These slides should be used in conjunction with the accompanying notes
Data from the 2007-2009 National Health Interview Survey reveal high rates of self-reported, doctor-diagnosed arthritis and limitations due to arthritis. 1 In addition, in every adult age group, women are more likely to be affected by arthritis than men. 2 Arthritis and rheumatism are the leading causes of disability in the United States, 3 and it is estimated that by 2030, 67 million Americans will have health care practitioner-diagnosed arthritis. 4 References: Centers for Disease Control and Prevention. Prevalence of doctor-diagnosed arthritis and arthritis-attributable activity limitation — United States, 2007–2009. MMWR Morb Mortal Wkly Rep . 2010;59(39):1261-1265. Centers for Disease Control and Prevention. NHIS Arthritis Surveillance: Arthritis Prevalence in Women and Men . www.cdc.gov/arthritis/data_statistics/national_nhis.htm. Accessed January 12, 2011. Centers for Disease Control and Prevention. Prevalence and most common causes of disability among adults—United States, 2005. MMWR Morb Mortal Wkly Rep . 2009;58(16):421-426. Hootman JM, Helmick CG. Projections of US prevalence of arthritis and associated activity limitations. Arthritis Rheum . 2006;54(1):226-229.
This slide provides an overview of the factors that can contribute to the development of OA. These factors can be divided into two groups: those placing abnormal stress on the cartilage, such as obesity and anatomic abnormalities, and those contributing to abnormalities of the cartilage, such as aging and genetic diseases. All of these factors can contribute to compromised cartilage and ultimately result in cartilage breakdown. Reference: Mandelbaum B, Waddell D. Etiology and pathophysiology of osteoarthritis. Orthopedics . 2005;28(2 suppl):s207-s214.
In 2010, the European League Against Rheumatism (EULAR) provided six criteria—three symptoms and three signs—that could be used to correctly diagnose OA of the knee in 99% of cases, when all six criteria are present. The three symptoms are: Persistent knee pain Limited morning stiffness Reduced function The three signs are: Joint crepitus Restricted movement Bony enlargement Reference: Zhang W, Doherty M, Peat G, et al. EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis. Ann Rheum Dis . 2010;69(3):483-489.
In 1986 the American Rheumatism Association—now the American College of Rheumatology (ACR)—developed criteria to diagnose OA on the basis of knee pain and three of the following six criteria: Age older than 50 years Less than 30 minutes of morning stiffness Joint crepitus Bony tenderness Bony enlargement Absence of palpable warmth The sensitivity and specificity of these criteria were 95% and 69%, respectively. Reference: Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee. Arthritis Rheum . 1986;29(8):1039-1049.
Consensus guidelines from the Osteoarthritis Research Society International (OARSI) indicate six key goals for the treatment of knee and hip OA. Four of these goals relate to the patient’s physical state: Reduce joint pain and stiffness Maintain and improve joint mobility Reduce physical disability Limit progression of joint damage The other two key goals are to educate the patient about OA and its management, and to improve patient’s health-related quality of life. Reference: Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage . 2008;16(2):137-62.
The Osteoarthritis Research Society International (OARSI) consensus guidelines describe an integrated approach to treating patients with OA, including nonpharmacologic, pharmacologic, and surgical interventions. Nonpharmacologic aspects of treatment include such interventions as patient education, exercise, weight reduction, and the nondrug therapies transcutaneous electrical nerve stimulation (TENS) and acupuncture. Listed among the pharmacologic treatments are acetaminophen, selective and nonselective NSAIDs, steroid injections, glucosamine and chondroitin, and for some patients, weak opioids and narcotic analgesics. Surgical interventions listed in the guidelines include total joint replacement, joint fusion in cases of replacement failure, unicompartmental knee replacement, osteotomy, and lavage and debridement in knee OA, although this last approach is controversial. Reference: Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage . 2008;16(2):137-62.
