Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID‑19 (Bari‑SolidAct): a randomised, double‑blind, placebo‑controlled phase 3 trial

Background Baricitinib has shown efcacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifcally on severe/critical COVID, including vaccinated participants. Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/ critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. Results Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modifed intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49–69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute diference and 95% CI −0.1% [−8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (−3.2% [−9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a signifcant interac‑ tion between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated partici‑ pants were on average 11 years older, with more comorbidities. Conclusion This clinical trial was prematurely stopped for external evidence and therefore underpowered to con‑ clude on a potential survival beneft of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these fnd‑ ings warrant further investigation in other trials and real-world studies

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.[Background] Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants.[Methods] Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures.[Results] Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49–69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI − 0.1% [− 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (− 3.2% [− 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities.[Conclusion] This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu (2022-500385-99-00).EU-SolidAct is part of the European pandemic preparedness network EU RESPONSE, funded by the EU Horizon 2020 Research and Innovation programme, under grant number 101015736. EU-SolidAct has also received funding from CAPNET (France) and Klinbeforsk (Norway).Peer reviewe

HIGHER PREVALENCE OF NEPHROPATHY IN YOUNG ROMA FEMALES COMPARED WITH NON-ROMA FEMALES

Objectives: Ethnic differences in the prevalence of various chronic diseases, including end-stage renal disease, have been previously reported. Surprisingly, data focusing on the lower grade of chronic kidney disease (CKD) are scarce. Thus, the aim of this study was to explore differences in the prevalence of nephropathy between the Roma and non-Roma populations. Methods: Data from the cross-sectional population based HepaMeta study conducted in Slovakia were used. Nephropathy was defined as: a known history of any kidney disease; or the presence of proteinurialhematuria; or glomerular filtration rate (GFR) <60 ml/min. The odds ratio for the prevalence of nephropathy was calculated using binary logistic regression. Results: In an age-adjusted model, Roma females had OR of 1.56 for having nephropathy over non-Roma females (OR 1.56; 95% Cl 1.01-2.42; p <0.05). In addition, Roma females had a significantly lower GFR (mean difference 3.4 ml/min, t=-3.58, p <0.001); all female patients with proteinuria were Roma. Conclusions: This cross-sectional study on the young general population found that Roma females have half-higher odds for nephropathy than non-Roma females. Therefore, to prevent risks we should focus on searching for ethnic, social and medical determinants of CKD. Interventions to decrease the incidence of CKD in the target population should also address ethnic inequalities as well as female gender

Prevalence and Risk Factors for Hepatitis B Virus Infection in Roma and Non-Roma People in Slovakia

Prevalence of Hepatitis B is relatively low in developed European countries. However specific subpopulations may exist within each country with markedly different Hepatitis B burden. Roma minority is very numerous in Slovakia and their lifestyle is completely different to non-Roma population. The aim of this study is to map Hepatitis B prevalence in Roma and compare it to non-Roma population and to explore potential socio-economic and health related risk factors. Cross-sectional epidemiology study was performed in Slovakia that included randomly sampled Roma population and geographically corresponding random sampled non-Roma population. Comprehensive questionnaire about risk factors was administered and blood samples were drawn for Hepatitis B serology and virology tests. Altogether 855 participants were included. Global Hepatitis B surface Antigen (HBsAg) positivity rate was 7.7% (i.e., active Hepatitis B) and anti Hepatitis B core IgG antibody (antiHBcIgG) positivity rate was 34.6%. Roma population had significantly higher prevalence of Hepatitis B, both active chronic infection (12.4%; 95% Confidence Interval (CI) 9.58%&ndash;15.97% versus 2.8%; 95% CI 1.56%&ndash;4.91%; p &lt; 0.0001) and antiHBcIgG positivity (52.8%; 95% CI 48.17%&ndash;57.44% versus 25.9%; 95% CI 12.56%&ndash;20.02%; p &lt; 0.0001) Main risk factors for HBsAg positivity were Roma ethnicity, male sex and tattoo. Conclusion: There is a very high prevalence of Hepatitis B in Roma communities in Slovakia, with potential for grave medical consequences

