tocilizumab

In this episode, Patrick W. G. Mallon, MB, BCh, PhD, FRACP, FRCPI, discusses new data on COVID-19 presented at ECCMID 2023, including:

• Treatment in special populations
  • REDPINE: remdesivir in people with renal impairment hospitalized for COVID-19 pneumonia
  • Remdesivir and readmission for COVID-19 in immunocompromised patients
  • Molnupiravir vs nirmatrelvir plus ritonavir for COVID-19 with hematologic malignancy
• Management of patients with severe disease
  • RECOVERY: higher-dose vs standard-dose corticosteroids for hospitalized patients with COVID-19
  • Real-world study of tocilizumab vs baricitinib for severe COVID-19
• Novel antivirals
  • Ensitrelvir
  • Bemnifosbuvir
•  Novel vaccines
  • NB2155
  • AZD2816/AZD1222
  • qNIV/CoV2373
  • GRT-R910
  • NVX-CoV2373 in people with HIV

Faculty:  
Patrick W. G. Mallon, MB, BCh, PhD, FRACP, FRCPI
Professor of Microbial Diseases
Centre for Experimental Pathogen Host Research
University College Dublin
Dublin, Ireland

Content based on an online CME/CE program supported by independent educational grants from Gilead Sciences, Inc. and Novavax.  

Link to full program: 
bit.ly/3niXGJ6

Link to downloadable slides: 
bit.ly/3LUFejG

In this episode, Vikramjit Mukherjee, MD, and Cameron Smith, MPAS, PA-C, answer audience questions on how best to care for hospitalized patients with COVID-19 from a live, virtual question and answer webinar. This episode includes expert insights on:

• Supportive care management such as oxygen support, glycemic control, and anticoagulation
• Escalation of therapy in patients with worsening oxygen requirements
• Use of remdesivir in patients with renal dysfunction
• Brief commentary on long COVID

Presenters:

Vikramjit Mukherjee, MD
Assistant Professor  
Division of Pulmonary, Critical Care, & Sleep Medicine  
New York University School of Medicine  
Director
Medical Intensive Care Unit
Bellevue Hospital
New York

Cameron Smith MPAS, PA-C
Lead Advanced Practice Provider
Medical Intensive Care Unit
Bellevue Hospital
New York Health and Hospitals  
New York, New York

Content based on an online program supported by an independent educational grant from Gilead Sciences, Inc.
bit.ly/3z52c00

In this episode, Princy N. Kumar, MD, and Paul E. Sax, MD, discuss new COVID-19 data from IDWeek 2022, including:

• COVID-19 vaccines, including omicron BA.1 bivalent booster
• Risk factors for breakthrough COVID-19 infections
• COVID-19 diagnostics, including digital droplet PCR
• COVID-19 therapeutics, including:
  • Nirmatrelvir plus ritonavir
  • Tixagevimab plus cilgavimab
  • Baricitinib
  • Tocilizumab
  • Inhaled interferon β-1a
• COVID-19 therapeutics and outcomes in patients with immunocompromise
• Long COVID

Presenters:
Princy N. Kumar, MD, FIDSA, MACP
Professor of Medicine and Microbiology
Chief, Division of Infectious Diseases and Travel Medicine
Senior Associate Dean of Students
Georgetown University School of Medicine
Washington, DC

Paul E. Sax, MD
Clinical Director
HIV Program and Division of Infectious Diseases
Brigham and Women’s Hospital
Professor of Medicine
Harvard Medical School
Boston, Massachusetts

Follow along with the downloadable slideset at:
http://bit.ly/3gkJI67

Link to full program:
http://bit.ly/3TSVthM

Anti-inflammatory agents and immunomodulators are key components to treating patients who are severely or critically ill due to a COVID-19 infection.

In this episode, Vikramjit Mukherjee, MD, discusses the role and timing of these treatment options, including:

• High-titer convalescent plasma
• Corticosteroids
• Interleukin-6 inhibitors (eg, tocilizumab)
• Janus kinase inhibitors (eg, baricitinib)

Presenter:
Vikramjit Mukherjee, MD
Assistant Professor of Medicine
Division of Pulmonary, Critical Care, & Sleep Medicine
New York University School of Medicine
Director, Medical Intensive Care Unit
Bellevue Hospital
New York, New York 

Review the downloadable slidesets at: 
https://bit.ly/35NNb7Q

Link to full program: 
https://bit.ly/35SrxQ0

During this episode, Lynora Saxinger, MD, FRCPC, CTropMed, updates listeners on the latest Emergency Use Authorizations and guideline recommendations for optimal clinical management of COVID-19. Gain practical insights on patient identification, risk stratification, and treatment.

