Measuring Quality in Arthritis Care: The Arthritis Foundation s Quality Indicator Set for Analgesics

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1 Arthritis & Rheumatism (Arthritis Care & Research) Vol. 51, No. 3, June 15, 2004, pp DOI /art , American College of Rheumatology ORIGINAL ARTICLE Measuring Quality in Arthritis Care: The Arthritis Foundation s Quality Indicator Set for Analgesics KENNETH G. SAAG, 1 JASON J. OLIVIERI, 1 FAUSTO PATINO, 1 TED R. MIKULS, 2 JEROAN J. ALLISON, 1 AND CATHERINE H. MACLEAN 3 Objective. To develop systematically validated quality indicators (QIs) addressing analgesic safety. Methods. A comprehensive literature review of existing quality measures, clinical guidelines, and evidence supporting potential QIs concerning nonselective (traditional) nonsteroidal anti-inflammatory drugs (NSAIDs) and newer cyclooxygenase 2 selective NSAIDs was undertaken. An expert panel then validated or refuted potential indicators utilizing a proven methodology. Results. Eleven potential QIs were proposed. After panel review, 8 were judged to be valid; an additional 10 were proposed by the panel, of which 7 were rated as valid. Quality indicators focused upon informing patients about risk, NSAID choice and gastrointestinal prophylaxis, and side effect monitoring. Conclusion. The 15 validated indicators were combined, where appropriate, to yield 10 validated processes of care indicators for the safe use of NSAIDs. These indicators developed by literature review and finalized by our expert panel process can serve as a basis to compare the quality of analgesic use provided by health care providers and delivery systems. KEY WORDS. NSAIDs; Analgesics; Quality indicators; Patient safety. INTRODUCTION Prescription and over-the-counter analgesics, such as nonsteroidal antiinflammatory drugs (NSAIDs), aspirin, and acetaminophen, are among the most frequently used therapeutic agents in the United States (1 5). These medications assist in controlling the pain and inflammation associated with arthritis and related disorders. Despite their efficacy and popularity, this group of therapies can lead to significant adverse events, principally affecting the gastrointestinal (GI) tract and kidney. These toxicities are of Supported by a contract from the Arthritis Foundation to RAND and in part by AHRQ grant U18HS Kenneth G. Saag, MD, MSc, Jason J. Olivieri, MPH, Fausto Patino, MD, DrPH, Jeroan J. Allison, MD, MS: University of Alabama at Birmingham; 2 Ted R. Mikuls, MD, MSPH: University of Nebraska Medical Center and Omaha Veterans Administration Medical Center, Omaha, Nebraska; 3 Catherine H. MacLean, MD, PhD: RAND, Santa Monica, and University of California, Los Angeles, California. Address correspondence to Kenneth G. Saag, MD, MSc, Associate Professor and Director, Center for Education and Research on Therapeutics of Musculoskeletal Disorders, University of Alabama at Birmingham, Birmingham, AL ksaag@uab.edu. Submitted for publication November 17, 2002; accepted in revised form April 26, greatest concern among users of advanced age or with comorbidities (6 13). Various professional organizations and committees have promulgated guidelines designed to translate knowledge about analgesic safety into clinical practice (14 24). Such guidelines have been derived from a synthesis of expert opinion and a review of the existing literature. As part of the Arthritis Foundation Quality Indicator Project, we sought to develop 10 systematically validated (25) quality indicators (QIs) that would synthesize previous guidelines and use the current literature to address issues of analgesic safety. These indicators focused on 3 domains: 1) informing patients about risk, 2) NSAID choice and GI prophylaxis in patients at higher risk of GI side effects, and 3) side effect monitoring. METHODS The methods for developing NSAID and analgesic QIs, including initial indicator development, literature review, and QI validation, are detailed in a related manuscript (25). Briefly, we comprehensively reviewed existing quality measures and clinical guidelines on analgesic use, selecting those focused on processes of care and having the potential to significantly impact patient outcomes. We next conducted a systematic literature review of the Medline database (from 1980 through 2001) for evidence sup- 337

