1. MANAGEMENT OF OSTEOARTHRITIS Carrie Johnson, Pharm.D., CDE Assistant Professor cljohn1@email.uky.edu

2. Objectives  Understand the basic pathophysiology of osteoarthritis  Identify underlying etiology  Describe clinical manifestations of osteoarthritis  Understand diagnostic criteria for osteoarthritis  Recommend various non-pharmacologic and pharmacologic treatment strategies

3. Meet K.W. 70 YOF presents to your clinic for regular follow-up. She complains of increasing pain in her lower back, hips and right knee. Six months ago, she was started on APAP 500 mg 4x daily. Pt complains of continued moderate to severe pain despite treatment.  Review of systems:  pain / stiffness in right knee  shooting pain in lower back  Physical Exam  well-developed  obese

4. Meet K.W.  Osteoarthritis  APAP 500mg (2 PO QID PRN)  Type 2 DM  Metformin 500mg PO BID  Hyperlipidemia  Atorvastatin 10mg PO QHS  HTN  Lisinopril 10mg PO Qday  Obesity GGluc 248, A1C 8.1% NNa 135, K 4.7 BBUN 15, SCr 1.6 HHgb 12.8, Hct 36.7%, PLT 286k AAST 38, alk phos 96 TTG 184, TC 206, LDL 137 PMH (including medications)Pertinent Labs

5. Epidemiology  46 million adults have self-reported doctor- diagnosed arthritis.  19 million have arthritis and arthritis- attributable activity limitation.  67 million adults ≥ 18 years will have doctor- diagnosed arthritis by the year 2030.  25 million adults with arthritis will report arthritis-attributable activity limitations.

6. Epidemiology Kentucky (state data)200320052007 Adults with arthritis1,044,000879,000958,000 Adults limited by arthritis519,000395,000465,000 % of adults with arthritis352932 % women/men with arthritis38/3134/2435/28 % whites with arthritis352932 % blacks with arthritis282533 % Hispanics with arthritis261718 % 18–44 year olds with arthritis191415 % 45–64 year olds with arthritis464043 % 65+ year olds with arthritis615158 % with arthritis who are overweight or obese687273 % with arthritis who are physically inactive363532

7. Epidemiology

8. Etiology & Risk Factors  Age  Men vs. women  Obesity  Quadricep muscle weakness  Joint overuse / injury  Genetics

9. Which of these risk factors does K.W. have? Question about K.W.

10. Pathophysiology  Degradation > synthesis  Loss of articular cartilage  Subchondral bone thickening  Osteophyte formation  Progressive joint space narrowing  Decreased concentrations of hyaluronan  Overall thickened synovium Articular Cartilage Synovium

11. Pathophysiology

12. Signs & Symptoms  Stiffness of joints  Deep, aching pain  Crepitus  Joint enlargement

13. Joints Involved  Distal interphalangeal joint (DIP)  Herberden’s nodes  Proximal interphalangeal joint (PIP)  Bouchard’s nodes  Knees  Hips  Cervical / lumbar spine

14. Joints Involved

15. Diagnosis  History  Physical exam  Characteristic radiographic findings  Hip OA vs. knee OA  Different guidelines for different locations

16. Treatment Options

17. Treatment Goals  Patient education about disease state  Relieve pain and stiffness  Maintain or improve joint mobility  Limit functional impairment  Improve quality of life

18. Treatment Algorithm

20. Non-Pharmacologic Treatment  Educate patient about disease state  Weight loss  Physical therapy / Exercise  Heat / cold therapies  Assistance devices  Surgical procedures

21. Pharmacologic Treatment  Acetaminophen  NSAID  Glucosamine + chondroitin  Narcotic analgesics  Corticosteroids  Hyaluronate injections  Capsaicin  Counterirritants Oral AgentsNon-oral Agents

