Navigating MOGAD: Case-Based Insights Into Diagnosis, Treatment, and Management of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

Chair, Michael Levy, MD, PhD, discusses MOGAD in this CME activity titled “Navigating MOGAD: Case-Based Insights Into Diagnosis, Treatment, and Management of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.” For the full presentation, downloadable Practice Aids, and complete CME information, and to apply for credit, please visit us at https://bit.ly/40rN8Is. CME credit will be available until March 9, 2026.

1. Navigating MOGAD

Case-Based Insights Into Diagnosis, Treatment,
and Management of Myelin Oligodendrocyte
Glycoprotein Antibody-Associated Disease

Michael Levy, MD, PhD
Associate Professor

Harvard Medical School

Director

Neuroimmunology Clinic and Research Laboratory
Research Director

Division of Neuroimmunology & Neuroinfectious Disease
Department of Neurology

Massachusetts General Hospital

Boston, Massachusetts

Copyright © 2000-2025, PeerView

2. Introduction

Michael Levy, MD, PhD

Associate Professor

Harvard Medical School

Director

Neuroimmunology Clinic and Research Laboratory
Research Director

Division of Neuroimmunology & Neuroinfectious Disease
Department of Neurology

Massachusetts General Hospital

Boston, Massachusetts

Go online to access full CME information, including faculty disclosures.

Copyright © 2000-2025, PeerView

3. Our Goals for Today

Prepare you to apply the latest diagnostic guidance
Improve your skills in recognizing and assessing MOGAD

Enhance competence and confidence in preventing and
managing MOGAD relapses

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4. hat Is MOG Antibody Disease?

Anti-MOG

Multiple disease

sclerosis

Neuromyelitis optica
spectrum disorder
(NMOSD)

Short TM,
4%

[ON + TM, 9%

Bilateral ON
24%

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5. | MOGAD Sympto
ported Survey Respondents’

21
(n=41)

193
(0225 ea) 113
(n=) 92

= 82
9 (n= 16)

5146
01D (ne) wer

No. of Respondents, %

e
e pod e e S $
“df
> # Se
1. Santoro ID et al. Neuro! Tr, 2023.121081-1101. PeerView

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6. Distinctions Among MOGAD, NMOSD, and MS!

AQP4IGG +NMOSO

cana! course

Optic nerve

Optic neuritis

Spinal cord

Brain MRI

C5F—oligodonal bands

MOG-IgG seropositive
Otigodendroglopathy
Peciatie and acu

Monophasio or relapsing
Resembles AQP4.IgG + NMOSD

Lesion usually lateral and anterior at onset;
Iongtudnaly extensivo; recovery favorable

Bilateral ON seen in 31%-58% of cases

= Single or multiple longitudinal extensive
lesions

Gray matter involvement leading to H-2ign
and conos lesions

Encephalopathy, seizures, focal dect and
‘cerebral coral encepnalis

+ Might be normal in optic neurti or myekts,

Integuent

+ AQPA-IgO seropositve
+ Astoeytopathy
Beery

+ Usually reapsing

+ Lesion bilateral or unlatera; longitudinally
“extensive and chiasma rk or poor recovery

+ Bilateral or uniateral seen in 13%-37% of cases

+ Single longtucinaly extensive lesion
+ Commonly involves entre ransverse diameter

+ Area postrema symptoms, hiccups
hyparsomnolence, and focal neurological
secas

Multocal 72 lesions mote common in AOP4-
rh regions; may appear near and along
corticospinal trat or medulla

+ Inreguent

1. Hennes EM eta Neuopediaics. 2018;493-11. 2. Kaneko K et al J euro! Neurosurg Psychiatry. 20160 227-356
3. BanwellB el al Lancet Neurol, 2023 22 288-282.

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MOGIgG detected 2%
rta)
Usually aut

Relapsing, secondary progressive, er progressive

Unilateral and anterior: recovery favorable
Unilateral, seen in ess than 5% of cases

Multiple focal cord lesions, ofen posterior and
Inveling ony porton of the cross-sectional area
ofthe cord conus rarely involved

Muklocal T2hyperinense white mater lesions

Rare ovoid or round, weltdemarcated T2 lesions:
Dawsen's fingers, S-shaped or Ufer lesions:
central vein sign; smoldering or slowly evohing
lesions

Residual T1-hypointense lesions frequent

Extremely frequent

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7. International MOGAD Panel: Diagnostic Criteria‘

