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

10/1/2018 NO DISCLOSURES Rheumatoid Arthritis in Asians Mary C. Nakamura M.D. Professor of Medicine, UCSF Rheumatoid Arthritis 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% 1

10/1/2018 RA: articular symptoms Inflammatory vs Degenerative Arthritis RA is an inflammatory arthritis: • OA • RA • Pain with use • Swelling, effusion, warmth, erythema • Pain after rest • Stiffness <30 min • Morning stiffness • am Stiffness >30 min • Bony hypertrophy • Often lasts hours • Soft tissue swelling • Can be the dominant symptom • Progressive course • variable course with • Joint pain and stiffness improve with activity with chronic sx flares • “ gel phenomenon ” • Weight bearing joints • Specific joint pattern • Stiffness recurs after prolonged inactivity not related to weight • Systemically well bearing • Systemic illness Inflammatory vs Degenerative Arthritis • Treat to Target • OA • Genetics and RA • RA • NOT WRISTS • Ethnicity and Treatment Response • WRISTS • NOT MCPs • MCPs • Comorbidities • PIPs • Osteoporosis • PIPs • Cardiovascular Disease • DIPs • NOT DIPs • Systemic illness • RA Treatment and Hepatitis B • Systemically well 2

10/1/2018 Treat to Target Early RA • 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 RA: general features Barriers • Female:male ratio of 3:1 • Non‐rheumatologists not as comfortable with RA • Peak onset (but can develop at any age) medications particularly biologics • 4 th or 5 th decades (women) • Access to rheumatologist often not rapid • 6 th to 8 th decades (men) • Not all rheumatologist measure disease activity • Genetic Predisposition • Medication side effects • HLA Class II – shared epitope • Costs of medications • Environmental Risk • Smoking • Patient preferences 3

10/1/2018 HLA HLA 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 The Shared Epitope (DRB1*0401) 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 A74 Q70 0408 Q R R A A A73 1402 Q R R A R72 A 1001 R R R A A CONSENSUS Q/R R/K R A A ‐ confers susceptibility to RA ‐increases likelihood of CCP+ RA 4

10/1/2018 HLA shared epitope + smoking Global prevalence rates of rheumatoid increases risk for RA (anti-CCP+) arthritis (RA) EVER Relative SMOKING Risk 0 NO SMOKING 1 11 2 Copies of HLA shared epitope Klareskog Arth Rheum 2006 Genetic Heterogeneity between Asian and Ethnicity and Treatment Response European patients with RA • 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 5

10/1/2018 RA – Co‐morbidities RA Co‐morbidities Cardiovascular Disease Osteoporosis • Increased risk with RA active disease or long • Increased risk in small Asian females standing • Increased risk with RA / prednisone • Comparable to that of Type II DM as risk factor • Often Low calcium diet in Asians • Higher CV morbidity and mortality • Asians have lower hip fracture than Caucasians but similar • CAD and CHF vertebral fracture rates in general • Risk decreased with adequate treatment with • RA patients had a 2.2‐fold increased risk of fractures as methotrexate or biologics compared with general population • Study of 571 RA pts in Japan 11% Cardiovascular • In Asian RA patients, advanced age and history of prior fracture events 1990‐2000: cardiac death, ACS, were the most important risk factors for new fractures symptomatic CVA, or CHF • Increased Risk with high CCP Antibody titers Nurmohamed Autoimmun Rev 2009 8: 663 Kim Rheum Int 2016 36:1205 Gabriel Curr Opin Rheum 2012 24:171 Xue Medicine 2017 96: e6983 RA Treatments and Hepatitis B Hepatitis B and RA • Asian Americans and Pacific Islanders (AAPIs) account for more than 50% of nearly one million • Retrospective Case Control Study in China, 32 with Americans living with chronic hepatitis B Chronic active Hep B, 128 age/sex/baseline disease • Nearly 70% of Asian Americans are foreign‐born activity matched and estimates have found that approximately 58% • Higher percentage of pt with radiographic of foreign‐born people with chronic hepatitis B are progression from Asia • Higher percentage of pt with active disease f • Immunosuppressive therapy carries risks of • HBV reactivation in 34% (most not on prophylaxis) worsening chronic active disease and reactivating virus in those with latent disease Chen Arth Research and Therapy 2018 20:81 https://www.cdc.gov/hepatitis/populations/api.htm 6

10/1/2018 All RA patients should be Rituximab for RA tested for Hep B status Depletes peripheral B cells for > 6 months • 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 N Engl J Med 350: 2572, 2004 Elkayam Ann Rheum Dis 2002 61:623 No Antibody Response to Immunization RA patients receiving following Rituximab until B cells return 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 Pescovitz et al J Allergy Clin Immunol 128:1295, 2011 Seetharam Curr Hepatol Rep 2014 13:235 7

10/1/2018 RA patients receiving Vaccinations for RA patients immunosuppressive treatment • Yearly Flu vaccine • antiviral treatment should generally be continued • Pneumococcal PCV‐13 (prevnar conjugate) vaccination once. for six months after immunosuppressive drug • Pneumococcal PPSV‐23 (pneumovax polysaccharide) and therapy is discontinued revaccination 5 years later. • For persons ≥65 yo, consider the high‐dose formulation of influenza • Antiviral treatment should be continued for vaccine which might be more effective. 12 months when rituximab is used or whenever • PCV13 vaccination should not be performed if the patient has received PPSV23 vaccination within the prior 12 months. HBV DNA above 2000 IU or 10,000 copies/mL is • PPSV23 vaccination should not be performed if the patient has received observed at baseline PCV13 within the past 8 weeks. • Patients who received PPSV23 before age 65 should receive another dose of 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 RA in Asian Populations • General guidelines favor more aggressive treatment to Hepatitis B screening prior to immunosuppression remission • Follow HBV DNA in HBcAb pos/HBsAb neg patient • Refer early to rheumatologists • anti‐viral prophylaxis for high risk patients • 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 8

10/1/2018 Thanks!! • UCSF/SFGH RA Cohort Patients, Physicians and Coordinators Russell/Engleman Rheumatology Research Center 9