Search

Background: Tocilizumab and baricitinib are considered standard treatments for hospitalized COVID-19 patients with an inflammatory status. However, the effects of co-administering these medications aiming for more rapid patient recovery are controversial among practitioners. The potential benefits include the rapid improvement of patients and regulation of the immune system, and the potential risks include the increased chance of serious adverse events, including infections. This study aimed to investigate the effects of co-administering these two medications on the 28-day mortality rate, other efficacy parameters, and safety issues. Methods: In this randomized open-label trial, 68 patients were recruited. The study was conducted at Dr. Masih Daneshvari Hospital during 6 months (from 21 March 2022 to 23 August 2022). Severely ill patients aged between 18 and 100 years old with confirmed COVID-19 were enrolled. The primary outcomes included the need for invasive mechanical ventilation and a 28-day mortality rate. Secondary outcomes included the need for non-invasive mechanical ventilation, the need for admission to the intensive care unit (ICU), the length of hospital stay, and the need for a second dose of tocilizumab. Safety assessments were also performed for 28 days. The data were collected from the patients' medical records, which included age, gender, and comorbidities. Results: The 28-day mortality rate or the need for mechanical ventilation was not statistically different among the two groups (p-value = 0.49 for both outcomes). The need for non-invasive mechanical ventilation, the need for admission to the ICU, or the need for a second dose of tocilizumab and the length of hospital stay was not affected either (p-value = 1; 0.1; 0.49 and 0.9, respectively). One patient developed thrombosis in the combination group. No adverse events related to infectious complications were recorded in any groups. Conclusion: This study showed no beneficial effects of combining tocilizumab and baricitinib in managing severe COVID-19 cases. However, the need for ICU admission was meaningfully lower in the combination group. Studies with larger sample sizes are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Background: Tocilizumab has shown promising effects in the management of coronavirus disease 2019 (COVID‑19) patients. Nebulized tocilizumab might reduce this inflammation while also reducing the potential side effects of systemic administration, including infectious complications. This study aimed to compare the efficacy of tocilizumab in the management of COVID‑19 in two administration routes(intravenous versus nebulization). Methods: The study was a randomized, outcome assessor-blinded clinical trial performed on 101 patients. For the 1st 72 h after their admission, all patients received dexamethasone and remdesivir. Any patients who did not respond to treatment after 2 days received 400 mg intravenous tocilizumab on day 3. Patients who were eligible for receiving the second dose of tocilizumab were randomized into two groups. Group one received the second dose of tocilizumab 400 mg 12 h later through the intravenous route, while the patients in group two received a total of 400‑mg tocilizumab through nebulization of 5 cc every 6 h after the first intravenous dose. The primary outcomes were the need for ventilation and admission in the intensive care unit, as well as the mortality rate. Reults: There was no significant difference between the two groups in terms of mortality rate, the need for mechanical ventilation, the length of hospital stay, lung radiologic changes, or laboratory values. The need for noninvasive mechanical ventilation was lower in the nebulized tocilizumab group than in the intravenous tocilizumab group (P = 0.05). Conclusion: Administration of tocilizumab through nebulization may have the same beneficial effects with less potential side effects than intravenous tocilizumab. [ABSTRACT FROM AUTHOR]

Currently published papers and clinical guidelines regarding the effects of tocilizumab in severe and critical COVID-19 are contradictory. The aim of this meta-analysis was to combine the results of clinical studies of different designs to investigate the efficacy and safety of tocilizumab in severely-to-critically ill COVID-19 patients. A systematic search was performed in PubMed, Embase, CENTRAL, ClinicalTrials.gov, Scopus, and preprint servers up to 26 December 2020. Since a substantial heterogeneity was expected, a random-effects model was applied to calculate the pooled effect size (ES) and 95% confidence interval (CI) for each study outcome. Forty-five comparative studies involving 13,189 patients and 28 single-arm studies involving 1,770 patients were analyzed. The risk of mortality (RR of 0.76 [95%CI 0.65 to 0.89], P < 0.01) and intubation (RR of 0.48 [95%CI 0.24 to 0.97], P = 0.04) were lower in tocilizumab patients compared with controls. We did not find any significant difference in secondary infections, length of hospital stay, hospital discharge before day 14, and ICU admission between groups. Tocilizumab can improve clinical outcomes and reduce mortality rates in severe to critical COVID-19 patients. Large-scale randomized controlled trials are still required to improve the statistical power of meta-analysis. [ABSTRACT FROM AUTHOR]

