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Convalescent Plasma and Antibody Therapy in COVID-19
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Didem Rıfkı, Eymen Ü. Kılıç, Şükrü Tüzmen
Siltuximab, another mAb, blocks IL-6 signaling by preventing IL-6 from binding to both soluble and membrane-bound IL-6 receptors. This drug is currently being tested in four clinical trials in COVID-19 patients [21].
Impact of Evolving Regulatory Pathways on Statistical Considerations in Oncology Clinical Trials
Published in Satrajit Roychoudhury, Soumi Lahiri, Statistical Approaches in Oncology Clinical Development, 2018
Randomized Clinical Trials: Randomized clinical trials with unequal allocation such as a 2:1 or 3:1 randomization with fewer patients assigned to receive placebo, best supportive care, or standard of care can be considered. While they are not as efficient as those using a 1:1 design, in such trials, fewer patients are exposed to placebo or best supportive care, and therefore, they may be attractive to patients considering enrolling in a clinical trial. This would be a good design to evaluate both efficacy and safety. For example, siltuximab was approved (regular approval) for the treatment of Castleman’s disease (prevalence < 1/100,000) based on a placebo-controlled, double-blind, randomized study with a 2:1 randomization allocation (53 patients: 26 patients) demonstrating a durable tumor and symptomatic response (34% response in siltuximab arm versus 0% in the placebo arm) [7].
The role of platelets, neutrophils and endothelium in COVID-19 infection
Published in Expert Review of Hematology, 2022
E. Falcinelli, E. Petito, P. Gresele
Given the reported key role of the cytokine storm in severe COVID-19, targeting pro-inflammatory cytokines may represent a potentially important therapeutic approach. Anti-inflammatory therapies have been explored to ameliorate the cytokine storm-related morbidity and mortality in COVID-19 patients, including the blockade of some specific cytokines, the antagonism of some cytokine receptors or the inhibition of downstream intracellular signaling. Among cytokine blocking agents, the safetyand efficacy of anti-IL-6 clazakizumab and siltuximab, anti-IL-1β canakinumab, anti-TNF-α infliximab and adalimumab, anti-IFN-β emapalumab and anti-IL-8 BMS-986253 have been tested. Clazakizumab significantly improved 28-day ventilator-free survival, 28- and 60-day overall survival, as well as clinical outcomes in COVID-19 hospitalized patients [181], and siltuximab reduced inflammation and improved the ventilation and respiratory function. However, validated and properly designed clinical trials are needed to confirm the clinical use of siltuximab compared to other IL-6 pathway blocking drugs [182]. A recent meta-analysis showed that treatment with canakinumab reduced COVID-19 severity and the overall mortality. Additional studies are required to confirm these findings [183]. Clinical trials evaluating the efficacy of anti-TNF-α, anti-IFN-β, and anti-IL-8 in reducing COVID-19 severity are ongoing [184].
The role of IL-6 and IL-6 blockade in COVID-19
Published in Expert Review of Clinical Immunology, 2021
Nicola Potere, Alberto Batticciotto, Alessandra Vecchié, Ettore Porreca, Antonella Cappelli, Antonio Abbate, Francesco Dentali, Aldo Bonaventura
Siltuximab is a chimeric monoclonal antibody that prevents IL-6 from binding to its receptors and inhibits the biological activity of IL-6 [125]. 125 Siltuximab has been recently deemed of interest for the treatment of COVID-19. Although there are no published studies supporting the use of siltuximab for COVID-19, findings from a non-peer reviewed report from Italy suggest that siltuximab, administered intravenously at a dose of 11 mg/kg to 30 patients requiring noninvasive mechanical ventilation, induced a rapid and sustained decline in CRP, was well-tolerated, and associated with a significantly lower mortality rate compared to standard-of-care alone [153]. A multicenter Belgian RCT (NCT04330638) comparing siltuximab (11 mg/kg intravenously, alone or in combination with the IL-1 blocker anakinra) to other cytokine inhibitors (anakinra and tocilizumab, alone or in combination) has just completed the enrollment, with results being expected soon [154].
Biologic and advanced immunomodulating therapeutic options for sarcoidosis: a clinical update
Published in Expert Review of Clinical Pharmacology, 2021
Ogugua Ndili Obi, Elyse E. Lower, Robert P. Baughman
There are two classes of anti-IL-6 biologic agents. Tocilizumab [312] and sarilumab [313,314] are non-chimeric IgG1monoclonal antibodies directed against the IL-6 receptor and are FDA approved for the treatment of moderate to severe rheumatoid arthritis refractory to anti-TNF therapy and other DMARDs [315]. Siltuximab is a chimeric/humanized monoclonal antibody that binds directly to circulating and membrane-bound IL-6 and prevents their binding to IL-6 receptor. Siltuximab is FDA approved for the treatment of multicentric Castleman’s disease [316]. Although siltuximab showed similar clinical efficacy to the anti-IL-6 receptor blockers, it was not approved for the treatment of rheumatoid arthritis due to an excess mortality in preclinical trials [317]. Sirukumab is another non-chimeric IgG1 kappa monoclonal antibody to circulating IL-6 that was not FDA approved for the treatment of rheumatoid arthritis due to safety concerns [318].