美国风湿协会骨关节炎治疗指南ACR_2000

RECOMMENDATIONS FOR THE MEDICAL MANAGEMENT OF OSTEOARTHRITS OF THE HIP AND KNEE American College of Rheumatology Subcommittee on Osteoarthritis Guidelines Members of the Subcommittee on Osteoarthritis Guidelines arc as follows. Roy D. Altman, MD: Department of Veterans Affairs Medical Center, and University of Miami School of Medicine, Miami, Florida; Marc C. Hochberg, MD, MPH: University of Maryland School of Medicine, Baltimore; Roland W. Moskowitz, MD: Case Western Reserve University School of Medicine, Cleveland, Ohio; Thomas J. Schnitzer, MD, PhD: Northwestern University Medical School, Chicago, Illinois. Members of the Subcommittee have relationships with the following pharmaceutical or biotechnology companies. Roy D. Altman, MD: Abbott, Aventis Pharmaceutical Co., BoehringerIngelheim, Eutovita, Fidia Co., Johnson & Johnson, Ortho-McNeil, Merck Sharp and Dohme, Novartis, Pierre Farber, Procter and Gamble, Sanofi, Searle, United Therapeutics, Whitehall Robbins, Negma, and NeuColl Corp. Marc C. Hochberg, MD, MPH: Merck & Co., Aventis Pharmaceutical Co., NEGMA Laboratories, Procter and Gamble, Roche, Wyeth-Ayerst, Johnson & Johnson, Eli Lilly, and Schering Plough. Roland W. Moskowitz, MD: Searle (Pharmacia), Sanofi-Synthelab, Fidia Co., and NeuColl Corp. Thomas J. Schnitzer, MD, PhD: Abbott, Boehringer-Ingelheim, Johnson & Johnson, McNeil Consumer, Merck & Co., Novartis, Ortho-McNeil, Parke-Davis, Searle, Wyeth-Ayerst, and SmithKline Beecham. The American College of Rheumatology is an independent professional, medical, and scientific society which does not guarantee, warrant, or endorse any commercial product or service. Address reprint requests to American College of Rheumatology, 2200 Lake Boulevard NE, Atlanta, GA 30319. Submitted for publication January 29, 2000; accepted in revised form May 12, 2000. Osteoarthritis (OA) is the most common form of arthritis in the United States (1). Patients with OA have pain that typically worsens with weight bearing and activity and improves with rest, as well as morning stiffness and gelling of the involved joint after periods of inactivity. On physical examination, they often have tenderness on palpation, bony enlargement, crepitus on motion, and/or limitation of joint motion. Unlike the case with rheumatoid arthritis (RA) and other inflammatory arthritides, inflammation, if present, is usually mild and localized to the affected joint. Although the causes of OA are not completely understood, biomechanical stresses affecting the articular cartilage and subchondral bone, biochemical changes in the articular cartilage and synovial membrane, and genetic factors are all important in its pathogenesis (2-4). Although there is no known cure for OA, treatment designed for the individual patient can reduce pain, maintain and/or improve joint mobility, and limit functional impairment. In 1995, the American College of Rheumatology (ACR) published recommendations for the medical management of OA of the hip and knee (5,6). Those guidelines outlined the use of nonpharmacologic modalities, including patient education and physical and occupational therapy-the foundation of treatment of individuals with OA, as well as the use of pharmacologic agents. Specific recommendations for surgical management of OA, however, were not included. Since that time, several systematic reviews of drug therapy for OA have been published (7-11), and many clinical trials john 高亮 john 高亮 john 高亮 john 高亮 have been conducted which have resulted in the approval, or pending review, by the Food and Drug Administration (FDA) of new devices and drug treatments for OA. In 1998, the ACR established an ad hoc subcommittee, comprising several of the American authors of the 1995 recommendations, to review interim developments in the field and update the recommendations. As in the original review, the subcommittee followed the 1905 principles of evidence-based medicine as used in the process of making clinical decisions (12). As stated by Guyatt, "Physicians practicing [evidence-based medicine] will search for the highest evidence available, integrate this evidence with their clinical experience and judgment, and acknowledge the value judgments implicit in moving from evidence to action" (12). The strongest weight was given to data from systematic reviews, meta-analyses, and published findings of randomized controlled trials; data from randomized controlled trials presented as abstracts at scientific meetings were also considered. Where such data were not available, however, the subcommittee followed the approach taken by the Agency for Health Care Policy and Research, as outlined in the ACR document "Guidelines for the Development of Practice Guidelines," which combines a detailed, evidence-based approach with a process that accommodates expert opinion. This was utilized particularly