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Background: Systemic atopic dermatitis treatments that have acceptable safety are needed., Objective: To evaluate the safety of the oral Janus kinase inhibitor upadacitinib in combination with topical corticosteroids (TCSs) for the treatment of atopic dermatitis., Methods: In this phase 3, double-blind study (Rising Up), Japanese patients (12-75 years) with moderate-to-severe atopic dermatitis were randomized in a 1:1:1 ratio to receive 15 mg of upadacitinib + TCS, 30 mg of upadacitinib + TCS, or a placebo + TCS (rerandomized in a 1:1 ratio to receive either 15 or 30 mg of upadacitinib + TCS at week 16). Adverse events and laboratory data were assessed for safety., Results: In 272 treated patients, the serious adverse event rates were similar for 15- and 30-mg upadacitinib + TCS at week 24 (15 mg, 56%; 30 mg, 64%) but greater than those for placebo + TCS (42%). Acne (all mild or moderate; none leading to discontinuation) occurred more frequently with upadacitinib + TCS (15 mg, 13.2%; 30 mg, 19.8%) than with placebo + TCS (5.6%). Furthermore, herpes zoster infection (4.4% vs 0%), anemia (1.1% vs 0%), neutropenia (4.4% vs 1.1%), and creatine phosphokinase elevations (2.2% vs 1.1%) occurred more frequently with 30-mg upadacitinib + TCS than with 15-mg upadacitinib + TCS; none of these events were reported with placebo + TCS. No thromboembolic events, malignancies, gastrointestinal perforations, active tuberculosis, or deaths occurred., Limitations: The limitations included a small sample size and short observation period as well as nongeneralizability of the results beyond Japanese populations., Conclusions: The results were generally consistent with those of previous reports; no new safety risks were detected., Competing Interests: Dr Katoh has received honoraria as a speaker or consultant for AbbVie, Eli Lilly Japan, Janssen, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Sanofi, and Taiho Pharmaceutical and has received grants as an investigator from 10.13039/100006483AbbVie, 10.13039/100014422Eli Lilly Japan, 10.13039/501100004095Kyowa Kirin, LEO Pharma, Maruho, 10.13039/501100012351Mitsubishi Tanabe Pharma, and 10.13039/100004339Sanofi. Dr Ohya has received funding or grant support from Maruho and 10.13039/501100012030Yakult and honorarium as a speaker or consultant from AbbVie, Bayer, Chugai, Lilly, Torii Pharmaceutical, Towa Pharmaceutical, Maruho, Mylan, and Sanofi. Dr Murota has received funding or grant support from Maruho, 10.13039/501100012351Mitsubishi Tanabe Pharma, and 10.13039/100009954Taiho Pharmaceutical and honorarium as a consultant from Japan Tobacco, Kaken Pharmaceutical, Maruho, Mitsubishi Tanabe Pharma, Sanofi, Shiseido Japan, and Taiho Pharmaceutical. Dr Ikeda has received a scholarship donation from the Central Research Institute of Pias Co, Ltd. Drs Chu, Hu, Ikeda, Liu, and Teixeira and Author Sasaki are full-time employees of AbbVie Inc and may own AbbVie stock or stock options. Dr Saeki has received funding or grant support from 10.13039/501100003769Eisai, Maruho, 10.13039/501100012351Mitsubishi Tanabe Pharma, and Torii Pharmaceutical and honorarium as a consultant from AbbVie, LEO Pharma, and Sanofi., (© 2021 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Objective: To explore the survival benefit of tofacitinib in addition to dexamethasone in hospitalized patients treated for coronavirus disease 2019 (COVID-19)-related pneumonia., Patients and Methods: This is a single-center retrospective observational study. All patients who were hospitalized at Delta Regional Medical Center (a regional hospital in the Mississippi Delta) with a COVID-19 diagnosis and discharged between March 1 and September 30, 2020, are included. The primary outcome was in-hospital mortality in relation to receipt of tofacitinib alone or in addition to dexamethasone (designated as the tofacitinib group), versus dexamethasone alone (designated as the dexamethasone group)., Results: Of 269 eligible patients, 138 (51.3%) received tofacitinib uniformly and 131 (48.7%) patients received dexamethasone without tofacitinib. A total of 44 patients expired: 14 (31.8%) in the tofacitinib group and 30 (68.2%) in the dexamethasone group. The proportions of death among the tofacitinib and dexamethasone groups were, respectively, 10.1% and 22.9%. This represents a 70% reduction in odds of dying among the tofacitinib group compared to the dexamethasone group after adjusting for age and clinical parameters captured at hospitalization (adjusted odds ratio: 0.30; 95% CI: 0.12 to 0.76; P =.01)., Conclusion: The in-patient treatment of COVID-19 pneumonia has rapidly evolved. The addition of dexamethasone has made a relevant improvement on survival. Other immunomodulators have yet to show an impact. Here we present the potential survival benefit of the Janus kinase-signal transducer and activator of transcription inhibitor tofacitinib on COVID-19 pneumonia. We found that adding tofacitinib-based anti-inflammatory therapy to a treatment regimen including dexamethasone in COVID-19 pneumonia seems to have potential benefit of improving survival when compared to dexamethasone alone., (© 2021 The Authors.)

The novel severe acute respiratory syndrome coronavirus 2, the causal agent of coronavirus disease 2019 (COVID-19), quickly spread around the world, resulting in the most aggressive pandemic experienced in more than 100 years. Research on targeted therapies and vaccines has been initiated on an unprecedented scale and speed but will take months and even years to come to fruition. Meanwhile, the efficacy of emerging therapeutics for use in treating COVID-19 is feverishly being investigated to identify the best available treatment options for dealing with the current wave of disease. This review of publications with a "treatment" tag through June 29, 2020 in the National Library of Medicine's LitCovid literature hub, provides frontline clinicians with a pragmatic summary of the current state of the rapidly evolving evidence supporting emerging candidate therapeutics for COVID-19. Two main categories of pharmaceutical therapeutics are showing promise: those with antiviral activity directly addressing infection and those that counteract the inflammatory cytokine storm induced by severe disease. Preliminary results suggest that other approaches such as convalescent plasma therapy and lung radiation therapy may have some efficacy. The current clinical evidence for potential treatments is preliminary-often small retrospective series or early results of randomized trials-and the science is evolving rapidly. The long-term results from large, well-designed randomized controlled trials will provide definitive evidence for therapeutic effectiveness and are likely months away. The trial landscape for promising therapies is described., (© 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)