Early Identification and Management of Rheumatoid Arthritis: The Critical Role of Primary Care
Learning Objectives • Assess patients for symptoms and signs of rheumatoid arthritis (RA) • Identify standard and novel therapies for RA and their appropriate use in clinical practice • Apply strategies to evaluate patients with RA for extra-articular manifestations and comorbidities 2
Prevalence of RA • 1.5 MILLION ADULTS in the United States have RA • 3x more women than men = 10,000 people Dadoun S, et al. Joint Bone Spine. 2013;80:29-33; Gonzalez A, et al. Arthritis Rheum. 2007;56:3583-3587; Humphreys JH, et al. Arthritis Care Res 3 (Hoboken). 2014;66:1296-1301; Myasoedova E, et al. Arthritis Rheum . 2010;62:1576-1582; Sokka T, et al. Arthritis Res Ther . 2010;12:R42.
Environmental and Genetic Risk Factors for RA • RA is thought to be associated with: ‒ Genetics ‒ Female sex Environmental factors (eg, smoking, periodontitis, pollution, gut microbiota*, others) Preclinical Genetic Clinical Outcomes (disability, (autoimmunity) background (inflammation) joint surgery) Intermittent mono- or oligo- Persistent symmetric Asymptomatic arthritis polyarthritis *Gut dysbiosis in patients with RA may result from an increased abundance of certain rare bacterial lineages. Managing RA by manipulating the gut microbiota is a new area of research. 4 Abella V, et al. Life Sci. 2016;157:140-144; Chen J, et al. Genome Med . 2016;8:43; Yarwood A, et al. Rheumatology (Oxford). 2016;55:199-209.
Pathogenesis of RA Genetic factors and Environmental triggers Synovial inflammation Cytokines Anti-CCP = cyclic citrullinated peptide; Cit = citrullinated peptide; DC = dendritic cell; MØ = macrophage; RF = rheumatoid factor. Adapted from: Smolen JS, et al. Nat Rev Drug Discov . 2003;2:473-488. 5
Importance of Early Diagnosis in RA • RA is progressive, not benign • Structural damage and disability occur within first 2 to 3 years of disease • Slower disease progression is linked to early treatment with DMARDs • Once bone and cartilage are damaged, they never return to normal • Disease Severe functional decline onset • Radiographic damage Early Established End Stage • Work disability • Premature death Optimal window of opportunity 6 Smolen JS, et al. Ann Rheum Dis. 2010;69:631-637; Smolen JS, et al. Ann Rheum Dis . 2017;76:960-977.
Radiographic Progression of RA 1987 2007 Images courtesy of Brian Peck, MD and Rick Pope MPAS, PA-C. 7
Articular Manifestations of RA • Swelling, tenderness, warmth, and painful motion • Morning stiffness ‒ May also appear after brief periods of inactivity • Inflammation of synovial joints • Joint and periarticular tissue destruction • Joints most often involved: ‒ PIP ‒ Metacarpophalangeal (MCP) ‒ Wrists, elbows, shoulders, knees, ankles, and subtalar and metatarsophalangeal (MTP) PIP Swelling joints Haudenschild DR, et al. In: Kelley ’ s Textbook of Rheumatology , 9th ed. 2012. Image from: Ostendorf B, et al. Ann Rheum Dis. 2005;64:501-502. 8
Early RA in a Young Woman • Symmetrical joint swelling in the hands • Swelling prominent in the PIP joints and in the left thumb interphalangeal (IP) joint 9 Image courtesy of Lester Miller, MD.
Early RA in a Young Woman • Swelling is particularly prominent in the MTP joints, especially the 1st and 5th MTPs 10 Image courtesy of Lester Miller, MD.
Case Study: Cameron, a 35-Year-Old Woman • 3-month history of pain and stiffness in hands and right knee, as well as chronic fatigue • Morning stiffness >30 minutes and increased pain at work as a mail sorter at the post office • 2 MCP joints (left hand) and 1 PIP joint (right hand) are visibly swollen • Height: 5 ft 2 in; weight: 150 lbs; BMI: 27.4 kg/m 2 ; BP: 123/82 mm Hg • Primary care clinician had diagnosed OA, prescribed an NSAID, and suggested diet and exercise to lose weight • Mother had “bad arthritis” • Smoking status: 1/2 pack per day • Alcohol consumption: drinks socially 11 NSAID = nonsteroidal anti-inflammatory drug; OA = osteoarthritis.
Squeeze Test Assessment • Squeeze test allows for quick clinical evaluation of MTP/MCP joints • Tenderness identified by gentle palpation of \ the joints 12 Emery P, et al. Ann Rheum Dis . 2002;61:290-297.