Diagnosis of MOGAD (Requires Fulfilment of A, B, and C)
Core clinical | + Optic neuritis + Cerebral monofocal or polyfocal deficits:
A | demyelinating | - Myelitis + Brainstem or cerebellar deficits
arent |: ADEM + Cerebral cortealencephalis often wth seizures
Clear positive No additional supporting features required
Positive Cell-based Low positive
MOG-IgG test | assay: serum Positive without reported ter 2 SARA ENS

21 supporting clinical or MRI feature
Negative but CSF positive
+ Bilateral simultaneous clinical involvement — + Perineural optic sheath enhancement

Optic neuritis, Longitudinal optic nerve involvement (>50% + Optic disc edema
B | length of the optic nerve)

+ Longitudinally extensive myelitis

‘Supporting Myeliis + Central cord lesion or H-sign
clinical or Beanie baa
MRI features:

Multiple il-defined T2 hyperintense lesions in supratentorial and often infratentorial white matter
er Deep gray matter involvement

phar ll-defined T2-hyperintensity involving pons, middle cerebellar peduncle, or medulla

yt Cortical lesion with or without lesion and overlying meningeal enhancement

© Exclusion of better diagnoses, including multiple sclerosis

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Brain, brainstem,

1. Bannel B et al. Lancet Neuro. 2023:22:268-282,

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8. Standard of Care for Managem

Methylprednisolone IV 1,000 mg daily
(or 30 mg/kg in children)
x 5 days + prolonged oral taper

If no
improvement

PLEX 1-1.5 volumes x 5 cycles
OR
intravenous immunoglobulin (IVIG)
at 2 g/kg (divided over 1-5 days)

Second line

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9. Impact of Steroids on MOGAD Relapse Rate’

Episodes during oral
prednisone weaning

40
Episodes following oral
a M prodrisone cassation
$
El 20
E
10
0
Adult dosage, ES» az 8 oS & 8.6 P $
matey EPS LILIA AAA AA
Pediatric dosage, 1.0 0.75 05 0.25 0
mgkg/day AL |
Dosage of Prednisone Time From Prednisone
at Time of Relapse Cessation to Relapse, mo

1. Ramanathan . J Neuro! Neurosurg Psychiat. 201829127 PeerView

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10. IVIG for Acute MOG Relapses!

E

‘Attack phenotype, n (%)
‘Unilateral ON

Bilateral ON

Myeltis

Brainstem syndrome
Encephalitis

‘ADEM

Multifocal

ct

ities of MOG:

IMG treatment dose (protocol), (75)
08 gikg (04 gg x2 days)
199 (1 gkg x 1 day)
12909 (04 gkg x 3 days)
4132 gkg (0.66 go x 2 days)
1.6 g/kg (0.4 g/kg x 4 days)
1.98 gikg (0.56 gg x 3 days)
2909 (04 gkg x 5 days)

2 9/Kg (1 g/kg x 2 days)

24 ghkg (04 gg x6 days)
Additional treatments, n (%)
None

Im

MP + oral cS
IVMP + TPE

IVMP + oral CS + TPE

1. Lotan Het. Mult Solor, 2023,20:1080-1080.

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14859)
5(128)
307)
128)
128)
8205)
7079)

16)
125)
307)
125)
129)
2452)

1736)

1208)
126)

5(128)
15885)
5028)
9(231)
5(128)

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11. Efficacy of IVIG for Acute MOGAD Attacks’

8 P<.0001

P< 0001

Expanded Disability
Status Scale

Nadir End ofTx First Follow-Up

4 Loan leal. Mut Sele. 2023.20: 1080-1080

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P< 0001
2

P<.0001

22
5
3
<
=
E
21

o

Nadir EndofTx First Follow-Up
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12. Identifying Candidates for Pre: ive Treatment!

Unclear which patients will remain
monophasic after first attack

f + Attack severity and frequency + Relapse-free interval
+ MOG-IgG sero-status and titers + Spinal cord involvement
+ Patient age + Neurologic disability

vi
1.ALAN A et al. J euro 2023.8:1-19. rView

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13. abel Preventive T

rapy

IVIG 1 g/kg Q4W = 60% response rate
IVIG 2 g/kg Q4W = 80% response rate
SCIG 0.4 g/kg Q1W

Limited by cost and headaches
Try for as long as can be tolerated

~1,000 mg/m? PO daily
~500-600 mg/m? PO BID

Cost effective
Monitor absolute lymphocyte
count for efficacy

8 mg/kg IV Q4W
162 mg SC Q1W

Recently used as alternative
Some small observational trials
to support use

20 mg PO daily
Use when all else fails

Avoid long-term use because of AEs
Must taper when discontinuing!
Can be difficult to wean off