in reviewing the recommendations for nonpharmacologic modalities, especially the use of assistive devices, bracing, and footwear. Finally, recently published data on OA patients' preferences regarding treatment with analgesics and nonsteroidal antiinflammatory drugs (NSAIDs) were also reviewed (13,14). The goals of the contemporary management of the patient with OA continue to include control of pain and improvement in function and health-related quality of life, with avoidance, if possible, of toxic effects of therapy. The recommended approach to the medical management of hip or knee OA includes nonpharmacologic modalities and drug therapy. The Subcommittee on OA Guidelines emphasizes that these recommendations are not fixed, rigid mandates, and recognizes that the final decision concerning the therapeutic regimen for an individual patient rests with the treating physician. Nonpharmacologic modalities The components of nonpharmacologic therapy are outlined in Table 1. Patient education and, where appropriate, education of the patient's family, friends, or other caregivers are integral parts of the treatment plan for patients with OA. Patients should be encouraged to participate in self-management programs, such as the Arthritis Foundation Self-Management Program. Individuals who participate in these programs report decreases in joint pain and frequency of arthritis-related physician visits, increases in physical activity, and overall improvement in quality of life (15). Additional educational materials, including videos, pamphlets, and news letters, are available from the Arthritis Foundation and other national voluntary health organizations. Another cost-effective nonpharmacologic approach for patients with OA is provision of personalized social support, either directly or by periodic telephone contact. Studies of the results of monthly telephone calls by trained nonmedical personnel to discuss such issues as joint pain, medications and treatment compliance, drug toxicities, date of next scheduled visit, and barriers to keeping clinic appointments showed moderate-to-large degrees of improvement in pain and functional status without a significant increase in costs (16). These studies underscore the concept that improved communication and education are important factors in decreasing pain and improving function in patients with OA. Table 1. Nonpharmacologic therapy for patients with osteoarthritis Patient education Self-management programs (e.g., Arthritis Foundation Self-Management Program) Personalized social support through telephone contact Weight loss (if overweight) Aerobic exercise programs Physical therapy Range-of-motion exercises Muscle-strengthening exercises Assistive devices for ambulation Patellar taping Appropriate footwear Lateral-wedged insoles (for genu varum) Bracing Occupational therapy Joint protection and energy conservation Assistive devices for activities of daily living Individuals with OA of the lower extremity may have limitations that impair their ability to perform activities of daily living (ADLs), such as walking, bathing, dressing, use of the toilet, and performing household chores. Physical therapy and occupational therapy play central roles in the management of patients with functional limitations. The physical therapist assesses muscle strength, joint stability, and mobility; recommends the use of modalities such as heat (especially useful just prior to exercise); instructs patients in an exercise program to maintain or improve joint range of motion and periarticular muscle strength; and provides assistive devices, such as canes, crutches, or walkers, to improve ambulation. Similarly, the occupational therapist can be instrumental in directing the patient in proper joint protection and energy conservation, use of splints and other assistive devices, and improving joint function. In addition, the input of a vocational guidance counselor may be important to patients who are still actively employed. Quadriceps weakness is common among patients with knee OA, in whom it had been believed to be a manifestation of disuse atrophy, which develops because of unloading of the painful extremity. Recent studies, however, have indicated that quadriceps weakness may be present in persons with radiographic changes of OA who have no history of knee pain, and in whom lower extremity muscle mass is increased, rather than decreased (17); and that quadriceps weakness may be a risk factor for the development of knee OA, presumably by decreasing stability of the knee joint and reducing the shock-attenuating capacity of the muscle (18). These data have recently been reviewed by Hurley (19). The beneficial effects of both quadricepsstrengthening and aerobic exercise for patients with knee OA, noted in the original recommendations, were confirmed in the Fitness Arthritis and Seniors