisation's Good Clinical Practice and local regulations. Ethics committee approvals have been obtained for each centre from all participating countries and are listed in online supplementary file 1. Primary results will be published in a peer-reviewed journal.

Trial Registration Details: ClinicalTrials.gov identifier: NCT03782792; Pre-results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-043666DOI Listing
March 2021

"COVID arm": A reaction to the Moderna vaccine.

JAAD Case Rep 2021 Apr 25;10:92-95. Epub 2021 Feb 25.

The Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai Hospital, New York, New York.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jdcr.2021.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959672PMC
April 2021

Durable remissions of guttate psoriasis following short courses of IL-17 inhibitors.

Int J Dermatol 2021 Mar 2. Epub 2021 Mar 2.

Icahn School of Medicine at Mount Sinai, New York, NY, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijd.15478DOI Listing
March 2021

Unmet Medical Needs in the Treatment and Management of Generalized Pustular Psoriasis Flares: Evidence from a Survey of Corrona Registry Dermatologists.

Dermatol Ther (Heidelb) 2021 Apr 27;11(2):529-541. Epub 2021 Feb 27.

Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Introduction: Generalized pustular psoriasis (GPP) is a rare, severe, and potentially life-threatening systemic and chronic autoinflammatory disease characterized by sterile, neutrophilic pustules. The standard of care for GPP varies by region, with limited information and experience of flares and their treatment. Our aim was to establish current unmet needs in GPP by better understanding the natural history of GPP, examining how dermatologists diagnose GPP and GPP flares, and establishing the range and adequacy of GPP treatment options currently prescribed by dermatologists.

Methods: Eligible dermatologists (N = 29) completed a 28-question structured survey, covering ten themes, ranging from GPP diagnostic criteria to GPP symptoms and treatment.

Results: All dermatologists stated that pustules were necessary to diagnose a GPP flare. The most frequently reported triggering factors for GPP were steroid withdrawal (64%), infection (58%), and stress (50%). Most dermatologists indicated that available treatment options for GPP flares were adequate "most" (79%) or "all" (14%) of the time. Despite this reported adequacy, 38% of dermatologists reported that it was at least "somewhat common" for a flare to require hospitalization. Furthermore, 72% of dermatologists indicated that treatments were too slow to control flares, and 66% indicated that treatments did not adequately prevent new flares at least "sometimes".

Conclusion: This survey suggests that there are key features of GPP flares, and could initiate discussion around forming consensus guidelines for diagnosis and management. While the results suggest that moderately effective therapies may exist, the need for GPP-specific treatments remains.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13555-021-00493-0DOI Listing
April 2021

Bimekizumab versus ustekinumab for the treatment of moderate to severe plaque psoriasis (BE VIVID): efficacy and safety from a 52-week, multicentre, double-blind, active comparator and placebo controlled phase 3 trial.

Lancet 2021 Feb;397(10273):487-498

Icahn School of Medicine, New York, NY, USA.

Background: There is an unmet need for a treatment for psoriasis that results in complete skin clearance with a reliably quick response. Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. We aimed to compare the efficacy and safety of bimekizumab with placebo and ustekinumab in patients with moderate to severe plaque psoriasis over 52 weeks.

Methods: BE VIVID was a multicentre, randomised, double-blind, active comparator and placebo controlled phase 3 trial done across 105 sites (clinics, hospitals, research units, and private practices) in 11 countries in Asia, Australia, Europe, and North America. Adults aged 18 years or older with moderate to severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] score ≥12, ≥10% body surface area affected by psoriasis, and Investigator's Global Assessment [IGA] score ≥3 on a five point scale) were included. Randomisation was stratified by geographical region and previous exposure to biologics; patients, investigators, and sponsors were masked to treatment assignment. Patients were randomly assigned (4:2:1) using an interactive response technology to bimekizumab 320 mg every 4 weeks, ustekinumab 45 mg or 90 mg (baseline weight-dependent dosing) at weeks 0 and 4, then every 12 weeks, or placebo every 4 weeks. At week 16, patients receiving placebo switched to bimekizumab 320 mg every 4 weeks. All study treatments were administered as two subcutaneous injections. Coprimary endpoints were the proportion of patients with 90% improvement in the PASI (PASI90) and the proportion of patients with an IGA response of clear or almost clear (score 0 or 1) at week 16 (non-responder imputation). Efficacy analyses included the intention-to-treat population; safety analysis included patients who received at least one dose of study treatment. This trial was registered at ClinicalTrials.gov, NCT03370133 (completed).

Findings: Between Dec 6, 2017, and Dec 13, 2019, 735 patients were screened and 567 were enrolled and randomly assigned (bimekizumab 320 mg every 4 weeks n=321, ustekinumab 45 mg or 90 mg every 12 weeks n=163, placebo n=83). At week 16, 273 (85%) of 321 patients in the bimekizumab group had PASI90 versus 81 (50%) of 163 in the ustekinumab group (risk difference 35 [95% CI 27-43]; p<0·0001) and four (5%) of 83 in the placebo group (risk difference 80 [74-86]; p<0·0001). At week 16, 270 (84%) patients in the bimekizumab group had an IGA response versus 87 (53%) in the ustekinumab group (risk difference 30 [95% CI 22-39]; p<0·0001) and four (5%) in the placebo group (risk difference 79 [73-85]; p<0·0001). Over 52 weeks, serious treatment-emergent adverse events were reported in 24 (6%) of 395 patients in the bimekizumab group (including those who switched from placebo at week 16) and 13 (8%) of 163 in the ustekinumab group.

