Mavrilimumab for severe COVID-19
Authors: Adil Rashid Khan, Manish Soneja, Praveen Kumar Tirlangi, Naveet Wig
Journal: The Lancet Rheumatology (2020)

We read with interest the Article by Giacomo De Luca and colleagues1De Luca G Cavalli G Campochiaro C et al.GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study.Lancet Rheumatol. 2020; 2: e465-e473Summary Full Text Full Text PDF PubMed Scopus (159) Google Scholar in The Lancet Rheumatology, in which the authors showed that mavrilimumab treatment was associated with improved clinical outcomes compared with standard care in non-mechanically ventilated patients with severe COVID-19 pneumonia and systemic hyperinflammation. However, we would like to highlight important limitations of the study First, the authors used arbitrary cut-off points in continuous variables (serum C-reactive protein, ferritin, and lactate dehydrogenase) for selecting patients with hyperinflammation.2Dawson NV Weiss R Dichotomizing continuous variables in statistical analysis: a practice to avoid.Med Decis Making. 2012; 32: 225-226Crossref PubMed Scopus (130) Google Scholar Such cut-offs were not derived from or validated in any predictive or prognostic studies in patients with COVID-19 that we are aware of.3Wynants L Van Calster B Collins GS et al.Prediction models for diagnosis and prognosis of COVID-19 infection: systematic review and critical appraisal.BMJ. 2020; 369m1328Crossref PubMed Scopus (1904) Google Scholar Second, the authors have not provided any confidence limits for their test statistics, which hinders us from drawing any conclusions from the study (given the lack of analysing uncertainty in effect estimates). Third, the median duration of illness or fever was shorter in the control group than in the intervention group despite similar inflammatory markers and respiratory support in each group, suggesting that patients in the control group were in a more advanced stage of illness. Finally, median IL-6 concentrations in both groups were substantially lower than those seen in patients even with the so-called hypoinflammatory phenotype of non-COVID-19 acute respiratory distress syndrome,4Calfee CS Delucchi KL Sinha P et al.Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial.Lancet Respir Med. 2018; 6: 691-698Summary Full Text Full Text PDF PubMed Scopus (422) Google Scholar thereby casting doubt on whether IL-6 (and granulocyte–macrophage colony-stimulating factor as an upstream molecule) is the main driver of inflammation in COVID-19, and whether in future we should be more cautious when using further immunomodulation in this patient population, targeting single cytokines.4Calfee CS Delucchi KL Sinha P et al.Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial.Lancet Respir Med. 2018; 6: 691-698Summary Full Text Full Text PDF PubMed Scopus (422) Google Scholar We declare no competing interests. Mavrilimumab for severe COVID-19 – Authors' replyWe thank Mohamad Amin Pourhoseingholi and colleagues and Manish Soneja and colleagues for their interest in our Article.1 As we stated in our manuscript, we agree that the small number of enrolled patients does not allow us to draw definitive conclusions on the effect of mavrilimumab on mortality in patients with COVID-19, and that randomised controlled trials are needed to unequivocally assess the efficacy and safety of this therapeutic strategy. However, we feel that the clinical data on clinical improvement emerging even in our small cohort support the strength of our results. Full-Text PDF GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort studyMavrilimumab treatment was associated with improved clinical outcomes compared with standard care in non-mechanically ventilated patients with severe COVID-19 pneumonia and systemic hyperinflammation. Treatment was well tolerated. Confirmation of efficacy requires controlled testing. Full-Text PDF Mavrilimumab for severe COVID-19In The Lancet Rheumatology, Giacomo De Luca and colleagues1 examined whether mavrilimumab added to standard care could improve the clinical outcomes in patients with COVID-19 pneumonia and systemic hyperinflammation in a single-centre prospective cohort study. They compared 13 patients treated with mavrilimumab to 26 patients who received standard care. The analysis showed earlier clinical improvement in the intervention group than in the control group. However, the power of study was low due to the small sample size, and no statistical difference in mortality was found between the two groups (no patients died in the mavrilimumab group vs seven [27%] patients in the control group; p=0·086). Full-Text PDF