PARAMUS, N.J,--(BUSINESS WIRE)--An investigator-initiated study (IIS) supported by Octapharma USA has reported that intravenous immunoglobulin (IVIg) significantly improved hypoxia and reduced hospital length of stay and progression to mechanical ventilation in patients with COVID-19 pneumonia.1
Study data is available in the journal article “Intravenous Immunoglobulin (IVIg) Significantly Reduces Respiratory Morbidity in COVID-19 Pneumonia: A Prospective Randomized Trial,” published by lead investigator George Sakoulas, M.D. of Sharp Memorial Hospital and the Sharp Rees-Stealy Medical Group in San Diego, Calif. The paper is currently under review and was published on medRxiv.org to quickly make the data available to the public.
The randomized open label study evaluated the standard of care (SOC) plus high-dose Octagam® 10% [Immune Globulin Intravenous (Human)] compared to SOC alone in the treatment of COVID-19 infection, specifically in preventing mechanical ventilation in COVID-19 patients requiring high-flow oxygen. The study enrolled 33 COVID-19 patients experiencing hypoxia who were at risk of requiring mechanical ventilation.
“In this first prospective randomized study evaluating IVIg in the treatment of COVID-19 infection, the use of IVIg reduced the rate of progression of respiratory failure requiring mechanical ventilation in COVID-19 patients (13% with IVIg vs. 41% without IVIg, p=0.12),” said Dr. Sakoulas, Associate Professor in the Department of Pediatrics of the University of California San Diego School of Medicine. “While this did not achieve statistical significance among the collective subject cohorts, the reduced rate of progression to mechanical ventilation with IVIg achieved statistical significance among the subset with a calculated or estimated A-a (Alveolar–arterial) gradient of > 200 mm Hg (14% with IVIG vs. 58% without IVIg, p=0.038).”1
“This finding points not only to a potential benefit of IVIG in COVID-19, but the importance of optimal patient selection for IVIg in maximizing clinical benefit,” Dr. Sakoulas added. “COVID-19 patients with mild hypoxia may never warrant anything more than supportive low-flow oxygen therapy, such that intervening with IVIg may not change the course of an otherwise benign disease course. A cutoff A-a gradient of >200 mm Hg was chosen due to the fact that this represents a notable risk increase in APACHE 2 score calculation in predicting mortality. The potential benefit of IVIg in reducing respiratory failure morbidity in COVID-19 patients was further supported by the significant shortening of duration of length hospital stay and ICU length of stay, and improvement in oxygenation (PaO2/FiO2) at day 7. Mortality was numerically reduced from 3/17 (18%) to 1/16 (6%) with IVIG in this study, but the difference was not statistically significant due to sample size.”1
Among subjects with A-a gradient of >200 mm Hg at enrollment, the IVIG group showed:
- Lower rate of progression to requiring mechanical ventilation (2/14 vs 7/12, p=0.038);
- Shorter median hospital length of stay (11 vs 19 days, p=0.01);
- Shorter median ICU stay (2.5 vs 12.5 days, p=0.006);
- Greater improvement in PaO2/FiO2 at 7 days (median [range] change from time of enrollment +131 [+35 to +330] vs +44·5 [-115 to +157], p=0.01) than SOC.1
In addition to this investigator-initiated study, Dr. Sakoulas is leading a larger multicenter, randomized, double-blind, placebo-controlled study approved by the U.S. Food and Drug Administration (FDA) under an Investigational New Drug Application. The primary objective of this study is to determine if high-dose Octagam® 10% therapy will slow or stop respiratory deterioration in patients with severe coronavirus disease. The secondary objectives of the study are to measure the effects of a high-dose of Octagam® 10% on slowing or stopping the clinical progression of COVID-19 by improving pulmonary function, quality of life, and correlated impact on metabolic factors.
“The research results in the Sharp Memorial study are an important step in determining the optimum treatment for the most critically ill COVID-19 patients,” said Octapharma USA President Flemming Nielsen. “Octapharma is honored to be able to support these vital research initiatives. We are committed to partnering with the medical community to bring life-saving therapies to the most critical COVID-19 patients as well as those with bleeding and immune disorders and others requiring critical care.”