Although less common than OA, rheumatoid arthritis (RA) has a major impact on the lives of patients with this chronic disorder. Prevalence estimates vary, but RA may affect as many as 1.5 million adults in the United States. 1,2 The incidence of RA is lowest among individuals aged 34 years and younger; thereafter the incidence increases progressively with age. 2 The economic impact of RA is sizable. A recently published study using administrative claims databases covering privately insured and Medicare and Medicaid beneficiaries in the United States to compute the excess payer and beneficiary-paid costs per patient with RA compared with matched controls revealed 3 : $8.4 billion in annual direct costs (2005 US dollars), which includes medical visits and prescription medications. $10.9 billion in annual indirect costs (2005 US dollars), which includes expenses such as healthcare costs for family members, work-loss costs, formal and informal caregiving, home adaptations, and other costs related to consequences of RA On a per-patient basis, these cost represents approximately $14,900 per patient with RA. References: Myasoedova E, Crowson CS, Kremers HM, Therneau TM, Gabriel SE. Is the incidence of rheumatoid arthritis rising? Results from Olmsted County, Minnesota, 1955-2007. Arthritis Rheum . 2010;62(6):1576-1582. Helmick CG, Felson DT, Lawrence RC, et al; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum . 2008;58(1):15-25. Birnbaum H, Pike C, Kaufman R, Maynchenko M, Kidolezi Y, Cifaldi M. Societal cost of rheumatoid arthritis patients in the US. Curr Med Res Opin . 2010;26(1):77-90.
These photographs of the hands of patients with RA can be contrasted with those of patients with OA. In the upper left photograph, the hands of a patient with active, recent-onset RA show bilateral synovitis of the metacarpal phalangeal joints with subluxation, an early Z-shaped deformity of the right thumb, a developing boutonniere deformity of the right 3rd digit, and bilateral ulnar drift. In the lower right photograph, the hands show bilateral ulnar drift, subluxation of the metacarpal phalangeal joints, bilateral intrinsic muscle atrophy, fixed hyperextension deformities of the right 2nd-4th proximal interphalangeal joints with developing swan-neck deformities of the 4th and 5th digits, and fixed flexion deformities of the left 2nd-5th proximal interphalangeal joints (second to fifth), with fully developed boutonniere deformities of the left 2nd-5th digits. Reference: Towheed TE, Anastassiades TP. Rheumatoid hand: practical approach to assessment and management. Can Fam Phys . 1994;40:1303-1309.
In 2010, experts from the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) worked jointly to revise the diagnostic criteria for RA. The result is a score-based classification system for patients 1) with at least one joint showing definite clinical synovitis (swelling), and 2) whose synovitis is not better explained by another disease. Four categories are used to assess (A) joint involvement, (B) serology, (C) acute-phase reactants, and (D) duration of symptoms. The highest possible score is 10, and a score of six or higher is needed to classify the condition as definite RA. Reference: Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid Arthritis Classification Criteria: an American College of Rheumatology/European League Against Rheumatism Collaborative Initiative. Arthritis Rheum . 2010;62(9):2569-2581.
Guidelines from the American College of Rheumatology focus on early and sustained suppression of disease activity in RA, and present four key goals for management: Reduce pain Prevent or control damage to the affected joints Prevent functional decline Maximize quality of life for the patient Reference: ACR Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 update. Arthritis Rheum . 2002;46(2):328-46.
Treatment options for patients with RA can be divided into five categories: NSAIDs, disease-modifying agents, glucocorticoids, surgical approaches, and supportive strategies. 1-3 Symptomatic treatment with NSAIDs can reduce joint swelling and pain. disease-modifying antirheumatic drugs (DMARDs) can reduce or prevent joint damage and preserve joint integrity and function. Glucocorticoids can be used in the short term to treat flare-ups. Surgical approaches include carpal tunnel release, synovectomy, resection of metatarsal heads, total joint arthroplasty, and joint fusion. Lastly, supportive strategies include patient education, cognitive-behavioral therapy, and rehabilitation. References: ACR Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 update. Arthritis Rheum . 2002;46(2):328-46. Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum . 2008;59(6):762-784. Smolen JS, Aletaha D, Koeller M, Weisman MH, Emery P. New therapies for treatment of rheumatoid arthritis. Lancet . 2007;370(9602):1861-1874.
A number of features can be helpful in distinguishing OA from RA: OA is more than 20 times more prevalent than RA. 1-3 The pathophysiologic processes of the two arthritides are distinct: OA is primarily a degenerative process, whereas RA is an autoimmune, primarily inflammatory disease. 4 OA usually begins as a monoarticular condition, particularly of the large joints. Multiple joints are frequently affected simultaneously with RA, and the condition has a predilection for the smaller joints of the hands and feet. In RA, joint involvement is often symmetrical. 4 Clinical features of the diseases can also be distinguished by the duration of morning stiffness and the nature of joint swelling. When hand joints are involved, OA typically affects distal joints, whereas RA typically affects the proximal joints. 4 Extra-articular involvement—for example, of the skin, lungs, eyes, and blood vessels—in RA reflects the underlying autoimmune nature of the disease, and high levels of autoimmune markers are used for diagnosis. 4 References: Lawrence RC, Felson DT, Helmick CG, et al; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum . 2008;58(1):26-35. Helmick CG, Felson DT, Lawrence RC, et al; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum . 2008;58(1):15-25. Myasoedova E, Crowson CS, Kremers HM, Therneau TM, Gabriel SE. Is the incidence of rheumatoid arthritis rising? Arthritis Rheum . 2010;62(6):1576-1582. Goldman L, Ausiello D. Cecil Textbook of Medicine . 23rd ed. Philadelphia, PA: Saunders Elsevier; 2007.
