Osteoarthritis and RheumatoidArthritis: Disease State Overview
Factors Implicated in the Development of OA Obesity Aging Anatomic abnormalities Genetic and metabolic Microfractures diseases and bony Abnormal stresses Abnormal cartilage remodeling Inflammation Loss of joint stability Immune Compromised cartilage system Trauma activity Biophysical changes Biochemical changes • Collagen network fracture • Inhibitors reduced • Proteoglycan unraveling • Proteolytic enzymes increased Cartilage breakdownMandelbaum B et al. Orthopedics. 2005;28(2 suppl):s207-s214.Adapted with permission from 2002 Medtronic Sofamor Danek, Basic Bone Biology.
EULAR Diagnostic Criteria for Knee OA (2010) ■ Based on review of studies from 1950-2008 and expert consensus ■ Focuses on clinical diagnosis: presence of three symptoms and three signs correctly diagnoses 99% of cases Symptoms 1 Persistent knee pain √ 2 Limited morning stiffness √ 3 Reduced function √ Signs 4 Joint crepitus √ 5 Restricted movement √ 6 Bony enlargement √EULAR=European League Against Rheumatism.Zhang W et al. Ann Rheum Dis. 2010;69(3):483-489.
ACR Diagnostic Criteria for Knee OA (1986) ■ Clarified and standardized definition of osteoarthritis Joint symptoms and signs associated with defective integrity of articular cartilage and changes in underlying joints at bone margin ■ Focuses on clinical examination of knee pain plus: Presence of 3 of the following 1 Age >50 years √ 2 Morning stiffness <30 minutes √ 3 Joint crepitus on active motion √ 4 Bony tenderness √ 5 Bony enlargement √ 6 No palpable warmth of synovium √ ■ Sensitivity, 95%; specificity, 69%ACR=American College of Rheumatology.Altman RD et al. Arthritis Rheum. 1986;29(8):1039-1049.
Goals of OA Management: OARSI Recommendations Maintain and improve joint mobility Reduce Reduce joint pain and physical stiffness disability Knee and Hip OA: Goals of Treatment Improve Educate HRQoL patients Limit progression of joint damageHRQoL=health-related quality of life; OARSI=Osteoarthritis Research Society International.Zhang W et al. Osteoarthritis Cartilage. 2008;16(2):137-162.
Integrated Approach to Treating Patients With OA Nonpharmacologic Pharmacologic ■ Patient education ■ APAP ■ Phone contact (promote self-care) ■ Oral NSAIDs ■ Referral to physical therapist ■ Topical NSAIDs and capsaicin ■ Aerobic, strengthening, and/or water- ■ Corticosteroid injections based exercise ■ Hyaluronate injections ■ Weight reduction ■ Glucosamine, chondroitin sulphate, ■ Walking aids, knee braces and/or diacerein ■ Proper footwear, insoles ■ Weak opioids and narcotic analgesics ■ Thermal modalities for refractory pain* ■ TENS ■ Acupuncture Surgical ■ Total joint replacement ■ Lavage/debridement in knee OA† ■ Unicompartmental knee replacement ■ Joint fusion after failure of joint ■ Osteotomy and other joint preserving replacement surgical procedures* Pain resistant to ordinary treatment. † Controversial.TENS=transcutaneous electrical nerve stimulation.Zhang W et al. Osteoarthritis Cartilage. 2008;16(2):137-162.
US Prevalence of Rheumatoid Arthritis (RA) ■ May affect between 1.3 and 1.5 million adults1,2 Incidence lowest in individuals aged ≤34 years Incidence increases progressively with age Occurs more commonly in women than in men* Costs in 2005 US dollars.1. Myasoedova E et al. Arthritis Rheum. 2010;62(6):1576-1582.2. Helmick CG et al. Arthritis Rheum. 2008;58(1):15-25.3. Birnbaum H et al. Curr Med Res Opin. 2010;26(1):77-90.
Hand RAPhotos from Towheed TE, Anastassiades TP. Can Fam Phys. 1994;40:1303-1309. Used with permission.
