ABSTRACT
Background and importance Tocilizumab (TCZ) is an immunosuppressor drug, IL-6 inhibitor, indicated for the treatment of rheumatoid arthritis and cytokine release syndrome associated with CAR T cell therapy. It was proposed as a compassionate treatment for severe COVID-19 due to its potential benefit as anticytokine therapy with IL-6 as the target, one of the most relevant cytokines involved in the cytokine storm induced by COVID-19. Aim and objectives The main objective was to evaluate TCZ security and effectiveness in the treatment of COVID-19 pneumonia. Material and methods A retrospective observational study was conducted in patients with COVID-19 pneumonia treated with TCZ from 20 March to 20 May 2020 at a tertiary hospital. Study variables were: age, sex, need for invasive and noninvasive ventilation, intubation days and oxygen therapy. Days in inpatient care, admission to intensive care units (ICU) and time spent there, adverse reactions and deaths were also obtained. Data were recollected from the electronic clinical records. Results Data from 59 COVID-19 patients were collected in this study between March and May 2020. Median age (maxmin) was 62.4 (48-74) years and 76.3% of patients were men. Comorbidities were: hypertension in 37.3%, dyslipidaemia in 20.3% and diabetes in 15.2%. Six patients had asthma and 5 had cardiopathy. 72 hours after TCZ administration, 54.2% of patients had respiratory improvement with a reduced need for oxygen therapy, 32.2% had stabilisation of their condition and 13.6% had worsening of their condition, requiring orotracheal intubation. Seven days after TCZ administration, 44 had clinical improvement with a reduced need for oxygen therapy, 6 remained stable with VNI and 9 had worsening of their condition (6 passed out, 3 were admitted to the ICU). TCZ was well tolerated with no adverse effects detected. 28 days after TCZ administration, mortality was 15.2%, 69.6% were discharged and 15.2% remained in hospital at the end of the study. Conclusion and relevance The results of the study showed that TCZ was effective and safe in patients with COVID-19 pneumonia. Patient outcomes were favourable in most cases. During admission, patients showed clinical improvement with a reduced need for invasive ventilation and oxygen therapy. Due to the potential bias (patients received different treatments before and after TCZ) and the small sample size, it is necessary to confirm these results in controlled clinical trials.
ABSTRACT
Background and importance Tocilizumab (TCZ) is an immunosuppressor drug, IL-6 inhibitor, indicated for the treatment of rheumatoid arthritis and cytokine release syndrome associated with CAR T cell therapy. It was proposed as a compassionate treatment for severe COVID-19 due to its potential benefit as anticytokine therapy with IL-6 as the target, one of the most relevant cytokines involved in the cytokine storm induced by COVID-19. Aim and objectives The main objective was to evaluate TCZ effectiveness in the modification of inflammatory parameters in severe COVID-19 patients. Material and methods A retrospective observational study was conducted in 46 patients with COVID-19 admitted to an intensive care unit (ICU) and treated with TCZ from 20 March to 20 May 2020 at a tertiary hospital. Variables analysed were: age, sex, levels of IL-6, C reactive protein (CRP), ferritin, lymphocytes count and D-dimer on days 0, 1, 3, 7 and 14 after TCZ administration. Days in the ICU, deaths and patient outcomes were also obtained. Results Median age was 64 years and 67.4% of patients were men. IL-6 levels on day 0 were 293 pg/mL, peaking at 416 pg/mL on day 3 and decreasing to 241.9 pg/mL on day 7. CRP levels increased above the normal range (median 53.35 mg/L on day 0) in all patients before initiation of therapy with TCZ and decreased on day 7 (median 3 mg/L). Serum ferritin decreased from 1798 mg/L on day 1 to 1197.5 mg/L on day 7 before TCZ. Lymphocyte count increased from 570 to 1365 lymphocytes/mL on day 7. D-dimer level on day 0 was 2008 ng/mL and increased to 3910 ng/mL on day 7 and decreased to 1723 ng/mL on day 14. Length in ICU stay was 16.4 days compared with the mean stay of the total number of ICU COVID patients, which was 26.1 days. Mortality was 19.6%, 15.2% remained in hospital at the end of the study and 65.2% were discharged. Conclusion and relevance The results showed an improvement in inflammatory markers with TCZ treatment, as well as a decrease in length of stay in the ICU, similar to findings reported in the literature. Nevertheless, because of potential bias due to patients receiving different treatments before and after TCZ and the small sample size, it is necessary to confirm these results in controlled clinical studies.
ABSTRACT
Background and importance Baricitinib is an immunosuppressive agent included as one of the therapeutic options for COVID-19 in the Spanish protocol Agencia Española del Medicamento y Productos Sanitarios. Aim and objectives The objective was to assess the effectiveness of this drug in hospitalised but non-critically ill patients. Material and methods An observational retrospective study was conducted in a third level hospital from 26 March to 5 May. Inclusion criteria were: hospitalised patients diagnosed with COVID-19 pneumonia and treated with baricitinib. Data collected were: age, gender, comorbidities, severe pneumonia diagnosis, ferritin and interleukin 6 (IL-6) prior to the beginning of treatment with baricitinib, standard of care according to the hospital's protocol, concomitant treatment with anakinra, duration of treatment with baricitinib, average hospital stay (AHS), deaths and hospital discharges. The data were collected from the electronic medical records and the hospital's management department. Results 171 patients treated with baricitinib were included, with an average age of 69.5 (34-96) years. 71.3% (122) were men. 87.1% (149) had comorbidities and 73.1% (125) were diagnosed with a severe pneumonia, with 25% of them dying (31). Median duration of treatment with baricitinib was 5 days (1- 12). AHS for the baricitinib group was 14.60 (3-47) days, and AHS for the whole sample of patients diagnosed with COVID- 19 pneumonia was 17.2 days. 23.4% (40) of patients had high levels of ferritin (>2500 UI/L). Among them, 87.5% (35) were discharged and 12.5% (5) died. IL-6 levels were high (>40 U/ L) in 29.8% (51) of patients, <40 U/L in 37.4% (64) and not measured in 32.7% (56). In the group with high IL-6 levels, 70.6% (36) were discharged and 29.4% (15) died. Among those with normal levels of IL-6, 93.8% (60) were discharged and 6.3% (4) died. 84.2% (144) of baricitinib patients were also treated with the SoC. During the hospital stay, 31.0% (53) of patients were treated with anakinra and baricitinib, 83.0% (44) were discharged and 17.0% (9) died. Global mortality of the whole sample of patients diagnosed with COVID-19 pneumonia was 18.1% (31). Conclusion and relevance AHS for baricitinib patients was shorter than for the whole sample of COVID-19 patients. The percentage of patients with high levels of IL-6 was superior to that of patients with high ferritin, with mortality greater in patients with IL-6 >40 UI/L. Hence IL-6 level appears to be a better prognostic factor of mortality than ferritin. This could also be related to a greater patient's immune response. Regarding treatment effectiveness, mortality of patients who were treated with SoC plus baricitinib was similar to that of patients treated with anakinra plus baricitinib.