Leo Pharma Research Articles

P189 Comparison of secukinumab versus adalimumab efficacy on skin outcomes in psoriatic arthritis: 52-week results from the EXCEED study

Abstract Background/Aims Psoriatic arthritis (PsA) is a heterogeneous disease comprising musculoskeletal and dermatological manifestations, especially plaque psoriasis. Secukinumab, an interleukin17A inhibitor, provided significantly greater PASI75/100 responses in two head-to-head trials versus etanercept or ustekinumab, a tumour necrosis factor inhibitor (TNFi), in patients with moderate-to-severe plaque psoriasis. The EXCEED study (NCT02745080) investigated whether secukinumab was superior to adalimumab, another TNFi, as monotherapy in biologic-naive active PsA patients with active plaque psoriasis (defined as having ≥1 psoriatic plaque of ≥ 2 cm diameter, nail changes consistent with psoriasis or documented history of plaque psoriasis). Here we report the pre-specified skin outcomes from the EXCEED study in the subset of patients with ≥3% body surface area (BSA) affected with psoriasis at baseline. Methods In this head-to-head, Phase 3b, randomised, double-blind, active-controlled, multicentre, parallel-group trial, patients were randomised to receive subcutaneous secukinumab 300 mg at baseline and Weeks 1-4, followed by dosing every 4 weeks until Week 48, or subcutaneous adalimumab 40 mg at baseline followed by the same dosing every 2 weeks until Week 50. The primary endpoint was superiority of secukinumab versus adalimumab on ACR20 response at Week 52. Pre-specified outcomes included the proportion of patients achieving a combined ACR50 and PASI100 response, PASI100 response, and absolute PASI score ≤3. Missing data were handled using multiple imputation. Results Overall, 853 patients were randomised to receive secukinumab (n = 426) or adalimumab (n = 427). At baseline, 215 and 202 patients had at least 3% BSA affected with psoriasis in the secukinumab and adalimumab groups, respectively. At Week 52, more patients achieved simultaneous improvement in ACR50 and PASI100 response with secukinumab versus adalimumab (30.7% versus 19.2%, respectively; P = 0.0087). Greater efficacy was demonstrated for secukinumab versus adalimumab for PASI100 responses and for the proportion of patients achieving absolute PASI score ≤3 (Table 1). Conclusion In this pre-specified analysis, secukinumab provided higher responses compared with adalimumab in achievement of combined improvement in joint and skin disease (combined ACR50 and PASI100 response) and in skin-specific endpoints (PASI100 and absolute PASI score ≤3) at Week 52. P189 Table 1:Skin-specific outcomes at Week 52Endpoints, % responseSEC 300 mg (N = 215)ADA 40 mg (N = 202)P value (unadjusted)PASI10046300.0007Combined ACR50 and PASI10031190.0087Absolute PASI score ≤379650.0015P value vs ADA; unadjusted P values are presented. Multiple imputation was used for handling missing data. ADA, adalimumab; ACR, American College of Rheumatology; N, number of patients in the psoriasis subset; PASI, Psoriasis Area and Severity Index; SEC, secukinumab. Disclosure A. Gottlieb: Grants/research support; A.G. has received research support, consultation fees or speaker honoraria from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB. F. Behrens: Consultancies; F.B. is a consultant for Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer Ingelheim, Janssen, MSD, Celgene, Roche and Chugai. Grants/research support; F.B. has received grant/research support from Pfizer, Janssen, Chugai, Celgene, Lilly and Roche. P. Nash: Consultancies; P.N. is a consultant for AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc., Roche, Sanofi and UCB. Member of speakers’ bureau; for AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc., Roche, Sanofi and UCB. Grants/research support; P.N. has received research support from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi and UCB. J. Merola: Consultancies; J.F.M. is a consultant for Merck, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB Pharma, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and LEO Pharma. P. Pellet: Corporate appointments; P.P. is an employee of Novartis. Shareholder/stock ownership; P.P. is a shareholder of Novartis. L. Pricop: Corporate appointments; L.P. is an employee of Novartis. Shareholder/stock ownership; L.P. is a shareholder of Novartis. I. McInnes: Consultancies; I.M. is a consultant for AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer and UCB. Grants/research support; I.M. has received grant/research support from Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen and UCB.

