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Course: Ethnicity and Disease Biology: African-Americans and Other Minority Populations in MS

Track: Comprehensive Care

The 2014 Annual Meeting of the CMSC and the Sixth Cooperative Meeting with

ACTRIMSMay 28-May 31, 2014

Dallas, Texas

Multiple Sclerosis in African-Americans

Omar Khan, MDProfessor & Chair, Department of Neurology

Director, Sastry Foundation Advanced Imaging LaboratoryDirector, Multiple Sclerosis Center

Wayne State University School of Medicine, Detroit

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Objectives

• Clinical characteristics of multiple sclerosis in African-Americans

• MRI investigations of multiple sclerosis in African-Americans

• Retinal structure injury in African-Americans with multiple sclerosis

• CSF humoral and other environmental features related to African-Americans with multiple sclerosis

• Future directions and unmet needs

Multiple Sclerosis in African-Americans

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North African-MS European Caucasian-MS

Number of Patients 133 4144

Age at Diagnosis (yr) 29.7 32.5

RR (%) 66.6 61.5

Time from Dx to DMT (yr) 1.3 4.5

% EDSS 3 at Onset 40% 25%

Initial EDSS 3.1 2.4

Final EDSS 4.5 3.5

Mean Time to EDSS 6.0 6.0 16.0

African-Americans

(n=150)

Caucasians (n=150)

P-value

Gender (Females%) 79.3% 76.0% ns

Age (years) 38.48 + 7.95 37.99 + 8.77 ns

Disease Duration (years) 8.25 + 5.8 7.71 + 5.43 ns

Time to Onset of Rx (years) 3.55 + 3.32 3.46 + 2.28 ns

Mean EDSS 4.34 + 2.0 3.16 + 1.79 <0.0001

Patients Treated with DMT 140 138 ns

Wayne State University AA-MS Cohort

Khan et al. Neurology 2009

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Pediatric Neurol 2009

Annual Attack Rate

African-American children with MS: 1.8 + 1.14

vs

Caucasian children with MS: 1.13 + 0.5

P<0.001

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Quantifying CNS Tissue Injury in African-American with MS

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Voxels with demyelination

Voxels with stable MTR

Voxels with remyelination

Quantifying In-Vivo Myelin Content and Remyelination with vw-MTR

Lesions in African-Americans with MS on average have app 20% less remyelinating voxels after adjusting for age, disease duration,

gender, treatment exposure

Khan et al, works in progress

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Retinal Structure Imaging with

Optical Coherence Tomography

ILM – Inner Limiting MembraneNFL (RNFL) – Retinal nerve Fiber LayerGCL – Ganglion Cell Layer

IPL – Inner Plexiform LayerINL – Inner Nuclear layerOPL – Outer Plexiform Layer

ONL – Outer Nuclear LayerELM – External Limiting MembraneRPE – Retinal Pigment Epithelium

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Retinal Structure Injury in African-Americans with MS

AA-MS (n=61) vs CAU-MS (n=89)

Chorostecki et al., AAN 2014

Chorostecki et al., AAN 2014

Sub-Analysis: AA-MS (n=50) vs CAC-MS (n=68)(Without History of Optic Neuritis)

P<0.0001

AA-MS

CAU-MS

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Sub-Analysis: AA-MS (n=50) vs CAC-MS (n=68)(Without History of Optic Neuritis)

p=0.004

p=0.0004

Chorostecki et al., AAN 2014

AA MS CSF IgG Index: 1.35 + 0.62Caucasian MS CSF IgG Index: 1.05 + 0.55, (p=0.001)

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n African-Americans

n Caucasians P-value

Wash Univ Study CSF IgG Index

66 1.35 0.62 132 1.05 0.55 0.001

Wayne State UnivStudy CSF IgGIndex

150 1.50 + 0.86 150 1.08 + 0.88 <0.0001

Elevated African-American CSF IgG Index B-cell Humoral Response

Khan et al., 2009

SCC p value

CSF IgG Index & Time to EDSS 6.0

African-Americans

-0.41 0.002

Caucasians 0.004 0.96

Combined -0.54 <0.0001

500 600 700 800

Gray Matter Vol (ml)

1.00

2.00

3.00

4.00

5.00

6.00

IgG

ind

ex

CSF Humoral Response and Gray Matter Volume

Spearman Correlation Coefficient-0.565 (p=0.001)

Whole Group (n=196)

Spearman Correlation Coefficient -0.836

(P=0.0001)

Spearman Correlation Coefficient -0.018

(p=ns)

n=104 n=92

Khan et al., 2009

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Brain (2007), 130, 1089-1104

Perivascular cuffing a white matter phenomenon. Rarely seen in the gray Khan et al.

WCN 2009

Phase ImagingCourtesy: BruceTrapp

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Cortical Enhancing Lesions in African-Americans with MS

African-Americans

(n=92)

Caucasians (n-104)

P-value

% of Patients with Cortical Enhancing

Lesions29.7% 2.8% 0.0005

CSF IgG Index 1.50 + 0.86 1.08 + 0.88 <0.0001

Correlation between CSF IgG Index &

Cortical Enhancing Lesions

0.58 0.21<0.0001;<0.0001

Khan et al. WCN 2009

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HSG: High-school GraduateCG: College Graduate

DA: Disease Awareness

African-Americans (n=150) Caucasians (n=150)

Level of Education, Awareness, and Disease Severity

Ramesh and Khan, WSU GRS 2012

Klineova S, Nicholas J, Walker A.Response to disease modifying therapies in African Americans with multiple sclerosis. Ethn Dis 2012;22:221-5

Cree BA, Al-Sabbagh A, Bennett R, Goodin D.Response to interferon beta-1a treatment in African American multiple sclerosis patients. Arch Neurol2005;62:1681-3

Cree BA, Stuart WH, Tornatore CS, Jeffery DR, Pace AL, Cha CH. Efficacy of natalizumab therapy in patients of African descent with relapsing multiple sclerosis: analysis of AFFIRM and SENTINEL data.Arch Neurol 2011;68:464-8

Response to Disease Modifying Therapy

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Summary & Future Directions• Several studies indicate greater disability, CNS tissue injury, and sub-optimal response to therapy in African-Americans than Caucasians with MS.

• Quantitative MRI studies, retinal structure injury (OCT), and CSF studies suggest differences in disease biology.

• Prospectively designed multi-centered studies are warranted to examine the differences between African-Americans and Caucasians with MS including response to therapy.

• Studies must include impact of education, health awareness, and access to health care as covariates that may affect disease severity and outcomes