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Epidemiology and Pathogenesis of COVID-19
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Sidrah Tariq Khan, Sagheer Ahmed
Bevacizumab, an anti-VEGF drug has the ability to attenuate pulmonary edema in critically ill patients. The anti-rheumatoid IL-6 receptor-specific antibodies Sarilumab and Tocilizumab have shown to be very effective in controlling cytokine storm in critically ill COVID-19 patients, however their use in such instances requires further study. Currently, corticosteroids such as dexamethasone are being used in severely ill patients and has been shown to reduce fatalities caused by severe COVID-19 by at least 1/3rd. However, these drugs have not shown any significant benefit in treating non-critical patients.
Convalescent Plasma and Antibody Therapy in COVID-19
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Didem Rıfkı, Eymen Ü. Kılıç, Şükrü Tüzmen
Sarilumab is a human mAb that binds to the IL-6 receptor and blocks it. The efficacy and protection of sarilumab in adult COVID-19 patients with severe complications is currently being studied in a phase II/III trial [19]. Tocilizumab can cause acute pancreatitis, hypertriglyceridemia, cytopenia, hypofibrinogenemia, elevated ferritin levels, and lactate dehydrogenase in COVID-19 patients. Sarilumab and tocilizumab can cause a dose-dependent increase in liver enzymes in long-term use, which are temporary and/or reversible (occurring during the use of medication) (Table 8.2). Thrombocytopenia and neutropenia are uncommon complications. Long-term use of these medications has also been linked to severe bacterial or fungal infections, and bowel perforation [20].
Chest
Published in Henry J. Woodford, Essential Geriatrics, 2022
Steroids have a clear mortality benefit in severe COVID-19 but no beneficial effect in mild disease. Dexamethasone reduced 28-day mortality in people receiving mechanical ventilation (29.3% v 41.4%) and people receiving oxygen without ventilation (23.3% v 26.2%).68 There was no benefit for people not requiring oxygen. IL-6 receptor blockers (e.g. tocilizumab and sarilumab) are monoclonal antibodies originally used for rheumatoid arthritis. Their action reduces cytokine release. Trial results have been mixed.60 The RECOVERY trial recruited people (mean age 63) with hypoxia (oxygen saturation < 92% on air or requiring oxygen therapy) and evidence of systemic inflammation (serum CRP 75 mg/L or over).69 Mortality with tocilizumab was significantly lower than with usual care (31% v 35%). IL-6 receptor blockers are recommended, in addition to steroids, for people with severe or critical COVID-19.64 The monoclonal antibodies casirivimab and imdevimab can be used in combination for people hospitalised with COVID-19 who have no detectable serum SARS-CoV-2 antibodies.70 Remdesivir is an anti-viral drug that inhibits viral RNA transcription. It may improve time to recovery but has no mortality benefit for COVID-19. At the time of writing, its use is not currently recommended outside of clinical trials.70 Oral antiviral medications, including molnupiravir, are also being developed and appear to reduce the risk of hospital admission or death in people with mild to moderate symptoms.71
Comparing biologic options for the management of Behcet’s disease-related uveitis
Published in Expert Review of Clinical Immunology, 2023
Antonio Vitale, Valeria Caggiano, Virginia Berlengiero, Maria Orsetta Perfetti, Jurgen Sota, Gian Marco Tosi, Bruno Frediani, Luca Cantarini, Claudia Fabiani
In 2019, the Phase II SATURN study evaluated the efficacy of sarilumab, a human anti-IL-6 receptor antibody, for the treatment of posterior NIU in 58 patients. These patients received subcutaneous sarilumab at a dosage of 200 mg or placebo every other week for 16 weeks. The primary endpoint, consisting in the statistically significant difference between the sarilumab and the placebo groups in the reduction of at least two steps in vitreous haze on the Miami scale or in the reduction of systemic corticosteroids to a less than 10 mg/day (prednisolone or equivalent) dosage at week 16, was reached. The mean BCVA gain from baseline to week 16 was significantly greater with sarilumab compared to placebo. Worsening of uveitis and retinal infiltrates were the most common ocular AEs reported [105].
Refractory systemic onset juvenile idiopathic arthritis: current challenges and future perspectives
Published in Annals of Medicine, 2022
William G. Ambler, Kabita Nanda, Karen Brandt Onel, Susan Shenoi
Other IL-6 inhibitors which likely are similarly efficacious as tocilizumab exist. Siltuximab, an IL-6 binding chimeric monoclonal antibody, was effective in a 20-year-old patient with SJIA who failed multiple therapies including IL-1 blockade and was unable to tolerate tocilizumab because of infusion reactions [76]. Sarilumab is an alternate IL-6 binding monoclonal antibody currently approved for rheumatoid arthritis that is being studied for its utility in SJIA (NCT02991469). Although these alternative medications have not been rigorously studied in SJIA, and thus currently lack specific approval, it is likely that they are effective. It is unclear if patients that fail tocilizumab might respond to a different IL-6 inhibitor and more data is needed to evaluate this possibility.
A comprehensive review on sarilumab in COVID-19
Published in Expert Opinion on Biological Therapy, 2021
Sajad Khiali, Afra Rezagholizadeh, Taher Entezari-Maleki
Sarilumab contraindications include known hypersensitivity to the drug or any component of the formulation. Besides, the viral reactivation following the sarilumab administration has been reported. Considering the role of IL-6 in the immune system, COVID-19 patients should be monitored regarding concomitant infections, including serious and life-treating infections such as tuberculosis (TB), invasive fungal, bacterial, viral, and other opportunistic infections, and localized infections [10,48,51]. Based on the Massachusetts General Hospital guidelines, COVID-19 patients with suspected tuberculosis should be tested before administration steroids or immunotherapy [52]. Accordingly, the evaluation of patients for latent infections and TB risk factors before sarilumab administration seems rational. Furthermore, gastrointestinal (GI) perforation has been observed, especially secondary to diverticulitis, concomitant use of corticosteroids, or non-steroidal anti-inflammatory drug (NSAID) therapy. The beneficial effects of corticosteroids in some patients with COVID-19 highlight the importance of GI perforation adverse effect. The other common adverse reactions of sarilumab include neutropenia, thrombocytopenia, transaminase level elevation and hyperlipidemia [48]. Besides, sarilumab should be used with caution in patients with active hepatic disease or impairment and has not been studied in cases with creatinine clearance less than 30 mL per min [10,48,51,52].