2010 ACR / EULAR Diagnostic Criteria for RA Criterion Score 1 large joint 0 2-10 large joints 1 A Joint Involvement* 1-3 small joints (± large-joint involvement) 2 4-10 small joints (± large-joint involvement) 3 >10 joints (at least 1 small joint) 5 Negative RF and negative ACPA 0 B Serology† Low-positive RF or low-positive ACPA 2 High-positive RF or high-positive ACPA 3 Acute-Phase Normal CRP and normal VHS 0 C Reactants‡ Abnormal ESR or CRP Total score ≥6/10 Total score ≥6/10 1 needed to classify needed to classify Duration of Less than 6 weeks definite RA definite RA 0 D Symptoms§ 6 or more weeks 1* Any swollen or tender joint on examination. Excluded are distal interphalangeal joints, first carpometacarpal joints, and first metatarsophalangeal joints. Large joints = shoulders, elbows, hips, knees, and ankles. Small joints = metacarpophalangeal joints, proximal interphalangeal joints, 2nd through 5th metatarsophalangeal joints, thumb interphalangeal joints, and wrists. The >10 category can include large and small joints, and other joints not listed elsewhere (eg, temporomandibular, acromioclavicular, or sternoclavicular). † Negative: IU values ≤ULN for lab and assay. Low-positive: IU > ULN but ≤3x ULN. High-positive: IU >3x ULN. When only RF-positive or RF-negative is known, positive scored as low-positive. ‡ Normal/abnormal determined by local lab standards. § Patient self-report of duration of signs/symptoms of synovitis in joints clinically involved at time of assessment, regardless of treatment status.ACPA=anti-citrullinated protein/peptide antibodies; CRP=C-reactive protein; VHS =erythrocyte sedimentation rate; RF=rheumatoid factor.Aletaha D et al. Arthritis Rheum. 2010;62(9):2569-2581.
Goals of RA Management Early and Sustained Suppression of Disease Activity Prevent or Reduce pain control joint damage Prevent Maximize functional patient decline quality of lifeACR Subcommittee on Rheumatoid Arthritis Guidelines. Arthritis Rheum. 2002;46(2):328-346.
Treatment Options for Patients With RA1-3 NSAIDs Symptomatic treatment to reduce joint swelling and pain Reduce/prevent joint damage, preserve joint integrity and function Methotrexate, leflunomide, hydroxychloroquine, minocycline, DMARDs sulfasalazine (biologic and Etanercept, infliximab, adalimumab (TNF inhibitors) nonbiologic) Rituximab (anti-CD20) Abatacept (cytotoxic T-lymphocyte antigen 4 immunoglobulin) Tocilizumab (anti-interleukin 6 receptor) Short-term use during flare-ups (oral or intramuscular) Glucocorticoids Local treatment for individual active joints (intra-articular) Carpal tunnel release, synovectomy, resection of metatarsal heads, Surgery total joint arthroplasty, joint fusion Supportive Patient education, cognitive-behavioral interventions Strategies Rehabilitation interventionsDMARDs=disease-modifying antirheumatic drugs; TNF=tumor necrosis factor.1. ACR Subcommittee on Rheumatoid Arthritis Guidelines. Arthritis Rheum. 2002;46(2):328-346.2. Saag KG et al. Arthritis Rheum. 2008;59(6):762-784.3. Smolen JS et al. Lancet. 2007;370(9602):1861-1874.
Distinguishing OA From RA1 Characteristic OA RA Prevalence in US adults 27 million2 1.3–1.5 million3,4 Pathophysiologic process Degenerative Autoimmune Hips, knees, spine, Commonly affected joints Hands, feet fingers Typically symmetrical No Yes involvement Morning stiffness Transient Persistent Joint swelling Hard tissue Soft tissue Hand involvement Distal joints Proximal joints Extraarticular involvement No Yes Elevated autoimmune markers No Yes1. Goldman L, Ausiello D. Cecil Textbook of Medicine. 23rd ed. Philadelphia, PA: Saunders Elsevier; 2007.2. Lawrence RC et al. Arthritis Rheum. 2008;58(1):26-35.3. Helmick CG et al. Arthritis Rheum. 2008;58(1):15-25.4. Myasoedova E et al. Arthritis Rheum. 2010;62(6):1576-1582.
