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Anti-IL6.pptx
1. Ministry of Health and
Population
8 December 2020
Role of Anti-IL6 in COVID-
19
Prepared By: Ahmad Said
Lecturer of critical care medicine, Cairo University
Member of Egyptian Scientific Committee of COVID-19
3. Cytokine Storm
Cytokine storm is an umbrella term encompassing
several disorders of immune dysregulation
characterized by constitutional symptoms, systemic
inflammation, and multiorgan dysfunction that can
lead to multiorgan failure if inadequately treated.
The onset and duration of cytokine storm vary,
depending on the cause and treatments administered.
5. Cytokine Storm
The general treatment strategy for cytokine storm
involves supportive care to maintain critical organ
function, control of the underlying disease
and elimination of triggers for abnormal immune
system activation, and targeted immunomodulation
to limit the collateral damage of the activated
immune system.
7. Efficacy and Safety of IL-6 Blockade
Tocilizumab is a recombinant humanised monoclonal
antibody that inhibits both membrane bound and
soluble interleukin-6 (IL-6) receptors.
IL-6 is a pro-inflammatory cytokine that is a key driver
behind the cytokine-release syndrome seen in patients
with severe COVID-19.
By targeting IL-6 receptors, tocilizumab may mitigate
the cytokine-release syndrome and prevent
progression of disease.
11. COVACTA trial July 2020
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
The study is the first global, randomised, double-blind, placebo-
controlled phase III trial investigating Actemra/RoActemra in this
setting
12. EMPACTA trial September 2020
An update on phase III EMPACTA study showed
Actemra/RoActemra reduced the likelihood of
needing mechanical ventilation in hospitalised
patients with COVID-19 associated pneumonia
16. Patient Selection
Tocilizumab is indicated for severe and Critically ill cases that meet any of
the following criteria :
1- No improvement in Oxygenation in spite of Steroids and Prone position
for 12-24 h.
2- P/F ratio less than 200 in spite of Steroids and Prone position for 12-24
h.
3- Progressive worsening of radiologic findings in spite of Steroids and
Prone position for 12-24 h.
4- Escalating mechanical ventilation parameters in spite of Steroids and
Prone position for 12-24 h.
5- Progressive deterioration of Hemodynamics
6- Elevated Interleukin 6 level ( above 4 fold ULN) (if available)
17. Contraindications
1- Known hypersensitivity to tocilizumab
2- Co-existing active infection that might be worsened by
tocilizumab
3- A baseline ALT or AST more than 5 times the upper limit
of normal (caution is recommended if hepatic enzymes are
more than 1.5 times the upper limit of normal)
4- A baseline platelet count of less than 100000
5- A baseline absolute neutrophil count of less than 2000
19. Dosage
Recommended dose
4 – 8 mg/kg/day for 2 doses 12 to 24 hr apart
after failure of steroid therapy and prone position to
improve the case for 24 hr
20. Dosage Adjustment
Renal Impairment
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: has not been studied
Hepatic Impairment
There are no dosage adjustments provided in the
manufacturer's labeling
Initiation of therapy in patients with active hepatic disease or
hepatic impairment with baseline ALT or AST > 5 × ULN is not
recommended.
21. Warnings/Precautions
Risk of serious infections:
Patients treated with tocilizumab are at
an increased risk for developing serious infections that
may lead to hospitalization or death.
We must exclude active infection before initiation of
Tocilizumab by measuring inflammatory parameters
especially Procalcitonine.
22. Warnings/Precautions
Hematologic effects:
1- Neutropenia and thrombocytopenia may occur.
2- Monitoring of neutrophils and platelets is
mandatory.
3- Do not initiate treatment in patients with with an
ANC <2,000/mm3 or platelet count <100,000/mm3
4- Discontinue treatment for ANC<500/mm3 or
platelet count <50,000/mm3
23. Considerations in Pregnancy
There are insufficient data to determine whether there
is a drug-associated risk for major birth defects or
miscarriage.
Monoclonal antibodies are actively transported across
the placenta as pregnancy progresses (with greatest
transfer during the third trimester) and may affect
immune responses in utero in the exposed fetus.
24. Take Home message
Anti-IL6 medications may play beneficial role in the
management of severe and critically ill COVID-19
patients
Timing of administration and good patient selection
are crucial to achieve good therapeutic response
Exclusion of active infection is mandatory before
institution of Anti-IL6.
