Experts have outlined the most current treatment strategies for immunomodulators in moderate-to-severe and critical COVID-19, updating 12 EULAR ‘points to consider’ on their therapeutic use with the most recent clinical data.

Following a literature review, a multidisciplinary task force including Dr Pedro Machado, a consultant rheumatologist at University College Hospital, concluded that tocilizumab in combination with glucocorticoids “is beneficial in COVID-19 cases requiring oxygen therapy and in critical COVID-19,” and that use of Janus kinase inhibitors (baricitinib and tofacitinib) “is promising in the same populations”.

However, in the paper, published in Annals of the Rheumatic Diseases, the taskforce also said that immunomodulators “failed to consistently demonstrate efficacy on mortality”, while other clinical outcomes at any disease stage, or definitive evidence for biomarker-based stratification was “still lacking”.

“There is currently insufficient evidence to recommend use of other immunomodulatory drugs, including interferon alpha, interferon beta, interferon kappa, interferon lambda, leflunomide, non-SARS CoV-2 IVIg, eculizumab and cyclosporine,” they stressed.

Other PtCs state that in COVID-19 there is “no robust evidence” to support the use of anakinra and canakinumab or low-dose colchicine at any disease stage.

Also, in those patients who are at risk of severe COVID-19, with symptom onset <5 days or still seronegative, doctors should consider administering treatment with monoclonal antibodies against SARS-CoV-2 spike protein. “The combination of bamlanivimab and etesevimab as well as of casirivimab and imdevimab administered within the first week after symptom onset were able to significantly reduce viral load. However, casirivimab and imdevimab were effective only in patients seronegative at baseline,” the authors noted.

According to the taskforce, the updated EULAR ‘points to consider’ (PtCs) “provide relevant and updated guidance on immunomodulatory therapy utilisation from the rheumatology perspective”. They also pave the way for a new model in which the treatment of immunopathology linked with severe and critical acute infections “may benefit from immunomodulatory treatments usually given for autoimmune and inflammatory diseases”.

Acknowledging that the picture is constantly changing with the emergence of new clinical evidence, they also noted that “ongoing studies may unmask the potential application of other therapeutic approaches,” and stressed that “involvement of rheumatologists, as systemic inflammatory diseases experts, should be encouraged in clinical trials of immunomodulatory therapy in COVID-19”.