P171 Efficacy and safety of upadacitinib in patients with active PsA and inadequate response to biologic DMARDs (SELECT-PsA-2): a double-blind, randomised controlled Phase III trial

P171 Efficacy and safety of upadacitinib in patients with active PsA and inadequate response to biologic DMARDs (SELECT-PsA-2): a double-blind, randomised controlled Phase III trial

P173 Efficacy and safety of upadacitinib versus placebo and adalimumab in patients with active PsA and inadequate response to non-biologic DMARDs (SELECT-PSA-1): a double-blind, randomised controlled phase III trial

Abstract Background/Aims Upadacitinib (UPA) is a JAK inhibitor under evaluation for PsA treatment. We aimed to assess efficacy and safety of UPA vs placebo (PBO) and adalimumab (ADA) in patients with prior inadequate response (IR) or intolerance to ≥ 1 non-biologic DMARD. This research was previously presented at EULAR; published in Annals of Rheumatic Diseases. Methods Patients with active PsA (≥3 swollen, ≥3 tender joints), active/historical psoriasis, ≤2 non-bDMARDs were randomized 1:1:1:1 to once-daily UPA 15mg (UPA15), UPA 30mg (UPA30), ADA 40mg every other week, or PBO. Primary endpoint: proportion of patients achieving ACR20 for UPA vs PBO at Wk12. Secondary endpoints: change in HAQ-DI, FACIT-F, SF-36-PCS (Wk12), sIGA of Psoriasis 0/1, PASI75, change in Self-Assessment of Psoriasis Symptoms (Wk16), change in modified Sharp/van der Heijde Score (mTSS), proportion patients achieving MDA, resolution of enthesitis (LEI=0) and dactylitis (LDI=0) (Wk24), non-inferiority and superiority vs ADA for ACR20, superiority for HAQ-DI, patient assessment of pain NRS (Wk12). Additional secondary endpoints: ACR50/70 at Wk12 and ACR20 at Wk2. Treatment-emergent adverse events (TEAEs) through Wk24 reported for patients receiving ≥1 dose of study drug. Results 1,705 patients were randomised; 1,704 received study drug (mean age 50.8 yrs, mean duration of PsA diagnosis 6.1 yrs). 82% on ≥ 1 concomitant non-bDMARD. At Wk12, ACR20 rates were 70.6% with UPA15 and 78.5% with UPA30 vs 36.2% with PBO (p < 0.001 for UPA15/30 vs PBO) and 65.0% with ADA (non-inferiority, p < 0.001 for UPA15/30 vs ADA; superiority, p < 0.001 for UPA30 vs ADA). More patients achieved ACR50/70 with UPA15/30 vs PBO and UPA30 vs ADA. Improvements were observed with UPA15/30 vs PBO for all secondary endpoints and for UPA 15/30 vs ADA for HAQ-DI and UPA30 vs ADA for improvement in pain. At Wk24, change in mTSS was 0.25 for PBO, -0.04 for UPA15, 0.03 for UPA30, and 0.01 for ADA (p < 0.001 for UPA15/30 vs PBO). Rates of TEAEs and serious AEs, including serious infections, were similar in PBO, UPA15, and ADA arms and higher with UPA30. Herpes zoster rates were similar for PBO and UPA15/30. No MACE was reported with UPA. One malignancy occurred in both the PBO and UPA15 arms; 3 malignancies were reported in both UPA30 and ADA arms. VTE were reported in 1 PBO patient, 1 UPA30 patient and 2 ADA patients. One death occurred in the PBO arm. Conclusion In this non-bDMARD-IR PsA population UPA15/30 demonstrated improvement in musculoskeletal symptoms, psoriasis, physical function, pain, fatigue and inhibited radiographic progression; improvements observed by Wk2. At Wk12, UPA15/30 were non-inferior to ADA for ACR20, with superiority demonstrated for UPA30. Greater percentages of UPA vs PBO patients achieved stringent disease control measures (MDA, ACR50/70, sIGA 0/1). No new safety signals were identified compared to the safety profile observed in RA. Disclosure I. McInnes: Other; I.McI has received research grants and honoraria from Abbvie, BMS, Celgene, Novartis Lilly, Janssen, Pfizer, UCB. J. Anderson: Shareholder/stock ownership; J.A. may be a stock/ shareholder of AbbVie Inc. M. Magrey: Consultancies; M.M. has received consulting fees from Novartis, Eli Lilly, Pfizer, and Janssen. Grants/research support; M.M. has received grants/ research support from Amgen, AbbVie, and UCB Pharma. J.F. Merola: Consultancies; J.F.M. is a consultant for Merck, Abbvie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and Leo Pharma. Y. Liu: None. M. Kishimoto: Consultancies; M.K. has received consulting fees from AbbVie, Eli Lilly, Celgene, Pfizer, Gilead, Janssen, and UCB Pharma. Honoraria; M.K. has received honoraria/ speakers fees from AbbVie, Eisai, Celgene, Pfizer, Novartis, Eli Lilly, Tanabe-Mitsubishi, Ayumi, Janssen, Astellas, and UCB Pharma. S. Jeka: None. C. Pacheco-Tena: None. X. Wang: Shareholder/stock ownership; X.W. may be a shareholder of AbbVie Inc. L. Chen: Shareholder/stock ownership; L.C. may be a stock/shareholder of AbbVie Inc. P. Zueger: Shareholder/stock ownership; P.Z. may be a stock/shareholder of AbbVie Inc. A. Pangan: Shareholder/stock ownership; A.P. may be a stock/shareholder of AbbVie Inc. F. Behrens: Honoraria; F.B. has received honoraria and speakers fees from Pfizer, AbbVie, Sanofi, Lilly, Novartis, UCB, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai. Grants/research support; F.B. has received grants/ research support from Pfizer, Janssen, Chugai, Celgene and Roche.

