(V8.0 22 January 2021)
- A subset of patients with COVID-19 may experience an exaggerated hyperinflammatory response
- COVID-19 associated hyperinflammation predominantly involves the lung however may progress to secondary haemophagocytic lymphohistocytosis (sHLH) which is a systemic and multi-organ condition with significant morbidity and mortality
- CTAG strongly recommends systemic corticosteroids for patients who fit definitions of WHO-defined severe or critical COVID-19, or in patients who otherwise have a new oxygen requirement
- CTAG also recommends not to use corticosteroid therapy in patients with WHO-defined non-severe COVID-19 (i.e. the absence of any signs of severe or critical COVID-19).
- As far as possible, the use of investigative immunomodulatory medicines should be used in the context of a national priority clinical trial. This includes patients treated with remdesivir +/- corticosteroids
- CTAG recommend the continued randomisation of patients to IL-6 blockade trials in keeping with the advice from the CMO. Where patients clearly fit into the inclusion criteria of REMAP-CAP CTAG supports the use of off label IL-6 blockade. CTAG acknowledges the results of the REMAP-CAP preprint demonstrating a mortality benefit and reduced length of stay on ICU. However CTAG also acknowledges that the totality of the data, whilst heterogeneous, still does not identify use of IL-6 blockade as beneficial in general (or which subgroups of patients would benefit most), and therefore where there is equipoise CTAG recommends enrolment into trials.
- Clinicians who use IL-6 inhibitors should recognise its potentially longer term immunosuppressive effects, as well as their prolonged effects on directly suppressing CRP. Upon discharge, clinicians should inform other healthcare professionals involved in the ongoing management of the patient that an IL-6 inhibitor was administered.
- Clinicians using IL-6 inhibitors off label are encouraged to submit data on these patients through the ISARIC 4C protocols and case report forms available at https://isaric4c.net/protocols/ to provide information on real world outcomes.
- Patients who meet diagnostic criteria for sHLH should be managed within established pathways, guided by a specialist familiar with hyperinflammation
- IVIG for PIMS-TS should ideally be used within the context of the RECOVERY clinical trial
- Advice on the appropriate use of remdesivir is available at https://www.ctag-support.org.uk/antivirals
- Suspected side effects to medicines used in coronavirus treatment should be reported via the Yellow Card COVID-19 reporting site: https://coronavirus-yellowcard.mhra.gov.uk
CTAG acts as a formal advisory group to the Royal College of Physicians and this position statement is endorsed by:
- British Infection association
- British Pharmacological Society
- UK Clinical Pharmacy Association – Pharmacy Infection Network
The CTAG Immunomodulators subgroup takes its membership from HLH Across Specialities Collaboration (HASC) a group already formed for management and research of HLH and have expanded remit to include hyper-inflammation associated with COVID-19.
|22 April 2020||1.0||New document|
|07 May 2020||1.1||Updated evidence summaries in Appendix 1|
|01 June 2020||2.0||Updated tables of trials and evidence summaries to include new proposed investigational products|
|16 June 2020||2.1||Updated Table 1, Table 2 and Appendix 1 in line with new available trials, investigational medicines and confirmation where access to remdesivir EAMS is permitted prior to or during trial. Added mechanism of action to Table A1|
|30 June 2020||3.0||Included information on dexamethasone following the CMOs letter reporting on preliminary positive results from the RECOVERY trial|
|10 August 2020||4.0||Updated information for open trials and new emerging evidence|
Evidence tables method updated; tables split into those where benefit may exceed risk and where there is inadequate data to recommend use
|15 October 2020||5.0||Updated to include new evidence and guidance on corticosteroids from WHO and letter from the CMO office. Additional advice from CTAG to consider dexamethasone in patients with a new oxygen requirement|
|30 November 2020||6.0||Updated to provide supporting information on recent REMAP-CAP press release and subsequent NHS England position statement. Evidence table updated with RCT data from tocilizumab trials.|
Changes made to streamline position statement by removing introduction and signposting to clinical trials. Information on steroid use in pregnancy updated
|17 December 2020||7.0||Data for all immunomodulatory medicines correct to 17 December 2020|