Key points include:

• Treatment of COVID-19 can be broken into antiviral and immune-modulating therapies
• Each agent should be used at the correct disease stage to maximize benefit
• Antiviral medications and mAbs show the greatest promise early during COVID-19, before the host immune response is mounted
• Passive immunization with mAbs can prevent infection and severe disease—and mortality—if given early to hospitalized persons
• Operational challenges to using these medications exist, but given the epidemic of unvaccinated persons, these treatments become increasingly relevant to reduce burden on healthcare systems

Presenter:

Lynora Saxinger, MD, FRCPC, CTropMed
Cochair, Scientific Advisory Group  
Alberta COVID-19 Emergency Coordination Centre  
Associate Professor
Division of Infectious Diseases
Department of Medicine  
University of Alberta
Edmonton, Alberta, Canada

Content based on an online CME program supported by an educational grant from Gilead Sciences, Inc.

Follow along with the slides at:
https://bit.ly/3BxQKtD
 

Link to full program:
https://bit.ly/3BwzdlC

Theme: 
COVID-19. 

Participants: 

Dr Matthew O'Sullivan (infectious diseases specialist), Prof. Sanjay Swaminathan (immunologist), Dr George Zhou (intensivist), Ali Sayeed (ICU registrar), Dr James Tadros (ED consultant), Dr Pramod Chandru (ED consultant), Harry Hong, Samoda Wilegoda Mudalige, Shreyas Iyer, Kit Rowe, and Caroline Tyers.

Discussion:
Ansems, K., Grundeis, F., Dahms, K., Mikolajewska, A., Thieme, V., & Piechotta, V. et al. (2021). Remdesivir for the treatment of COVID-19. Cochrane Database Of Systematic Reviews, 2021(8). https://doi.org/10.1002/14651858.cd014962.

Presenter - Ali Sayeed, ICU Registrar at Westmead Hospital.

Summary:

• Remdesivir is a small molecule pro-drug that inhibits viral replication via its inhibition of RNA polymerase - In Australia, it has been provisionally approved by the TGA for its use in COVID-19. 
• The theory behind using Remdesivir is really in the early stages of COVID-19 pneumonitis (by reducing the viral load and thereby preventing the augmentation of the inflammatory response). 
• This was a systematic review with included meta-analyses looking at the use of Remdesivir in COVID-19 compared with placebo or standard care. 
• It included only randomised control trials, with the primary outcomes being all-cause mortality, changes in clinical status (such as time to liberation from mechanical intervention) and adverse events. 
• The 5 studies analysed for this review were: the Beigel study (ACTT-1 trial) which enrolled 1,000 patients, the Spinner trial which had 600 patients, the Wang trial with 230 patients, the Mahajan trial with 82 patients, and the WHO Solidarity trial with over 5,000 patients. 
• Remdesivir was found to have little to no impact on all-cause mortality at 28 days. 
• The duration to liberation from non-invasive and invasive mechanical ventilation was found to be 17 days in the Remdesivir group compared with 20 days in the control group in the Beigel study, and 7 days in the Remdesivir group compared with 15 days in the control group in the Wang study, although neither of these results were statistically significant. 
• The Beigel study demonstrated a difference in time to recovery in the Remdesivir group compared with the placebo group, with a median difference of 5 days (however it is unclear whether this result was statistically significant). 
• The significant heterogeneity in study protocols, methodology, subgroups and settings made it very difficult to compare these studies statistically. 

 Take-Home Points:

• Remdesivir likely has very limited or no effect on hard outcomes in COVID-19 (in particular on mortality). 
• The benefit of Remdesivir is not constant across disease severities; if there is a benefit it is likely to be a subset of patients (which appears to be those on low-flow oxygen).  
• It does not appear to affect hospital length of stay (there is not sufficient evidence to suggest it does). 
• All outcomes were based on low certainty evidence, and it is unlikely that there will be further evidence on Remdesivir alone to come, as most patients will be receiving combination therapy in ongoing studies.  
• Of all the treatment modalities that we have for COVID-19, Remdesivir appears to be the one that has the least impact, but it was the one that was available first, and has very few side effects.  
• At present in NSW, COVID-19 patients requiring oxygen are being treated with a combination of Dexamethasone, Remdesivir and Baracitinib (or Tocilizumab). 