The Roma Population Living in Segregated Settlements in Eastern Slovakia Has a Higher Prevalence of Metabolic Syndrome, Kidney Disease, Viral Hepatitis B and E, and Some Parasitic Diseases Compared to the Majority Population

Background: The Roma population is one of the largest marginalized population groups in Europe. The aim of our work was to summarize the morbidity of lifestyle-related diseases and infectious diseases in the Roma population living in segregated settlements. Methods: We used data from the cross-sectional study HepaMeta, in which we examined 452 Roma subjects with an average age of 34.7 ± 9.1 years, 35.2% of which were men, and 403 non-Roma subjects with an average age of 33.5 ± 7.4 years, 45.9% of which were men. We collected data by means of a questionnaire, anthropometric measures, and we analyzed blood and urine samples. Results: Roma subjects had a higher incidence of metabolic syndrome (RR: 1.478 (1.159–1.885), p &lt; 0.0001), obesity or waist circumference &gt;94 cm in men/80 cm in women (RR: 1.287 (1.127–1.470), p &lt; 0.0001), and HDL-C &lt; 1.03 mmol/L in men or &lt;1.29 in women (RR: 2.004 (1.730–2.321), p &lt; 0.0001) than their non-Roma counterparts. Subjects of the Roma population were more frequently diagnosed with kidney disease (RR: 1.216 (1.096–1.349), p &lt; 0.0001), HBsAg positivity (RR: 4.468 (2.373–8.415), p &lt; 0.0001), anti HBc IgG positivity (RR: 3.13 (2.598–4.224), p &lt; 0.0001), and anti HEV positivity (RR: 2.972 (1.226–7.287), p &lt; 0.0001). Serological markers of Toxoplasma gondii infection and Toxocara spp. were observed much more frequently among Roma than non-Roma subjects (RR: 1.868 (1.520–2.296), p &lt; 0.0001, for Toxoplasma gondii; and RR: 21.812 (8.097–58.761), p &lt; 0.0001, for Toxocara spp.). Conclusions: Poor socio-economic conditions, an unhealthy lifestyle, and barriers precluding access to healthcare are factors that affect the Roma population in settlements and lead to an increased prevalence of metabolic syndrome and its components, kidney disease, viral hepatitis B and E, and some parasitic diseases

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct) : a randomised, double-blind, placebo-controlled phase 3 trial

Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants.Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures.Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49-69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI - 0.1% [- 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (- 3.2% [- 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities.This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 )

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial

Abstract Background Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. Results Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49–69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI − 0.1% [− 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (− 3.2% [− 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. Conclusion This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 )

Tixagevimab-cilgavimab (AZD7442) for the treatment of patients hospitalized with COVID-19 (DisCoVeRy): A phase 3, randomized, double-blind, placebo-controlled trial

International audienc

Tixagevimab-cilgavimab (AZD7442) for the treatment of patients hospitalized with COVID-19 (DisCoVeRy): A phase 3, randomized, double-blind, placebo-controlled trial.

Dear Editor, We read with great interest the recent article by Kamboj et al., in which they described the risk of developing moderate to severe Coronavirus Disease 2019 (COVID-19) in patients with hematological malignancies receiving tixagevimab-cilgavimab (T-C) during a period in which the dominant circulating variants of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) were resistant to T-C.1 The authors highlight the ongoing need to urgently address the mAb treatment gap, particularly for immunocompromised patients. The unmet need is further highlighted by the DisCoVeRy Phase 3, adaptive, multicentre European, randomized, double-blind, superiority trial that evaluated the efficacy and safety of intravenous T-C in SARS-CoV-2 antigenic positive patients (i.e those with a high SARS-CoV-2 viral load) hospitalized with COVID-19 and followed-up to day 90. [...