PLACEBO-CONTROLLED EFFICACY AND SAFETY OF UPADACITINIB THROUGH ONE YEAR IN PATIENTS WITH NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS

BackgroundUpadacitinib (UPA), a Janus kinase inhibitor, was effective and well tolerated in patients (pts) with non-radiographic axial spondyloarthritis (nr-axSpA) through 14 weeks (wks) of treatment.[1]ObjectivesThis analysis assessed the efficacy and safety of UPA vs placebo (PBO) through 1 year.MethodsThe SELECT-AXIS 2 nr-axSpA study included a 52-wk randomized, double-blind, PBO-controlled period. Enrolled adults had a clinical diagnosis of active nr-axSpA fulfilling the 2009 ASAS classification criteria, objective signs of inflammation based on MRI sacroiliitis and/or elevated C-reactive protein, and an inadequate response to NSAIDs. One-third of pts had an inadequate response to biologic DMARDs. Pts were randomized 1:1 to UPA 15 mg once daily or PBO. Concomitant medications, including NSAIDs, had to be kept stable through wk 52. The study protocol outlined that pts who did not achieve ASAS20 at any two consecutive study visits between wks 24 to 52 should receive rescue therapy with NSAIDs, corticosteroids, conventional synthetic/biologic DMARDs, or analgesics. Cochran-Mantel-Haenszel (CMH) test with non-responder imputation incorporating multiple imputation (NRI-MI) was used to handle missing data and intercurrent events for binary efficacy endpoints. Mixed-effect model repeated measures (MMRM) was used to assess continuous efficacy endpoints. NRI was used for binary endpoints after rescue and as observed analysis excluding data after rescue for continuous endpoints. Treatment-emergent adverse events (TEAEs) are reported through wk 52.ResultsOf the 314 pts randomized, 259 (82%;UPA, n=130;PBO, n=129) completed wk 52 on study drug. More pts achieved an ASAS40 response with UPA vs PBO from wks 14 to 52 with a 20% treatment difference at wk 52 (63% vs 43%;nominal P <.001;Figure 1). The proportion of pts achieving ASDAS inactive disease with UPA remained higher than PBO at wk 52 (33% vs 11%;nominal P <.0001;Figure 1). Consistent improvements and maintenance of efficacy were also seen across other disease activity measures. Between wks 24 and 52, fewer pts on UPA (9%) than PBO (17%) received rescue therapy. A similar proportion of pts in each treatment group had a TEAE (Table 1). Infections were the most common TEAE;the rates of serious infections and herpes zoster were higher with UPA vs PBO, although no new serious infections were reported from wks 14 to 52. COVID-19 events were balanced between treatment groups. No opportunistic infections, malignancy excluding non-melanoma skin cancer, adjudicated major adverse cardiovascular events, inflammatory bowel disease, or deaths were reported. Two pts (1.3%) on PBO had adjudicated venous thromboembolic events.ConclusionUPA showed consistent improvement and maintenance of efficacy vs PBO through 1 year across multiple disease activity measures. No new safety risks were identified with longer-term UPA exposure. These results continue to support the benefit of UPA in pts with active nr-axSpA.Reference[1]Deodhar A, et al. Lancet. 2022;400(10349):369–379.Table 1.Safety through week 52Event, n (%)PBO (n = 157)UPA 15 mg QD (n = 156)Any AE103 (66%)107 (69%)Serious AE6 (3.8%)6 (3.8%)AE leading to D/C4 (2.5%)6 (3.8%)COVID-19-related AE22 (14%)24 (15%)Deaths00Infection60 (38%)68 (44%) Serious infection1 (0.6%)2 (1.3%) Herpes zoster1 (0.6%)5 (3.2%)Malignancy other than NMSC00NMSC1 (0.6%)0Hepatic disorder7 (4.5%)6 (3.8%)Neutropenia1 (0.6%)8 (5.1%)MACE (adjudicated)00VTE (adjudicated)2 (1.3%)a0Uveitisb3 (1.9%)2 (1.3%)Inflammatory bowel disease00aBoth patients had non-serious events of deep vein thrombosis in the lower limb with risk factors including obesity and prior deep vein thrombosis in one patient and concomitant COVID-19 infection in the other patient.bThree events of uveitis occurred in each treatment group (among n = 3 patients in the PBO group and n = 2 patients in the UPA group);two events in the PBO group and one in the UPA group occurred in patients with a history of uveitis.AcknowledgementsAbbVie funded this study and participated in the study design, res arch, analysis, data collection, interpretation of data, review, and approval of the . All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsFilip van den Bosch Speakers bureau: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, BMS, Celgene, GSK, Janssen, Lilly, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, GSK, Lilly, Novartis, Pfizer, and UCB, Denis Poddubnyy Speakers bureau: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Consultant of: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Lilly, MSD, Novartis, and Pfizer., Walter P Maksymowych Consultant of: AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, and UCB, Employee of: Director of Imaging Rheumatology BV, Tae-Hwan Kim Speakers bureau: AbbVie, Celltrion, Kirin, Lilly, and Novartis., Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi Sankyo, Eisai, Gilead, Janssen, Lilly, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB., Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, BMS, Chugai, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie and Novartis, Yuanyuan Duan Shareholder of: AbbVie, Employee of: AbbVie, Kristin D'Silva Shareholder of: AbbVie, Employee of: AbbVie, Peter Wung Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie, Employee of: AbbVie.