CECE

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14. 2
©
£ 10 mg fr 1m
= Smoke
&
¿mgrg
10
a)
1 a 215m6
moro
2 ¿m9%a,

¿mara

2 moo

40 9 8 7 6 5 4 3 2 1 0

1. Rigelsten Meta, Neurol Nourommanol Neuroinfamm. 2022.9:e1109.

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ater 11.5 mo, 162 mov, sc

À First attack

© Further attacks

1 Riwximab

1m Azathioprine

2 Belimumab

M Tociizumab

IE Mycophenolate mofetil
1 Tofacitnib

M Methyiprednisolone
M Methotrexate

IM Cyclophosphamide
mmc

10

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15. Current Phase 3 Trials in MOGAD Relapse Prevention
Ia Ad Rd LA

E

BAS

Satralizumab

Tocilizumab

Rozanolixizumab| Azathioprine

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16. Rozanolixizumab Ti

| Design!

Randomized, double-blind, placebo-controlled, phase 3 study (cosMOG)

Rozanolixizumab
subcutaneous infusion

+ Goal: 104 participants (recruiting)

* Initial double-blind period to be followed by
open-label extension

* Study start date: February 2022
+ Estimated primary completion: May 2027

* Estimated study completion: July 2027 Placebo
subcutaneous infusion

Primary outcomes:
+ Part A: time from randomization to first relapse
+ Part B: treatment emergent AEs; TEAE leading to study discontinuation

1. Ms si inc. goveshowNNCTOS060162 PeerView

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17. Clinical Rationale for a Neonatal Fc Receptor

in MOGAD Treatment!?

Clinical Outcome in MOG;;.;s EAE
With MOG-IgG Augmentation’

road

Preclinical evidence

+ Rozanolixizumab is a high-affinity mAb against
FeRn that favors the degradation of pathogenic
autoantibodies

Approved for the treatment of myasthenia gravis in
AChR or MuSK antibody-positive patients and
shows promise in trials in immune thrombocytopenia

al Score (mean + SEM)

Clinical evidence

eon Nweeauaro

In a study in murine MOG-IgG-associated
experimental autoimmune encephalomyelitis, OF Bi AOL RAA EUR
an anti-FeRn antibody prevented reduction in Days Postimmunization

visual acuity and showed positive effects on
spinal cord manifestations

= MOS), + MOG:EG: aeRO 27) } crn oF IgG sotype 30 mrtg
+ MOG,., +MOS BG: app tn 24) | MOGI8S 200 pg

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1. Reminger Jet al. Neurol Nevroimmuno! Neuroinlamım. 2022.9:e1134. 2. hips ww. govinews-eventspress-announcemens/kl-roundupjune-23-2023.

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18. Satralizumab Trial Design’

Randomized, double-blind, placebo-controlled, phase 3 study (Meteoroid)

Satralizumab
subcutaneous injection
* Loading dose of drug or placebo at weeks 0, (as monotherapy or in addition
2, and 4, and then monthly thereafter to baseline therapy)
Initial double-blind period (~44 months)
followed by OLE (~24 months)
Study start date: August 2022

Estimated primary completion: July 2026

* Goal: 152 participants (recruiting)

Placebo
subcutaneous injection

* Estimated study completion: December 2028

Primary outcome: time from randomization to the first MOGAD relapse in the double-blind
treatment period, as determined by an independent clinical adjudication committee

1. ipsa cial gout ho OTOS27 400, PeerView

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19. Clinical Rationale for IL-6 Inhibition in MOGAD!:!7

Preclinical evidence

CSF IL-6 Levels in Patients
2
+ IL-6 levels are increased in the CSF and possibly serum of MOGAD With Demvelinating Diseases
patients'+

+ Peripheral Th17-cell subset increases during MOGAD attacks and
decreases in the remission phases wo

IL-6, pg/mL
Bee 8

+ IL-6 receptor antagonist tocilizumab, used off label, was shown to be
effective in >20 patients with MOGADS-13

+ Satralizumab significantly reduced relapse risk in AQP4-IgG+ NMOSD,
an autoantibody-driven disease that is clinically similar to MOGAD'+"5

+ Satralizumab was investigated in adolescents and adults with NMOSD,
with up to 7 years of exposure'®.'7 MOG+ AQP4+ MS Control

1. KothurK et al, PLOS One 2016:11:e0149411, 2. Kaneko K etal. Neurol Neurosurg Paychistry.2018;89:827-938. 3 Serguera C et al. JNeuronfammaton.