Interpretation: Bimekizumab was more efficacious than ustekinumab and placebo in the treatment of moderate to severe plaque psoriasis. The bimekizumab safety profile was consistent with that observed in previous studies.

Funding: UCB Pharma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(21)00125-2DOI Listing
February 2021

Bimekizumab versus ustekinumab for the treatment of moderate to severe plaque psoriasis (BE VIVID): efficacy and safety from a 52-week, multicentre, double-blind, active comparator and placebo controlled phase 3 trial.

Lancet 2021 Feb;397(10273):487-498

Icahn School of Medicine, New York, NY, USA.

Background: There is an unmet need for a treatment for psoriasis that results in complete skin clearance with a reliably quick response. Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. We aimed to compare the efficacy and safety of bimekizumab with placebo and ustekinumab in patients with moderate to severe plaque psoriasis over 52 weeks.

Methods: BE VIVID was a multicentre, randomised, double-blind, active comparator and placebo controlled phase 3 trial done across 105 sites (clinics, hospitals, research units, and private practices) in 11 countries in Asia, Australia, Europe, and North America. Adults aged 18 years or older with moderate to severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] score ≥12, ≥10% body surface area affected by psoriasis, and Investigator's Global Assessment [IGA] score ≥3 on a five point scale) were included. Randomisation was stratified by geographical region and previous exposure to biologics; patients, investigators, and sponsors were masked to treatment assignment. Patients were randomly assigned (4:2:1) using an interactive response technology to bimekizumab 320 mg every 4 weeks, ustekinumab 45 mg or 90 mg (baseline weight-dependent dosing) at weeks 0 and 4, then every 12 weeks, or placebo every 4 weeks. At week 16, patients receiving placebo switched to bimekizumab 320 mg every 4 weeks. All study treatments were administered as two subcutaneous injections. Coprimary endpoints were the proportion of patients with 90% improvement in the PASI (PASI90) and the proportion of patients with an IGA response of clear or almost clear (score 0 or 1) at week 16 (non-responder imputation). Efficacy analyses included the intention-to-treat population; safety analysis included patients who received at least one dose of study treatment. This trial was registered at ClinicalTrials.gov, NCT03370133 (completed).

Findings: Between Dec 6, 2017, and Dec 13, 2019, 735 patients were screened and 567 were enrolled and randomly assigned (bimekizumab 320 mg every 4 weeks n=321, ustekinumab 45 mg or 90 mg every 12 weeks n=163, placebo n=83). At week 16, 273 (85%) of 321 patients in the bimekizumab group had PASI90 versus 81 (50%) of 163 in the ustekinumab group (risk difference 35 [95% CI 27-43]; p<0·0001) and four (5%) of 83 in the placebo group (risk difference 80 [74-86]; p<0·0001). At week 16, 270 (84%) patients in the bimekizumab group had an IGA response versus 87 (53%) in the ustekinumab group (risk difference 30 [95% CI 22-39]; p<0·0001) and four (5%) in the placebo group (risk difference 79 [73-85]; p<0·0001). Over 52 weeks, serious treatment-emergent adverse events were reported in 24 (6%) of 395 patients in the bimekizumab group (including those who switched from placebo at week 16) and 13 (8%) of 163 in the ustekinumab group.

Interpretation: Bimekizumab was more efficacious than ustekinumab and placebo in the treatment of moderate to severe plaque psoriasis. The bimekizumab safety profile was consistent with that observed in previous studies.

Funding: UCB Pharma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(21)00125-2DOI Listing
February 2021

National Psoriasis Foundation COVID-19 Task Force guidance for management of psoriatic disease during the pandemic: Version 2-Advances in psoriatic disease management, COVID-19 vaccines, and COVID-19 treatments.

J Am Acad Dermatol 2021 Jan 7. Epub 2021 Jan 7.

Division of Allergy, Immunology, and Rheumatology Division, University of Rochester Medical Center, Rochester, New York.

Objective: To update guidance regarding the management of psoriatic disease during the COVID-19 pandemic.

Study Design: The task force (TF) includes 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation staff. Clinical questions relevant to the psoriatic disease community were informed by inquiries received by the National Psoriasis Foundation. A Delphi process was conducted.

Results: The TF updated evidence for the original 22 statements and added 5 new recommendations. The average of the votes was within the category of agreement for all statements, 13 with high consensus and 14 with moderate consensus.

Limitations: The evidence behind many guidance statements is variable in quality and/or quantity.

Conclusions: These statements provide guidance for the treatment of patients with psoriatic disease on topics including how the disease and its treatments affect COVID-19 risk, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 (including novel vaccination), and what they should do if they develop COVID-19. The guidance is a living document that is continuously updated by the TF as data emerge.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2020.12.058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788316PMC
January 2021

Development and Content Validation of Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) in Adolescents and Adults with Moderate-to-Severe AD.

Dermatol Ther (Heidelb) 2021 Feb 3;11(1):221-233. Epub 2021 Feb 3.

Pfizer Inc., New York, NY, USA.

