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The drug eculizumab, a synthetic antibody that inhibits the inflammatory response, has significantly reduced the risk of relapse with the neurological disorder of the Optic Neuromyelitis Spectrum (NMOSD). This rare but serious autoimmune inflammatory disease can cause blindness, paralysis and death. Researchers at Mayo Clinic and international collaborators published their findings in a randomized, double-blind, placebo-controlled study published in the New England Journal of Medicine. Their work will also be presented at the Emerging Science Platform session, which is part of the 71st annual meeting of the American Academy of Neurology in Philadelphia from May 4th to May 10th.
Optic neuromyelitis, also known as Devic's disease, occurs when the body's immune system reacts against otherwise healthy nervous system cells in the optic nerves, spinal cord and sometimes the brain. Optic neuromyelitis is often misdiagnosed as multiple sclerosis (MS), but optic neuromyelitis is a distinct condition characterized by more severe attacks and less complete recovery. A single attack of optic neuromyelitis can leave a patient blind or paralyzed. With each relapse, disability can worsen. It affects up to 10 people out of 100,000.
Currently, immunosuppressive therapies used to prevent relapses of optic neuromyelitis have not been approved by the Food and Drug Administration. In addition, the authors note that 25 to 60% of patients receiving these drugs continue to have recurrent seizures.
In the PREVENT study (relapse prevention and evaluation of eculizumab for treatment with NMOSD), 143 adults were enrolled at 70 sites in 18 countries. All patients had aquaporin-4 immunoglobulin G (AQP4-IgG), an antibody badociated with most cases of optic neuromyelitis. Patients can continue their previous treatment if they wish. In addition, patients were randomized to receive regular doses of a placebo or IV eculizumab.
The study found that treatment with eculizumab reduced the risk of relapse by 94% compared with placebo. At 48 weeks, nearly 98% of patients treated with eculizumab had not relapsed, compared to 63% of patients in the placebo group.
"This study offers hope to patients because every stroke in an NMO can result in loss of visual or motor function," says Sean Pittock, MD, neurologist at Mayo Clinic and first author. "Stopping attacks can prevent disability and allow patients to retain their function and a better quality of life."
The Mayo Clinic is a recognized center of excellence for the diagnosis and treatment of optic neuromyelitis. In 2002, Mayo Clinic researchers, led by Claudia Lucchinetti, M.D., and their colleagues described the unique pathological features of NMOs and proposed that they be an autoimmune disease caused by one or more harmful antibodies. In 2004, Vanda Lennon, MD, Ph.D., Brian Weinshenker, M.D., and colleagues from Mayo announced the discovery of the AQP4-IgG biomarker, a blood test that differentiates between optic neuromyelitis and MS. It was later shown that the AQP4-IgG antibody was able to cause nerve cell damage, which was consistent with what Dr. Lucchinetti and his colleagues reported. The AQP4-IgG is now widely regarded as the cause of NMO.
"The Mayo Clinic team has subsequently demonstrated that, when the antibody binds to the AQP4 water channel on the nerve cells, a substance called" complement "activates and destroyed the cells, causing significant lesions, we thought that if we could block the activation of complement, then we could prevent the attacks, "says Dr. Pittock, director of the Multiple Sclerosis and Autoimmune Neurology Center Mayo Clinic and Mayo Neuroimmunology Laboratory.
Eculizumab has been used to treat disorders for which nighttime complement activation, such as myasthenia gravis, muscular disease, and paroxysmal nocturnal hemoglobinuria, a genetic disorder affecting red blood cells. In a first phase of clinical trials, the Mayo team observed an almost complete cessation of optic neuromyelitis attacks. On the basis of these first results, this vast multicentric international study was carried out.
"The results of this new study confirm the important role of complement in optic neuromyelitis and advance our understanding of how the disease works," said Dean Wingerchuk, MD, Mayo Clinic neurologist and lead author. "This study clearly demonstrates that we can positively alter the course of this often devastating neurological disease."
Side effects of eculizumab include the risk of meningococcal infections. Study participants were vaccinated against meningococcal infections and no cases were reported. A person receiving eculizumab died of an infection not badociated with complement inhibition.
This study included only patients with anti-AQP4-IgG antibodies. Therefore, the results can not be extrapolated to other inflammatory disorders of the central nervous system. The authors note that the long-term effect of eculizumab in patients with optic neuromyelitis requires further studies.
The study was supported by Alexion.
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