Rheumatoid Arthritis in Asians Mary C. Nakamura M.D. Professor of - - PDF document

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Rheumatoid Arthritis in Asians

Mary C. Nakamura M.D. Professor of Medicine, UCSF

NO DISCLOSURES

Rheumatoid Arthritis

• Polyarthritis of synovial lined joints
• Inflammatory
• Characteristic pattern, symmetric
• Cartilage degradation, erosion of juxtaarticular

bone, and joint deformities

• Systemic, Autoimmune disease
• Prevalence 1%

Rheumatoid Arthritis

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RA: articular symptoms

RA is an inflammatory arthritis:

• Swelling, effusion, warmth, erythema
• Morning stiffness
• Often lasts hours
• Can be the dominant symptom
• Joint pain and stiffness improve with activity
• “gel phenomenon”
• Stiffness recurs after prolonged inactivity

Inflammatory vs Degenerative Arthritis

• RA
• Pain after rest
• am Stiffness >30 min
• Soft tissue swelling
• variable course with

flares

• Specific joint pattern

not related to weight bearing

• Systemic illness
• OA
• Pain with use
• Stiffness <30 min
• Bony hypertrophy
• Progressive course

with chronic sx

• Weight bearing joints
• Systemically well

Inflammatory vs Degenerative Arthritis

• RA
• WRISTS
• MCPs
• PIPs
• NOT DIPs
• Systemic illness
• OA
• NOT WRISTS
• NOT MCPs
• PIPs
• DIPs
• Systemically

well

• Treat to Target
• Genetics and RA
• Ethnicity and Treatment Response
• Comorbidities
• Osteoporosis
• Cardiovascular Disease
• RA Treatment and Hepatitis B

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Early RA

Treat to Target

• Current recommended approach to RA treatment
• Setting specific goals to achieve remission or low

disease state, rapid escalation of treatment

• randomized controlled clinical trials demonstrated that

a TTT strategy can achieve superior clinical outcomes compared with usual care Potential Benefits

• Decreased long term joint damage
• Decreased symptoms
• ? Decreased comorbidities

Rev in Soloman Arth Rheum 2014 66:775

Treat to Target

Barriers

• Non‐rheumatologists not as comfortable with RA

medications particularly biologics

• Access to rheumatologist often not rapid
• Not all rheumatologist measure disease activity
• Medication side effects
• Costs of medications
• Patient preferences

RA: general features

• Female:male ratio of 3:1
• Peak onset (but can develop at any age)
• 4th or 5th decades (women)
• 6th to 8th decades (men)
• Genetic Predisposition
• HLA Class II – shared epitope
• Environmental Risk
• Smoking

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RA: genetic susceptibility

• Twin studies
• Concordance: monozygotic > dizygotic twins
• Concordance for monozygotic twins: 15‐30%
• Heritability 60%
• Multiple genes involved
• HLA
• 35% of overall genetic risk
• HLA‐DRB1 alleles (DR4)
• Relative risk for RA: 4 to 5‐fold
• Mechanism of risk uncertain

Manhattan plot from a GWAS study of RA

Criswell Immunological Reviews 233: 55, 2010

HLA

HLA

The Shared Epitope (DRB1*0401)

A74 Q70 A73 R72

‐confers susceptibility to RA

‐increases likelihood of CCP+ RA

Shared Epitope Hypothesis

HLA DRB1 alleles and RA

amino acid position on the DR chain DRB1 allele 70 71 72 73 74

0101 Q R R A A 0401 Q K R A A 0404 Q R R A A 0405 Q R R A A 0408 Q R R A A 1402 Q R R A A 1001 R R R A A CONSENSUS Q/R R/K R A A

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HLA shared epitope + smoking increases risk for RA (anti-CCP+)

Relative Risk

Copies of HLA shared epitope

EVER SMOKING NO SMOKING

Klareskog Arth Rheum 2006 11

1 2

Global prevalence rates of rheumatoid arthritis (RA)

Genetic Heterogeneity between Asian and European patients with RA

Ethnicity and Treatment Response

• Not well examined
• Study in UK retrospective look at RA pt receiving

DMARDs 1993‐2001

• 2 main ethnic groups N European and S Asian
• S Asian patients more likely to terminate DMARD

therapy.