Introduction: Most patient-reported outcome (PRO) instruments that measure atopic dermatitis (AD) symptoms do not have sufficient documented evidence of content validity to satisfy regulatory agency guidance for inclusion in product-labelling claims in the USA or Europe. The objective of this study was to develop a PRO instrument in accordance with regulatory agency guidance to assess daily AD symptoms during the course of therapy and to establish its content validity and psychometric properties.

Methods: The Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) daily diary was developed based on qualitative interviews with US adolescents and adults with mild-to-severe AD. Content validity, test-retest reliability, internal consistency reliability, clinically important difference, clinically important responder, convergent validity, and known-group validity were evaluated using correlational and regression methods from phase 2b data from US adults with moderate-to-severe AD who were treated with abrocitinib.

Results: Patient interviews conducted with US adolescents and adults with mild-to-severe AD identified 11 relevant symptoms (itch, dryness, redness, flaking, discolouration, pain, bleeding, cracking, bumps, swelling, and weeping/oozing) for inclusion in the PSAAD instrument. All PSAAD psychometric parameters were acceptable based on phase 2b data from US adults with moderate-to-severe AD. Convergent validity and known-group validity were confirmed by significant correlations between PSAAD and six other PRO measures (r = 0.24-0.91, all p ≤ 0.01) and Dermatology Life Quality Index category (p ≤ 0.0001), respectively.

Conclusions: Evidence supports the PSAAD instrument validity, reliability, responsiveness and definitions of clinically important changes/differences for adults with moderate-to-severe AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13555-020-00474-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859139PMC
February 2021

Development and Content Validation of Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) in Adolescents and Adults with Moderate-to-Severe AD.

Dermatol Ther (Heidelb) 2021 Feb 3;11(1):221-233. Epub 2021 Feb 3.

Pfizer Inc., New York, NY, USA.

Introduction: Most patient-reported outcome (PRO) instruments that measure atopic dermatitis (AD) symptoms do not have sufficient documented evidence of content validity to satisfy regulatory agency guidance for inclusion in product-labelling claims in the USA or Europe. The objective of this study was to develop a PRO instrument in accordance with regulatory agency guidance to assess daily AD symptoms during the course of therapy and to establish its content validity and psychometric properties.

Methods: The Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) daily diary was developed based on qualitative interviews with US adolescents and adults with mild-to-severe AD. Content validity, test-retest reliability, internal consistency reliability, clinically important difference, clinically important responder, convergent validity, and known-group validity were evaluated using correlational and regression methods from phase 2b data from US adults with moderate-to-severe AD who were treated with abrocitinib.

Results: Patient interviews conducted with US adolescents and adults with mild-to-severe AD identified 11 relevant symptoms (itch, dryness, redness, flaking, discolouration, pain, bleeding, cracking, bumps, swelling, and weeping/oozing) for inclusion in the PSAAD instrument. All PSAAD psychometric parameters were acceptable based on phase 2b data from US adults with moderate-to-severe AD. Convergent validity and known-group validity were confirmed by significant correlations between PSAAD and six other PRO measures (r = 0.24-0.91, all p ≤ 0.01) and Dermatology Life Quality Index category (p ≤ 0.0001), respectively.

Conclusions: Evidence supports the PSAAD instrument validity, reliability, responsiveness and definitions of clinically important changes/differences for adults with moderate-to-severe AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13555-020-00474-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859139PMC
February 2021

Long-term efficacy and safety of ixekizumab: A 5-year analysis of the UNCOVER-3 randomized controlled trial.

J Am Acad Dermatol 2020 Nov 28. Epub 2020 Nov 28.

Toulouse University and Larrey Hospital, Toulouse, France.

Objective: To report the efficacy and safety of the approved ixekizumab (IXE) dose over 5 years from UNCOVER-3 (NCT01646177).

Methods: Patients (N = 1346) were randomized 1:2:2:2 to receive subcutaneous injections of placebo, etanercept 50 mg twice weekly, or IXE 80 mg every 2 weeks or every 4 weeks after an initial dose of IXE 160 mg, respectively. At week 12, patients entered the long-term extension period with dosing of IXE every 4 weeks and could escalate to every 2 weeks after week 60. Efficacy was reported for the IXE every 2 weeks/every 4 weeks group of the intent-to-treat population. Safety was reported for patients who received at least 1 dose of IXE every 2 or every 4 weeks.

Results: Using modified nonresponder imputation, 78.8%/67.1%/46.2% of patients receiving the approved dose of IXE every 2 weeks/every 4 weeks (n = 385) achieved ≥75%, ≥90%, or 100% improvement from baseline in the Psoriasis Area and Severity Index, respectively, at week 264; static Physician's Global Assessment score of 0/1 and 0 responses were 69.2% and 45.3%, respectively. Infections were the most observed treatment-emergent adverse event (72.7% of patients).

Limitations: Lack of comparison treatment group after week 12.

Conclusion: IXE demonstrates sustained efficacy and consistent safety through 264 weeks in patients using the approved dose.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2020.11.022DOI Listing
November 2020

Risk of Skin Disorders in Patients with Celiac Disease: A Population-Based Cohort Study.

J Am Acad Dermatol 2020 Oct 31. Epub 2020 Oct 31.

Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York NY, USA; Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden.

Background And Aims: Although dermatitis herpetiformis is closely associated with celiac disease (CD), data on the relationship between CD and other dermatologic disorders have been mixed. We aimed to quantify the risk of skin disorders in patients after CD diagnosis in a population-based setting.