Common Disorders to Consider in the Differential Diagnosis of Arthritides RA OA PsA Gout Peripheral disease Symmetric Asymmetric Asymmetric Asymmetric (monoarticular) Axial joint/spondylitis No No Yes Infrequent Stiffness Morning/ With activity Morning/ Yes immobility immobility Enthesitis No No Yes Yes Nail lesions No No Yes No Psoriasis Uncommon Uncommon Yes Uncommon Female:male ratio 3:1 Hand/knee > in women 1:1 1:3 to 1:4 Gottlieb A, et al. J Am Acad Dermatol. 2008;58:851-864; Jin HJ, et al. Front Med (Lausanne) . 2020;7:339-346; Mease PJ, Armstrong AW. Drugs. 13 2014;74:423-441; Wallace KL, et al. J Rheumatol . 2004;31:1582-1587.
Key Biomarker in RA: Anti-CCP Progression of Joint Damage in Subgroups 40 of Early RA Radiographic Joint Damage Score 30 Anti-CCP+ 20 10 Anti-CCP – 0 2 4 0 Time (Years ) 14 Van der Helm-van Mil AH, et al . Arthritis Res Ther . 2005;7:R949-R958.
Case Study (cont’d): Cameron’s Lab and Imaging Results • ANA: 1:60 (positive) • Anti-CCP: >250 U/mL (positive) • CRP: 20.5 mg/L (positive) • ESR: 48 mm/hr (positive) • RF: 87 U/mL (positive) • Uric acid: 4.5 mg/dL (normal) • X-rays of hands and feet: normal 15 ANA = antinuclear antibodies; ESR = erythrocyte sedimentation rate.
Case Study (cont’d): Next Steps • Rheumatologist performs a full workup and concludes that Cameron has early, moderately active RA • Rheumatologist discusses with Cameron the advantages of treating RA aggressively to achieve clinical remission (or at least low disease activity [LDA]) 16
Treatment Strategy for RA: Treat-to-Target Task Force Algorithm Clinical Clinical Active MAIN TARGET remission sustained RA (eg, DAS) remission • Measure disease • Measure disease activity about activity about every 1-3 months every 3-6 months • Adapt therapy • Adapt therapy if accordingly state is lost Sustained LDA ALTERNATIVE TARGET LDA DAS = disease activity score. Task Force definitions: active RA = DAS44 score >2.4; remission = absence of signs and symptoms of significant inflammatory disease activity; sustained remission = remission sustained for 3-6 months; LDA = DAS44 score ≥1.6 to ≤2.4; sustained LDA = LDA sustained for 3 -6 months. Adapted from: Smolen JS, et al. Ann Rheum Dis. 2010;69:631-637. 17 Grigor C, et al. Lancet. 2004;364:263-269.
Criteria for Clinical Remission • Definition: absence of signs and symptoms of significant inflammatory disease activity • According to ACR and EULAR, remission is achieved when: ‒ Tender joint count, swollen joint count, CRP level (in mg/L), and Patient Global Assessment* (on a scale of 0-10 cm) are all ≤1; or ‒ SDAI score is ≤3.3 *Patient Global Assessment = patient self-reporting questionnaire. ACR = American College of Rheumatology; EULAR = European League Against Rheumatism; SDAI = Simplified Disease Activity Index. 18 Felson DT, et al. Ann Rheum Dis . 2011;70:404-413.
ACR Guideline for Early RA: How it Applies to Cameron DMARD-naïve early RA Moderate or high Low disease activity Cameron disease activity DMARD monotherapy DMARD monotherapy Treat to target Moderate or high disease activity • MTX is the anchor drug for treatment of RA Combination traditional DMARDs or TNFi +/- MTX or non-TNF biologic +/- MTX Strong recommendation Moderate or high disease activity Conditional recommendation See established RA algorithm MTX = methotrexate; TNFi = tumor necrosis factor inhibitor. Singh JA, et al. Arthritis Care Res (Hoboken) . 2016;68:1-25. 19
Case Study (cont’d): Cameron’s Management Plan • Cameron is prescribed MTX (20 mg/week orally) and folic acid • She is counseled on: ‒ Need for reliable contraception ‒ No alcohol within 24 hours of MTX dose ‒ Smoking cessation ‒ Diet and exercise to reduce weight 20
Case Study (cont’d): 3 -month Follow-up • Cameron complains that she’s had only minimal improvement in symptoms and that she has some nausea, vomiting, and hair loss from the MTX • Other findings ‒ Has reduced alcohol intake as instructed ‒ Has lost 5 lbs ‒ Hasn’t stopped smoking ‒ Still has 2 swollen MCP joints and knee pain 21
ACR Guideline for Early RA: Where Cameron Is Now • MTX is the anchor drug DMARD-naïve early RA for treatment of RA Moderate or high Low disease activity disease activity Strong recommendation Conditional DMARD monotherapy DMARD monotherapy recommendation Treat to target Moderate or high disease activity Cameron Combination traditional DMARDs or TNFi +/- MTX or non-TNF biologic +/- MTX Moderate or high disease activity See established RA algorithm Singh JA, et al. Arthritis Care Res (Hoboken) . 2016;68:1-25. 22
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