CME/CE NMOSD Abstract Highlights from AAN 2020 Michael Levy, MD, PhD Associate Professor of Neurology, Massachusetts General Hospital
What is NMOSD? Neuromyelitis Optica Spectrum Disorder Autoimmune disorder with antibodies towards aquaporin-4 water (AQP-4) • channel Symptoms vary but most common symptoms associated with inflammation • of optic nerve and spinal cord • Eye pain, loss of visual acuity, spine pain, paraparesis or paraplegia, GI symptoms • Other symptoms may include persistent hiccup, nausea/vomiting, headache, depression, fatigue, sleep disorders • May be misdiagnosed as multiple sclerosis Borisow et al. Front Neurol. 2018; 9: 888. NORD Rare Disease Database: Neuromyelitis Optica. 2018.
What is NMOSD? Treatment Team approach • Immunosuppressive therapy (off label) • FDA approved treatment • Eculizumab • Under investigation • Inebilizumab (MEDI-551) • Cladribine • Rituximab • Satralizumab •
What is AAN 2020? AAN Annual Meeting Scheduled for April • Cancelled due to Covid-19 • Abstracts published in Neurology Journal •
NMOSD vs MS Maria Alkhasova et al. Neuromyelitis Optica Spectrum Disorders Misdiagnosed as Multiple Sclerosis: Can Current Diagnostic Guidelines Separate the Two Diseases? • Can McDonald criteria properly differentiate MS from NMOSD? • Retrospective study (2009-2016) extracting data from Truven Health Analytics database of 319,994 MS patients. Of those, 2,001 were NMOSD patients. • Authors concluded “Since no single test can conclusively establish a diagnosis of MS, perhaps NMOSD may have to be excluded first despite typical radiological findings pointing to MS.” Alkhosova M et al. Neurol. 2020; 94 (suppl).
NMOSD vs MS New studies show there are differences in the two diseases. More studies needed to better differentiate • Laura Cacciaguerra et al. Hippocampal Regional Vulnerability to Damage Differs Between MS and NMO • Seyedamirhosein Motamediet al. Foveal Shape Differs Between Neuromyelitis Optica and Multiple Sclerosis Patients • Eun-Jae Leeet al. Serum biomarkers and patient age in multiple sclerosis and aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders Cacciaguerra L et al. Neurol. 2020; 94 (suppl). Motamedi S et al. Neurol. 2020; 94 (suppl). Lee E-Jet al. Neurol. 2020; 94 (suppl). Image of fovea courtesy of Dr. Levy
Treatment Options: FDA Approved Eculizumab • Approved in 2019 to treat adults with NMOSD who are AQP4 antibody positive • PREVENT Study • 143 patients with AQP4 positive NMOSD (median age 45.0 years; 90% female) • Randomized 2:1 to receive eculizumab, n = 96; placebo, n = 47), eculizumab (maintenance dose, 1200 mg/2 weeks; n=96) or placebo (n=47) • Numerous post-hoc analysis studies published for AAN 2020 Pittock SJ et al. New Engl J Med. 2019; 381: 614-625.
Treatment Options: FDA Approved Jacqueline Palace et al. Impact of Eculizumab on Disability Worsening and Quality of Life in Patients with Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder: Results from the Phase 3 PREVENT Study. • At study end, the proportion of patients with worsening EDSS scores was significantly lower for eculizumab (11.5%; n = 96) than for placebo (23.4%; n = 47; P = .0493). Achim Berthele et al. The Impact of Relapses on Quality of Life in Patients with Neuromyelitis Optica Spectrum Disorder: Data from the Phase 3 PREVENT Study. • There were significant differences between pre- and post-relapse scores in the SF-36 domains bodily pain, physical functioning, role emotional and vitality. Palace J et al. Neurol. 2020; 94 (suppl). Berthele A et al. Neurol. 2020; 94 (suppl).
Treatment Options: FDA Approved Michael Levy et al. Efficacy and Safety of Eculizumab in Patients with Neuromyelitis Optica Spectrum Disorder Previously Treated with Rituximab: Findings from the Phase 3 PREVENT Study • Post-hoc analysis of patients previously given rituximab • 26 of 96 patients in eculizumab arm; 20 of 47 patients in placebo arm Relapse Rate Serious AEs Serious infections/infestations Eculizumab 3.8% 38.9% 11.1% Placebo 35.0% 47.1% 11.8% Dean Wingerchuk et al. Long-term Safety and Efficacy of Eculizumab in Neuromyelitis Optica Spectrum Disorder • Combined safety data from PREVENT study plus open label extension (137 patients for a median of 107.9 weeks • Most common AEs headache (27.0%), upper respiratory tract infection (25.5%), nasopharyngitis (22.6%), urinary tract infection (16.8%), nausea (16.1%), back pain (15.3%) and diarrhea (15.3%) • Percentage of patients relapse-free at 192 weeks was 93.9% Levy M et al. Neurol. 2020; 94 (suppl). Wingerchuk D et al. Neurol. 2020; 94 (suppl).