Methods: Using data from all 28 pathology departments in Sweden 1969-2016, we identified patients with CD. Each patient was matched by age, sex, calendar year, and geographic region to up to 5 population controls. We calculated the risk of any skin disease and specific skin diseases using Cox proportional hazards.

Results: We identified 43,300 patients with CD and 198,532 matched controls. After a median follow-up time of 11.4 years, the incidences of skin disease in CD patients and controls were 22.6 and 14.8 per 1000 person-years respectively (HR=1.55; 95%CI 1.51-1.58). Increased risks were present for eczema (HR=1.67; 95%CI 1.56-1.79), psoriasis (HR=1.55; 95%CI 1.43-1.68), urticaria (HR=1.52; 95% CI 1.42-1.64), vitiligo (HR=1.90; 95%CI 1.52-2.39), acne (HR=1.39; 95%CI 1.29-1.50), and alopecia areata (HR=1.78; 95%CI 1.43-2.20).

Conclusions: Compared to the general population, patients with CD are at increased risk of multiple common skin disorders, a risk that persists in the long-term.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2020.10.079DOI Listing
October 2020

Treatment of COVID-19 induced chilblains with topical nitroglycerin.

Int J Dermatol 2020 Dec 20;59(12):1522-1524. Epub 2020 Oct 20.

Department of Dermatology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijd.15253DOI Listing
December 2020

Clinical efficacy and safety of secukinumab in patients with psoriasis and comorbidities: pooled analysis of 4 phase 3 clinical trials.

J Dermatolog Treat 2020 Oct 21:1-9. Epub 2020 Oct 21.

Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: The influence of comorbidities on the efficacy and safety of biologic therapies in psoriasis has not been rigorously explored.

Objective: To assess the incremental burden of comorbidities on clinical efficacy and safety of secukinumab vs. etanercept and placebo among patients with plaque psoriasis pooled from 4 phase 3 trials.

Methods: Efficacy was assessed at week 12 according to achievement of Psoriasis Area and Severity Index (PASI) and Investigator's Global Assessment (IGA; modified 2011) responses. Efficacy comparisons between treatment arms stratified by comorbidity status were made using logistic regression analysis with nonresponder imputation. Relationships between baseline characteristics and clinical responses were evaluated by tests.

Results: Of 2401 patients, 1469 (61.2%) had ≥1 active baseline comorbidity. Regardless of comorbidity status, patients receiving secukinumab were more likely to achieve PASI and IGA responses than those receiving etanercept or placebo at week 12 ( < .05 for all comparisons). Body weight of ≥90 kg was consistently associated with a decreased likelihood of achieving PASI and IGA responses ( < .01 for all comparisons). Safety was comparable across treatment arms stratified by comorbidity.

Conclusions: Secukinumab improved clinical outcomes and was well tolerated in patients with concomitant baseline comorbid conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09546634.2020.1832187DOI Listing
October 2020

Association of Secukinumab Treatment With Tuberculosis Reactivation in Patients With Psoriasis, Psoriatic Arthritis, or Ankylosing Spondylitis.

JAMA Dermatol 2021 01;157(1):43-51

Icahn School of Medicine at Mount Sinai, Department of Dermatology, New York, New York.

Importance: Approximately one-quarter of the global population have latent tuberculosis infection (LTBI), and tuberculosis (TB) is accountable for more than 1.5 million deaths annually. Methotrexate, cyclosporine, and tumor necrosis factor inhibitors may be associated with increased risk of TB and LTBI reactivation, although data are limited on the risks of TB with use of newer biologics.

Objective: To assess the association of secukinumab with reporting of active TB development, TB reactivation, and LTBI activation as an adverse event (AE) in patients with psoriasis, psoriatic arthritis, or ankylosing spondylitis.

Design, Setting, And Participants: This pooled cohort study pooled data from 28 clinical trials of secukinumab used in psoriasis (17 phase 3 or 3b and 2 phase 4 trials), psoriatic arthritis (5 phase 3 trials), and ankylosing spondylitis (4 phase 3 trials). A search of the Novartis Secukinumab Compound Pool Database was conducted for the 28 trials. All trial participants who had received at least 1 approved subcutaneous dose of secukinumab (150 mg or 300 mg) were included. Before randomization in these trials, patients underwent screening for TB. Patients with active TB were excluded, and patients with LTBI were treated according to local guidelines. Data were analyzed from the start of treatment in the individual studies through December 25, 2018.

Main Outcomes And Measures: Reporting of active TB or LTBI as an AE over a 5-year period using exposure-adjusted incidence rates (EAIR; incidence rates per 100 patient-years).

Results: A total of 12 319 patients were included, of whom 8819 patients had psoriasis (71.6%; 5930 men [67.2%]; mean [SD] age, of 44.9 [13.5] years), 2523 had psoriatic arthritis (20.5%; 1323 women [52.4%]; mean [SD] age, 48.8 [12.1] years), and 977 had ankylosing spondylitis (7.3%; 658 men [67.3%]; mean [SD] age, 42.3 [11.9] years). In the total population, 684 patients (5.6%) had tested positive for LTBI at screening. Over 5 years, LTBI as an AE during secukinumab treatment was reported in 13 patients (0.1% of 12 319). Of these 13 patients, 6 had a prior positive LTBI test result, and 7 were newly diagnosed as having LTBI. Four of the 7 patients had psoriasis (EAIR, 0.03; 95% CI, 0.01-0.07), 1 had psoriatic arthritis (EAIR, 0.02; 95% CI, 0.00-0.11), and 2 had ankylosing spondylitis (EAIR, 0.08; 95% CI, 0.01-0.28). No cases of active TB were reported.