• The pathophysiology of SARS-CoV-2 infection may be attributed to cytokine release syndrome. • In this syndrome, interleukin 6 is released after the activation of the inflammatory cascade. • The mortality rate in the current study was 16%. • Tocilizumab may be a promising agent to decrease the mortality rate in severe or critical SARS-CoV-2 infection. The clinical presentation of SARS-CoV-2 infection ranges from mild symptoms to severe complications, including acute respiratory distress syndrome. In this syndrome, inflammatory cytokines are released after activation of the inflammatory cascade, with the predominant role of interleukin (IL)-6. The aim of this study was to evaluate the effects of tocilizumab, as an IL-6 antagonist, in patients with severe or critical SARS-CoV-2 infection. In this prospective clinical trial, 76 patients with severe or critical SARS-CoV-2 infection were evaluated for eligibility, and ultimately, 42 patients were included. Tocilizumab was administered at a dose of 400 mg as a single dose via intravenous infusion. Primary outcomes included changes in oxygenation support, need for invasive mechanical ventilation, and death. Secondary outcomes included radiological changes in the lungs, IL-6 plasma levels, C-reactive protein levels, and adverse drug reactions. The data were analyzed using SPSS software. Of the 42 included patients, 20 (48%) patients presented the severe infection stage and 22 (52%) were in the critical stage. The median age of patients was 56 years, and the median IL-6 level was 28.55 pg/mL. After tocilizumab administration, only 6 patients (14%) required invasive ventilation. Additionally, 35 patients (83.33%) showed clinical improvement. By day 28, a total of 7 patients died (6 patients in the critical stage and 1 patient in the severe stage). Neurological adverse effects were observed in 3 patients. Based on the current results, tocilizumab may be a promising agent for patients with severe or critical SARS-CoV-2 infection, if promptly initiated during the severe stage. [ABSTRACT FROM AUTHOR]

• Pathophysiological studies have demonstrated the role of inflammatory mediators in COVID-19 pneumonia. • In some COVID-19 cases, especially those with impaired immune function, an uncontrolled immune response that triggers an overproduction of immune cells and their signaling molecules occurs. • Cytokine release syndrome may be the underlying pathophysiology of refractory cases. • Tocilizumab, as an IL-6 antagonist, may have a promising role in the cytokine release syndrome that occurs in COVID-19. • Clinicians should be aware of the precautions and contraindications of tocilizumab. [ABSTRACT FROM AUTHOR]

• Excessive inflammation leads to lung damage in complicated COVID-19 patients. • Tocilizumab, an IL-6 inhibitor, was added to the standard treatment in this study. • Comparably low mortality rate (6.98%) was observed in severe patients. • Benefits of tocilizumab were less considerable in patients with critical disease. • Appropriate timing is important in the administration of tocilizumab for COVID-19. Potential therapeutic approaches in coronavirus disease 2019 (COVID-19) comprise antiviral and immunomodulatory agents; however, no immunomodulator drug has been approved. This multicenter, prospective, open-label, uncontrolled study aimed to assess the use of subcutaneous tocilizumab in adult patients with severe and critical COVID-19. Tocilizumab was added to the standard care of therapy at a dose of 324 mg (<100 kg bodyweight) or 486 mg (≥100 kg bodyweight). The study endpoints were all-cause mortality rate, changes in oxygen-support level, oxygen saturation, body temperature, respiratory rate, and laboratory variables during the study, and drug safety. Of 126 patients enrolled, 86 had severe and 40 had critical disease. Most patients were male (63.49%) and aged below 65 (78.57%). By day 14 of the study, 4.65% (4/86) of severe patients and 50.00% (20/40) of critical patients died. By the end, 6.98% (6/86) of severe patients and 60.00% (24/40) of critical patients died. Outcomes concerning three additional endpoints (oral temperature, oxygen saturation, and respiratory rate) were significantly improved as early as three days after tocilizumab administration in both groups of subjects, more considerably in severe patients. Significant improvement in the required level of oxygenation was reported in severe patients seven days after tocilizumab administration. No tocilizumab-related serious adverse event occurred in this study. Subcutaneous tocilizumab might improve some clinical parameters and reduce the risk of death in COVID-19 patients, particularly if used in the early stages of respiratory failure. [ABSTRACT FROM AUTHOR]