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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
Eculizumab is a “humanized monoclonal IgG antibody.” It has the ability to bind with the C5 complement protein and prevents its conversion into C5a and C5b; thus, by blocking the formation of C5b, it inhibits terminal C5b-9 complex or membrane attack complex (MAC) formation [46].
Neuromuscular Junction Disorders
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Diana Mnatsakanova, Qin Li Jiang
Eculizumab is given intravenously. Initially it is given 900 mg IV weekly for first 4 weeks, followed by 1200 mg IV for the fifth dose 1 week later, followed by 1200 mg IV every 2 weeks thereafter.
The complement system in health and disease
Published in Gabriel Virella, Medical Immunology, 2019
Atypical hemolytic uremic syndrome (aHUS) is a rare disease that causes blood clots that, over time, reduce significantly the blood flow in the kidneys, impairing its ability to remove waste products, which ultimately leads to kidney failure. aHUS is associated with mutations in proteins of the alternative pathway, primarily factor H, that lead to uncontrolled complement activation. Recent clinical trials have shown that eculizumab therapy improves outcomes, which has led to the approval of its use in aHUS.
C5a Serum Levels in Patients with Endometriosis: A Cross-Sectional Study
Published in Immunological Investigations, 2023
Danilo Rahal, Carlos Bezerra Sobrinho, Laura Vilas Boas, Cesar Augusto Capellari, Fabiana Antunes Andrade, Renato Nisihara
Our findings raise some questions about therapeutic target in patients with EM. There are some drugs that target the C5a or C5a receptors (Allegretti et al. 2012; Quadros and Cunha 2016; Vitiello et al. 2021; Vlaar et al. 2020; Zelek and Morgan 2020). Clinically, eculizumab has important holes in paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome treatment. Thus, drugs that block C5a, such as eculizumab, may contribute to control the inflammatory response, and control pain and/or infertility in patients with endometriosis, as it has been shown in other inflammatory diseases, including Coronavirus Disease 19 (COVID-19), neuromyelitis optica and refractory generalized Myasthenia Gravis (Diurno et al. 2020; Hawksworth et al. 2017). However, further studies are needed to assess these findings.
Monoclonal antibodies for treatment of cold agglutinin disease
Published in Expert Opinion on Biological Therapy, 2023
Georg Gelbenegger, Sigbjørn Berentsen, Bernd Jilma
The safety and efficacy of eculizumab in patients with CAD was evaluated in a prospective, open-label, bicentric, nonrandomized phase II trial [21] (Table 3, Supplementary Table S2). Patients were eligible for inclusion if they were 18 years of age or older, required treatment because of CAD-related symptoms or had transfusion dependency, and had LDH levels that were at least double the upper limit of normal. Cold agglutinin disease was defined as chronic hemolysis, a cold agglutinin titer of 64 or more at 4°C, and a DAT strongly positive for C3d but negative or only weakly positive for IgG. Key exclusion criteria were treatment with rituximab, alkylating agents, human immunoglobulins, or plasmapheresis at least four weeks before screening. Patients were vaccinated for Neisseria meningitidis before receiving complement inhibition treatment. Included patients received treatment with eculizumab 600 mg weekly for four weeks, followed one week later by eculizumab 900 mg every other week through week 26. The primary endpoint was the difference in LDH level between the first and the last day of eculizumab treatment. The trial included 13 CAD patients. Eleven patients completed the 26-week treatment phase and received all 16 scheduled eculizumab infusions. Eculizumab significantly reduced LDH levels from 572 U/L to 334 U/L (p = 0.0215) but did not significantly increase hemoglobin levels. Despite failure to increase hemoglobin levels, eight patients achieved transfusion independency. Eculizumab was well tolerated, and no meningococcal infections occurred.
Transitioning immunotherapy in neuromyelitis optica spectrum disorder – when and how to switch
Published in Expert Opinion on Biological Therapy, 2022
Anastasia Vishnevetsky, Tamara B. Kaplan, Michael Levy
Patients may consider transitioning therapy due to considerations relating to breastfeeding. Monoclonal antibodies are increasingly used in pregnancy and may be potential options during breastfeeding. Given their high molecular weight, only small amounts are transferred into breast milk, where proteolytic enzymes likely destroy the drug in the infant’s gastrointestinal tract. The concentration of rituximab in breast milk is 240 times lower than in maternal serum [80]. The relative infant dose was <1%, well below the accepted relative infant dose of 10% for medications excreted into breast milk. Eculizumab has also not been detected in mothers’ breastmilk, suggesting this may be a potential treatment option for pregnant and lactating NMOSD patients. However, larger case series and long-term follow-up are needed.