Conclusions And Relevance: This study found that LTBI reported as an AE after secukinumab treatment was uncommon and appeared to support the use of secukinumab in chronic systemic inflammatory conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamadermatol.2020.3257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527940PMC
January 2021

PSO-LONG: Design of a Novel, 12-Month Clinical Trial of Topical, Proactive Maintenance with Twice-Weekly Cal/BD Foam in Psoriasis.

Adv Ther 2020 11 23;37(11):4730-4753. Epub 2020 Sep 23.

Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Psoriasis vulgaris is commonly treated with topical corticosteroids and vitamin D analogues. Although potent and super-potent topical corticosteroids are very effective at clearing psoriasis, with short-term reactive treatment durations, symptoms usually recur after treatment discontinuation, necessitating long-term disease management strategies. A foam formulation of calcipotriol and betamethasone dipropionate (Cal/BD foam), consisting of calcipotriol 50 μg/g and betamethasone dipropionate 0.5 mg/g, is approved for the daily treatment of psoriasis for up to 4 weeks. Here, we describe a clinical trial protocol for evaluating the long-term safety and efficacy of twice-weekly Cal/BD foam as a proactive topical maintenance therapy for plaque psoriasis for up to 52 weeks.

Objective: The aim of this trial was to evaluate the safety and efficacy of Cal/BD foam when applied twice weekly for up to 52 weeks as proactive maintenance therapy, with the goal of preventing or delaying disease relapse as long as possible while minimizing adverse effects.

Methods: Once-daily Cal/BD foam treatment responders from an initial 4-week open-label period were randomized to receive Cal/BD foam or foam vehicle applied to previously cleared plaques twice weekly for up to 52 weeks. In case of relapse, affected subjects in either group received rescue therapy with once-daily Cal/BD foam for 4 weeks on active areas. Thus, the trial (NCT02899962) compared the long-term use of Cal/BD foam in a proactive approach with a conventional, reactive approach.

Planned Outcomes: Efficacy endpoints included the time to first relapse, the number of relapse-free days, and the number of relapses during the maintenance phase. Safety assessments included adverse events, incidence of rebound, local safety and tolerability scores, and effects on calcium metabolism and hypothalamic-pituitary-adrenal axis function.

Trial Registration: ClinicalTrials.gov identifier, NCT02899962.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12325-020-01497-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547957PMC
November 2020

Tildrakizumab efficacy, drug survival, and safety are comparable in patients with psoriasis with and without metabolic syndrome: Long-term results from 2 phase 3 randomized controlled studies (reSURFACE 1 and reSURFACE 2).

J Am Acad Dermatol 2021 Feb 19;84(2):398-407. Epub 2020 Sep 19.

Division of Dermatology, Baylor Scott & White, Dallas, Texas; Texas A&M College of Medicine, Dallas, Texas.

Background: Data for the effect of metabolic syndrome (MetS) on the efficacy and safety of biologic agents for psoriasis treatment are limited.

Objective: To evaluate long-term tildrakizumab efficacy, drug survival, and safety in patients with psoriasis by baseline MetS status.

Methods: Post hoc analyses of up to 3 years of efficacy data and 5 years of safety data from the phase 3, double-blind, randomized controlled reSURFACE 1 and 2 trial (NCT01722331 and NCT01729754) base and extension studies were conducted for patients receiving continuous tildrakizumab 100 or 200 mg.

Results: Of 338 (n = 124/214 in reSURFACE 1/2) and 307 (n = 147/160 in reSURFACE 1/2) patients continuously receiving tildrakizumab 100 and 200 mg, respectively, throughout the studies, 26/44 (21%/21%) and 34/30 (23%/19%) met MetS criteria. Proportions of patients who achieved a 75% improvement in the Psoriasis Area and Severity Index (PASI) in reSURFACE 1/2 were generally comparable among those with versus without MetS at week 52 (tildrakizumab 100 mg, 85%/86% vs 86%/94%; tildrakizumab 200 mg, 76%/87% vs 76%/87%) and through week 148. Results were similar for responders with 90% and 100% improvement in the PASI. Tildrakizumab's safety profile did not vary by MetS status.

Limitations: Small sample size and post hoc analysis limit interpretation.

Conclusion: Long-term tildrakizumab efficacy and safety were comparable between patients with and without MetS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2020.09.047DOI Listing
February 2021

Large inflamed facial cysts in teenagers.

Pediatr Dermatol 2020 Nov 19;37(6):1055-1056. Epub 2020 Sep 19.

Icahn School of Medicine at Mt Sinai, New York, New York, USA.

Background: Facial cysts can become large (1-5 cm) or giant (>5 cm) on the face.

Objective: To describe the medical course of large and giant facial cysts in adolescents.

Methods: A case series of 11 patients with large or giant facial cysts seen in an outpatient pediatric dermatology practice.

Results: Seven patients underwent incision and drainage with culture of cyst contents growing Cutibacterium acnes in six, while the seventh grew Cutibacterium acnes from a frequently worn hat. All patients were treated with traditional therapeutics for cystic acne including intralesional triamcinolone (n = 9), oral antibiotics (n = 10), and isotretinoin (n = 1). Three patients who did not undergo cyst drainage had persistent symptomatology requiring cyst excision, whereas the seven patients whose cysts were drained (3 on initial management and 4 after recurrence) eventually had complete healing without need for surgery.

