Infliximab in the treatment of patients with severe COVID-19 (INFLIXCOVID): protocol for a randomised, controlled, multicentre, open-label phase II clinical study

Abstract

Background Despite the intense global research endeavour to improve the treatment of patients with COVID-19, the current therapy remains insufficient, resulting in persisting high mortality. Severe cases are characterised by a systemic inflammatory reaction driven by the release of pro-inflammatory cytokines such as IL-6 and tumour-necrosis-factor alpha (TNF-α). TNF-α-blocking therapies have proved beneficial in patients with chronic inflammatory diseases and could therefore pose a new treatment option in COVID-19. Hitherto, no results from randomised controlled trials assessing the effectiveness and safety of infliximab—a monoclonal antibody targeting TNF-α—in the treatment of COVID-19 have been published. Methods In this phase-2 clinical trial, patients with COVID-19 and clinical and laboratory signs of hyperinflammation will be randomised to receive either one dose of infliximab (5 mg/kg body weight) in addition to the standard of care or the standard of care alone. The primary endpoint is the difference in 28-day mortality. Further assessments concern the safety of infliximab therapy in COVID-19 and the influence of infliximab on morbidity and the course of the disease. For the supplementary scientific programme, blood and urine samples are collected to assess concomitant molecular changes. The Ethics Committee of the Friedrich Schiller University Jena (2021-2236-AMG-ff) and the Paul-Ehrlich-Institute (4513/01) approved the study. Discussion The results of this study could influence the therapy of patients with COVID-19 and affect the course of the disease worldwide, as infliximab is globally available and approved by several international drug agencies. Trial registration The trial was registered at clinicaltrials.gov (NCT04922827, 11 June 2021) and at EudraCT (2021-002098-25, 19 May 2021).

SARS-CoV-2 Infection and Outcomes in Children with Inflammatory Bowel Diseases: A Systematic Review

“…All the above conclusions are drawn from the meta-analysis of Tripathi et al [ 25 ] in adult patients with IBD and COVID-19, suggesting that the use of biologics leads to a favorable outcome due to reduction of cytokine storm. In line with this finding, a very recent protocol for a phase-2 randomized controlled trial for testing the efficacy and safety of infliximab in treating COVID-19 has been published [ 30 ].…”

Delayed cutaneous hypersensitivity reactions following the use of infliximab or adalimumab in patients with coronavirus disease 2019

“…Data revealed that infliximab‐related delayed cutaneous hypersensitivity accounted for 83.33% in 0–30 days and 16.67% in 180–210 days, and adalimumab‐related delayed cutaneous hypersensitivity accounted for 31.82% in 0–30 days, and the others were evenly reported in the remaining stages, with a median of 166.5 days (interquartile range [IQR]: 18–889.5). Adalimumab at 40 mg was given as a single subcutaneous injection 19 and infliximab at 5/mg/kg body weight was given as a single subcutaneous injection according to the usual regimen of drug treatment 20 . Notably, delayed cutaneous hypersensitivity may occur after the first infliximab dosage for COVID‐19 treatment, whereas adalimumab showed a small peak after the first dose and more extensive distribution, which may be related to the different drug structure.…”

“…Adalimumab at 40 mg was given as a single subcutaneous injection 19 and infliximab at 5/mg/kg body weight was given as a single subcutaneous injection according to the usual regimen of drug treatment. 20 Notably, delayed cutaneous hypersensitivity may occur after the first infliximab dosage for COVID‐19 treatment, whereas adalimumab showed a small peak after the first dose and more extensive distribution, which may be related to the different drug structure. A statistically significant difference was found in the time to onset associated with delayed cutaneous hypersensitivity for COVID‐19 treatment in infliximab or adalimumab (Mann–Whitney U test, p < 0.05).…”

Effects of Infliximab on patients with COVID-19: a systematic review and meta-analysis

“…We conclude that Infliximab exerts favorable impact in terms of lowering the mortality rate of SARS-CoV-2 infection. More studies on the effects of Infliximab on severe COVID-19 should be conducted [28].…”