09/25/09 Key point: Celecoxib relieves OA pain of the knee as effectively as diclofenac. Background: All efficacy outcomes were significantly superior with celecoxib compared with placebo at both week 2 and week 6. In the primary efficacy analysis of patient’s assessment of pain by VAS, there was no statistically significant difference between celecoxib and diclofenac. Reference: McKenna F et al. Celecoxib versus diclofenac in the management of osteoarthritis of the knee: a placebo-controlled, randomised, double-blind comparison. Scand J Rheumatol 2001;30:11-18.
09/25/09 Key point: Celecoxib decreased APS pain measure of worst pain in the past 24 hours as effectively as diclofenac. Background: Celecoxib reduced the amount of acute pain experienced by patients with knee OA compared with placebo within the first 24 hours of therapy. The American Pain Society (APS) pain measures were significantly improved with celecoxib compared with placebo on day 1, and this response was maintained throughout the 7-day evaluation period ( p <0.01). By day 7, 7% of patients taking placebo, 17% of those treated with celecoxib, and 15% of those treated with diclofenac reported no pain ( p <0.01, active treatment vs. placebo). Pain response was similar between celecoxib and diclofenac groups. Reference: McKenna F et al. Celecoxib versus diclofenac in the management of osteoarthritis of the knee: a placebo-controlled, randomised, double-blind comparison. Scand J Rheumatol 2001;30:11-18.
Patients with risk factors for cardiovascular disease (i.e., prior history of a cardiovascular event, diabetes, hypertension, hyperlipidemia, and obesity) oI en receive prophylactic aspirin. - ey may bene5 t from the substitution of a less cardiotoxic NSAID instead of a COX-2 inhibitor. Naproxen may be the agent of choice as it may have some cardioprotective properties (76,98,108,109,112) . In addition, these patients should receive a PPI or misoprostol because the combination of naproxen and low-dose aspirin markedly increases the risk of GI bleeding. Patients at very high GI risk who also have increased CV risk should not be treated with NSAIDs or coxibs and another form of treatment should be considered. Reference: Lanza FL et al. Am J Gastroenterol 2009;104:728-738 09/25/09
In April 2005, the FDA issued request letters to manufacturers of all NSAIDs, asking that they make labeling changes to their products. 1 These letters included recommended labeling for both prescription and over-the-counter NSAIDs and a medication guide for the entire class of prescription products. All manufacturers of marketed prescription NSAIDs, including Celebrex (celecoxib), were asked to revise the labeling (package insert) for their products to include a boxed warning (shown), which highlights the potential for an increased risk of cardiovascular (CV) events. 2-4 Manufacturers of over-the-counter NSAIDs were also asked to revise their labeling to provide more specific information about the potential CV risks of their individual products. References: FDA. COX-2 selective (includes Bextra, Celebrex, and Vioxx) and non-selective non-steroidal anti-inflammatory drugs (NSAIDs). April 7, 2005. www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ ucm103420.htm. Accessed January 12, 2011. Celebrex [package insert]. New York, NY: Pfizer Inc.; June 2009. EC-Naprosyn/Naprosyn/Anaprox/Anaprox DS [package insert]. Nutley, NJ: Roche Pharmaceuticals; July 2008. Voltaren-XR [package insert]. East Hanover, NJ: Novartis; March 2009.