Conclusion: Incision and drainage (I & D) and culture of cyst contents can identify cases of cysts related to Cutibacterium acnes. For some cases of large facial cysts related to Cutibacterium acne, I&D combined with conservative acne management (using standard acne guidelines) can prevent the need for surgical excision in some patients. Prospective studies are needed to determine whether this combination of therapy leads to best outcomes clinically and cosmetically.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pde.14344DOI Listing
November 2020

Twice-weekly topical calcipotriene/betamethasone dipropionate foam as proactive management of plaque psoriasis increases time in remission and is well tolerated over 52 weeks (PSO-LONG trial).

J Am Acad Dermatol 2020 Sep 18. Epub 2020 Sep 18.

Department of Dermatology and Allergology, Ludwig Maximilian University Munich, Munich, Germany.

Background: Topical psoriasis treatment relies on a reactive rather than a long-term proactive approach to disease relapse.

Objective: Assess long-term efficacy and safety of proactive psoriasis management with twice-weekly calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) foam.

Methods: Phase III trial (NCT02899962) included a 4-week open-label lead-in phase (Cal/BD foam once daily) and a 52-week, randomized, double-blind, maintenance phase. A total of 545 patients achieved treatment success (physician's global assessment "clear"/"almost clear," ≥2-grade improvement from baseline) and were randomized to proactive management (Cal/BD foam; n = 272) or reactive management (vehicle foam; n = 273) twice-weekly, with rescue treatment of Cal/BD foam once daily for 4 weeks upon relapse. Primary endpoint was time to first relapse (physician's global assessment "mild" or higher).

Results: A total of 251 randomized patients (46.1%) completed the trial. Median time to first relapse was 56 days (proactive) and 30 days (reactive). Patients in the proactive group had an additional 41 days in remission compared with the reactive group over 1 year (P < .001). Number of relapses per year of exposure was 3.1 (proactive) and 4.8 (reactive). Cal/BD foam was well tolerated.

Limitations: Maintenance phase dropout rate (53.9%) was within the expected range but provides challenges in statistical analysis.

Conclusion: Long-term proactive management with Cal/BD foam demonstrated superior efficacy vs reactive management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2020.09.037DOI Listing
September 2020

Apremilast and systemic retinoid combination treatment for moderate to severe palmoplantar psoriasis.

Cutis 2020 07;106(1):E15-E17

Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12788/cutis.0042DOI Listing
July 2020

National Psoriasis Foundation COVID-19 Task Force Guidance for Management of Psoriatic Disease During the Pandemic: Version 1.

J Am Acad Dermatol 2020 Dec 4;83(6):1704-1716. Epub 2020 Sep 4.

Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester, New York.

Objective: To provide guidance about management of psoriatic disease during the coronavirus disease 2019 (COVID-19) pandemic.

Study Design: A task force (TF) of 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care was convened. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation (NPF) staff. Clinical questions relevant to the psoriatic disease community were informed by questions received by the NPF. A Delphi process was conducted.

Results: The TF approved 22 guidance statements. The average of the votes was within the category of agreement for all statements. All guidance statements proposed were recommended, 9 with high consensus and 13 with moderate consensus.

Limitations: The evidence behind many guidance statements is limited in quality.

Conclusion: These statements provide guidance for the management of patients with psoriatic disease on topics ranging from how the disease and its treatments impact COVID-19 risk and outcome, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 and what they should do if they develop COVID-19. The guidance is intended to be a living document that will be updated by the TF as data emerge.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471802PMC
December 2020

The Effect of Tildrakizumab on Cardiometabolic Risk Factors in Psoriasis by Metabolic Syndrome Status: Post Hoc Analysis of Two Phase 3 Trials (ReSURFACE 1 and ReSURFACE 2).

J Drugs Dermatol 2020 Aug;19(8):703-708

Background: Metabolic syndrome (MetS) is the most prevalent comorbidity in psoriasis and increases the risk of cardiovascular disease, diabetes, and mortality. Assessment of impacts of biologic therapies on cardiometabolic risk factors are relatively limited. This study evaluated the effect of tildrakizumab on cardiometabolic risk factors in patients with moderate to severe plaque psoriasis and stratified by MetS status. Methods: In this post hoc analysis of reSURFACE 1/2, tildrakizumab 100 and 200 mg were continuously administered to patients with moderate to severe plaque psoriasis at weeks 0 and 4, and every 12 weeks thereafter. Mean and mean percent changes from baseline were assessed for fasting serum glucose, low/high-density lipoprotein-cholesterol, total cholesterol, triglyceride levels, body weight, and blood pressure at week 64/52 for reSURFACE 1 and 2, respectively, in patients with and without MetS. Results: A total of 369 patients in reSURFACE 1 and 2 received continuous tildrakizumab 100 mg and 330 received tildrakizumab 200 mg; 21.4% and 20.3% in reSURFACE 1 and 2, respectively, had MetS. At week 64/52, mean changes in cardiometabolic risk factors from baseline did not significantly differ regardless of MetS status. Numerically larger mean decreases in fasting glucose, triglycerides, and systolic blood pressure following tildrakizumab 100 mg and in systolic and diastolic blood pressure following tildrakizumab 200 mg were observed in patients with MetS relative to those without MetS. Conclusions: Changes in cardiometabolic disease risk factors following tildrakizumab treatment were limited. Risk factors were not increased in patients with MetS vs without MetS. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.5337.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.36849/JDD.2020.5337DOI Listing
August 2020

