Rheumatoid Arthritis (RA) - European University of Cyprus PDF

Arthriti (Rheumatoid Arthritis Dimitrioi Pappai MD MPH Aiiiitant Profeiior of Medicine Department of Medicine, Diviiion of Rheumatology Columbia Univeriity 1 Typei of Arthriti Degeneratve Arthriti – aka : oiteoarthriti, “wear and tear” arthriti … old age arthriti Infammatory arthriti – Rheumatoid ar...

Arthriti (Rheumatoid Arthritis Dimitrioi Pappai MD MPH Aiiiitant Profeiior of Medicine Department of Medicine, Diviiion of Rheumatology Columbia Univeriity 1 Typei of Arthriti Degeneratve Arthriti – aka : oiteoarthriti, “wear and tear” arthriti … old age arthriti Infammatory arthriti – Rheumatoid arthriti – Seronegatve ipondyloarthropathy Ankyloiing ipondyliti Pioriatc Arthriti Enteropathic Arthriti Reactve Arthriti – Juvenile arthriti – Cryitalline arthriti ( gout , pieudogouts – Other ( Lupui arthriti, HIV arthriti, hepatti related arthriti, Lyme arthriti etcs 3 4 5 6 7 8 9 Typei of Arthriti Degeneratve Arthriti – aka : oiteoarthriti, “wear and tear” arthriti … old age arthriti Infammatory arthriti – Rheumatoid arthriti – Seronegatve ipondyloarthropathy Ankyloiing ipondyliti Pioriatc Arthriti Enteropathic Arthriti Reactve Arthriti – Juvenile arthriti – Cryitalline arthriti ( gout , pieudogouts – Other ( Lupui arthriti, HIV arthriti, hepatti related arthriti, Lyme arthriti etcs 11 Typei of Arthriti Degeneratve Arthriti – aka : oiteoarthriti, “wear and tear” arthriti … old age arthriti Infammatory arthriti – Rheumatoid arthriti – Seronegatve ipondyloarthropathy Ankyloiing ipondyliti Pioriatc Arthriti Enteropathic Arthriti Reactve Arthriti – Juvenile arthriti – Cryitalline arthriti ( gout , pieudogouts – Other ( Lupui arthriti, HIV arthriti, hepatti related arthriti, Lyme arthriti etcs 12 Epidemiology of RA Annual incidence : 40/100,000 Prevalence: – Caucaiiani 1% – Rural Africani: 0.1% – Pima, Blackfeet, Chippeawa Indiani : 5% Lifetme riik – Femalei : 3.6% ( 1 in 28s – Malei: 1.7% (1 in 59s Gender: female >male Age: any – Peak : 50-75 yo – Prevalence in femalei >60yo : 5% – Juvenile formi of RA ( JRAs Complicated by blindneii Leg length diicrepancy 13 Riik Factori Gender ipecifc factori – Nulliparity – Poitpartum period – Lower teitoiterone leveli in men 14 Riik Factori Genetc factori contribute 53 -65% of the riik for RA – Twin iibling itudiei MZ concordance : 15% DZ concordance: 3.5% – HLA and non-HLA genei Shared epitope SNPi – PTPN22 minor allele of SNP 17% of gen populaton vi 28% in RA Aho K, Koikenvuo M, Tuominen J, Kaprio J Rheumatol. 15 1986;13(5s:899. Riik Factori Cigarete imoking – Cigi/day OR duraton – Interacton with genetc prediipoiiton – Increaiei concordance in twini Infecton – Proteui, Mycoplaima? – Viral – Porphyromonai gingivalii -> periodontal diieaie Occupatonal expoiurei – Silica (RR: 3.43, 95% CI: 2.25-5.22s 16 Pathophyiiology of RA RA Joint Normal Joint Early Capsule Angiogenesis Established Neutrophils T cells Synovial membrane Synoviocytes Synoviocyte accumulaton Dendritc cell Cartlage Adapted from Choy EH et al. N Engl J Med. 2001;344:907-916. B cells Plasma cell Neutrophils Bone erosion Pannus 17 RA Pathobiology Antgen-presentng Cells (APC) – B cells – Dendritc cells – Macrophages APC Rheumatoid factor (RF), ant–cyclic citrullinated peptde (ant-CCP) antbodies IL-4 IL-6 IL-10 B cell IL-6, TNF, IFNγ, IL-10, Lymphotoxin T cell IL-2 IFNγ TNF IL-17 RANKL Pannus Plasma cell MΦ Immune complexes Complement fxaton Attract infammatory cell infltrates TNF, IL-1, IL-6, Metalloproteinases Osteoclast Synoviocytes Chondrocytes JAKs Artcular cartlage Producton of metalloproteinases and other efector molecules Migraton of polymorphonuclear cells Erosion of bone and cartlage Adapted from Smolen and Steiner. Nature Rev Drug Discovery. 2003;2;473; Choy and Panayi. N Engl J Med. 2001;344:907., Silverman and Carion. Arthrits Res Ther 2003; 59(iuppl 4s:S1 18 Rheumatoid Arthriti Joint iwelling (iynovitis, tenderneii, warmth, erythematoui Morning itfneii Fatgue In ievere caiei : fever, anorexia, weight loii 19 Early PIP swelling Actve with some deformity Late-stage deformites 20 21 22 Diagnoitc evaluaton Phyiical examinaton for iynoviti Infammatory markeri RF , CCP antbodiei Serologiei/ teiti to diferentate from other infammatory arthritdei Imaging (xrayi, ultraiound, MRIs 23 Eroiioni – Earlier than xray Synoviti – More ieniitve US guided injectoni Guided injectoni more accurate – (93% veriui 66%; P 0.010). Earlier and greater improvement in joint functon Eipecially for complex jointi 28 29 RA: Guiding Principlei of Treatment Treat early Treat “hard” Treat with a targeted goal Aim for an acceptable beneft to risk rato 30 31 32 Treatment algorithm 1. 