These slides should be used in conjunction with the accompanying notes
Rheumatic pain management
Rheumatic pain managementIn daily practice
Pain GridI II III IV V VIAcute (Incident Focused)Monophasic PainAcute (DiagnosticallyFocused) RecurrentPainChronic MalignancyBased PainChronic ProgressiveNon-Malignancy BasedPainChronicNonProgressiveNonMalignancy BasedPainChronic Benign PainExamples Examples Examples Examples Examples ExamplesPost Operative, MajorTrauma, Acute Phase ofBurns, Fractures, Pre- andPost-Procedural Scenarios,Acute Back Pain SyndromesSickle Cell Crisis, AcuteFlare of InflammatoryBowel Disease, AcuteFlares of InflammatoryArthropathies, HemophilicArthropathy, RenalCalculi, Forms of BackPain, Dysmenorrhea,MigraineSelf Explanatory basedon local spread,metastatic invasion,pressure or obstructionA.I.D.S. Progression,Sickle Cell Patients,Hemophilia Patients,Some Connective TissueDiseases, InflammatoryBowel Disease with ShortGut and ExtraGutAutoimmuneManifestationsMusculoskeletal PainSyndromes(Osteoporosis,spondylolisthesis), TMJ,Neuropathic PainSyndromes (Postherpeticneuralgia, painfulpolyneuropathy, RSD),Forms of Back PainPain Associated with aMarked Discrepancy inPathologic Findingscompared against Strongand Typical Axis I, Axis IIand PremorbidPsychosocial FeaturesOpioid Advisability Opioid Advisability Opioid Advisability Opioid Advisability Opioid Advisability Opioid AdvisabilityOK Ok (with cautions) Advised OKRelativeContraindicationOpioid AvoidanceCourtesy of Craig Pratt, MD (with somechanges)
What are the benefits and risks fromNSAIDs?How do I reduce the GI risks?How do I reduce the CV risks?Are there specific safety concerns withNSAIDs?*Note by NSAIDs we mean traditional NSAIDs (e.g. diclofenac,naproxen, ibuprofen); etodolac, meloxicam, or coxibs (e.g. celecoxib,etoricoxib)Key questions regarding NSAIDs*
Common Rheumatic problems:Osteoarthritis and Rheumatoid Arthritis
Prevalence of Arthritis in US Adults*■ 49.9 million (22.2%) with self-reported, physician-diagnosed arthritis†1■ 21.1 million (9.4%) with arthritis and arthritis-attributable activity limitation1■ Affects more women than men in every age group202040608010018–24 25–34 35–44 45–54 55–64 65–74 75–84 85+Women MenAge Group, years* Data sources: 2007-2009 data from the National Health Interview Survey (NHIS). † Includes multiple forms of arthritis.HCP=health care professional.1. CDC. MMWR Morb Mortal Wkly Rep. 2010;59(39):1261-1265.2. Graphic adapted from CDC. NHIS Arthritis Surveillance: Arthritis Prevalence in Women and Men.www.cdc.gov/arthritis/data_statistics/national_nhis.htm. Accessed January 12, 2011.3. CDC. MMWR Morb Mortal Wkly Rep. 2009;58(16):421-426.4. Hootman JM, Helmick CG. Arthritis Rheum. 2006;54(1):226-229.■ Arthritis and rheumatism → leading causes of disability in US3■ By 2030, a projected 67 million in US will have HCP-diagnosed arthritis4USAdults(%)WithArthritis
Factors Implicated in the Development of OACartilage breakdownObesityObesityAnatomicabnormalitiesAnatomicabnormalitiesMicrofracturesand bonyremodelingMicrofracturesand bonyremodelingLoss of jointstabilityLoss of jointstabilityTraumaTraumaAgingAgingGenetic andmetabolicdiseasesGenetic andmetabolicdiseasesInflammationInflammationImmunesystemactivityImmunesystemactivityCompromised cartilageBiophysical changes• Collagen network fracture• Proteoglycan unravelingBiochemical changes• Inhibitors reduced• Proteolytic enzymes increasedAbnormal stresses Abnormal cartilageMandelbaum 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 andthree signs correctly diagnoses 99% of casesSymptomsSymptoms1 Persistent knee pain √2 Limited morning stiffness √3 Reduced function √SignsSigns4 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 ofarticular cartilage and changes in underlying joints at bone margin■ Focuses on clinical examination of knee pain plus:■ Sensitivity, 95%; specificity, 69%Presence of 3 of the followingPresence of 3 of the following1 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 √ACR=American College of Rheumatology.Altman RD et al. Arthritis Rheum. 1986;29(8):1039-1049.