Perceptions of health status, physical fitness, and participation in physical activity among adolescents before and after COVID-19: analysis of 2019-2021 data from the Republic of Korea national sports survey

Research has examined the detrimental effects of the coronavirus disease (COVID-19) pandemic on health and physical fitness in adolescents;however, studies comparing these parameters before and after the COVID-19 outbreak have been scarce. Therefore, this study investigated differences in perceived health status, perceived physical fitness, and participation in physical activity among adolescents in the Republic of Korea before and after the COVID-19 outbreak. We chose a sample of data from 2102 adolescents aged 14-19, collected as part of a national survey by the Republic of Korea Ministry of Culture, Sports, and Tourism from 2019 to 2021. We focused on five items from the survey related to health awareness and physical activity. Although perceived health status was lower in 2021 than in 2019 or 2020, there were no differences in perceived physical fitness during the three years of the study. Regular participation in physical activity was less common in 2020 than in 2019 or 2021. The proportion of adolescents reporting sufficient rest and sleep was lower in 2021 than in 2020. In addition, fewer adolescents reported eating regular meals and engaging in nutritional supplementation in 2021 than in 2019 and 2020. Rates of abstinence from alcohol and smoking cessation were higher in 2021 than in 2019 or 2020. For all three years, adolescents reported the following as the primary reasons for engaging in regular physical activity (in order): "maintenance of mental health", "maintenance of physical health", "help in daily life", and "reduction of medical expenses". In preparation for the post-COVID-19 era, these results highlight the need to prepare measures and countermeasures to promote health and physical activity among adolescents in the Republic of Korea.Copyright ©2023 The Author(s). Published by MRE Press.

Polyethyleneimine based Delivery System Coated with Hyaluronate Amine for Improved pDNA Transfection Efficiency

Since the pandemic of COVID-19, active investigation to develop immunity to infectious disease by delivering nucleic acids has been proceeded. Particularly, many studies have been conducted on non-viral vector as several vital side-effects which were found on nucleic acid delivery system using viral vectors. In this study, we have developed plasmid DNA (pDNA) load-ed-hyaluronic acid derivative (HA) coated-polyethyleneimine (PEI) based polyplex for enhanced nucleic acid delivery efficiency. We have optimized the ratio of pDNA: PEI: HA by measuring size and protein transcription efficiency. The final product, polyplex-HA, was characterized through measuring size, zeta-potential and TEM image. Intracellular uptake and protein transcription efficiency were compared to commercially available transfection reagent, lipofectamine, through fluo-rescence image and flow cytometry. In conclusion, polyplex-HA presents a novel gene delivery system for efficient and stable protein transcription since it is available for delivering various genetic materials and has less immunoreactivity. © 2022, Korean Society of Industrial Engineering Chemistry. All rights reserved.

