Selectivity, efficacy and safety of JAKinibs: new evidence for a still evolving story

Annals of the Rheumatic Diseases, Journal Year: 2023, Volume and Issue: 83(2), P. 139 - 160

Published: Nov. 3, 2023

Fundamental insight gained over the last decades led to discovery of cytokines as pivotal drivers inflammatory diseases such rheumatoid arthritis, psoriasis/psoriasis bowel diseases, atopic dermatitis and spondylarthritis. A deeper understanding pro-inflammatory anti-inflammatory effects various has prompted new cytokine-targeting therapies, which revolutionised treatment options in years for patients with disorders. Disease-associated immune responses typically involve a complex interplay multiple cytokines. Therefore, blockade one single cytokine does not necessarily lead persistent remission all disorders fostered therapeutic strategies targeting intracellular pathways shared by By inhibiting JAK-STAT signalling common families cytokines, JAK-inhibitors (JAKinibs) have created paradigm diseases. Multiple agents been approved more are being investigated several indications. Second-generation selective JAKinibs devised aim achieve an increased selectivity possible reduced risk side effects. In current review, we will summarise body evidence pan versus most recent insights on indications, including COVID-19.

Language: Английский

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Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia

JAMA, Journal Year: 2023, Volume and Issue: 330(4), P. 328 - 328

Published: July 10, 2023

Importance Immune dysregulation contributes to poorer outcomes in COVID-19. Objective To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added standard care for COVID-19 pneumonia. Design, Setting, and Participants Randomized, double-masked, placebo-controlled clinical trial using a master protocol immunomodulators treatment of participants hospitalized with The results 3 substudies are reported from 95 hospitals at 85 research sites the US Latin America. Hospitalized patients 18 years older confirmed SARS-CoV-2 infection within 14 days evidence pulmonary involvement underwent randomization between October 2020 December 2021. Interventions Single infusion abatacept (10 mg/kg; maximum dose, 1000 mg) (5 mg/kg) 28-day oral course cenicriviroc (300-mg loading dose followed by 150 mg twice per day). Main Outcomes Measures primary outcome was time recovery day 28 evaluated an 8-point ordinal scale (higher scores indicate better health). Recovery defined as first participant scored least 6 on scale. Results Of 1971 randomized across substudies, mean (SD) age 54.8 (14.6) 1218 (61.8%) were men. end point pneumonia not significantly different (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), (RRR, 1.01 0.86-1.18]; .94), 0.99-1.28]; .08) compared placebo. All-cause mortality 11.0% vs 15.1% placebo (odds [OR], 0.62 0.41-0.94]), 13.8% 11.9% (OR, 1.18 CI 0.72-1.94]), 10.1% 14.5% 0.59 0.39-0.90]). Safety comparable active placebo, including secondary infections, all substudies. Conclusions Relevance Time among Trial Registration ClinicalTrials.gov Identifier: NCT04593940

Language: Английский

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Impact of COVID-19 on the liver and on the care of patients with chronic liver disease, hepatobiliary cancer, and liver transplantation: An updated EASL position paper

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 77(4), P. 1161 - 1197

Published: July 20, 2022

Language: Английский

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Janus kinase inhibitors for the treatment of COVID-19

Cochrane library, Journal Year: 2022, Volume and Issue: 2022(6)

Published: June 13, 2022

Language: Английский

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A Review of Safety Outcomes from Clinical Trials of Baricitinib in Rheumatology, Dermatology and COVID-19

Advances in Therapy, Journal Year: 2022, Volume and Issue: 39(11), P. 4910 - 4960

Published: Sept. 5, 2022

Baricitinib is an oral, selective inhibitor of Janus kinase (JAK)1/JAK2 that transiently and reversibly inhibits many proinflammatory cytokines. This mechanism a key mediator in number chronic inflammatory diseases; accordingly, baricitinib has been studied approved for the treatment several rheumatological dermatological disorders, as well COVID-19. narrative review summarises discusses safety profile across these diseases, with special focus on adverse events interest (AESI) JAK inhibitors, using integrated data sets clinical trial data, puts findings into context underlying risk respective disease populations, supporting literature. We show rates infection generally reflected inherent populations being treated, serious infections herpes zoster more frequent rheumatic diseases than simplex reported particularly atopic dermatitis. Similarly, major cardiovascular (MACE), venous thromboembolism (VTE) malignancies were within or below ranges thereby reflecting risk; therefore patients those latter whom had low absolute risk. AESI usually common factors specific each event. When population similar to ORAL Surveillance was considered, incidence rate MACE numerically lower tofacitinib tumour necrosis factor inhibitors. No concerns observed hospitalised COVID-19 who received up 14 days. Identifying patterns likelihoods AEs occur during large groups different can help physician patient better contextualise benefit-to-risk ratio individual patient. The oral elements pathway, which are mechanisms chronic, but, all drugs, it be associated unwanted effects. baricitinib, considered such either because characteristics treated (rheumatological disorders COVID-19) action drug. light event diseases. therapy most dermatitis, likely disease-related factors. MACE, VTE occurred baricitinib-treated frequency populations. Rates higher mostly occurring AESI. Characterising put actual perspective.

