Tocilizumab photo
This webpage is focused on tocilizumab for COVID-19.
KEY POINTS
- Tocilizumab (Actemra) is a humanized monoclonal antibody targeting IL-6R and it inhibits binding of IL-6 to its receptors while not blocking the signaling of other IL-6 family cytokines
- Tocilizumab holds FDA approvals for rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and systemic juvenile idiopathic arthritis.
- Tocilizuamab is not FDA-approved for COVID-19, but an FDA Emergency Use Authorization (EUA) for tocilizumab for COVID-19 was released on 24 June 2021.
- So called “cytokine storm” has been associated with severe COVID-19 disease and it is hypothesized tocilizumab may help avert it
- Is a “Cytokine Storm” Relevant to COVID-19?
- Comparative Survival Analysis of Immunomodulatory Therapy for COVID-19 ‘Cytokine Storm’
- COVID-19: consider cytokine storm syndromes and immunosuppression
- Provides the H-score, which may be helpful in determining if tocilizumab is a potential option
- Cytokine Levels in Critically Ill Patients With COVID-19 and Other Conditions
- So called “cytokine storm” has been associated with severe COVID-19 disease and it is hypothesized tocilizumab may help avert it
- Tocilizumab carries a boxed warning for serious infections leading to hospitalization or death including tuberculosis (TB), bacterial, invasive fungal, viral, and other opportunistic infections
- Secondary infections in hospitalized patients with severe COVID-19 is a major concern
- There is much debate about when (and if) to give tocilizumab for COVID-19
- Giving it too early may unnecessarily predispose people to risk of infection without providing a benefit
- Giving it too late may not augment the COVID-19 inflammatory process as hoped
- Some experts have proposed that the effect of tocilizumab may be determined by patient-specific factors, much interest exists in using various markers to determine when to give tocilizumab (as well as who to give it to)
- There is no consensus on what dose (if any) of tocilizumab should be used for COVID-19
- Some strategies have been to give a single dose, while others have been to give up to two doses
- Tocilizumab is available in multiple in 80mg, 200mg, and 400mg vials
- The REMAP-CAP and RECOVERY trials have found positive benefits of tocilizumab for COVID-19 and in February 2021 various guidelines are making updates to reflect this
- Tocilizumab is expensive and not widely available
RESOURCES/ LITERATURE
- Tocilizumab (Actemra) Package Insert
- COVID-19 NIH Guidelines (a go-to resource for all COVID-19 therapies)
- Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19
- Interventional & Observational Studies / Reports:
- Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia – COVACTA in NEJM
- Editorial commentary: Interleukin-6 Receptor Inhibition in Covid-19 — Cooling the Inflammatory Soup
- Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19 – REMAP-CAP in NEJM
- Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial – LANCET
- Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): preliminary results of a randomised, controlled, open-label, platform trial – PREPRINT
- Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial
- In patients with severe or critical covid-19, tocilizumab plus standard care was not superior to standard care alone in improving clinical outcomes at 15 days, and it might increase mortality.
- REMAP-CAP Website
- REMAP-CAP Pre-Print Sudy
- UK Interim Position Statement: Interleukin-6 inhibitors (tocilizumab or sarilumab) for patients admitted to ICU with COVID-19 pneumonia (adults)
- Provides recommended inclusion/ exclusion criteria based upon REMAP-CAP
- Impact of Interleukin-6 receptor blockade with Tocilizumab on Cardiac Injury in Patients with COVID-19: a retrospective cohort study
- Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19 – Preliminary report (pre-print)
- Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia
- In hospitalized patients with Covid-19 pneumonia who were not receiving mechanical ventilation, tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, but it did not improve survival.
- Efficacy of Tocilizumab in Patients Hospitalized with Covid-19
- Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide.
- Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia: Randomized Clinical Trial
- The administration of tocilizumab in patients with COVID-19 pneumonia and a Pao2/Fio2 ratio between 200 and 300 mm Hg did not reduce the risk of clinical worsening; further blinded, placebo-controlled randomized clinical trials are needed to confirm the results and to evaluate possible applications of tocilizumab in different stages of the disease.
- Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia A Randomized Clinical Trial
- Tocilizumab may reduce the need for mechanical and noninvasive ventilation or death by day 14 but not mortality by day 28; further studies are necessary to confirm these preliminary results.
- Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19
- These findings suggest that among critically ill patients with COVID-19, early treatment with tocilizumab may reduce mortality, although the findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed.
- Decreased mortality in COVID-19 patients treated with Tocilizumab: a rapid systematic review and meta-analysis of observational studies
- Results showed that mortality was 12% lower for COVID-19 patients treated with tocilizumab compared to COVID-19 patients who were not treated with tocilizumab. The number needed to treat was 11, suggesting that for every 11 (severe) COVID-19 patients treated with tocilizumab 1 death is prevented. These results require confirmation by randomized controlled trials.