References: 

• Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the treatment of COVID-19 – final report. New England Journal of Medicine 2020;383:1813-26.[DOI: 10.1056/NEJMoa2007764]. 
• Spinner CD, Gottlieb RL, Criner GJ, Arribas Lopez JR, Cattelan AM, Soriano Viladomiu A, et al. Effect of remdesivirvs standard care on clinical status at 11 days in patientswith moderate COVID-19: a randomised clinical trial. JAMA2020;324(11):1048-57. [DOI: 10.1001/jama.2020.16349] [PMID:32821939]. 
• Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. The Lancet2020;395(10236):1569-78. [CLINICALTRIALS.GOV: NCT04257656][DOI: 10.1016/s0140-6736(20)31022-9]. 
• Mahajan L, Singh AP, GiSy. Clinical outcomes of using Remdesivir in patients with moderate to severe COVID-19: a prospective randomised study. Indian Journal of Anaesthesia2021;65:41-6. [DOI: 10.4103/ija.IJA_149_21]. 
• WHO Solidarity Trial Consortium. Repurposed antiviral drugs for COVID-19 - interim WHO solidarity trial results. New England Journal of Medicine 2021;384(8):497-511. [CLINICALTRIALS.GOV:NCT04315948] [DOI: 10.1056/NEJMoa2023184] [EUCTR:EUCTR2020-001366-11] [ISRCTN: ISRCTN83971151]. 
• Living Guidelines [Internet]. Caring for people with COVID-19. 2021 [cited 16 September 2021]. Available from: https://covid19evidence.net.au/#living-guidelines. 
• The RECOVERY Collaborative Group. Dexamethasone in Hospitalized Patients with Covid-19. New England Journal of Medicine [Internet]. 2021 [cited 16 September 2021];384(8):693-704. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2021436.  
• Kalil AC, Patterson TF, Mehta AK, Tomashek KM, et al. Baricitinib plus Remdesivir for Hospitalized Adults with COVID-19. N Engl J Med 2021; 384:795-807. 
• Gupta A, Gonzalez-Rojas Y, Juarez E, Crespo Casal M, Moya J, Falci DR, Sarkis E, Solis J, Zheng H, Scott N, Cathcart AL, Hebner CM, Sager J, Mogalian E, Tipple C, Peppercorn A, Alexander E, Pang PS, Free A, Brinson C, Aldinger M, Shapiro AE. Early COVID-19 Treatment with SARS-CoV-2 Neutralizing Antibody Sotrovimab [Internet]. medRxiv; May 2021 [cited 16 September 2021]. Available from: https://www.medrxiv.org/content/10.1101/2021.05.27.21257096v1.  
• Tomazini B, Maia I, Cavalcanti A, Berwanger O, Rosa R, Veiga V et al. Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19. JAMA [Internet]. 2020 [cited 16 September 2021];324(13):1307. Available from: https://jamanetwork.com/journals/jama/fullarticle/2770277. 
• Hasan MJ, Rabbani R, Anam AM, Huq SMR, Polash MMI, Nessa SST, Bachar SC. Impact of high dose Baracitinib in severe COVID-19 pneumonia: a prospective cohort study in Bangladesh. BMC Infect Dis. May 2021; 21(1): 427. Available from: https://pubmed.ncbi.nlm.nih.gov/33962573/. 

Kit's Corner 

• Signbank [Internet]. Auslan.org.au. 2021 [cited 01 October 2021]. Available from: https://www.auslan.org.au/dictionary/words/COVID-19-1.html. 

Credits:
This episode was produced by the ­­­­Emergency Medicine Training Network 5 with the assistance of Dr Kavita Varshney and, Deepa Dasgupta. 

Music/Sound Effects

• Angel by Ikson | https://youtube.com/ikson, Music promoted by

In this podcast episode, Sharon R. Lewin, AO, FRACP, PhD, FAHMS, and Arthur Kim, MD, discuss data on the potential use of monoclonal antibodies (mAb) for the prevention and treatment of COVID-19, including:

• Rationale for use of mAb
• Potential for resistance to mAb
• Single vs combination therapy with mAb
• Challenges in implementation of mAb as treatment or prevention
• Bamlanivimab
• Sotrovimab
• Casirivimab plus imdevimab

Link to full program, including downloadable slidesets:  https://bit.ly/3zVTwYW

Presenters: 