The potential role of IVIG in COVID-19 has been further evaluated in three recent studies, published in The New England Journal of Medicine, The Lancet, and The Journal of the Pediatric Infectious Diseases Society. All three studies focused on treating severe Kawasaki-like disease or Multisystem Inflammatory Syndrome observed in pediatric patients with high-dose IVIg therapy with positive results.2,3,4,5
COVID-19 causes an immune response in some patients that ranges from insufficient to overly-active. In an earlier clinical trial in Wuhan, China, where the coronavirus outbreak began, it was noted that death from the disease is frequently the result of an abnormal pulmonary immune system response with multiple respiratory viral infections in which there is an elevation of cytokine and chemokine production referred to as a “cytokine storm” and associated with poor clinical outcomes.6,7
For more information on the Sharp Memorial IIS or the Octagam® 10% clinical trial, please contact Huub Kreuwel, Ph.D., Octapharma USA, Vice President of Scientific and Medical Affairs, at usmedicalaffairs@octapharma.com. For additional information on Octapharma’s research initiatives in the fight against COVID-19, please visit covid19.octapharmausa.com.
About Octagam® 10%
Octagam® 10% [Immune Globulin Intravenous (Human)] is an immune globulin intravenous (human) liquid preparation indicated for the treatment of chronic immune thrombocytopenic purpura (ITP) in adults.
WARNINGS
Thrombosis may occur with immune globulin intravenous (IGIV) products, including Octagam® 10%. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling vascular catheters, hyperviscosity, and cardiovascular risk factors. Renal dysfunction, acute renal failure, osmotic nephropathy, and death may occur with the administration of immune globulin intravenous (Human) (IGIV) products in predisposed patients. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. Octagam® 10% does not contain sucrose. For patients at risk of thrombosis, renal dysfunction or renal failure, administer Octagam® 10% at the minimum infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. For full prescribing information, including complete boxed warning and other important information, please visit octagamus.net.
About the Octapharma Group
Headquartered in Lachen, Switzerland, Octapharma is one of the largest human protein products manufacturers in the world and has been committed to patient care and medical innovation since 1983. Its core business is the development and production of human proteins from human plasma and human cell lines. Octapharma employs more than 10,000 people worldwide to support the treatment of patients in over 115 countries with products across the following therapeutic areas: Hematology (coagulation disorders), Immunotherapy (immune disorders) and Critical Care. The company’s American subsidiary, Octapharma USA, is located in Paramus, N.J. Octapharma operates three state-of-the-art production sites licensed by the U.S. Food and Drug Administration (FDA), providing a high level of production flexibility. For more information, please visit www.octapharmausa.com.
REFERENCES
1. Sakoulas, G., Geriak, M., et al. (2020). Intravenous Immunoglobulin (IVIG) Significantly Reduces Respiratory Morbidity in COVID-19 Pneumonia: A Prospective Randomized Trial. medRxiv.
2. Dufort, E. M., Koumans, et al. (2020). Multisystem inflammatory syndrome in children in New York State. New England Journal of Medicine, 383(4), 347-358.
3. Verdoni, L., Mazza, A., et al. (2020). An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. The Lancet.
4. Chiotos, K., Bassiri, H., et al. (2020). Multisystem Inflammatory Syndrome in Children during the COVID-19 pandemic: a case series. Journal of the Pediatric Infectious Diseases Society.
5. Feldstein, L.R., Rose E.B., et al. (2020) Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. New England Journal of Medicine.383, 334-346
6. Cao, W., Liu, X., et al. (2020, March). High-dose intravenous immunoglobulin as a therapeutic option for deteriorating patients with coronavirus disease 2019. In Open forum infectious diseases (Vol. 7, No. 3, p. ofaa102). US: Oxford University Press.
7. Ruan, Q., Yang, K., et al. (2020). Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive care medicine, 46(5), 846-848.
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