Trial (20), in which patients with mild disability due to symptomatic knee OA were randomly assigned to aerobic exercise, resistive (muscle-strengthening) exercise, or an education/attention control group. Patients in both exercise groups had modest but significant improvement compared with the control group; this improvement was sustained over an 18-month followup period. In post hoc analyses, the authors found that the degree of adherence to the exercise regimen was significantly associated with the magnitude of improvement in pain and functional limitation. The ability of elderly subjects to maintain conditioning levels of exercise is noteworthy, since many patients with advanced hip or knee OA are sedentary, deconditioned, and at increased risk for cardiovascular disease (21). Another recent study demonstrated the efficacy of an exercise program in improving muscle strength, mobility, and coordination in patients with OA of either the knee or hip (22). In this study, patients randomly assigned to the exercise group not only had improvement in pain and observed disability, but also reported taking less acetaminophen and had made fewer physician visits by 12 weeks after entry. The effectiveness of exercise was similar in patients with hip or knee OA. These exercise programs, however, require a commitment of time, and effort on the part of the patient. In addition to quadriceps weakness, sensory dysfunction, reflected by a decrease in proprioception, has been documented in patients with knee OA (23,24). Hurley and Scott (25) showed that an easily performed exercise regimen improved knee joint position sense as well as quadriceps strength and performance of ADLs, 1907 and that these improvements were maintained for as long as 6 months. The 1995 ACR guidelines also recommended that overweight patients with hip or knee OA lose weight. A randomized open trial of an appetite suppressant and low-calorie diet was completed in 40 overweight patients with knee OA; all patients received instruction in an exercise walking program (26). Patients randomly assigned to the appetite suppressant group lost a mean of 3.9 kg over the course of 6 weeks, and also had significant improvement in their knee OA, as measured by the Lequesne algofunctional index. Although this study had limitations, it provided the only data from a randomized trial demonstrating a relationship between loss of body fat (rather than loss of body weight) and improvement in symptoms of knee OA. As noted in the 1995 ACR recommendations (5,6), proper use of a cane (in the hand contralateral to the affected knee) reduces loading forces on the joint and is associated with a decrease in pain and improvement of function. In addition, patients may benefit from wedged insoles to correct abnormal biomechanics due to varus deformity of the knee (27,28). Another useful maneuver for patients with OA of the knee who have symptomatic patellofemoral compartment involvement is medial taping of the patella (29). Pharmacologic therapy All of the pharmacologic agents discussed in this section should be considered additions to nonpharmacologic measures, such as those described above, which are the cornerstone of OA management and should be maintained throughout the treatment period. Drug therapy for pain management is most effective when combined with nonpharmacologic strategies (30). For many patients with OA, the relief of mild-to-moderate joint pain afforded by the simple analgesic, acetaminophen, is comparable with that achievable with an NSAID (8,10;31-33). Furthermore, Bradley and colleagues failed to demonstrate differences in responses to acetaminophen and ibuprofen in knee OA patients with clinical features of joint inflammation (34). However, this finding was based on a post hoc analysis with limited statistical power that used a definition of inflammation which included joint-line and soft-tissue tenderness or soft-tissue swelling. Eccles and colleagues, in a metaanalysis of trials comparing simple analgesics with NSAIDs in patients with knee OA, did note that NSAID-treated patients had significantly greater improvement in both pain at rest and pain on motion (33). aries.xu 高亮 Two recent trials, findings of which were presented at the ACR's 1999 annual meeting, also provide data on the relative efficacy of acetaminophen and NSAIDs in patients with OA. In one study, acetaminophen and ibuprofen were comparably effective in patients with mild-to-moderate pain, but ibuprofen was statistically superior to acetaminophen in patients with severe pain (35); in the other study, diclofenac was statistically superior to acetaminophen for both pain and function measured with several validated outcome measures (36). Furthermore, two recent studies of patients with OA demonstrated greater preference for NSAIDs than for acetaminophen, although many patients continue