Sharon R. Lewin, AO, FRACP, PhD, FAHMS
Director, The Peter Doherty Institute for Infection and Immunity
Professor of Infectious Diseases
Faculty Medicine Dentistry and Health Sciences
University of Melbourne and Royal Melbourne Hospital
Consultant Infectious Diseases Physician
Department of Infectious Diseases
Royal Melbourne Hospital and Alfred Hospital
Melbourne, Australia

Arthur Kim, MD
Associate Professor
Department of Medicine
Harvard Medical School
Director, Viral Hepatitis Clinic
Division of Infectious Diseases
Massachusetts General Hospital
Boston, Massachusetts

Sharon R. Lewin, AO, FRACP, PhD, FAHMS, has disclosed that she has received consulting fees from AbbVie, Gilead Sciences, and ViiV Healthcare; funds for research support from Leidos; and other financial or material support from Gilead Sciences, Merck, and ViiV Healthcare.

Arthur Kim, MD, has disclosed that he has served on the drug and safety monitoring board for Kintor.

In this episode, Caron A. Jacobson, MD; Jae H. Park, MD; and Noopur Raje, MD, answer audience questions from a live CCO webinar focused on current best practices and emerging strategies in CAR T-cell therapy, with questions including:

• At what time in the treatment journey should CAR T-cell therapy be considered?
• How to select among 3 approved products for relapsed/refractory large B-cell lymphoma?
• How is CAR T-cell therapy best used for multiple myeloma?
• What qualities of bridging therapy are most preferred?
• When do patients receiving CAR T-cell therapy need COVID-19 or other vaccinations?  
• How are steroids optimally used in managing CAR T-cell therapy–related toxicities?

Presenters:

Caron A. Jacobson, MD
Assistant Professor
Division of Medical Oncology
Department of Medicine
Harvard Medical School
Dana-Farber Cancer Institute
Boston, Massachusetts

Jae H. Park, MD
Associate Member  
Leukemia Service and Cellular Therapeutics Center  
Memorial Sloan Kettering Cancer Center
New York, New York

Noopur Raje, MD
Director
Center for Multiple Myeloma
Massachusetts General Hospital Cancer Center  
Professor of Medicine
Harvard Medical School
Boston, Massachusetts

Content based on an online CME program supported by an educational grant from Bristol-Myers Squibb.

Link to full program:
https://bit.ly/3BfbEOf

In September 2020, a multi-disciplinary team at Takshashila came out with a policy proposal to vaccinate 80% of India's population by December 2021. Seven months down the line, co-authors Shambhavi Naik, Mihir Mahajan, and Pranay Kotasthane reflect on the government's vaccine deployment strategy and compare it with Takshashila's recommendations. They also discuss ways to accelerate vaccination going forward.

If these policy conversations interest you, consider applying for Takshashila's Graduate Certificate in Public Policy. Applications for the monsoon cohort close soon. You can check out our courses here.

Read more:

A COVID-19 vaccine deployment strategy for India. Takshashila Discussion SlideDoc, September 2020 - https://takshashila.org.in/wp-content/uploads/2020/09/COVID-19-Vaccine-Strategy-for-India_TDD_SN-et-al_04092020.pdf 

A COVID-19 vaccine deployment strategy for India. Indian Public Policy Review, Vol 1 No 2, pg 42-58 - https://ippr.in/index.php/ippr/article/view/20/11

You can follow Shambhavi Naik on Twitter: @TheNaikMic

You can follow Mihir Mahajan on Twitter: @mihirmahajan

You can follow Pranay Kotasthane on Twitter: @pranaykotas

You can listen to this show and other awesome shows on the IVM Podcasts app on Android: https://ivm.today/android or iOS: https://ivm.today/ios, or any other podcast app

See omnystudio.com/listener for privacy information.

As urgent requests for convalescent plasma, Remdesivir and Tocilizumab increase, Ruturaj Gowaikar and Shambhavi Naik discuss the application of these therapeutics and the unnecessary shortage caused by poor public engagement over their utility.

If these policy conversations interest you, consider applying for Takshashila's Graduate Certificate in Public Policy. Applications for the monsoon cohort close soon. You can check out our courses here - www.takshashila.org.in/courses

You can follow Ruturaj Gowaikar on Twitter: @RuturajGowaikar

You can follow Shambhavi Naik on Twitter: @TheNaikMic

You can listen to this show and other awesome shows on the IVM Podcasts app on Android: https://ivm.today/android or iOS: https://ivm.today/ios, or any other podcast app

See omnystudio.com/listener for privacy information.