Goals of OA Management:OARSI RecommendationsReducejoint pain andstiffnessReducephysicaldisabilityImproveHRQoLEducatepatientsLimitprogression ofjoint damageKnee and Hip OA:Goals ofTreatmentHRQoL=health-related quality of life; OARSI=Osteoarthritis Research Society International.Zhang W et al. Osteoarthritis Cartilage. 2008;16(2):137-162.Maintain andimprove jointmobility
Integrated Approach to Treating Patients With OANonpharmacologicNonpharmacologic PharmacologicPharmacologic■ Patient education■ Phone contact (promote self-care)■ Referral to physical therapist■ Aerobic, strengthening, and/or water-based exercise■ Weight reduction■ Walking aids, knee braces■ Proper footwear, insoles■ Thermal modalities■ TENS■ Acupuncture■ APAP■ Oral NSAIDs■ Topical NSAIDs and capsaicin■ Corticosteroid injections■ Hyaluronate injections■ Glucosamine, chondroitin sulphate,and/or diacerein■ Weak opioids and narcotic analgesicsfor refractory pain*SurgicalSurgical■ Total joint replacement■ Unicompartmental knee replacement■ Osteotomy and other joint preservingsurgical procedures■ Lavage/debridement in knee OA†■ Joint fusion after failure of jointreplacement* Pain resistant to ordinary treatment. † Controversial.TENS=transcutaneous electrical nerve stimulation.Zhang W et al. Osteoarthritis Cartilage. 2008;16(2):137-162.
US Prevalence and Burden ofRheumatoid Arthritis (RA)■ May affect between 1.3 and 1.5 millionadults1,2Incidence lowest in individuals aged ≤34 yearsIncidence increases progressively with ageOccurs more commonly in women than in men■ Societal costs3* 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 RACriterionCriterion ScoreScoreA Joint Involvement*1 large joint 02-10 large joints 11-3 small joints (± large-joint involvement) 24-10 small joints (± large-joint involvement) 3>10 joints (at least 1 small joint) 5B Serology†Negative RF and negative ACPA 0Low-positive RF or low-positive ACPA 2High-positive RF or high-positive ACPA 3CAcute-PhaseReactants‡Normal CRP and normal VHS 0Abnormal ESR or CRP 1DDuration ofSymptoms§Less than 6 weeks 06 or more weeks 1Total score ≥6/10Total score ≥6/10needed to classifyneeded to classifydefinite RAdefinite RATotal score ≥6/10Total score ≥6/10needed to classifyneeded to classifydefinite RAdefinite RA* Any swollen or tender joint on examination. Excluded are distal interphalangeal joints, first carpometacarpal joints, and firstmetatarsophalangeal joints. Large joints = shoulders, elbows, hips, knees, and ankles. Small joints = metacarpophalangeal joints, proximalinterphalangeal joints, 2nd through 5th metatarsophalangeal joints, thumb interphalangeal joints, and wrists. The >10 category can include largeand 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 ofsynovitis 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 ManagementReduce painPrevent orcontrol jointdamagePreventfunctionaldeclineMaximizepatientquality of lifeEarly and SustainedSuppression of Disease ActivityACR Subcommittee on Rheumatoid Arthritis Guidelines. Arthritis Rheum. 2002;46(2):328-346.
Treatment Options for Patients With RA1-3NSAIDsNSAIDs Symptomatic treatment to reduce joint swelling and painDMARDsDMARDs(biologic and(biologic andnonbiologic)nonbiologic) Reduce/prevent joint damage, preserve joint integrity and function Methotrexate, leflunomide, hydroxychloroquine, minocycline,sulfasalazine Etanercept, infliximab, adalimumab (TNF inhibitors) Rituximab (anti-CD20) Abatacept (cytotoxic T-lymphocyte antigen 4 immunoglobulin) Tocilizumab (anti-interleukin 6 receptor)GlucocorticoidsGlucocorticoids Short-term use during flare-ups (oral or intramuscular) Local treatment for individual active joints (intra-articular)SurgerySurgery Carpal tunnel release, synovectomy, resection of metatarsal heads,total joint arthroplasty, joint fusionSupportiveSupportiveStrategiesStrategies Patient education, cognitive-behavioral interventions 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 RA1CharacteristicCharacteristic OAOA RARAPrevalence in US adults 27 million21.3–1.5 million3,4Pathophysiologic process Degenerative AutoimmuneCommonly affected jointsHips, knees, spine,fingersHands, feetTypically symmetricalinvolvementNo YesMorning stiffness Transient PersistentJoint swelling Hard tissue Soft tissueHand involvement Distal joints Proximal jointsExtraarticular involvement No YesElevated 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.