to take acetaminophen (13,14). Nevertheless, although a number of patients may fail to obtain adequate relief even with full doses of acetaminophen, this drug merits a trial as initial therapy, based on its overall cost, efficacy, and toxicity profile (33,37). In patients with knee OA with moderate-to-severe pain, and in whom signs of joint inflammation are present, joint aspiration accompanied by intraarticular injection of glucocorticoids or prescription of an NSAID merits consideration as an alternate initial therapeutic approach. The daily dose of acetaminophcn should not exceed 4 gm. Although it is one of the safest analgesics, acetaminophen can be associated with clinically important adverse events. Recent reports have highlighted long-recognized conditions in which increased awareness of potential toxicity is important. For example, because acetaminophen can prolong the half-life of warfarin sodium, careful monitoring of the prothrombin time is recommended in patients taking warfarin sodium who subsequently begin high-dose acetaminophen treatment (38,39). Hepatic toxicity with acetaminophen is rare with doses of <_4 gm/day. Nonetheless, the drug should be used cautiously in patients with existing liver disease and avoided in patients with chronic alcohol abuse because of known increased risk in these settings (40-42). Even though acetaminophen was reported to be weakly associated with end-stage renal disease, the Scientific Advisory Committee of the National Kidney Foundation recommends it as the drug of choice for analgesia in patients with impaired renal function (43). For those patients who fail to obtain adequate symptomatic relief with the above measures, alternative or additional pharmacologic agents should be considered. The choice should be made after evaluation of risk factors for serious upper gastrointestinal (GI) and renal toxicity. Data from epidemiologic studies show that among persons of age >=65 years, 20-30% of all hospitalizations and deaths due to peptic ulcer disease were attributable to therapy with NSAIDs (44-46). Furthermore, in the elderly, the risk of a catastrophic GI event in patients taking NSAIDs is dose dependent (44). Risk factors for upper GI bleeding in patients treated with NSAIDs include age >=65 years, history of peptic ulcer disease or of upper GI bleeding, concomitant use of oral glucocorticoids or anticoagulants, presence of comorbid conditions, and, possibly, smoking and alcohol consumption (Table 2) (47-49). Risk factors for reversible renal T2 failure in patients with intrinsic renal disease (usually defined as a serum creatinine concentration of >=2.0 mg/dl) who are treated with NSAIDs include age >=65 years, hypertension and/or congestive heart failure, and concomitant use of diuretics and angiotensin-converting enzyme inhibitors (50). Table 2. Risk factors for upper gastrointestinal adverse events Age >=65 Comorbid medical conditions Oral glucocorticoids History of peptic ulcer disease john 高亮 john 高亮 john 高亮 john 高亮 john 高亮 john 高亮 History of upper gastrointestinal bleeding Anticoagulants Additional considerations involved in a practitioner's decision to treat the individual OA patient include existing comorbidities and concomitant therapy, as well as the side effects and costs of specific treatments. In individuals with OA of the knee who have mild-to-moderate pain, do not respond to acetaminophen, and do not wish to take systemic therapy, the use of topical analgesics (e.g., methylsalicylate or capsaicin cream) is appropriate as either adjunctive treatment or monotherapy. Capsaicin cream should be applied to the symptomatic joint 4 times daily; a local burning sensation is common, but rarely leads to discontinuation of therapy. A systematic review of topical NSAIDs also demonstrated efficacy in patients with OA (51); there are no published findings of trials comparing the same NSAID administered orally versus topically. Initiation of treatment in the patient at increased risk for an upper GI adverse event The options for medical management of OA that has not responded to the above measures in patients who are at increased risk for a serious upper GI adverse event, such as bleeding, perforation, or obstruction, are summarized in Table 3; these include either oral agents 13 or local intraarticular therapy. Two cyclooxygenase 2 (COX-2)-specific inhibitors, celecoxib and rofecoxib, have been studied in patients with OA (52,53). Celecoxib has been found to be more effective than placebo and comparable in efficacy with naproxen in patients with hip or knee OA (54-56). Rofecoxib has also been found to be more effective than placebo and is comparable in efficacy with both ibuprofen and diclofenac in patients with hip or knee OA (57,58). Endoscopic studies have shown that celecoxib and rofecoxib are both associated with an incidence of gastroduodenal