Clinical Challenges in Arthritis: Care Plans and Interventions That Achieve Results Primary Care Updates Boston, Massachusetts September 19, 2013

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1 Clinical Challenges in Arthritis: Care Plans and Interventions That Achieve Results Primary Care Updates Boston, Massachusetts September 19, 2013 Content Collaborator:

Session 1: Clinical Challenges in Arthritis: Care Plans and Interventions that Achieve Results Learning Objectives 1.

Ensure early recognition and treatment of rheumatoid arthritis to prevent joint damage and disease progression Faculty M.

Medicine Senior Advisor, Internal Medicine Clinical Care Center Lankenau Medical Center Philadelphia, Pennsylvania Dr M.

2 Session 1: Clinical Challenges in Arthritis: Care Plans and Interventions that Achieve Results Learning Objectives 1. Help your osteoarthritis patients manage their symptoms and improve their functioning by implementing proven, evidence-based clinical interventions 2. Ensure early recognition and treatment of rheumatoid arthritis to prevent joint damage and disease progression Faculty M. Susan Burke, MD, FACP Clinical Assistant Professor Thomas Jefferson University Medical School Adjunct Clinical Associate Professor Department of Geriatrics Philadelphia College of Osteopathic Medicine Senior Advisor, Internal Medicine Clinical Care Center Lankenau Medical Center Philadelphia, Pennsylvania Dr M. Susan Burke is a clinical assistant professor of medicine at Thomas Jefferson University in Philadelphia; an adjunct associate professor of geriatrics at the Philadelphia College of Osteopathic Medicine; and a senior advisor at the Lankenau Internal Medicine Clinical Care Center in Wynnewood, Pennsylvania. Dr Burke graduated from the University of Pennsylvania School of Medicine in 1979 and completed a residency in internal medicine at Lankenau Hospital (now the Lankenau Medical Center) in She is board certified in internal medicine and geriatrics and a fellow of the American College of Physicians. Dr Burke is a two-time recipient of the Osler-Blockley Teaching Award from Jefferson and has also received the residents best teacher award from the Lankenau internal medicine house staff. She has been named Top Doctor for Women and, more recently, Top Doctor, by Main Line Today magazine. Dr Burke lectures nationally and has published chapters, articles, and CD-ROMs on numerous primary care and geriatric topics in publications such as the Journal of the American Osteopathic Association and the Annals of Long-Term Care. Faculty Financial Disclosure Statement The presenting faculty reports the following: Dr Burke receives speaking and teaching honoraria from Merck, and served on an advisory board for Iroko Pharmaceuticals.

3 Presenter Disclosure Information SESSION 1 8 9:15am Clinical Challenges in Arthritis: Care Plans and Interventions That Achieve Results SPEAKER M. Susan Burke, MD, FACP The following relationships exist related to this presentation: Dr Burke is on the speaker s bureau for Merck, Inc. Off-Label/Investigational Discussion In accordance with pmicme policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations. Learning Objectives Arthritis Prevalence in U.S : 50 million adults Implement proven, evidence-based clinical interventions that will help your osteoarthritis patients manage their symptoms and improve their functioning Ensure early recognition and treatment of rheumatoid arthritis to prevent joint damage and disease progression Impact of arthritis on quality of life Now: >9% adults have limitation 2030 projection: 37% adults will have limitation _nhis.htm#gender_specific Approach to the Patient With Joint Symptoms Duration of symptoms Pattern of joint involvement Number of joints involved Mono-, oligo-, or polyarthritis Small joints and/or large joints Axial joints and/or peripheral joints Symmetry Are there symptoms of inflammation? Or, is the problem primarily mechanical? Patterns of Joint Involvement in Arthritis Rheumatoid Arthritis Osteoarthritis 1