2019:16:244. 4. Hofer LS etal. Mu Sr J Exp Trane! Cin. 2018: 2055217319848483, 5. Lu Jet al J Newel Neurosurg Poychiaty. 2020:91:132-139.

8. Hayward Koennecke H et al, Neurology 2019:92:785-787. 7. NoviG et al Mult Scer Rat Disord, 2019.27-312-314. 8. Lota let al. Mat Scie Relat Disord.

2019:30-101620 9 elec et al. J Newreophthalmel.2019;30:3-7. 10. Ral Jet al. Mult Scler Relat Disord. 2020;48 102483. 11. Elsbernd PM et al. Mut Seler Relat

Disora. 2021:48;102606, 12. Masucco FG et al Mult Soler Relat Dis 2020-46:102502. 13. Rngesten M et al, euro! Neuroimmunot eurent.

2022821100. 14. Yamamura Teta. N Engl Med, 2019:3812114-2124. 15. Traboulsee A et al. Lancet Neurol 2020:19:402-12 PeerView
16. Yamamura T et al. Mult See Rola! Disord, 2022:66:104025. 17. Kite | et al. Neuro! Neuremmunol Neurinfarm. 2022:10:e200071.

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20. Navigating MOGAD Treatment
Case-Based Considerations

Michael Levy, MD, PhD

Associate Professor

Harvard Medical School

Director

Neuroimmunology Clinic and Research Laboratory
Research Director

Division of Neuroimmunology & Neuroinfectious Disease
Department of Neurology

Massachusetts General Hospital

Boston, Massachusetts

Go online to access full CME information, including faculty disclosures.

Copyright © 2000-2025, PeerView

21. Clinical Case: Sarah
4-year-old girl

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oe,

=

E

wwe

Seizure Confusion

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22. Clinical Case: Sarah
4-year-old girl

How would you approach assessing and diagnosing her case?
Any diagnostic considerations for a child her age?

What therapies would you consider in her treatment?

Is there is any evidence specifically supporting or contraindicating
any therapeutic approach?

What are her risks for relapse?
What are long-term therapeutic implications in this case?

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23. Clinical Case: Sarah
13-year-old girl

&

Sudden vision loss Orbital pain

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24. Clinical Case: Sarah

13-year-old girl

How would you approach assessing and diagnosing her case?

Any diagnostic considerations for based on her age? Anything different
from a younger or older child?

What therapies would you consider in her treatment?

Is there is any evidence specifically supporting or contraindicating any
therapeutic approach?

What are her risks for relapse?

What are long-term therapeutic implications in this case?

je}
Q
a
a

oo

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25. Clinical Case: Sarah
35-year-old woman

Blurred vision Urinary incontinence

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26. Clinical Case: Sarah

35-year-old woman

How would you approach assessing and diagnosing her case?
Any diagnostic considerations for based on her age? Anything different

from a child or adolescent?

What therapies would you consider in her treatment?

Is there is any evidence specifically supporting or contraindicating any
therapeutic approach?

What are her risks for relapse?

What are long-term therapeutic implications in this case?

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27. Conclusions

Michael Levy, MD, PhD

Associate Professor

Harvard Medical School

Director

Neuroimmunology Clinic and Research Laboratory
Research Director

Division of Neuroimmunology & Neuroinfectious Disease
Department of Neurology

Massachusetts General Hospital

Boston, Massachusetts

Go online to access full CME information, including faculty disclosures.

Copyright © 2000-2025, PeerView

28. Y MOGAD was identified as a distinct disease only recently, and it
remains challenging to diagnose

Y Recommended diagnostic tools, including the MOG antibody test,
can distinguish MOGAD from NMOSD and MS

Y To date, no therapies are specifically indicated for MOGAD, but we
have off-label strategies for acute care and prevention

W Phase 3 trials are ongoing to assess safety and efficacy of multiple
agents in relapse prevention

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29. Y MOGAD was identified as a distinct disease only recently, and it
remains challenging to diagnose

Y Recommended diagnostic tools, including the MOG antibody test,
can distinguish MOGAD from NMOSD and MS

Y To date, no therapies are specifically indicated for MOGAD, but we
have off-label strategies for acute care and prevention

W Phase 3 trials are ongoing to assess safety and efficacy of multiple
agents in relapse prevention

PeerView

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