In this episode, Noopur Raje, MD, answers audience questions from a live CCO Webinar focused on emerging strategies in the use of CAR T-cell therapy for patients with multiple myeloma and key toxicities associated with CAR T-cell therapy, with questions including:

• Now that belantamab mafodotin is approved for relapsed/refractory multiple myeloma, what are your thoughts on how BCMA-directed CAR T-cell therapy might be sequenced? Is there reason to think CAR T-cell therapy would still be efficacious following belantamab mafodotin?
• Could BCMA-directed CAR T-cell therapy replace transplant in the first-line setting for multiple myeloma?
• What are key considerations surrounding the use of tocilizumab for managing cytokine-release syndrome?
• What are some of the longer-term toxicities associated with CAR T-cell therapy? When do they emerge and how long do they typically last?

Presenter:

Noopur Raje, MD
Professor of Medicine
Harvard Medical School
Director
Center for Multiple Myeloma
Massachusetts General Hospital Cancer Center
Boston, Massachusetts

Content based on an online CME program supported by educational grants from Bristol-Myers Squibb and Kite Pharma.

Link to full program:
http://bit.ly/3rDeFCV 

In episode 17 of this series, Arthur Kim, MD, provides a brief update on the latest COVID-19 treatment options and guidelines. After the update, Dr. Kim answers questions submitted by healthcare professionals on various aspects of COVID-19.  

Presenter:

Arthur Kim, MD
Associate Professor
Department of Medicine
Harvard Medical School
Director, Viral Hepatitis Clinic
Division of Infectious Diseases
Massachusetts General Hospital
Boston, Massachusetts  

Content based on an online CME program supported by an independent educational grant from Gilead Sciences.

Link to full program:
https://bit.ly/3eDoJF0

Today I am joined by Infectious Disease expert Dr. Emily Spivak to talk about the latest batch of tocilizumab trials for COVID-19 and a meta-analysis of all the convalescent plasma trials.  Check it out!


Tocilizumab in Hospitalized Patients with COVID-19 (COVACTA)
IL-6 Receptor Antagonists in Critically Ill Patients with COVID-19 (REMAP-CAP)
RECOVERY Tocilizumab pre-print
Meta-analysis of Convalescent Plasma for COVID-19










Music from https://filmmusic.io
"Sneaky Snitch" by Kevin MacLeod (https://incompetech.com)
License: CC BY (http://creativecommons.org/licenses/by/4.0/)

WARNING: This episode is long on banter.  If you would like to skip the intro conversation and get right to the articles, skip ahead to 12:13. 

Today we are joined by Dr. Jason Carr, pulmonary-critical care all-star, to talk about how often PE is present in patients with acute COPD exacerbations.  We also review more tocilizumab RCTs because they just keep coming.

Prevalence of Pulmonary Embolism in Acute COPD Exacerbation
STOP-IT COVID trial
RCT-TCZ-COVID-19 trial
CORIMUNO-TOCI-1 trial
REMAP-CAP trial pre-print









Music from https://filmmusic.io
"Sneaky Snitch" by Kevin MacLeod (https://incompetech.com)
License: CC BY (http://creativecommons.org/licenses/by/4.0/)

The president's supporters may have stormed the capitol and attempted a coup today, but the show must go on.  Today I'm joined by Dr. Dani Babbel to talk about treatment of hypertension in the hospital, as well as testing for primary aldosteronism in patients with resistant hypertension.  Check it out! 


Treatment and Outcomes in Inpatient Hypertension
Testing for Primary Aldosteronism and MRA Use Among US Veterans
Tocilizumab in Hospitalized Patients with COVID-19














Music from https://filmmusic.io
"Sneaky Snitch" by Kevin MacLeod (https://incompetech.com)
License: CC BY (http://creativecommons.org/licenses/by/4.0/)

We're back after a prolonged hiatus, ready to break down the latest and greatest in the medical literature.  Today's episode will get you caught up on the newest treatments for COVID-19.  We promise to talk about something else next time :)

If you want to skip all the banter about Baby Yoda and politics, go to 8:36.

Remdesivir for COVID-19 Final Report

Tocilizumab for Hospitalized COVID-19 Patients

Bamlanivimab

Pfizer Vaccine

Moderna Vaccine

Music from https://filmmusic.io
"Sneaky Snitch" by Kevin MacLeod (https://incompetech.com)
License: CC BY (http://creativecommons.org/licenses/by/4.0/)