Treatment Options: Under Investigation Satralizumab Benjamin Greenberg et al. Safety of Satralizumab Based on Pooled Data from Phase 3 Studies in Patients with Neuromyelitis Optica Spectrum Disorder (NMOSD) • Satralizumab is a IL-6 receptor antibody • Two phase 3 studies (SAkuraSky and SAkuraStar) • Combined safety analysis of 178 patients (satralizumab, n=104; placebo, n=74) • AE and SAE rates similar in both treatment arms • Most common AEs on both groups were urinary and upper respiratory tract infections. • Most AEs were mild to moderate • Study withdrawal due to AEs were • 4 in satralizumab arm • 6 in placebo arm Greenberg B et al. Neurol. 2020; 94 (suppl).
Treatment Options: Under Investigation Tocilizumab Itay Lotan et al. Effectiveness of Subcutaneous Tocilizumab therapy in Neuromyelitis Optica Spectrum Disorder • Tocilizumab is a IL-6 receptor antibody • Intravenous tocilizumab shown to be effective but requires trip to infusion center • Testing Subcutaneous tocilizumab 13 patients with NMOSD Average Annualized Relapse Rate Before treatment 2.2 + 2.0 After treatment (mean 29.8 + 19.8 months) 0.6 + 0.9 • Authors concluded that subcutaneous tocilizumab as effective as intravenous formulation Lotan I et al. Neurol. 2020; 94 (suppl).
Treatment Options: Under Investigation Inebilizumab B.A.C. Cree et al. Long-term Efficacy and Safety of Inebilizumab for Neuromyelitis Optica Spectrum Disorder in the Randomized, Double-blind N-MOmentum Study and Extension • Inebilizumab is a CD19 monoclonal antibody • N-MOmentum study randomized NMOSD patients (3:1) to receive inebilizumab (n=174) or placebo (n=56) for 6.5 months followed by open-label extension (n=216) • In randomized study, inebilizumab reduced risk of NMOSD attack by 77% • With open-label extension, 84.4% of patients did not have a NMOSD attack • Most common AEs were: urinary tract infection (22%), nasopharyngitis (16%) infusion- related reactions (12%) and back pain (12%) Cree BAC et al. Neurol. 2020; 94 (suppl).
Treatment Options: Under Investigation Cladribine Kondra Rejdak, Ewa Papuc. Cladribine supresses the activity of neuromyelitis optica: two year follow up study • Cladribine is a chemotherapy agent approved to treat RRMS • Retrospective medical records study of NMOSD patients treated with cladribine between 2013 and 2018 (n=11) • Cladribine was given at a cumulative dose of 1.8 mg/kg (s.c.) (divided into 6 courses every 5 weeks given for 4–6 days, depending on a patient’s body weight) Average Annualized Relapse Rate EDSS Score Before treatment or baseline 1.0 + 0.4 2.2 + 1.5 Two years after receiving treatment 0.23 + 0.3 2.3 + 1.3 • No signs of toxicity in any patients Rejdak K, Papuc E. Neurol. 2020; 94 (suppl).
Quantifying Paroxysmal Symptoms via Social Media Itay Lotan et al. Harnessing the power of social media to learn about a very rare disorder: survey of Facebook group about paroxysmal symptoms in Neuromyelitis Optica Spectrum Disorder • Facebook group (NMO Clinic’ Facebook ) survey used to assess paroxysmal symptoms • 206 NMOSD patients responded to the survey • 147 (71.4%) reported having at least 1 paroxysmal symptom lasting at least 2 minutes • Symptoms: • Tingling/numbness; 70.1% • Involuntary muscle contraction/abnormal posture; 61.9% • Hot/cold/burning sensations; 55.8% • Shock-like pain sensations; 49.7% • Paroxysmal symptoms aggravated by: • Fatigue; 71.8% • Physical activity; 58.5% • Neck bending; 24.6% Lotan Iet al. Neurol. 2020; 94 (suppl).
Summary • NMOSD is a rare autoimmune disorder • Symptoms vary and MS misdiagnosis common • Treatment available and many more under investigation • AAN 2020 • Improving diagnostic journey • Improving treatment options
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