23. Glucosamine + Chondroitin  Dose: 1500mg/day glucosamine; 1200mg/day chondroitin  Can be initiated at any time during treatment algorithm  > 15 double-blind, placebo controlled trials  Slows loss of cartilage in knees  Reduces joint space narrowing and pain  At 8 years, rates of lower limb joint replacement was 50% that of placebo

24. Glucosamine + Chondroitin  Contraindications  Shellfish allergy  Asthma  Adverse effects  GI  Possible hypersensitivity  Interactions  Warfarin  Diabetes medications S Dahmer, Schiller RM. Am Fam Physician. 2008;78(4):471–476, 481

25. Acetaminophen  First line therapy  MOA: central COX inhibition  Dose: 325mg – 650mg 4x daily  Well-tolerated  DDI  Caution with patients with baseline liver dysfunction  Pt education

26. What is K.W. doing wrong with her therapy? Question about K.W.

27. NSAIDs  Second line therapy  MOA: central & peripheral COX inhibition  Analgesic effect within 1-2 hours  Controversy of COX-2 inhibitors  All have similar efficacy in pain management  Adverse effects  Drug – drug interactions

28. Capsaicin  Extracted from red peppers  Depletes substance P from nerve fibers  Must use regularly  4x daily  Can taper to BID application  Adverse Effects: burning / stinging

30. Corticosteroids  Dosing  Systemic therapy not recommended  Rapidly effective / short duration of efficacy  Intra-articular injections  Pain relief with local inflammation / joint effusion  Uncertain long-term benefit  Limit of 3-4 injections / year  Minimize joint activity / stress directly after injection

31. Hyaluronate Injections  Lubricant in normal cartilage  Efficacy  Amount decreases in OA  Reduces symptoms of OA  Alternative for those unable to tolerate systemic therapy  $$$$$

32. Hyaluronate Injections

33. Tramadol  MOA: Weak μ opiod agonist  Efficacy ~ NSAIDS for hip / knee  Preferred to other opioids  Many formulations available  Co-formulated with APAP  Avoid in patients with:  Comorbid seizure disorders  Addictive behavior patterns

34. Narcotic Analgesics  Alternative to those refractory to other treatment modalities  Many, many formulations  Adverse Effects:  GI: N/V, constipation  Somnolence  Confusion / increase fall risk in elderly  Abuse potential

35. What would you recommend for K.W.? Question about K.W.

36. Summary  Maximize non-pharmacologic treatment modalities discussed  Tailor treatment to patient  Symptom severity  Medications tried  Patient expectations and preferences

37. References 1. Altman R, Barkin RL. Topical therapy for osteoarthritis: clinical and pharmacologic perspectives. Postgrad Med 2009 Mar; 121(2): 139-147. 2. Bingham CO, Smugar SS, Wang H, Tershakovec AM. Early response to COX-2 inhibitors as a predictor of overall response in osteoarthritis: pooled results from two identical trials comparing etoricoxib, celecoxib, and placebo. Rheumatology. 2009 Sep;48(9): 1122-7. 3. http://www.cdc.gov/arthritis/index.htm (accessed 3/7/2010) http://www.cdc.gov/arthritis/index.htm 4. http://www.rheumatology.org/practice/clinical/guidelines/oa-mgmt/oa-mgmt.asp (accessed 3/7/2010) http://www.rheumatology.org/practice/clinical/guidelines/oa-mgmt/oa-mgmt.asp 5. Lane NE. Clinical practice: Osteoarthritis of the hip. NEJM 2007 Oct 4;357(14): 1413-21. 6. Scanzello CR, Moskowitz NK, Gibofsky A. The post-NSAID era: what to use now for the pharmacologic treatment of pain and inflammation in osteoarthritis. Curr Pain Headache Rep 2007 Dec;11(6):415-22. 7. Y Zhang, Jordan JM. Epidemiology of osteoarthritis. Rheum Dis Clin North Am. 2008 Aug;34(3):515-29.

38. QUESTIONS? Management of Osteoarthritis