CTAG: Immune-modulating agents

Download the Position Statement

(V8.0 22 January 2021)

Key messages

  • 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:

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.


Date publishedVersionAmendment
22 April 20201.0Download PDFNew document
07 May 20201.1Download PDFUpdated evidence summaries in Appendix 1
01 June 20202.0Download PDFUpdated tables of trials and evidence summaries to include new proposed investigational products
16 June 20202.1Download PDFUpdated 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 20203.0Download PDFIncluded information on dexamethasone following the CMOs letter reporting on preliminary positive results from the RECOVERY trial
10 August 20204.0Download PDFUpdated 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 20205.0Download PDFUpdated 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 20206.0 Download PDFUpdated 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 20207.0 Download PDFData for all immunomodulatory medicines correct to 17 December 2020