• More common rash/lack of effect/concern re side effects
• Less GI and respiratory adverse events
• ? Communication
• ?cultural differences
• ?Genetic polymorphisms in drug metabolism
• More studies needed to understand cultural and

genetic differences

Helliwell Rheumatology 2003 42:1197

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RA Co‐morbidities

Osteoporosis

• Increased risk in small Asian females
• Increased risk with RA / prednisone
• Often Low calcium diet in Asians
• Asians have lower hip fracture than Caucasians but similar

vertebral fracture rates in general

• RA patients had a 2.2‐fold increased risk of fractures as

compared with general population

• In Asian RA patients, advanced age and history of prior fracture

were the most important risk factors for new fractures

• Increased Risk with high CCP Antibody titers

Kim Rheum Int 2016 36:1205 Xue Medicine 2017 96: e6983

RA – Co‐morbidities

Cardiovascular Disease

• Increased risk with RA active disease or long

standing

• Comparable to that of Type II DM as risk factor
• Higher CV morbidity and mortality
• CAD and CHF
• Risk decreased with adequate treatment with

methotrexate or biologics

• Study of 571 RA pts in Japan 11% Cardiovascular

events 1990‐2000: cardiac death, ACS, symptomatic CVA, or CHF

Nurmohamed Autoimmun Rev 2009 8: 663 Gabriel Curr Opin Rheum 2012 24:171

RA Treatments and Hepatitis B

• Asian Americans and Pacific Islanders (AAPIs)

account for more than 50% of nearly one million Americans living with chronic hepatitis B

• Nearly 70% of Asian Americans are foreign‐born

and estimates have found that approximately 58%

• f foreign‐born people with chronic hepatitis B are

from Asia

• Immunosuppressive therapy carries risks of

worsening chronic active disease and reactivating virus in those with latent disease

https://www.cdc.gov/hepatitis/populations/api.htm

Hepatitis B and RA

• Retrospective Case Control Study in China, 32 with

Chronic active Hep B, 128 age/sex/baseline disease activity matched

• Higher percentage of pt with radiographic

progression

• Higher percentage of pt with active disease f
• HBV reactivation in 34% (most not on prophylaxis)

Chen Arth Research and Therapy 2018 20:81

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All RA patients should be tested for Hep B status

• Testing should include
• HBsAb
• HBsAg
• HBcAb
• RA patients can be vaccinated against

HBV, considered safe and produces antibodies in 68%

• CANNOT Vaccinate pts that are receiving

Rituximab

Elkayam Ann Rheum Dis 2002 61:623

Rituximab for RA

Depletes peripheral B cells for > 6 months

N Engl J Med 350: 2572, 2004

No Antibody Response to Immunization following Rituximab until B cells return

Pescovitz et al J Allergy Clin Immunol 128:1295, 2011

RA patients receiving immunosuppressive treatment

Highest Risk Pt +HBVDNA >2000IU or HBeAg +

(>10% risk reactivation)

• HBsAg+ / HBcAb+ / HBsAb neg or
• HBsAb‐/ HBcAb+/ HBsAb neg

Need antiviral therapy prior to or concurrently with immunosuppression

• Lamivudine, entecavir only agents studied though tenofovir has been used in

reports

Moderate Risk Pt no detectable HBV DNA

(1‐10% risk reactivation)

• HBsAg neg /HBcAb+/HBsAb‐

Follow HBV DNA levels q2‐3 months

Seetharam Curr Hepatol Rep 2014 13:235

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RA patients receiving immunosuppressive treatment

• antiviral treatment should generally be continued

for six months after immunosuppressive drug therapy is discontinued

• Antiviral treatment should be continued for

12 months when rituximab is used or whenever HBV DNA above 2000 IU or 10,000 copies/mL is

• bserved at baseline

Vaccinations for RA patients

• Yearly Flu vaccine
• Pneumococcal PCV‐13 (prevnar conjugate) vaccination once.
• Pneumococcal PPSV‐23 (pneumovax polysaccharide) and

revaccination 5 years later.

• For persons ≥65 yo, consider the high‐dose formulation of influenza

vaccine which might be more effective.

• PCV13 vaccination should not be performed if the patient has received

PPSV23 vaccination within the prior 12 months.

• PPSV23 vaccination should not be performed if the patient has received

PCV13 within the past 8 weeks.

• Patients who received PPSV23 before age 65 should receive another dose
• f the vaccine at age 65 or later if at least 5 years have elapsed since their

previous PPSV23 dose.

• Hepatitis B
• Shingrix (new Shingles vaccine)

RA in Asian Populations

• General guidelines favor more aggressive treatment to

remission

• Refer early to rheumatologists
• Advance therapy with shared decision making
• Vaccinations for immunocompromised patients
• Genetic associations differ in Asian populations
• May have implications in drug response
• Comorbidities can be significant
• Osteoporosis Screening for all‐ limit steroids
• Cardiovascular Risk Assessments
• Treat other risk factors

RA in Asian Populations

Hepatitis B screening prior to immunosuppression

• Follow HBV DNA in HBcAb pos/HBsAb neg patient
• anti‐viral prophylaxis for high risk patients

10/1/2018 9 Thanks!!

• UCSF/SFGH RA Cohort

Patients, Physicians and Coordinators Russell/Engleman Rheumatology Research Center