4 Case Study 1 Andy Osteoarthritis Symptoms and Signs A 58-year-old man comes to your office complaining of a one year history of progressive left knee pain. He has no other joint complaints His pain is more prominent after he has been standing or walking There is joint stiffness in the morning lasting minutes He has not noted any swelling Symptoms Pain worse with use Pain worse later in the day Minimal AM stiffness Diminished range of motion Signs Joint tenderness Crepitus Bony enlargement Restricted movement Variable swelling or instability Distribution of Primary OA Radiographic Features Spine- cervical and lumbar Hips Knees Hands 1 st MTP Joint space narrowing Marginal osteophytes Subchondral cysts Bony sclerosis Malalignment Laboratory Studies OA: Hip Joint No specific tests ESR and CRP are typically normal If there is a concern for RA, a RF and anti-ccp should be performed and should be negative Synovial fluid analysis is non-inflammatory WBC < 2,000 No crystals X-ray shows osteophytes, subchondral sclerosis, and complete loss of joint space Patients often present with deep groin pain that radiates into the medial thigh ESR= erythrocyte sedimentation rate RF= rheumatoid factor CRP= C reactive protein anti-ccp = anti-cyclic citrullinated peptide antibodies 2

5 OA: Risk Factors Age: 75% of persons over age 70 have radiographic OA Female sex Obesity Hereditary Trauma Neuromuscular dysfunction Metabolic disorders Diabetes Hemochromatosis OA Progression Natural history of OA: Progressive cartilage loss, subchondral thickening, marginal osteophytes American College of Rheumatology Case Study 2 Maggie A 68-year-old woman presents to your office with complaints of pain and stiffness in both knees, hips, and thumbs. She also has occasional back pain Family history reveals that her mother had a total knee arthroplasty and her sister is scheduled for hip arthroplasty On exam she has bony enlargement of both knees, restricted ROM of both hips, squaring at base of both thumbs, and multiple Heberden s and Bouchard s nodes Case Study Maggie: OA Hands OA: Carpometacarpal Joint Radiograph shows severe changes Most common location in hand May cause significant loss of function Non-Pharmacologic Therapy for Hand OA ACR Conditional Recommendations Evaluate ADLs Instruct joint protection techniques Provide assistive devices Thermal modalities Splints for carpometacarpal OA Hochberg MC, et al. Arthritis Care Res (Hoboken) Apr;64(4):

6 Hand OA: Pharmacologic Recommendations ACR Conditional Recommendations Use: Topical capsaicin Topical NSAIDs Oral NSAIDs Tramadol Do Not Use: Intraarticular therapies Opioid analgesics In persons >75 yrs of age Topical over oral NSAIDs ACR Knee OA: Non-Pharmacologic Recommendations Strong Recommendations: A physical activity program should be considered for patients of all ages Cardiovascular and/or resistance land-based exercise Quad weakness may be risk for knee OA progression Aquatic exercise Hochberg MC, et al. Arthritis Care Res (Hoboken) Apr;64(4): Hochberg MC et al. Arthritis Care Res (Hoboken) Apr;64(4): ACR Knee OA: Non-Pharmacologic Recommendations Weight loss Patients who lose weight are less likely to have pain and x-ray progression of disease 1 Reduction in symptoms more associated with changes in body fat than weight reduction 2 1 Felson DT et al. Arthritis Rheum, 1997;40: Toda Y et al. J Rheumatol, 1998;25: Hochberg MC et al. Arthritis Care Res (Hoboken) Apr;64(4): The Management of Persistent Pain in Older Patients. JAGS, 2002;6:S205-S224. Jordan, KM et al. Ann Rheum Dis, 2003;62: ACR Knee OA: Non-Pharmacologic Recommendations Conditional recommendations Self-management programs Manual PT Psychosocial interventions Thermal agents, rubs Patellar taping or wedged insoles for selected patients Participate in Tai Chi programs Receive walking aids as needed; teach proper cane use If can t have surgery, can consider: treatment with traditional Chinese acupuncture or transcutaneous electrical stimulation Hochberg MC et al. Arthritis Care Res (Hoboken) Apr;64(4): American Academy of Orthopedic Surgeons (AAOS) Knee OA Recommendations Knee OA: Common Sense Recommendation: Appropriate footwear! #1 Strong: Self-management, strengthening/lowimpact aerobics and neuromuscular education; exercise per national guidelines #2 Moderate: Weight loss if BMI 25 #3A Strong: Cannot recommend acupuncture #3B Inconclusive: physical agents (including electrotherapeutic modalities #3C Inconclusive: manual therapy accessed 8/21/13 4