Treating Scalp Psoriasis with Calcipotriene/Betamethasone Dipropionate Fixed-dose Combination Cutaneous Foam: Review of Phase 2 Data

J Drugs Dermatol 2020 08;19(8):784-786

Two Phase 2 studies investigated the effect of a fixed-dose combination foam containing calcipotriene monohydrate (Cal) and betamethasone dipropionate (BD) on scalp psoriasis in adult and adolescent patients. Patients had psoriasis classified as at least 'mild' per PGA. NCT01536938 enrolled adult patients (≥18 years) randomized 1:1:1 to once-daily (QD) Cal/BD foam (Cal 0.005%, BD 0.064%), Cal foam (0.005%) or BD foam (0.064%). NCT02387853 enrolled adolescent patients (12- <17 years) to Cal/BD foam QD (dose as previously). Treatment success was based on improvement in PGA classification at week 4. Additional efficacy endpoints included mPASI in adults and effect on extent of scalp surface area (SSA) in adolescents. Safety was also assessed. Overall, 302 adults (n=100 Cal/BD foam; n=101 Cal foam; n=101 BD foam) and 106 adolescents received treatment. Treatment success in adults was significantly higher with Cal/BD vs Cal foam (53.0% vs 35.6%, P=0.021) and numerically higher than with BD foam (47.5%, P=0.45). Mean percentage changes in mPASI were -80.0%, -57.8% and -71.2%, for Cal/BD, Cal and BD foam, respectively. In adolescents, 73.6% of patients treated with Cal/BD foam achieved treatment success and mean SSA fell from 50.6% at baseline to 12.5% at week 4. All treatment-related AEs were considered mild-to-moderate across both studies, except one severe AE (hypersensitivity reaction with urticaria) in the adult Cal/BD foam group, which led to withdrawal from the study. In these studies, treatment of scalp psoriasis with Cal/BD foam provided good efficacy for adults and adolescents and was generally well tolerated. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.5168.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.36849DOI Listing
August 2020

Efficacy of Fixed-combination Calcipotriene 0.005% and Betamethasone Dipropionate 0.064% Foam for Scalp Plaque Psoriasis: Additional Analysis of a Phase II, Randomized Clinical Study.

J Clin Aesthet Dermatol 2020 May 1;13(5):12-18. Epub 2020 May 1.

Drs. Patel and Veverka are with LEO Pharma in Madison, New Jersey.

There are a variety of treatment options currently available for plaque psoriasis affecting the scalp, yet scalp psoriasis remains one of the most frustrating and difficult-to-manage forms of the disease. We investigated the efficacy of fixed-combination calcipotriene 0.005% plus betamethasone dipropionate 0.064% (Cal/BD) foam for the treatment of scalp psoriasis. Additional (including ) analysis was conducted on data from a Phase II, randomized, double-blind, multicenter study of Cal/BD foam for the treatment of psoriasis vulgaris (NCT01536938). A total of 302 patients, ages 18 years or older, with psoriasis vulgaris of at least mild severity (scalp involvement of at least 10%) were included; 100, 101, and 101 patients were randomized to once-daily Cal/BD foam, Cal foam, or BD foam, respectively. Assessments included a severity score for lesion redness, scaliness, and plaque thickness, modified Psoriasis Area and Severity Index (mPASI) score, proportion of patients with reduction of 50 percent or greater in total sign score (TSS-50), and proportion of patients with at least a 75-percent reduction in mPASI score (mPASI-75). Patients achieved greater improvements in their scalp psoriasis with Cal/BD foam versus BD or Cal foam alone at Week 4 considering mPASI, mPASI-75, and TSS-50 outcomes. After four weeks of treatment, more patients receiving Cal/BD foam had a severity score for redness, scaliness, and thickness indicating "none" or "mild" versus BD foam or Cal foam alone. Improvements on the scalp appear to be consistent with those on the trunk and limbs. Scalp lesion severity improved considerably and rapidly with a four-week regimen of Cal/BD foam, suggesting that Cal/BD foam is an effective topical treatment option for scalp psoriasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380692PMC
May 2020

Joint AAD-NPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures.

J Am Acad Dermatol 2021 Feb 30;84(2):432-470. Epub 2020 Jul 30.

Baylor Scott and White, Dallas, Texas.

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

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2020.07.087DOI Listing
February 2021

Reply to research letter.

J Am Acad Dermatol 2020 12 29;83(6):e443. Epub 2020 Jul 29.

Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mt Sinai Hospital, New York, New York.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2020.07.101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387278PMC
December 2020

A Preliminary F-FDG-PET/MRI Study Shows Increased Vascular Inflammation in Moderate-to-Severe Atopic Dermatitis.

J Allergy Clin Immunol Pract 2020 Nov - Dec;8(10):3500-3506. Epub 2020 Jul 25.

Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; The Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

Background: Recent data suggest that patients with atopic dermatitis (AD) have increased systemic immune activation and cardiovascular risk. However, unlike psoriasis, evaluation of active vascular inflammation using state-of-the-art imaging is lacking in AD.

