NMOSD Abstract Highlights from AAN 2020 Michael Levy, MD, PhD - - PowerPoint PPT Presentation

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NMOSD Abstract Highlights from AAN 2020 Michael Levy, MD, PhD - - PowerPoint PPT Presentation

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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

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CME/CE

NMOSD Abstract Highlights from AAN 2020

Michael Levy, MD, PhD Associate Professor of Neurology, Massachusetts General Hospital

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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
  • f 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.

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What is NMOSD?

Treatment

  • Team approach
  • Immunosuppressive therapy (off label)
  • FDA approved treatment
  • Eculizumab
  • Under investigation
  • Inebilizumab (MEDI-551)
  • Cladribine
  • Rituximab
  • Satralizumab
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What is AAN 2020?

AAN Annual Meeting

  • Scheduled for April
  • Cancelled due to Covid-19
  • Abstracts published in Neurology Journal
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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).

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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

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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.

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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).

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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

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).

Relapse Rate Serious AEs Serious infections/infestations Eculizumab 3.8% 38.9% 11.1% Placebo 35.0% 47.1% 11.8%

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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).

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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
  • Authors concluded that subcutaneous tocilizumab as effective as intravenous formulation

Lotan I et al. Neurol. 2020; 94 (suppl).

Average Annualized Relapse Rate Before treatment 2.2 + 2.0 After treatment (mean 29.8 + 19.8 months) 0.6 + 0.9

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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).

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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)

  • No signs of toxicity in any patients

Rejdak K, Papuc E. Neurol. 2020; 94 (suppl).

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

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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).

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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