Language: Английский

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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

Critical Care, Journal Year: 2023, Volume and Issue: 27(1)

Published: Jan. 10, 2023

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, trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients COVID-19 were randomised 4 mg once daily or placebo, added standard of care. The primary endpoint was all-cause mortality within 60 days. Participants remotely followed day 90 safety and patient related outcome measures. Results Two hundred ninety-nine screened, 284 275 received study drug placebo included the modified intent-to-treat analyses (139 receiving baricitinib 136 placebo). Median age (IQR 49–69) years, 77% male 35% had at least one dose SARS-CoV2 vaccine. There 21 deaths each group, 15.1% group 15.4% (adjusted absolute difference 95% CI − 0.1% [− 8·3 8·0]). In sensitivity analysis censoring observations after discontinuation rescue therapy (tocilizumab/increased steroid dose), proportions death 5.8% versus 8.8% (− 3.2% 9.0 2.7]), respectively. 148 serious adverse events 46 (33.1%) 155 51 (37.5%) placebo. subgroup analyses, there potential interaction between vaccination status treatment allocation 60-day mortality. subsequent post hoc significant occurrence events, more respiratory complications severe infections treated baricitinib. Vaccinated average 11 years older, comorbidities. Conclusion This clinical trial evidence therefore underpowered conclude survival benefit COVID-19. We observed possible signal participants, who older Although based post-hoc analysis, these findings warrant further investigation other real-world studies. Trial registration registered NCT04891133 (registered May 18, 2021) EUClinicalTrials.eu ( 2022-500385-99-00 ).

Language: Английский

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Mitigating neurological, cognitive, and psychiatric sequelae of COVID-19-related critical illness

The Lancet Respiratory Medicine, Journal Year: 2023, Volume and Issue: 11(8), P. 726 - 738

Published: July 17, 2023

Despite advances in the treatment and mitigation of critical illness caused by infection with SARS-CoV-2, millions survivors have a devastating, post-acute syndrome known as long COVID. A large proportion patients COVID nervous system dysfunction, which is also seen distinct but overlapping condition post-intensive care (PICS), putting COVID-19-related at high risk long-lasting morbidity affecting multiple organ systems and, result, engendering measurable deficits quality life productivity. In this Series paper, we discuss neurological, cognitive, psychiatric sequelae who survived due to COVID-19. We review current knowledge epidemiology pathophysiology persistent neuropsychological impairments, outline potential preventive strategies based on safe, evidence-based approaches management pain, agitation, delirium, anticoagulation, ventilator weaning during illness. highlight priorities for future research, including possible therapeutic approaches, offer considerations health services address escalating burden

Language: Английский

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Could the fibromyalgia syndrome be triggered or enhanced by COVID-19?

Inflammopharmacology, Journal Year: 2023, Volume and Issue: 31(2), P. 633 - 651

Published: Feb. 27, 2023

Language: Английский

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COVID-19 therapeutics

Clinical Microbiology Reviews, Journal Year: 2024, Volume and Issue: 37(2)

Published: May 21, 2024

SUMMARYSince the emergence of COVID-19 in 2020, an unprecedented range therapeutic options has been studied and deployed. Healthcare providers have multiple treatment approaches to choose from, but efficacy those often remains controversial or compromised by viral evolution. Uncertainties still persist regarding best therapies for high-risk patients, drug pipeline is suffering fatigue shortage funding. In this article, we review antiviral activity, mechanism action, pharmacokinetics, safety therapies. Additionally, summarize evidence from randomized controlled trials on various antivirals discuss unmet needs which should be addressed.

Language: Английский

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National Institutes of Health COVID-19 Treatment Guidelines Panel: Perspectives and Lessons Learned

Annals of Internal Medicine, Journal Year: 2024, Volume and Issue: 177(11), P. 1547 - 1557

Published: Sept. 30, 2024

In March 2020, the White House Coronavirus Task Force determined that clinicians in United States needed expert treatment guidelines to optimally manage patients with COVID-19, a potentially life-threatening disease caused by new pathogen for which no specific treatments were known be effective.

Language: Английский

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