Long-term recurrence rates of actinic keratosis: A systematic review and pooled analysis of randomized controlled trials

Long-term recurrence rates of actinic keratosis: A systematic review and pooled analysis of randomized controlled trials

Cost-effectiveness of oral semaglutide added to current antihyperglycemic treatment for type 2 diabetes

BACKGROUND: Oral semaglutide is the first oral formulation of a glucagon-like peptide 1 (GLP-1) receptor agonist to be approved in the United States for glycemic control in people with type 2 diabetes mellitus (T2DM). While oral semaglutide is not indicated for reduction of cardiovascular event risk, its label does include evidence of no increase in cardiovascular risk in people who received oral semaglutide. OBJECTIVE: To estimate the incremental value of oral semaglutide added to existing antihyperglycemic treatment for people with T2DM with additional risk for cardiovascular disease. METHODS: We estimated the lifetime cost-effectiveness of oral semaglutide added to current antihyperglycemic treatment for T2DM using a microsimulation model based primarily on the UK Prospective Diabetes Study (UKPDS) Outcomes Model 2 (OM2) equations. Oral semaglutide added to current antihyperglycemic treatment was separately compared with (a) ongoing background antihyperglycemic treatment, (b) sitagliptin, (c) empagliflozin, and (d) liraglutide. Comparators sitagliptin, empagliflozin, and liraglutide were added to ongoing antihyperglycemic treatment. We applied hazard ratios derived from a network meta-analysis for cardiovascular and renal outcomes to the UKPDS OM2 estimated baseline rates. Health state utilities and costs were derived from the published literature. We estimated total costs, life-years (LYs), quality-adjusted life-years (QALYs), clinical events, and cost per major adverse cardiovascular event (MACE) avoided, over a lifetime time horizon using discount rates of 3% for costs and outcomes. RESULTS: The lifetime total cost for people treated with oral semaglutide was $311,300, with costs for the other comparators ranging from $262,800 (background treatment alone) to $287,800 (liraglutide). Oral semaglutide resulted in the fewest MACE, including the fewest cardiovascular deaths. Among the 5 modeled treatment strategies, oral semaglutide had the highest LYs gained (8.43 vs. 7.76 [background treatment alone] to 8.29 [empagliflozin and liraglutide]) and the highest QALYs gained (4.11 vs. 3.70 [background treatment alone] to 4.03 [empagliflozin]). Oral semaglutide would likely be considered cost-effective compared with liraglutide (incremental cost-effectiveness ratio [ICER] = $40,100), and moderately cost-effective versus background treatment alone ([ICER] = $117,500/QALY) and sitagliptin (ICER = $145,200/QALY). The ICER for oral semaglutide compared with empagliflozin was approximately $458,400 per QALY. CONCLUSIONS: As modeled, oral semaglutide as an add-on therapy to background antihyperglycemic treatment produced incremental benefits in MACE avoided, along with greater QALYs compared with background antihyperglycemic treatment alone. Oral semaglutide use resulted in better outcomes than background treatment alone or sitagliptin, and similar outcomes to liraglutide or empagliflozin with overlapping 95% confidence ranges for QALYs. Oral semaglutide was estimated to be cost-effective compared with liraglutide and to have incremental cost-effectiveness ratios between $100,000 and $150,000 per QALY versus sitagliptin and background therapy alone, but it did not meet these thresholds compared with empagliflozin. DISCLOSURES: Funding for this study was provided by the Institute for Clinical and Economic Review, an independent organization that evaluates the evidence on the value of health care interventions. ICER reports grants from Laura and John Arnold Foundation, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Rind, Fazioli, Chapman, and Pearson are employed by ICER. Guzauskas and Hansen have nothing to disclose. Study results were presented at the New England Comparative Effectiveness Public Advisory Council (New England CEPAC), November 14, 2019, at Brown University, Providence, RI.