- These conclusions should be interpreted with caution
- Results showed that mortality was 12% lower for COVID-19 patients treated with tocilizumab compared to COVID-19 patients who were not treated with tocilizumab. The number needed to treat was 11, suggesting that for every 11 (severe) COVID-19 patients treated with tocilizumab 1 death is prevented. These results require confirmation by randomized controlled trials.
- Roche’s phase III EMPACTA study showed Actemra/RoActemra reduced the likelihood of needing mechanical ventilation in hospitalised patients with COVID-19 associated pneumonia
- Tocilizumab for severe COVID‐19 in solid organ transplant recipients: a matched case‐control study
- In this matched control cohort study, tocilizumab appeared to be safe but was not associated with decreased 90‐day mortality.
- Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study
- In this observational study, patients with COVID-19 requiring ICU support who received tocilizumab had reduced mortality. Results of ongoing randomised controlled trials are awaited.
- Tocilizumab for treatment of mechanically ventilated patients with COVID-19
- Early combination of Tocilizumab and Corticosteroids: An upgrade in anti-inflammatory therapy for severe COVID
- The Combination of Tocilizumab and Methylprednisolone Along With Initial Lung Recruitment Strategy in Coronavirus Disease 2019 Patients Requiring Mechanical Ventilation: A Series of 21 Consecutive Cases
- Tocilizumab in patients with severe COVID-19: a retrospective cohort study
- Compassionate Use of Tocilizumab for Treatment of SARS-CoV-2 Pneumonia
- Tocilizumab treatment for Cytokine Release Syndrome in hospitalized COVID-19 patients: survival and clinical outcomes
- No comparator group, but includes a cohort of 239 patients
- Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia
- Describes outcomes for 62 hospitalized patients with COVID-19 that received tocilizumab, finding it had a positive impact if used early during COVID-19 pneumonia with severe respiratory syndrome in terms of increased survival and favorable clinical course.
- Tocilizumab treatment in COVID‐19: a single center experience
- Reports on 15 patients who received tocilizumab
- Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia – COVACTA in NEJM
- Commentaries:
- It is time to determine Tocilizumab place in COVID-19 – CID
- Tocilizumab in COVID-19: Give it time!
- Time to Reassess Tocilizumab’s Role in COVID-19 Pneumonia
- Newly released randomized trials suggest a potential role for tocilizumab in COVID-19 but do not show clear evidence of efficacy, in contrast to observational studies. Their findings do not support the routine use of tocilizumab for COVID-19 in most settings.
- Tocilizumab versus the covid19 tempest: all’s well that ends well or much ado about nothing?
- Efficacy of Tocilizumab for treatment of severe COVID-19 Pneumonia: more evidence is needed
- Therapy of Sars-Coronavirus-2 pneumonia: is there an optimal IL-6 cut-off for successful tocilizumab treatment?
- COVID-19: Clean up on IL-6
- To Toci or Not to Toci for COVID-19: Is That Still the Question?
- Is a “Cytokine Storm” Relevant to COVID-19?
- The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality
- Reviews the potential benefit of toccilizumab for COVID-19
- Media Releases:
- Roche’s phase III EMPACTA study showed Actemra/RoActemra reduced the likelihood of needing mechanical ventilation in hospitalised patients with COVID-19 associated pneumonia
- Roche provides an update on the phase III COVACTA trial of Actemra/RoActemra in hospitalised patients with severe COVID-19 associated pneumonia
- COVACTA trial did not meet its primary endpoint of improved clinical status in patients with COVID-19 associated pneumonia, or the key secondary endpoint of reduced patient mortality
- COVACTA pre-print is here
- Other:
- Cost-effectiveness of tocilizumab in severe COVID-19: to see or not to see – CID
- Fixed dosing of tocilizumab in ICU admitted COVID-19 patients is a superior choice compared to bodyweight based dosing; an observational population pharmacokinetic and pharmacodynamic study – Pre-Print
The first 12 months of COVID-19: a timeline of immunological insights - Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Provisional 7th Edition) states:
- For patients with extensive and bilateral lung disease and severely ill patients with elevated IL-6 levels, treatment with tocilizumab may be attempted
- The initial dose should be 4-8mg/kg, with the recommended dosage being 400mg
- Dilute with 0.9% saline to 100ml and infuse over the course of more than 1 hour
- Repeat once after 12 hours (same dosage) if the response to the first dose was poor, mximum two cumulative doses
- Single maximum dose is 800mg
- Pay attention to allergic reactions
- Prohibited in patients with active infections such as tuberculosis
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