Combination therapy with tocilizumab and corticosteroids for aged patients with severe COVID-19 pneumonia: a single-center retrospective study

Background The role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear. Methods We conducted a retrospective single-center study including consecutive patients ≥65 years that developed severe COVID-19 between March 3 and May 1, 2020 and were treated with corticosteroids at various doses (methylprednisolone [0.5 mg/Kg/12 hours to 250 mg/24 hours]), either alone (“CS group”) or associated to intravenous tocilizumab (400-600 mg, one to three doses) (“CS-TCZ group”). Primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2-point decrease on a six-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied. Results Overall, 181 and 80 patients were included in the CS and CS-TCZ groups. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.17 – 0.68; P- value = 0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21 – 0.68; P -value = 0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21 – 0.72; P -value = 0.003). Clinical improvement by day +14 was higher in the CS-TCZ group in the IPTW analysis only (OR: 2.26; 95% CI: 1.49 – 3.41; P -value <0.001). The occurrence of secondary infection was similar between both groups. Conclusions The combination of corticosteroids and TCZ was associated with better outcomes among patients ≥65 years with severe COVID-19. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (COVID-19 call COV20/00181) co-financed by European Development Regional Fund A way to achieve Europe. M.F.R. holds a research contract Miguel Servet (CP 18/00073) from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Comite de Investigacion Clinica CEIC Instituto de Investigacion i+12 Hospital Universitario 12 de Octubre Madrid Spain All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Available under request