The effectiveness and value of digital health technologies as an adjunct to medication-assisted therapy for opioid use disorder

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Whittington, Campbell, and Pearson are employed by ICER. Tice reports contracts to his institution, University of California, San Francisco, from ICER during the conduct of this study.

Oral dapsone for the treatment of generalized granuloma annulare: A retrospective case series

Oral dapsone for the treatment of generalized granuloma annulare: A retrospective case series

Frequency of procedural and medical treatments of actinic keratosis

Frequency of procedural and medical treatments of actinic keratosis

Association between psoriasis and thyroid dysfunction among US adults in the 2009-2014 National Health and Nutrition Examination Survey

Association between psoriasis and thyroid dysfunction among US adults in the 2009-2014 National Health and Nutrition Examination Survey

IL-36 and IL-17A Cooperatively Induce a Psoriasis-Like Gene Expression Response in Human Keratinocytes

IL-36 and IL-17A Cooperatively Induce a Psoriasis-Like Gene Expression Response in Human Keratinocytes

Two identically designed studies to test the effectiveness of tralokinumab for treatment of atopic dermatitis in adults

British Journal of DermatologyVolume 184, Issue 3 p. e101-e102 Plain Language SummaryFree Access Two identically designed studies to test the effectiveness of tralokinumab for treatment of atopic dermatitis in adults First published: 05 March 2021 https://doi.org/10.1111/bjd.19778AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Abstract Atopic dermatitis, or eczema, is a chronic, itchy skin disease that is common in children and adults. Atopic dermatitis occurs when the barrier function of the skin is disrupted, allowing chemicals and allergens (that cause an allergic reaction) to enter the skin and cause inflammation. Tralokinumab is a drug injected under the skin that targets interleukin (IL)-13, a molecule that is important in causing the skin inflammation associated with atopic dermatitis. Tralokinumab, which belongs to a class of drugs called biologics, is not yet licensed for medical use, but is being investigated in clinical trials as a potential treatment for atopic dermatitis. Two identically designed clinical trials, ECZTRA 1 and ECZTRA 2, investigated if tralokinumab alone (used without any other atopic dermatitis treatment) was more effective than a nonactive drug (placebo) for improving the severity and symptoms of atopic dermatitis. The trials, funded by LEO Pharma, involved over 1500 patients from Europe, North America, Asia and Australia. Adult patients who had moderate-to-severe atopic dermatitis for more than 1 year that had not improved sufficiently with topical treatments (treatments applied directly to the skin) were included. Patients received tralokinumab 300 mg or placebo every 2 weeks for an initial 16 weeks. Patients who showed a good response to tralokinumab either continued with the same treatment, received less-frequent dosing of tralokinumab (once every 4 weeks), or received placebo for a further 36 weeks to assess long-term safety. Neither the patients nor the medical team knew which treatment the patients were receiving. The medical team monitored patients throughout the trials to assess changes in the amount and severity of atopic