Objective: To assess aortic and carotid vascular inflammation using F-fluorodeoxyglucose-positron emission tomography/magnetic resonance imaging (F-FDG-PET/MRI) imaging in moderate-to-severe AD versus healthy individuals.

Methods: A total of 27 patients with moderate-to-severe AD and 12 healthy controls were imaged using F-FDG-PET/MRI. Target-to-background ratio (TBR) values were calculated in multiple segments of the aorta and carotid vessels.

Results: Patients with AD had elevated aortic max TBR (fold change [FCH] = 1.45, P = .057) versus healthy controls and significantly elevated mean TBR (FCH = 1.20; P < .05) in the right carotid (RC) arteries versus controls. When examining greatest focal inflammation (most diseased segment [MDS] TBR), patients with AD had higher aortic inflammation (FCH = 1.28; P = .052). AD clinical severity significantly correlated with C-reactive protein (ρ = 0.60, P < .01) and with RC mean TBR levels (ρ = 0.60, P = .04). Stratifying patients into moderate-to-severe and very severe AD showed greater RC mean TBR in patients with very severe AD versus controls (FCH = 1.31; P = .02) and versus patients with moderate/severe AD (FCH = 1.23, P = .05). Aortic inflammation was also significantly greater in patients with very severe AD versus controls (max TBR: FCH = 1.6, P = .04; MDS TBR: FCH = 1.73, P = .03).

Conclusions: This preliminary study is the first that establishes greater vascular (aorta and carotid) inflammation in moderate-to-severe AD versus healthy controls. Furthermore, very severe AD showed higher inflammation than both moderate/severe patients and healthy controls. Future studies with larger patient cohorts and evaluation before and after treatment are needed to determine the extent to which vascular inflammation in AD is modifiable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2020.07.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655511PMC
July 2020

Trial of Roflumilast Cream for Chronic Plaque Psoriasis.

N Engl J Med 2020 07;383(3):229-239

From the Icahn School of Medicine at Mount Sinai, New York (M.G.L., L.H.K.); Probity Medical Research and K. Papp Clinical Research, Waterloo (K.A.P.), and the SkiN Centre for Dermatology, Probity Medical Research and Queen's University, Peterborough (M.J.G.) - both in Ontario, Canada; Henry Ford Medical Center, Detroit (L.S.G.); Indiana Medical Center, Indianapolis (L.H.K.); Physicians Skin Care and DermResearch, Louisville, KY (L.H.K.); Dermatology Consulting Services, High Point, NC (Z.D.D.); Minnesota Clinical Study Center, Fridley (S.E.K.); Dermatologists of the Central States, Probity Medical Research, and Ohio University, Bexley (M.Z.); and Arcutis Biotherapeutics, Westlake Village (K.S., D.W.O., L.N., C.M., D.R.B., H.W.), and ML Trotman Consulting, Newbury Park (M.-L.T.) - both in California.

Background: Systemic oral phosphodiesterase type 4 (PDE-4) inhibitors have been effective in the treatment of psoriasis. Roflumilast cream contains a PDE-4 inhibitor that is being investigated for the topical treatment of psoriasis.

Methods: In this phase 2b, double-blind trial, we randomly assigned adults with plaque psoriasis in a 1:1:1 ratio to use roflumilast 0.3% cream, roflumilast 0.15% cream, or vehicle (placebo) cream once daily for 12 weeks. The primary efficacy outcome was the investigator's global assessment (IGA) of a status of clear or almost clear at week 6 (assessed on a 5-point scale of plaque thickening, scaling, and erythema; a score of 0 indicates clear, 1 almost clear, and 4 severe). Secondary outcomes included an IGA score indicating clear or almost clear plus a 2-grade improvement in the IGA score for the intertriginous area and the change in the Psoriasis Area and Severity Index (PASI) score (range, 0 to 72, with higher scores indicating worse disease). Safety was also assessed.

Results: Among 331 patients who underwent randomization, 109 were assigned to roflumilast 0.3% cream, 113 to roflumilast 0.15% cream, and 109 to vehicle cream. An IGA score indicating clear or almost clear at week 6 was observed in 28% of the patients in the roflumilast 0.3% group, in 23% in the roflumilast 0.15% group, and in 8% in the vehicle group (P<0.001 and P = 0.004 vs. vehicle for roflumilast 0.3% and 0.15%, respectively). Among the approximately 15% of patients overall who had baseline intertriginous psoriasis of at least mild severity, an IGA score at week 6 indicating clear or almost clear plus a 2-grade improvement in the intertriginous-area IGA score occurred in 73% of the patients in the roflumilast 0.3% group, 44% of those in the roflumilast 0.15% group, and 29% of those in the vehicle group. The mean baseline PASI scores were 7.7 in the roflumilast 0.3% group, 8.0 in the roflumilast 0.15% group, and 7.6 in the vehicle group; the mean change from baseline at week 6 was -50.0%, -49.0%, and -17.8%, respectively. Application-site reactions occurred with similar frequency in the roflumilast groups and the vehicle group.

Conclusions: Roflumilast cream administered once daily to affected areas of psoriasis was superior to vehicle cream in leading to a state of clear or almost clear at 6 weeks. Longer and larger trials are needed to determine the durability and safety of roflumilast in psoriasis. (Funded by Arcutis Biotherapeutics; ARQ-151 201 ClinicalTrials.gov number, NCT03638258.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa2000073DOI Listing
July 2020