2. 3. 4. 5. 6. MTX 15 mg po weekly Eicalate MTX doie to 25 mg Add other traditonal DMARD ( SSZ,LEF, PLQs Add TNF-a inhibitor Switch to another TNF inhibitor Switch to an alternatve acton biologic 1. Abatacept (Orencias 2. Rituximab (Rituxans 3. Tocilizumab (Actemras , Sarilumab (Kevzaras 7. OR iwitch to a Κinaie inhibitor- JAK inhibitor 1. Tofacitnib (Xeljanzs 2. Baricitnib (Olumiants 3. Upadacitnib (Rinvoqs 33 It’s not just the joints CVD 10 Years Earlier  Osteoporosis Joint Destruction Disability Pain 2x  Rate Malignancy CVD=cardiovascular disease. Deane K. J Musculoskel Med. 2006;23:S24-S31. 6-9x  Serious Infection Rate  Pulmonary Disease  GI Bleeding 34 Systemic Manifestations of RA Eye – Scleritis, Episcleritis, Sjogren’s Cardiovascular – Atherosclerosis, Vascultitis, Pericarditis ENT – Sjogren’s, Cricoarytenoid Lung – Nodules, Fibrosis, Effusion Kidney and Gut – Amyloidosis, PUD (NSAID/Steroid) Dermatologic – Vasculitis, Nodules, Raynaud’s, Skin thinning (Steroid) Nervous System – Peripheral neuropathy Hematologic – Granulocytopenia, Anemia, Thrombocytosis, Splenomegaly 35 Increased Mortality in Patients with RA Kaplan-Meier Survival Curves in a U.S. Population U.S. Females U.S. Males Stanford RA Females Stanford RA Males Survival Probability 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 Standardized Mortality Ratio = 3.08 for RA pts 0.2 0.1 0.0 0 5 10 15 Years After Entry into Study N=886 RA patients. Wolfe F, et al. Arthritis Rheum. 1994;37:481-494. 20 25 36 Risk of MI, Stroke and CV-related Death are all Increased for Persons with Rheumatoid Arthritis Event Rate per 1000 person-years RR 1.6 (1.5 – 1.7) * RR 1.8 (1.7 - 2.0) RR 1.9 (1.7 - 2.1) RR 1.3 (1.2 – 1.4) Myocardial infarction (MI), stroke, or cardiovascular (CV) death defined by ICD-9 codes in B.C. population 37 Solomon DH, et al. Ann Rheum Dis. 2006;65:1608-1612. Lung involvement in RA Lung involvement in RA – common extraarticular manifestation of RA – confers significant morbidity and mortality Kim DS. Interstitial lung disease in Rheumatoid arthritis: recent advances. Curr Opin Pulm Med. 2006 Sep;12(5):346-53. 38 - Lifetime risk of ILD: 7.7% for RA patients vs 0.9% for non-RA subjects. - (HR) of 8.96 [95% CI] 4.02– 19.94). Bongartz T, et al. Arthritis Rheum. 2010 Jun;62(6):1583-91 39 -Risk of death for RA patients with ILD: 3 times higher vs RA patients without ILD. -(HR 2.86 [95% CI 1.98-4.12]). - Similar contribution as CVD to excess mortality in RA. Bongartz T, et al. Arthritis Rheum. 2010 Jun;62(6):1583-91 40 Chronic obstructive pulmonary disease (COPD) more frequent in patients with RA than in the general population – after adjusting for smoking – greater impact on survival Nannini C, et al. Does the incidence and mortality of obstructive lung disease difer between subjects with and those without rheumatoid arthritis? A population-based study. http://www.abstractsonline.com/viewer/SearchResults.asp. 2007. Geddes DM, Webley M, Emerson PA. Airways obstruction in rheumatoid arthritis. Ann Rheum Dis. 1979 Jun;38(3):222-5. 41 “Early Intervention” Can Alter the Disease Course of RA: How about RA co-morbidities? Early RA Intermediate Late Severity (arbitrary units) Inflammation Disability Radiographs © ACR 0 5 10 15 20 25 30 Duration of Disease (years) Graph: Adapted from Kirwan JR. J Rheumatol. 2001;28:881-886. Photo: Copyright © American College of Rheumatology. 42 Methotrexate Use Associated with a Reduction in All-Cause and CV Mortality in Patients with RA Hazard ratio: 95% CI All-Cause Mortality Cardiovascular Mortality Non-Cardiovascular Mortality.2.4.8 1.0 1.5 2.0 4.0 Methotrexate Superior vs Other Treatments Adjusted for age, sex, RF, calendar year, duration of disease, smoking, education, disease activity measures, and prednisone status. Methotrexate Inferior Choi HK et al, Lancet. 2002;359:1173-1177. 43 TNF Inhibitor Use is Associated with Reduced Mortality in Patients with RA Hazard ratio: 95% CI Anti-TNF exposed adjusted for age and sex Anti-TNF exposed adjusted for age, sex, HAQ Anti-TNF exposed adjusted for age, sex, HAQ, and co-morbidity 0 0.5 1 1.5 Registry of Swedish RA patients 7mg 46 Solomon DH et al. Presented at ACR 2008; San Francisco, CA. Abstract 1016.