1991: A New Paradigm for COX BiologyGlucocorticoidsGlucocorticoids(block mRNA(block mRNAexpression)expression)Arachidonic AcidArachidonic AcidCOX-1COX-1(Constitutive)(Constitutive)COX-2COX-2(Cytokine(CytokineInducible)Inducible)StomachStomachIntestineIntestineKidneyKidneyPlateletPlateletInflammatory Site:Inflammatory Site:• MacrophagesMacrophages• SynoviocytesSynoviocytes• Endothelial cellsEndothelial cellsNSAIDsNSAIDsx x
McKenna F et al. Scand J Rheumatol 2001;30:11–18.VAS=visual analogue scale.LessPainPatient’s Assessment of Pain (VAS): Mean change atweek 6MeanChange(mm)*p=0.001 vs. placeboplacebo(n=200)celecoxib100 mg BID(n=199)diclofenac50 mg TID(n=199)Coxibvs. diclofenac:6-week Knee OA TrialMcKenna et al. 2001: Patient’s Assessment of Pain
McKenna F et al. Scand J Rheumatol. 2001;30:11-18.American Pain Society (APS) Pain Measure:Worst Pain in the Past 24 HoursMeanChangeinScorep=0.05, active treatment vs.placebo (days 1-7).-4.0-3.5-3.0-2.5-2.0-1.5-1.0-0.50.0Baseline Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7placebo (n=200)celecoxib 100 mg BID (n=199)diclofenac 50 mg TID (n=199)LessPainCoxibsvs. diclofenac:6-week Knee OA TrialMcKenna et al. 2001: American Pain Society – PainMeasure
Primary Endpoint: Cumulative Incidence ofThrombotic CV Events30Etoricoxib (320 events)Diclofenac (323 events)MonthsNo. of patients at risk*EtoricoxibDiclofenac16,81916,48313,359 10,733 8277 6427 4024 80581538326213790110,14212,8007.06.05.04.03.02.01.006 12 18 24 30 36 420Cumulativeincidence(%)with95%CIEtoricoxib vs diclofenacHR = 0.9595% CI = (0.81-1.11)*Per protocol population.
Boxed Warning for All Prescription NSAIDsCardiovascular RiskNSAIDs may cause an increased risk of serious cardiovascular thrombotic events,myocardial infarction, and stroke, which can be fatal. This risk may increase withduration of use. Patients with cardiovascular disease or risk factors forcardiovascular disease may be at greater risk.[Product] is contraindicated for the treatment of perioperative pain in the settingof coronary artery bypass graft (CABG) surgery.Gastrointestinal RiskNSAIDs, including Coxibs, cause an increased risk of serious gastrointestinaladverse events including bleeding, ulceration, and perforation of the stomach orintestines, which can be fatal. These events can occur at any time during use andwithout warning symptoms. Elderly patients are at greater risk for seriousgastrointestinal (GI) events.Cardiovascular RiskNSAIDs may cause an increased risk of serious cardiovascular thrombotic events,myocardial infarction, and stroke, which can be fatal. This risk may increase withduration of use. Patients with cardiovascular disease or risk factors forcardiovascular disease may be at greater risk.[Product] is contraindicated for the treatment of perioperative pain in the settingof coronary artery bypass graft (CABG) surgery.Gastrointestinal RiskNSAIDs, including Coxibs, cause an increased risk of serious gastrointestinaladverse events including bleeding, ulceration, and perforation of the stomach orintestines, which can be fatal. These events can occur at any time during use andwithout warning symptoms. Elderly patients are at greater risk for seriousgastrointestinal (GI) events.
So what does this mean for us?■ BOTH NSAIDs and coxibs are associated tovarying degrees with increased CV risk■ We must consider co-morbidities and concurrentmedications that may sway risk■ Older patients are at increased risk of CV, GI andrenal side effects – weigh up risk/benefit■ Both NSAIDs and coxibs are viable and effectiveoptions to treat pain and have manageable sideeffect profiles
NSAIDs: Renal risksMHRA DSU. May 2009Renal risk
SUMMARY■ Arthritis Pain is major health problem in our population■ NSAIDs is scientifically proven to alleviate arthritis pain(OA, RA)■ In patients with risk of GI tract afflection combinediclofenac with PPI■ Diclofenac has a well-tolerated safety profille35
■ NICE advises against use of any NSAID in thosetaking low-dose aspirin■ Avoid tNSAIDs and coxibs in those with history ofheart failure■ Avoid tNSAID or coxib in those with GFR <30, use withcaution when GFR 30<6036
Practical Advice■ Prescribe lowest effective dose for the shortest period oftime■ In chronic pain consider as required dosing and reviewregularly■ Advise patient regarding potential side effects and do whatyou can to minimise risks■ Monitor BP, renal function and liver function in those onlong term