CELECOXIB vs. diclofenac:6-week Knee OA TrialMcKenna et al. 2001: Patient’s Assessment of Pain Patient’s Assessment of Pain (VAS): Mean change at week 6 *p=0.001 vs. placebo Mean Change (mm) Less Pain placebo celecoxib diclofenac (n=200) 100 mg BID 50 mg TID (n=199) (n=199) VAS=visual analogue scale. McKenna F et al. Scand J Rheumatol 2001;30:11–18.
CELECOXIB vs. diclofenac:6-week Knee OA TrialMcKenna et al. 2001: American Pain Society – PainMeasure American Pain Society (APS) Pain Measure: Worst Pain in the Past 24 Hours Baseline Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 0.0 -0.5 p=0.05, active treatment vs. Mean Change in Score placebo (days 1-7). -1.0 Less Pain -1.5 -2.0 -2.5 -3.0 placebo (n=200) -3.5 celecoxib 100 mg BID (n=199) -4.0 diclofenac 50 mg TID (n=199) McKenna F et al. Scand J Rheumatol. 2001;30:11-18.
Adult RA: Celecoxib Significantly Reduced the Number of Tender/Painful and Swollen Joints Tender/Painful Joints Swollen Joints 0 Reduction in Mean Number of Affected Joints at 12 Weeks -5 -5.5 -6.9* -7.6 -7.5* -10 -9.5 -9.1* t ne m v o p m e r I -11.6* -11.7* -15 Placebo (n=231) Celecoxib 100 mg BID (n=240) Celecoxib 200 mg BID (n=235) -20 Naproxen 500 mg BID (n=225)* P<.05 vs placebo.Simon LS et al. JAMA. 1999;282(20):1921-1928.
Adult RA: Celecoxib and Naproxen ImprovedPhysical Function 0.4 HAQ-FDI Score at 12 Weeks LS Mean Improvement in 0.29* 0.3 0.22* 0.2 0.17 0.1 0.1 0 Placebo Celecoxib Celecoxib Naproxen (n=231) 100 mg BID 200 mg BID 500 mg BID (n=240) (n=235) (n=225)* Statistically significant vs placebo.HAQ-FDI=Health Assessment Questionnaire Functional Disability Index.Zhao SZ et al. Arthritis Care Res. 2000;13(2):112-121.
Ankylosing Spondylitis: Celecoxib and Naproxen Reduced Pain, Disease Activity, and Functional Impairment (12 Weeks) Pain Intensity Disease Activity BASFI 10 Baseline to Week 12 (100 mm VAS) LS Mean (± SE) Change From 0 -10 -20 † -30 t ne m v o p m e r I * Placebo Celecoxib 200 mg QD -40 Celecoxib 400 mg QD Naproxen 500 mg BID -50P<.001 for all active treatments vs placebo.* P<.05 vs celecoxib 200 mg QD.† P<.01 vs celecoxib 200 mg QD.BASFI=Bath Ankylosing Spondylitis Functional Index.Barkhuizen A et al. J Rheumatol. 2006;33(9):1805-1812.