7 AAOS Knee OA Recommendations (continued) # 4 Inconclusive: Use of valgus directing force brace (medial compartment unloader) for patients with medial knee OA # 5 Moderate: Cannot suggest lateral wedge insoles be used for patients with symptomatic medial compartment knee OA # 6 Strong: Cannot recommend using glucosamine and chondroitin accessed 8/21/13 ACR Knee and Hip OA Pharmacologic Recommendations Acetaminophen Oral NSAIDs Topical NSAIDs (not for hip) Tramadol Intraarticular corticosteroids Not recommended: Chondroitin sulfate Glucosamine Topical capsaicin Hochberg MC, et al. Arthritis Care Res (Hoboken) Apr;64(4): Osteoarthritis Additional Therapies Case Study 3 Sara Duloxetine (SNRI) 1 FDA approved for the treatment of chronic musculoskeletal pain 30 mg daily, may increase to 60 mg daily Intra-articular hyaluronans 2 Small benefit in Knee OA Joint surgery Suspension arthroplasty for 1 st CMC OA Total joint arthroplasty for Hip and Knee OA 34-year-old presents with a symmetric inflammatory polyarthritis of 6 months duration She has not responded to NSAIDs Examination: swelling and tenderness of MCPs bilaterally, R elbow, R ankle and bilateral MTPs General medical examination otherwise normal 1. Chappel AS. Pain Practice. 2011;11: Rutjes JW. Ann Intern Med Aug 7;157(3): Rheumatoid Arthritis Chronic multisystem inflammatory disease Cause unknown Evidence of interaction between genetic factors and environment Stretching of tendons and ligaments results in deformity Erosion of cartilage and bone causes joint destruction Worldwide distribution varies according to region More common in Europe and North America, less common in poorer regions like rural West Africa Affects 0.5-1% of the U.S. population ~1.5 million adults Highest incidence in persons in their 60 s, but can occur in children Prevalence 2-3 x higher in women Rheumatoid Arthritis Risk Factors Genetic: HLA class II genotypes Smoking is the strongest and most consistent risk factor for RA Irregular menses, early menopause, polycystic ovary syndrome may increase risk Breastfeeding, live birth may lower risk 5

Rheumatoid Arthritis Joints affected Small joints in a symmetrical pattern Hands usually first affected Almost any joint can be involved Symptoms Stiffness Pain with soft

EARLY RHEUMATOID ARTHRITIS Capilary formation Hyperplastic synovial membrane Hypertrophic synovicytes Neutrophilis NORMAL KNEE JOINT T cells B cells Synovial membrane Capsule

Arthritis Rheumatoid Arthritis Osteoarthritis Extra-articular Manifestations of RA Heart Pericarditis, premature CAD Lung Pleurisy, ILD, nodules, bronchiolitis obliterans Skin

syndrome Bone Osteopenia, osteoporosis Eye Sjogren s syndrome, episcleritis, scleritis, ulcerative keratopathy, scleromalacia perforans The Importance of Early RA Diagnosis

8 Rheumatoid Arthritis Joints affected Small joints in a symmetrical pattern Hands usually first affected Almost any joint can be involved Symptoms Stiffness Pain with soft tissue swelling (synovitis) Loss of normal range of motion Fatigue Low-grade fever RA Effect on Synovial Joint Femur Cartilage Capsule Synovial membrane Synoviocytes Tibia EARLY RHEUMATOID ARTHRITIS Capilary formation Hyperplastic synovial membrane Hypertrophic synovicytes Neutrophilis NORMAL KNEE JOINT T cells B cells Synovial membrane Capsule Cartilage Femur Tibia ESTABLISHED RHEUMATOID ARTHRITIS Neutrophilis Plasma cell Synovial villi Extensive angiogenesis Pannus Eroded bone Patterns of Joint Involvement in Arthritis Rheumatoid Arthritis Osteoarthritis Extra-articular Manifestations of RA Heart Pericarditis, premature CAD Lung Pleurisy, ILD, nodules, bronchiolitis obliterans Skin Nodules, vasculitis Neuro Entrapment neuropathy, mononeuritis multiplex, peripheral neuropathy, cervical myelopathy Heme Anemia, thrombocytosis, lymphadenopathy, Felty s syndrome Bone Osteopenia, osteoporosis Eye Sjogren s syndrome, episcleritis, scleritis, ulcerative keratopathy, scleromalacia perforans The Importance of Early RA Diagnosis Damage may occur very early Joint damage can occur while disease is subclinical Remissions are rare Rheumatoid Arthritis INFLAMMATION X TIME = JOINT DAMAGE Early aggressive management improves outcomes 6