dermatitis. Patients also self-recorded changes in itch, sleep disruption and quality of life. The medical team also documented the occurrence of any side-effects of the drug. In both trials at week 16, more patients receiving tralokinumab had an improvement in their atopic dermatitis compared with patients receiving placebo. Patients felt meaningful improvements in itch (Figure 1), sleep and quality of life as early as 1–2 weeks after starting tralokinumab. Figure 1Open in figure viewerPowerPoint Top panel: Graphs show the percentage of patients who had a meaningful improvement in their perceived itch at 16 weeks. In the ECZTRA 1 trial (left), more tralokinumab-treated patients (20.0%, green bar) had a meaningful improvement in their perceived itch compared with those who received placebo (10.3%, blue bar). In the ECZTRA 2 trial (right), more tralokinumab-treated patients (25.0%) had a meaningful improvement in their perceived itch compared with placebo (9.5%). Bottom panel: Patients recorded how bad their itch was each day on a scale of 0 (no itch) to 10 (worst itch imaginable); a meaningful improvement was defined as a reduction of 4 points or more from the start of the trial on the itch scale. The majority of patients who had high levels of improvement at week 16 with tralokinumab maintained that level of improvement after another 36 weeks of treatment with dosing every 2 weeks. In addition, some patients maintained their improved skin with less-frequent dosing every 4 weeks. The most common side-effects with tralokinumab were upper respiratory tract infections (mainly common cold) and conjunctivitis (inflammation of the eye or eyelid). Based on the results from these trials, tralokinumab may be a long-term treatment option for adult patients with moderate-to-severe atopic dermatitis. Acknowledgements: the authors thank Korey Capozza, MPH, Director, Global Parents for Eczema Research, for critical review of this summary. Linked Article: Wollenberg et al. Br J Dermatol 2021; 184:437–449. Volume184, Issue3March 2021Pages e101-e102 FiguresRelatedInformation

Long-term dupilumab treatment for chronic refractory generalized prurigo nodularis: A retrospective cohort study

Long-term dupilumab treatment for chronic refractory generalized prurigo nodularis: A retrospective cohort study

The effectiveness and value of novel treatments for cystic fibrosis.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Seidner, Rind, and Pearson are employed by ICER. Tice reports contracts to his institution, University of California, San Francisco, from ICER during the conduct of this study. Wherry has nothing to disclose.

The Effect of Four Approaches to Treat Actinic Keratosis on the Health-Related QOL, as Assessed by the Skindex-29 and Actinic Keratosis QOL

To evaluate the impact of actinic keratosis (AK) and the effect of four AK treatments on the health-related QOL (HRQOL), the Skindex-29 and AK QOL (AKQOL) questionnaires were completed by 624 patients with AK participating in a randomized controlled trial comparing 5% fluorouracil cream (Efudix, Meda Pharma B.V., Amstelveen, the Netherlands), 5% imiquimod cream (Aldara, Meda Pharma B.V., Solna, Sweden), methyl aminolevulinate (Metvix, Galderma SA, Penn Pharmaceutical Services, Gwent, UK) photodynamic therapy (MAL-PDT), and 0.015% ingenol mebutate gel (Picato, LEO Pharma A/S, Bellerup, Denmark) (Jansen et al., 2019).