Guidelines for Prevention of NSAID-Related Ulcer Complications (ACG Practice Guidelines 2009)za FL et al. Am J Gastroenterol 2009;104:728-738
Celecoxib vs Omeprazole aNd Diclofenac in patients with Osteoarthritis and Rheumatoid arthritis (CONDOR) Chan FKL et al. Lancet 2010. DOI:10.1016/S0140-6736(10)60673-3n FKL et al. Lancet 2010. DOI:10.1016/S0140-6736(10)60673-3
Chan FKL et al. Lancet 2010. DOI:10.1016/S0140-6736(10)60673-3
RESULT OF CONDOR STUDY 2010 Patient with celecoxib has lower risk on gastrointestinal events than those with diclofenac SR + omeprazole 4 3.8 Proportion of patients % 3.5 (81 events, 3 95% CI, 2.9- 2.5 4.3) 2 1.5 0.9 1 0.5 (20 events, 95% CI, 0.5-1.3) 0 celecoxib 200 mg BID (n=2238) diclofenac SR 75 mg BID + omeprazole 20 mg OD (n=2246)P<0.0001Chan FKL et al. Lancet 2010; DOI:10.1016/S0140-6736(10)60673-3
Conclusion CONDOR Study Risk of clinical outcomes throughout the upper & lower GI tract was lower in patients treated with a COX-2-selective NSAID than in those receiving a non-selective NSAID plus a PPI. Celecoxib, when used alone, carries less risk of clinically significant events through the entire GI tract when compared with diclofenac + omeprazoleChan FKL et al. Lancet 2010. DOI:10.1016/S0140-6736(10)60673-3
Boxed Warning for All Prescription NSAIDsCardiovascular Risk Cardiovascular RiskNSAIDs may cause an increased risk of serious cardiovascular thrombotic NSAIDs may cause an increased risk of serious cardiovascular thromboticevents, myocardial infarction, and stroke, which can be fatal. This risk may events, myocardial infarction, and stroke, which can be fatal. This risk mayincrease with duration of use. Patients with cardiovascular disease or risk increase with duration of use. Patients with cardiovascular disease or riskfactors for cardiovascular disease may be at greater risk. factors for cardiovascular disease may be at greater risk.[Product] is contraindicated for the treatment of perioperative pain in the [Product] is contraindicated for the treatment of perioperative pain in thesetting of coronary artery bypass graft (CABG) surgery. setting of coronary artery bypass graft (CABG) surgery.Gastrointestinal Risk Gastrointestinal RiskNSAIDs, including [product], cause an increased risk of serious NSAIDs, including [product], cause an increased risk of seriousgastrointestinal adverse events including bleeding, ulceration, and gastrointestinal adverse events including bleeding, ulceration, andperforation of the stomach or intestines, which can be fatal. These events perforation of the stomach or intestines, which can be fatal. These eventscan occur at any time during use and without warning symptoms. Elderly can occur at any time during use and without warning symptoms. Elderlypatients are at greater risk for serious gastrointestinal (GI) events. patients are at greater risk for serious gastrointestinal (GI) events.
APTC Composite End Point (Adjudicated): Celecoxib vs ns-NSAIDs Meta-analysis of 25 RCTs 2.0 P =.59 (NS) Relative Risk (CI) of Serious 1.5 CV Adverse Events 1.0 0.90 1.0 (95% CI: 0.60-1.33) 49 events 54 events 0.5 0 ns-NSAIDs Celecoxib 200-800 mg daily (n=13,990) (n=19,773)White et al. Am J Cardiol. 2007. 09/25/09
CELECOXIB vs. diclofenac Dahlberg et al. 2009: CV / renal & hepatic AEs Incidence of patients with treatment-related CV, renal, and hepatic AEs 6 5.2 5 4.1 % Patients 4 3 1.7 2 1.1 1 0 CV / renal AE Hepatic AE celecoxib 200 mg OD diclofenac 50 mg BIDOne-year, randomized, multicentre, double-blind, parallel-group study to assess the AE-related discontinuation rate withcelecoxib and diclofenac in elderly patients with OA.No p-values reported for related/not-related-to-treatment incidence. Significantly fewer patients in the celecoxib group thanthe diclofenac group experienced cardiovascular/renal AEs (70/458 vs. 95/458, p=0.039) or hepatic AEs (10/458 vs. 39/458,p<0.0001).Dahlberg LE et al. Scand J Rheumatol 2009;38:133-143.
SUMMARY■ Arthritis Pain is major health problem in elderly patients■ Selective COX-2 inhibitors relief pain by selectively inhibit COX-2 enzyme which is mainly responsible for inflammation and pain process■ Celecoxib is scientifically proven to alleviate arthritis pain (OA, RA, and AS)■ Celecoxib, when used alone, carries less risk of clinically significant events through the entire GI tract when compared with diclofenac + omeprazole■ Celecoxib is the only coxib approved by US FDA■ Celecoxib has a well-tolerated safety profille 35 Please see Full Prescribing Information available at this presentation.
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