Characteristics and prognosis of COVID-19 induced olfactory and gustatory dysfunction in Daegu

Background and Objectives Olfactory and gustatory dysfunctions have been known as characteristic symptoms of coronavirus disease 2019 (COVID-19). However, the study of the clinical features of olfactory and gustatory dysfunctions in COVID-19 is still insufficient. Subjects and Method Mild COVID-19 patients who complained of olfactory or gustatory dysfunctions in the telephone monitoring from March 8 to April 8, 2020 were included in this study. Patient information was collected using a Google questionnaire. COVID-19 symptoms, severity and improvement of olfactory and gustatory dysfunctions of patients were investigated. Results A total of 228 patients participated in this study. The number of male and female were 76 and 152, and the average age was 32.1±11.5 years. There were 210 patients (92.1%) of olfactory dysfunction, 179 patients (78.5%) of gustatory dysfunction, and 165 patients (71.4%) who complained of both symptoms. The 18.4% of patients complained only olfactory or gustatory dysfunction without other symptoms of COVID-19, and 51.1% of patients presented olfactory and gustatory dysfunctions as the first symptoms. Most of the patients (95.6%) improved olfactory and gustatory dysfunctions within several months, but only 79.8% of patients were normalized. Conclusion Since olfactory and gustatory dysfunctions are the first symptoms in the numerous COVID-19 patients, and continued research on these patients play an important role in the screening and prevention of COVID-19. Long-term observation and further studies of treatment are needed for 20.2% of patients who have not fully recovered. Copyright © 2021 Korean Society of Otorhinolaryngology-Head and Neck Surgery.

3D architectured air sensing tubes for a portable mechanical ventilator

Today, respiratory ventilators are in high demand at the peak of the COVID-19 outbreak. However, there are concerns regarding insufficient supply of ventilators to handle the impending surge due to the high cost, and slow production and deliveries. Thus, the development of a low-cost portable ventilator becomes essential. The mechanical ventilator requires two main components including an active airbag and its venting control system. We developed a reliable active airbag designed with mechanically tunable 3D origami structures. The 3D origami structure based active airbag demonstrates reliable and reconfigurable characteristics. The active airbag's volume can be tuned by controlling the triangular angles in the 3D origami-folding plates. Moreover, its volumetric ratio before and after compression is around 85%. Also, the rotating behavior of 3D origami tube under the compressive force allows more functionalities in the airbag such as the architectured pressure sensing. The 3D printed origami sensor measures the compressed angle to confirm the accuracy of detected pressure in the ventilator circuit. We achieved accurate delivery of targeted air volume with specific airflow rate by 3D printed reconfigurable origami tubes.

Broad-Spectrum Antiviral Activity of 3D8, a Nucleic Acid-Hydrolyzing Single-Chain Variable Fragment (scFv), Targeting SARS-CoV-2 and Multiple Coronaviruses In Vitro

The virus behind the current pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the etiology of novel coronavirus disease (COVID-19) and poses a critical public health threat worldwide. Effective therapeutics and vaccines against multiple coronaviruses remain unavailable. Single-chain variable fragment (scFv), a recombinant antibody, exhibits broad-spectrum antiviral activity against DNA and RNA viruses owing to its nucleic acid-hydrolyzing property. The antiviral activity of 3D8 scFv against SARS-CoV-2 and other coronaviruses was evaluated in Vero E6 cell cultures. Viral growth was quantified with quantitative RT-qPCR and plaque assay. The nucleic acid-hydrolyzing activity of 3D8 was assessed through abzyme assays of in vitro viral transcripts and cell viability was determined by MTT assay. We found that 3D8 inhibited the replication of SARS-CoV-2, human coronavirus OC43 (HCoV-OC43), and porcine epidemic diarrhea virus (PEDV). Our results revealed the prophylactic and therapeutic effects of 3D8 scFv against SARS-CoV-2 in Vero E6 cells. Immunoblot and plaque assays showed the reduction of coronavirus nucleoproteins and infectious particles, respectively, in 3D8 scFv-treated cells. These data demonstrate the broad-spectrum antiviral activity of 3D8 against SARS-CoV-2 and other coronaviruses. Thus, it could be considered a potential antiviral countermeasure against SARS-CoV-2 and zoonotic coronaviruses.