Long COVID in the skin: a registry analysis of COVID-19 dermatological duration

Long COVID in the skin: a registry analysis of COVID-19 dermatological duration

Senior-COVID-Rea Multicentre Observational Cohort Study: Development of a Geriatric Prediction Model of Day 30 Mortality in Patients Over 60 in ICU

Background: Current SARS-COV2 pandemic induces tensions on the health systems and ethical dilemmas. A triage tool is needed to define older patients with individual advantage to be considered for intensive care unit (ICU) transfer.Methods: This multicentre observational cohort study included patients over 60 admitted into 7 ICUs between 7th March and 7th May 2020. The primary objective was to evaluate age impact on 30-day mortality, to construct a multivariate prognostic model. This analysis explores the prediction value of geriatric parameters 1 month before ICU admission. This trial is registered with ClinicalTrials.gov, number NCT04422340.Findings: Among 290 screened patients, 231 were included in the cohort. In univariate analysis, factors associated with decreased day-30 survival were: age>75 (OR 4·82 [95%CI: 2·56-9·06]), three or more CIRS-G grade ≥2 comorbidities (OR 2·49 [95%CI: 1·36-4·56]), impaired ADL (Activities of Daily Living), (OR 4·86 [95%CI: 2·44-9·72]), impaired IADL8 (Instrumental ADL, 8 variables, OR 6·33 [95%CI: 3·31-12·10], p75 (OR 4·64 [95%CI: 2·36-9·39], pInterpretation: Age and IADL8 provide independent prognostic factors for day-30 mortality in patients over 60 admitted in ICU for severe COVID-19 infection. Our triage model proposes 3 classes of day-30 mortality risks: 8-14% for patients younger than 80 with no impairment in IADL, 30-40% for patients either younger than 70 with at least one impairment in IADL8 or older than 80 with no impairment in IADL and 67-88% for patients over 80 with at least one impairment in IADL.Trial Registration: ClinicalTrials platform on June 9, 2020 (NCT04422340).Funding Statement: Hospices Civils de LyonDeclaration of Interests: All the authors declare grants from Hospices Civils de Lyon, during the conduct of the study, no other competing interests with the considered topic. CF reports outside of the present work consulting/advisory roles for GSK, Leo Pharma, Pfizer, MSD Oncology, Teva, AstraZeneca, Baxter, Eisai, Janssen, and Novartis; research funding from Chugai Pharma, Pfizer, Pierre Fabre, and Astellas Pharma; and travel/accommodation/expenses from Janssen Oncology, Pierre Fabre, and Leo Pharma.Ethics Approval Statement: The study protocol (V1.0 of April 7, 2020) was approved by a COVID-19-dedicated Ethics Committee of the Hospices Civils de Lyon on May 12, 2020.

Tranexamic Acid to Reduce Bleeding in Patients Treated With Non-Vitamin K Oral Anticoagulants Undergoing Dental Extraction: The EXTRACT-NOAC Randomized Clinical Trial

Background: Oral bleeding after dental extraction in patients on non-vitamin K oral anticoagulants is a frequent problem. We investigated whether 10% tranexamic acid mouthwash decreases post-extraction bleeding in patients treated with non-vitamin K oral anticoagulants. Methods: The EXTRACT-NOAC study is a randomized, double blind, placebo-controlled, multi-center, clinical trial. Patients were randomly assigned to 10% tranexamic acid or placebo mouthwash, and were instructed to use the mouthwash prior to dental extraction, and three times a day for three days thereafter, and were followed-up for seven days. The primary outcome was the number of patients with any post-extraction oral bleeding up to day 7. Secondary outcomes include the number and type of bleeds and unplanned medical contacts. Findings: 218 patients were included in the full analysis set of which 106 patients were assigned to tranexamic acid (74.8 (±8.8) years; 81 men) and 112 to placebo (72.7 (±10.7) years; 64 men). Post-extraction bleeding occurred in 28 (26.4%) patients in the tranexamic acid group and in 32 (28.6%) patients in the placebo group (relative risk, 0.92; 95% confidence interval [CI], 0.60 to 1.42; P =.72). There were 46 bleeds in the tranexamic acid group and 85 bleeds in the placebo group (rate ratio, 0.57; 95% CI, 0.31 to 1.05; P= .07). Extraction-related bleeds (rate ratio 0.56; 95% CI, 0.32 to 0.96) and delayed bleeds (rate ratio, 0.32; 95% CI, 0.12 to 0.89) were lower in the tranexamic acid group. Patients using tranexamic acid had fewer unplanned medical contacts (rate ratio, 0.39; 95% CI, 0.16 to 0.98). Interpretation: In patients on non-vitamin K oral anticoagulants undergoing dental extracting, tranexamic acid mouthwash did not reduce the number of patients with post-extraction oral bleeding. Tranexamic acid may reduce the number of post-extraction bleeds and unplanned medical contacts. Trial Registration: The trial is registered at ClinicalTrials.gov (Identifier: NCT03413891). Funding Statement: This clinical trial was funded through a grant of the Research Foundation Flanders (Applied Biomedical Research Grant with a Primary Social finality, T002117N) and through a European Thrombosis Investigator Initiated Research Program (ERISTA) grant sponsored by Bristol Myers-Squibb and Pfizer. Declaration of Interests: None of the authors reported a conflict of interest with respect to the EXTRACT-NOAC study. Dr. Verhamme received grants and personal fees from Bayer Healthcare, grants and personal fees from Boehringer Ingelheim, Pfizer, BMS, Daiichi-Sankyo, Leo Pharma, and Portola and Medtronic outside the submitted work. Ethics Approval Statement: The EXTRACT-NOAC study is a prospective, randomized, double blind, placebo-controlled, multicenter, investigator-initiated, clinical trial. The Medical Ethics Committee of University Hospitals Leuven approved the study in July 2017.