9 2010 ACR/EULAR* Classification Criteria for RA Target population (Who should be tested?): Have at least 1 joint with definite clinical synovitis (swelling) Synovitis not better explained by another disease A score of 6 indicates definite disease Aletaha et al, Arthritis Rheum.2010;62(9): Dharmarajan K et al. JAMA. 2013;309(4): Dharmarajan K et al. JAMA. 2013;309(4): A. Joint Involvement 1 large joint large joints small joints (w/ or w/o involvements of large joints) small joints (w/ or w/o involvement of large joints) 3 >10 joints (at least 1 small joint) 5 B. Serology Negative RF and negative ACPA 0 Low positive RF or low positive ACPA 2 High positive RF or high positive ACPA 3 C. Acute phase reactants Normal CRP and normal ESR 0 Abnormal CRP or abnormal ESR 1 D. Duration of symptoms <6 weeks 0 6 weeks 1 *EULAR = European League Against Rheumatism Collaborative Initiative Baseline Evaluation for New RA COMPLETE H&P Careful RA history Duration of disease Duration of morning stiffness Pattern of joint involvement Functional problems? Common extra-articular features Sicca, nodules Detailed musculoskeletal examination Synovitis, squeeze tenderness, loss of ROM, deformities Baseline Evaluation of New RA: Tests Laboratory studies CBC with diff; chemistries including LFTs Urinalysis RF and CCP (cyclic citrullinated peptide) Other serologies as clinically indicated (ANA, ANCA, etc.) Acute phase reactant ESR or CRP Hep B and C serologies TSH X-rays of hands and feet, other joints as indicated Chest x ray PPD Case Study Sara Radiographic Changes: Early Soft tissue swelling (white arrow), joint space narrowing (blue arrow), and proximal interphalangeal (PIP) joint erosions (red arrows) Erosions first occur adjacent to articular cartilage (periarticular erosions) Radiographic Changes: Late Ulnar deviation/ subluxation of fingers at MCP joints (white arrows) from articular damage Other changes: swan neck or boutonniere deformities may develop In very late RA, fusion or joint ankylosis may occur Case Study Sara Lab Results CBC- Mild normocytic anemia, Hct 31 Mild thrombocytosis, 470 RF is negative CCP is positive in high titer ESR 54 AST, ALT and creatinine are normal HBsAg negative, HCV negative CXR normal PPD negative 7

10 Factors that Predict Poor Prognosis in RA ACR Guidelines for Treatment of Early RA (< 6 months disease duration) Earlier age at onset High titer RF or CCP Elevated ESR > 20 joints involved Extra-articular disease Singh JA. Arthritis Care & Research. 2012;64(5): Commonly Prescribed Oral DMARDs So, treat as early as possible with DMARDS!!! DMARD Dose Toxicity Monitoring Methotrexate mg Q week Hepatotoxicity, pneumonitis, marrow suppression, oral ulcers, alopecia Teratogenic Leflunomide mg Q day Hepatotoxicity, diarrhea, long half life Teratogenic Sulfasalazine mg BID Nausea/diarrhea Leukopenia Rash Hydroxychloroquine 400 mg Q day Retinopathy Rash Neuromyopathy CBC, LFTs, Cr every weeks CBC, LFTs, Cr every 6-12 weeks CBC, LFTS, Cr every 8-12 weeks Annual eye examinations Case Study Sara Therapeutic Plan Prednisone 10 mg daily or lowest effective dose Methotrexate 10 mg weekly x2 weeks 15 mg weekly x2 weeks mg weekly (target dose) Folic acid 1 mg daily Stop NSAIDs Follow-up in 6-8 weeks Corticosteroids Rapid, potent suppression of inflammation Short term efficacy Significant long term toxicity? Disease modifying Systemic or intra-articular Low dose can be used for up to 6 months (along with DMARD) accessed 8/22/13 8

