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Recent Developments in Therapies and Strategies Against COVID-19
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Misbah Hameed, M. Zia-Ul-Haq, Marius Moga
Tocilizumab is a monoclonal whole antibody that has been designed to counter the interleukin-6 receptor (IL-6R), which is one of the cytokine linked with the development of some autoimmune diseases. Different cells like B-cells and T-cells, monocytes, fibroblasts, and lymphocytes produce IL-6. IL-6 is also associated with T-cell activation, initiation of protein synthesis in hepatic acute-phase and the instigation of immunoglobulin secretion. Tocilizumab is used in case serious cytokine release syndrome. FDA has permitted phase II clinical trials to evaluate the efficacy of tocilizumab in pneumonia associated with COVID-19 in hospitals. The practice of tocilizumab in patients having severe COVID-19 in China showed positive outcomes to control lung inflammation. Thus “seventh edition of the Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment” included tocilizumab as an option to be used in critical COVID-19 patients showing prevalent lung lesions and higher IL-6 levels [42]. However, some serious side effects associated with the drug has also been observed, such as drug-induced liver injuries and acute liver failure. It can also result in concomitant opportunistic serious infections like Tuberculosis, specially when used in combination with immunosuppressants or corticosteroids.
Myositis
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Tocilizumab is an IL-6 antagonist, currently approved for patients with rheumatoid arthritis. Since there is evidence of a correlation between serum levels of IL-6 and DM activity,105 IL-6 antagonist therapy would have biologic plausibility as a potential DM treatment. A murine model study of IL-6 antagonism in refractory cases of PM and ASS showed promising results,106, 107 which led to a randomized, placebo-controlled trial of tocilizumab in refractory DM/PM patients. However, tocilizumab treatment did not meet the primary or secondary efficacy outcomes.22
Convalescent Plasma and Antibody Therapy in COVID-19
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Didem Rıfkı, Eymen Ü. Kılıç, Şükrü Tüzmen
The IL-6 cytokine is the most studied cytokine that has been linked to viral load, incidence, severity, and prognosis in COVID-19 patients. Many clinical trials have focused on IL-6 for the treatment of extreme stages of COVID-19. As a result, tocilizumab is thought to be the most promising candidate for cytokine storm control in COVID-19 [5]. Tocilizumab blocks the IL-6 receptor signaling pathway. It has been tested in COVID-19 patients alone or in combination with other antiviral therapies including hydroxychloroquine, remdesivir, and favipiravir, as well as a broad-spectrum of antibiotics and dexamethasone to treat ARDS. It has been approved by the FDA for the treatment of cytokine storm caused by a variety of diseases [5].
Identifying and managing CAR T-cell–mediated toxicities: on behalf of an Italian CAR-T multidisciplinary team
Published in Expert Opinion on Biological Therapy, 2022
Massimo Martino, Sebastiano Macheda, Umberto Aguglia, Luciano Arcudi, Giulia Pucci, Bruno Martino, Maria Altomonte, Antonio Maria Rossetti, Giuseppa Cusumano, Letteria Russo, Lucrezia Imbalzano, Caterina Stelitano, Caterina Alati, Jessyca Germano’, Demetrio Labate, Vincenzo Amalfi, Maria Teresa Florenzano, Antonella Morabito, Vittoria Borzumati, Vincenzo Dattola, Caterina Gattuso, Antonio Moschella, Domenico Quattrone, Francesco Curmaci, Claudio Franzutti, Giuseppe Scappatura, Carmelo Massimiliano Rao, Viviana Loddo, Antonella Pontari, Maria Pellicano’, Rosangela Surace, Cristina Sanguedolce, Virginia Naso, Anna Ferreri, Giuseppe Irrera, Giuseppe Console, Tiziana Moscato, Barbara Loteta, Filippo Antonio Canale, Alfonso Trimarchi, Renza Monteleone, Said Al Sayyad, Frank Cirrone, Benedetto Bruno
Patients with some grade 2 and severe CRS (grade 3 or 4) require daily laboratory and clinical status monitoring. Initial treatment of CRS grade 2 should be with tocilizumab alone. Two doses of tocilizumab per patient must be on-site and available for administration before CAR-T infusion. The CAR-T team should have access to additional quantities of tocilizumab within 8 hours. In the United States, at least two doses of tocilizumab per patient must be available for 28 days following administration of CAR T-cells. Tocilizumab has been administered intravenously over one hour with this schedule: for patients <30 kg – 12 mg/kg; patients ≥30 kg – 8 mg/kg; the total dose should not exceed 800 mg. If there is no clinical improvement after the first dose, tocilizumab can be repeated after at least 8 hours and, in any case, not exceeding four doses in total.
A rare case of idiopathic multicentric Castleman disease in a patient with long-standing systemic autoimmunity
Published in Scandinavian Journal of Rheumatology, 2022
M Saleh, M Hallbeck, C Sjöwall
This woman, with a 25 year history of Sjögren-like lupus, developed abdominal lymphadenopathy, irresponsive to anti-rheumatic therapy, combined with constitutional symptoms, hypergammaglobulinaemia, and severe cytopenia. Extensive investigation was necessary to exclude malignancy (particularly lymphoma), but the case illustrates that non-malignant lymphoproliferative disorders should also be considered. The diagnosis was facilitated by radiology, demonstrating multiple locations with lymphadenopathy combined with typical histopathology (major criteria). Additional clinical and laboratory findings (minor criteria) were also met to satisfy the diagnostic international consensus criteria for iMCD (8–10). In line with the international, evidence-based consensus treatment guidelines for iMCD, IL-6 inhibition was initiated (10). The patient has received a first infusion of tocilizumab without side-effects, and additional infusions are planned for every fourth week. The plan is further to evaluate the efficacy of tocilizumab with a new PET scan within 6–12 months.
An update on COVID-19 pandemic: the epidemiology, pathogenesis, prevention and treatment strategies
Published in Expert Review of Anti-infective Therapy, 2021
Hin Fung Tsang, Lawrence Wing Chi Chan, William Chi Shing Cho, Allen Chi Shing Yu, Aldrin Kay Yuen Yim, Amanda Kit Ching Chan, Lawrence Po Wah Ng, Yin Kwan Evelyn Wong, Xiao Meng Pei, Marco Jing Woei Li, Sze-Chuen Cesar Wong
SARS-CoV-2 infection induces excessive cytokine release, followed by lung injury and results in COVID-19. Elevated serum interleukin-6 (IL-6) level is associated with worse outcome in COVID-19 patients. Tocilizumab is a recombinant-humanized monoclonal antibody targeting both soluble and membrane-bound forms of IL-6 receptor. Tocilizumab is recommended for the treatment of severe rheumatoid arthritis, systemic juvenile idiopathic arthritis, giant cell arthritis, and life-threatening cytokine release syndrome. It is proposed that treatment with tocilizumab might have a clinical benefit because of its anti-IL-6 nature. In a multicentre, retrospective study (n = 544), patients treated with tocilizumab, either administered intravenously or subcutaneously, could reduce the risk of invasive mechanical ventilation or death [47]. In another study (n = 100), patients treated with tocilizumab (8 mg/kg intravenous infusions 12 h apart for 2 days) showed significant clinical improvement in respiratory condition [48]. However, in a meta-analysis that assessed the efficacy of tocilizumab for the treatment of severe COVID-19, there is no conclusive evidence that treatment with tocilizumab would provide additional benefit to patients with severe COVID-19. Therefore, the effects on clinical outcomes of tocilizumab in the treatment of COVID-19 remain to be determined [49].