Comparative Effectiveness of SGLT2i Versus DPP4i on Cardiovascular, Kidney and Hyperkalemia Outcomes in Individuals from Routine Clinical Practice: Observational Cohort Study

Background: While clinical trials have demonstrated efficacy for SGLT2 inhibitors (SGLT2i) on preventing cardiovascular and kidney damage, few high-quality studies have expanded to routine-care settings of low-risk patients. Previous observational studies were limited by immortal time bias or did not adjust for laboratory measurements. Methods: We compared clinical outcomes of adults who started SGLT2i or DPP4i therapy in Stockholm, Sweden, during 2013-2019. The primary outcome was a composite of cardiovascular (CV) death and hospitalization for heart failure (HHF). Secondary outcomes included major adverse cardiovascular events (MACE), all-cause mortality, atrial fibrillation, hyperkalemia and kidney disease progression (composite kidney failure and doubling of serum creatinine). Propensity score weighted Cox regression was used to estimate hazard ratios and balance 56 covariates. Results: We included 16,537 individuals (5526 SGLT2i; 11,011 DPP4i users), followed for median 1.9 years. Median age was 64 years (36% women), median estimated glomerular filtration rate 87 ml/min/1.73m2 and 31% had albuminuria. After weighting, patients starting SGLT2i therapy were at lower risk for the composite of CV death/HHF (HR 0.65; 95% CI 0.47-0.89) and hyperkalemia (HR 0.41; 95% CI 0.20-0.83) compared with DPP4i, without an increase in hypokalemia (HR 0.98; 95% CI 0.72-1.34). The adjusted HRs (95% CI) were 0.82 (0.64-1.06) for MACE, 0.74 (0.52-1.06) for all-cause mortality, 0.95 (0.68-1.33) for atrial fibrillation and 0.54 (0.27-1.08) for kidney disease progression. Conclusions: SGLT2i use compared with DPP4i was associated with a reduction in cardiovascular and kidney outcomes similar in magnitude to trials, as well as a lower risk of hyperkalemia. Funding: Research reported in this publication was supported by the Swedish Research Council (#2019-01059), the Swedish Heart and Lung Foundation and the Westman Foundation. ELF acknowledges support by a Rubicon Grant of the Netherlands Organization for Scientific Research (NWO). Declaration of Interests: JC acknowledges consultancy for Baxter and AstraZeneca, and grant support to Karolinska Institutet from AstraZeneca, Viforpharma and Astellas, all outside the submitted work. CMC has received consultation, advisory board membership or research funding from the Ontario Ministry of Health, Sanofi, Johnson & Johnson, Pfizer, Leo Pharma, Astellas, Janssen, Amgen, Boehringer-Ingelheim and Baxter, all outside the submitted work. None of the other authors declare relevant financial interests that would represent a conflict of interest. MJJ is responsible for research programs that have received unrestricted funding from Gambro, Baxter, Commonwealth Serum Laboratories (CSL), Amgen, Eli Lilly, and Merck; has served on advisory boards and steering committees sponsored by Akebia, Baxter, Boehringer Ingelheim, CSL, Janssen, and Vifor; and spoken at scientific meetings sponsored by Janssen, Amgen, and Roche, with any consultancy, honoraria, or travel support paid to her institution. Ethics Approval Statement: The study utilized only de-identified data and thus was deemed not to require informed consent, being approved by the regional ethical review boards and the Swedish National Board of Welfare.