11 Starting Methotrexate for RA Begin at 10 mg and titrate up to mg weekly as tolerated Oral therapy to start, may transition to SQ if necessary Supplement folic acid 1mg daily Check labs Q4-6 weeks initially CBC with diff, LFTs Less frequently once stable dose is reached and interim lab screening is OK Assess efficacy/toxicity at 8-12 weeks Methotrexate What the Patient Must Know Nausea is common, may be dose limiting Most prominent with first few doses or dosing increases SQ formulation may be more tolerable Oral ulcers very common, may be dose limiting Folic acid supplement is recommended May also use Leucovorin 5 mg taken 24 hours after the MTX dose Liver toxicity No alcohol; liver biopsy not usually recommended Cytopenias Monitor at least every 8-12 weeks, more frequently in the beginning Pregnancy You MUST stop the MTX at least 3 months prior to attempting conception Pneumonitis (rare) Patient Counseling (most important part of the visit!) Discussion about RA Supplemented with literature from the ACR or AF Risks and benefits of the medical therapies Particular attention to symptoms of infection Other important interventions Exercise, sleep hygiene, healthy diet and weight Importance of close clinical follow up Rheumatoid Arthritis Other Important Considerations Bone Health Supplement Ca and Vit D Screen for osteoporosis Consider bisphosphonates when patient is on chronic steroids Cardiovascular Health Assess and treat modifiable risk factors DM, HTN, lipids Inflammation is potent risk factor also Immunizations Annual flu; pneumococcal vaccine in all patients NO LIVE VACCINE if patient on biologic therapy Zoster vaccine OK for: Prednisone < 10 mg/day Low dose weekly MTX Grossman. AC&R. 2010;62(11): Follow-up and Monitoring Assess disease activity Swollen and tender joints, AM stiffness, ESR or CRP, patient s assessment of disease activity Assess drug toxicity Nausea, vomiting, abdominal pain, fatigue, oral ulcers, hair loss, other adverse reactions Lab screening CBC, AST, ALT, ESR Adjust medications accordingly Improvement with MTX should be seen within 3 months; consider different agent if target not reached by 6 mo accessed 8/22/13 Case Study Sara : Six Weeks Later Assessment of Disease Activity Patient report Morning stiffness reduced to 2 hours Less pain, better movement of hands Still with significant foot pain especially in the AM Mild nausea for 24 hours after MTX Examination Reduced MCP and R ankle synovitis R elbow with normal ROM and no swelling Persistent MTP squeeze tenderness Lungs are clear O/P no ulcers Labs: WBC 5.5, Hct 34, platelets 300, AST 32, ALT 35 9

12 Case Study Sara Next Steps Continue MTX 20 mg weekly with folic acid supplementation Continue prednisone 10 mg weekly Could consider starting a slow taper by 1 mg per week Follow up visit in 6-8 weeks Consider referral to rheumatologist if patient has inadequate response to MTX? Add/switch to different DMARD or consider biologic therapies SUMMARY OA is very common and can be effectively treated by primary care clinicians Exercise and assistive devices improve ADLs Oral therapies include NSAIDs, acetaminophen, and tramadol RA must be recognized and treated early to reduce joint damage RA patients require: Early and aggressive medical therapy Education and ongoing monitoring for treatmentrelated side effects and signs of disease progression Attention to bone and CV health, and updated immunizations Question & Answer 10

Patient #1. Rheumatoid Arthritis. Rheumatoid Arthritis. 45 y/o female Morning stiffness in her joints >1 hour

Patient #1. Rheumatoid Arthritis. Rheumatoid Arthritis. 45 y/o female Morning stiffness in her joints >1 hour Patient #1 Rheumatoid Arthritis Essentials For The Family Medicine Physician 45 y/o female Morning stiffness in her joints >1 hour Hands, Wrists, Knees, Ankles, Feet Polyarticular, symmetrical swelling