2020 Symposia Series 2
Rheumatoid Arthritis: Best Practices in Diagnosis and Management in the Era of Novel Agents
Learning Objectives • Assess patients for signs and symptoms of rheumatoid arthritis (RA) • Identify novel therapies for RA and their appropriate use in clinical practice • Evaluate patients with RA for extra-articular manifestations and comorbidities 3
Prevalence of RA • 1.5 MILLION ADULTS in the United States have RA • 3x as many women as 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 (Hoboken). 4 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. 5 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 Anti-CCP = antibodies to 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. 6
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 progression of disease is linked to early treatment with DMARDs • Once bone and cartilage are damaged, they never return to normal • Severe functional decline • Radiographic damage Disease • Work disability onset • Premature death Optimal window of opportunity 7 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 Radiographs courtesy of Brian Peck, MD and Rick Pope MPAS, PA-C. 8
Radiographic Progression of RA (cont’d) • Joint-space narrowing 20 and erosion are seen in 16 up to two-thirds of patients within the first 12 Count 2 to 5 years of disease 8 • Irreversible damage can develop within 4 months of RA onset 0 0 5 10 15 20 Disease Duration (Years) Joint-space narrowing count Erosion count Deformity count 9 Wolfe F, et al. Arthritis Rheum. 1998;41:1571-1582.
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: ‒ Proximal interphalangeal (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. 10
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 11 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 12 Image courtesy of Lester Miller, MD.
Case Study: Tara, a 42-year old woman • Presents with a 3-month history of pain and stiffness in hands and right knee, as well as chronic fatigue • Complains of morning stiffness >30 minutes and increased pain at work as a post office mail sorter • 2 MCP joints (left hand) and 1 PIP joint (right hand) are visibly swollen • Height: 5 ft 2 in; weight: 150 lb; BMI: 27.4 kg/m 2 ; BP: 123/82 mm Hg • Previous clinician had diagnosed OA, prescribed NSAIDs, and suggested diet and exercise to lose weight • Mother had RA • Smoking status: 1/2 pack per day • Alcohol consumption: drinks socially 13 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 14 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 Axial joint/spondylitis No No Yes Less often 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 PsA = psoriatic arthritis. 15 Gottlieb A, et al. J Am Acad Dermatol. 2008;58:851-864; Mease PJ, Armstrong AW. Drugs. 2014;74:423-441.
Key Biomarker in RA: Anti-CCP 40 Progression of Joint Damage in Subgroups Radiographic Joint Damage Score of Early RA 30 Anti-CCP+ 20 10 Anti-CCP – 0 2 4 0 Time (Years ) 16 Van der Helm-van Mil AH, et al . Arthritis Res Ther . 2005;7:R949-R958.
Case Study: Tara’s Lab and Imaging Results • ANA: 1:60 (positive) • Anti-CCP: >250 u/mL (positive) • CRP: 20.5 (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 17 ANA = antinuclear antibodies; ESR = erythrocyte sedimentation rate.
Case Study: Next Steps • Based on the history, physical exam, lab tests, and x-rays, you suspect an inflammatory arthritis, most likely RA • You refer Tara to a rheumatology specialist for confirmation and management • Specialist performs a full workup and concludes that Tara has early, moderately active RA • Specialist discusses with Tara the advantages of treating RA aggressively to achieve clinical remission (or at least low disease activity [LDA]) 18
Treatment Strategy for RA: Treat-to-Target Task Force Algorithm Clinical Clinical Active remission sustained MAIN TARGET RA (eg, DAS) remission • Measure disease • Measure disease activity every activity ~3-6 months 1-3 months • Adapt therapy if • Adapt therapy state is lost accordingly 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. Grigor C, et al. Lancet. 2004;364:263-269. 19
Criteria for Clinical Remission • Definition: absence of signs and symptoms of significant inflammatory disease activity • According to ACR and EULAR, remission is achieved when: ‒ TJC, SJC, 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; SJC = swollen joint count; TJC = total joint count. 20 Felson DT, et al. Ann Rheum Dis . 2011;70:404-413.
The ACR Guideline for Early RA: How it Applies to Tara DMARD-naïve early RA Moderate or high Low disease activity Tara 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. 21
Case Study: Tara’s Management Plan • Tara 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 22
Case Study: 3-month Follow-up • Tara 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 23
Where Tara Is Now in the ACR Guideline for Early RA • 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 Tara 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. 24
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