Clinical Outcomes and the Impact of Oral Anticoagulants Prior to Diagnosis of COVID-19 on Clinical Outcomes in Patients Admitted to Hospitals in the UK – a Multicentre Observational Study

Coagulation dysfunction and thrombosis are major complications in patients with coronavirus disease-19 (COVID-19). Patients on oral anticoagulants prior to diagnosis of COVID-19 may therefore have better outcomes. We aimed:To first document the frequency of thrombosis, major bleeding and multiorgan failure (MOF) in patients admitted with COVID-19 and the contribution of these complications to 90-day mortality.To then determine the effects of oral anticoagulation, use prior to admission on the same outcomes as well as the requirement for Intensive Care Unit (ICU) admission, when compared to a propensity matched cohort of patients not taking oral anticoagulants prior to admission.Methods: This was a multicentre observational cohort including adult patients (≥18 years) admitted to 26 UK hospitals between 1st of April 2020 and 31 July 2020.Findings: A total of 5883 patients were included in the study. Overall mortality was 29.2%. Incidences of thrombosis, major bleeding and MOF were 5.4%,1.7% and 3.3% respectively. The presence of thrombosis, major bleeding, or MOF were associated with a 1.8, 4.5 or 5.9-fold increased risk of dying, respectively. Of the 5883 patients studied, 83.6% (n= 4920) were not on oral anticoagulants (OAC) and 16.4% (n=963) were taking OAC at the time of admission. There was no difference in mortality between patients on OAC vs no OAC prior to admission when compared in an adjusted multivariate analysis (HR 1.05 (95%CI 0.93-1.19) P=0.15) or in an adjusted propensity score analysis (HR 0.92 (95%CI 0.58-1.450, P=0.18). In multivariate and adjusted propensity score analyses, the only significant association of no anticoagulants prior to admission was treatment in ICU (HR 1.98 [95%CI 1.37-2.85]).Interpretation: Thrombosis, major bleeding, and MOF were associated with higher mortality. Our results indicate that patients may continue to benefit from OAC after admission, especially reduced admission to ICU, without any increase in bleeding.Funding: Bayer plc supported the study by providing the investigator-initiated funding (P87339) to setup the multicentre database of the study.Declaration of Interest: DJA received funding from Bayer plc to setup the multicentre database of the study as an investigator-initiated funding and received research grant from Leo Pharma. ML received consultation and speaker fees from Astra-Zeneca, Sobi, Leo-Pharma, Takeda and Pfizer. PN received research grants from Novartis, Principia and Rigel, unrestricted grants from Sanofi, Chugai and Octapharma and honoraria from Bayer. RA received fees from Alexion, Bayer, BMS, Pfizer and Portola. SS has received meeting sponsorship, speaker fees and/or consultancy from Bayer, Pfizer, NovoNordisk, Sobi, Chugai/Roche and Shire/Takeda. SS receives funding support from the Medical Research Council (MR/T024054/1). The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). SL has received speaker fees from Bayer, BMS and Pfizer. Others have no conflict of interests to declare. Ethical Approval: The study was approved by the Health Research Authority (HRA), Health and Care Research Wales (HCRW) and received local Caldicott Guardian support in Scotland (reference number: 20/HRA/1785). Data was collected both retrospectively and prospectively from patient clinical records by the treating medical team with no breach of privacy or anonymity by allocating a unique study number with no direct patient identifiable data; therefore, consent was waived by the HRA.

A systematic review of eczematous eruptions in patients receiving biologic therapy

A systematic review of eczematous eruptions in patients receiving biologic therapy