Hospital in-patient: Tocilizumab for (SARS-COV-2 Infection) (Guidelines)

Warning

NHS Highland Guidance on use of interleukin-6 inhibitors (tocilizumab) for adult hospital in-patients with confirmed SARS-CoV-2 infection

(based on CEM/CMO/2021/016 interim clinical commissioning policy published 12th September 2021 and updated NICE Guideline NG191 published 22 June 2023.

Tocilizumab is a monoclonal antibody that binds to the receptor for IL-6, blocking IL-6 signalling and reducing inflammation. 

In 2022 tocilizumab was licensed to treat SARS-COV-2 infection. It is also licensed for use in rheumatoid arthritis and in patients aged at least 2 years with chimeric antigen receptor (CAR) T-cell induced or life-threatening cytokine release syndrome.

Severe COVID-19 is associated with a hyper-inflammatory state with elevated ESR, C-reactive protein, D-dimers, lactate dehydrogenase, ferritin and increased levels of pro-inflammatory cytokines including IL-1 and IL-6.  There have been published and unpublished (pre-print) case series reports of the successful treatment of COVID-19 patients with IL-6 inhibitors. 

The recommendations in this policy have been taken from NICE Guideline [NG191] COVID-19 rapid guideline – managing COVID-19 (last updated 22 June 2023).

Criteria for use

CRITERIA FOR USING TOCILIZUMAB (INTRAVENOUS)
NB must meet ALL criteria

  • Adults aged 18 or over
  • COVID-19 infection confirmed or suspected using clinical and/or radiological information
  • Admitted for treatment of COVID-19 pneumonia
  • Have not received tocilizumab during this admission
  • Already be receiving steroid as per current recommendations  (dexamethasone or equivalent) unless contra-indicated 
  • AND
    • Hypoxemia with a measured CRP of 75mg/L or more AND oxygen saturation of less than 94% (see local NHS Highland oxygen policy) or on low flow oxygen
  • OR
    • Within 48 hours of commencing additional respiratory support defined as high flow nasal oxygen, continuous positive airway pressure (CPAP) or non-invasive ventilation or invasive ventilation.

Note: therapy with tocilizumab should be considered within 24 hours of meeting the inclusion criteria.

Exclusion criteria

  • Known hypersensitivity to tocilizumab 
  • Administration of another interleukin-6 inhibitor during this admission

 

Cautions

CAUTIONS (from SmPC)

  • Clear evidence of active bacterial, fungal, viral (other than COVID-19) or other infection that might be worsened by IL-6 inhibitor therapy.
  • Baseline ALT or AST levels at 5 times the upper limit of normal.
  • Pre-existing condition or treatment resulting in ongoing immunosuppression
  • Current neutropaenia or thrombocytopaenia

Pregnancy and breast feeding are not contra-indications but tocilizumab should not be used during pregnancy unless clinically necessary.  Follow the Royal College of Obstetrics and Gynaecology guidance on coronavirus (COVID-19) infection and pregnancy.  Women of child-bearing potential should be advised to use effective contraception for 3 months after treatment.

See manufacturer’s summary of product characteristics (tocilizumab)for more information, section 4.6. 

Tocilizumab use in a child should be agreed following MDT discussions with paediatric infection specialists.  

Dosing schedule

Tocilizumab

Dose is 8mg/kg as an intravenous infusion with a maximum dose of 800mg.  A second dose should not be considered due to uncertainty of additional benefit and to maximise available supply.

Use the dosing table below as per RECOVERY trial.  

  • Dilute the required dose in 100mL of sodium chloride 0.9%
  • Give over one hour at the following rate:
    • 10mL/hour for 15 minutes.
    • 130mL/hour for the remaining 45 minutes.

Weight*

Dose

>40 and ≤65 kg

400mg

>65 and ≤90 kg

600mg

>90kg

800mg

*For lower weights, dosing should be 8mg/kg rounded to the nearest 20mg

 

Co-administration with other COVID-19 treatments

There is no interaction expected between tocilizumab  and dexamethasone, hydrocortisone or remdesivir.  For further information, please visit the University of Liverpool COVID-19 Drug Interactions

Safety reporting

Any suspected adverse drug reactions (ADRs) for patients receiving tocilizumab for this indication should be reported directly to the MHRA via the new dedicated COVID-19 Yellow Card reporting site

Handover in hospital and discharge information for GP to be added to the IDL

Tocilizumab can cause immunosuppression that renders patients at risk of bacterial and fungal infections. Low clinical threshold for identification and management of infection must be used.  CRP level may be a less reliable marker of active infection and procalcitonin may be negative. All handovers of clinical care (including between hospitals if patients are transferred, between levels of care and clinical teams within hospitals, and between hospitals and primary care) must explicitly mention that an IL-6 inhibitor has been given and the date of administration. Clinicians must ensure the GP is aware the patient has received an IL-6 inhibitor and provide information to the patient to such effect.

The following standard text should be added to the hospital discharge letter:

**** Your patient received tocilizumab on../../.. Immune function will be suppressed for the next 3 months.  Clinical assessment is required to diagnose and manage infection as inflammatory markers will be unreliable ****

Clinical Outcome reporting

The Deputy Chief Medical Officer recommends that data on all patients with COVID-19 should be captured through the ISARIC 4C Clinical Characterisation Protocol (CCP) case report forms (CRFs), as coordinated by the COVID-19 Clinical Information Network (CO-CIN) (link to forms).

Patient and GP information leaflet

• RoActemra SPC
• RoActemra PIL
Risk materials, including RoActemra (tocilizumab) Patient Card

Abbreviations

Abbreviation  Meaning 
ALT alanine aminotransferase
AST aspartate aminotransferase
CRP C-reactive protein
eGFR estimated glomerular filtration rate
ICU intensive care unit (consultant)
ID  infectious disease (consultant)
IL interleukin
ISARIC 4C UK-wide consortium of doctors and scientists
IV intravenous
LFT liver function test
MHRA Medicines and Healthcare Products Regulatory Agency
NNT  numbers needed to treat
SmPC (manufacturer's) summary of product characteristics
TB tuberculosis

 

Editorial Information

Last reviewed: 29/09/2023

Next review date: 30/09/2026

Author(s): Antimicrobial Management Team .

Version: 3

Approved By: Approved TAMSG of the ATDC

Reviewer name(s): Alison Macdonald Antimicrobial Pharmacist , Dr Alex Cochrane, Infectious Diseases Consultant .

Document Id: COVID099