2 338 Saag et al Table 1. The Arthritis Foundation s quality indicators for analgesic use* Informing patients about risks Gastrointestinal prophylaxis Selection of NSAID Monitoring 1. IF a patient is prescribed an NSAID (nonselective or selective), THEN the patient should be advised of the associated gastrointestinal bleeding risks and renal risks and the gastrointestinal risks should be documented. 2. IF a patient is prescribed low-dose ( 325 mg/day) aspirin, THEN the patient should be advised of the associated gastrointestinal bleeding risks. 3. If a patient is prescribed acetaminophen AND the patient has risk factors for liver disease OR if the patient is treated with high-dose ( 4 gm/day) acetaminophen, THEN the patient should be advised of the associated risk of liver toxicity. 4. IF a patient is treated with a nonselective NSAID, AND the patient has risk factors for gastrointestinal bleeding, THEN the patient should be treated concomitantly with either misoprostol or a PPI. 5. IF a patient is treated with a COX-2 selective NSAID AND the patient takes low-dose aspirin daily AND the patient has risk factors for gastrointestinal bleeding, THEN the patient should be treated concomitantly with either misoprostol or a PPI. 6. IF a patient is treated with low-dose aspirin daily AND the patient has 2 or more risk factors for gastrointestinal bleeding, THEN the patient should be treated concomitantly with either misoprostol or a PPI. 7. IF a patient who is NOT treated with low-dose aspirin, has risk factors for gastrointestinal bleeding, and is prescribed an NSAID, THEN the patient should receive EITHER a nonselective NSAID plus a gastroprotective agent (PPI or misoprostol) OR a COX-selective NSAID. 8. IF a patient who takes coumadin is prescribed an NSAID, THEN the NSAID should be either COX-2 selective or a nonacetylated salicylate. 9. IF a patient is treated with daily NSAIDs (selective or nonselective) and has risk factors for gastrointestinal bleeding, THEN a CBC should be performed at baseline and during the first year after initiating therapy. 10. IF a patient is treated with daily NSAIDs (selective or nonselective) AND the patient has risk factors for developing renal insufficiency, THEN a serum creatinine should be assessed at baseline and at least once in the first year following the initiation of therapy. * NSAID nonsteroidal antiinflammatory drug; COX cyclooxygenase; PPI proton pump inhibitor; CBC complete blood count. Risk factors for gastrointestinal bleeding for indicators 4 7 defined as any of the following: age 75 years, peptic ulcer disease, gastrointestinal bleeding, or glucocorticoid use. Risk factors for gastrointestinal bleeding for indicator 9 defined as any of the following: age 75 years, peptic ulcer disease, gastrointestinal bleeding, glucocorticoid use, or coumadin use. Risk factors for renal insufficiency defined as any of the following: age 75 years, diabetes mellitus, hypertension, angiotensin converting enzyme inhibitor use, or diuretic use. porting potential QIs concerning nonselective (traditional) NSAIDs, such as ibuprofen and naproxen, as well as newer cyclooxygenase 2 (COX-2) selective NSAIDs, such as celecoxib and rofecoxib. The structured literature search identified 1,569 titles, from which 189 relevant articles were identified. On the basis of the published literature, 11 potential quality indicators were proposed. Full search terms and results of the literature review are available (see Appendix A, available at com/jpages/ :1/suppmat/index.html). An expert panel then considered evidence and validated or refuted the indicators as per previous validation methodology (26). RESULTS Of the 11 initial NSAID and analgesic QIs created for panel review, 8 were judged to be valid by the expert panel process; an additional 10 indicators were proposed by the panel, of which 7 were rated as valid. Where appropriate, validated indicators were combined to produce a final list of 10 indicators (Table 1). A list of the original indicators and voting results is available (see Appendix A, available at : 1/suppmat/index.html). Informing patients about the risks of NSAIDs and acetaminophen. The first 3 QIs deal with informing patients about risks. QI 1: IF a patient is prescribed an NSAID (nonselective or selective), THEN the patient should be advised of the associated gastrointestinal (GI) bleeding and renal risks and the GI risks should be documented BECAUSE the risks are increased compared with nonusers. QI 2: IF a patient is prescribed low-dose ( 325 mg/day) aspirin, THEN the patient should be advised of the associated GI bleeding risks BECAUSE the risks are increased compared with nonusers. QI 3: IF a patient is prescribed acetaminophen AND the patient has risk factors for liver disease OR if the patient is treated with high-dose ( 4 gm/day) acetaminophen, THEN the patient should be advised of the associated risk of liver toxicity BECAUSE these risks are increased compared with nonusers. GI risks of nonselective NSAIDs. A number of metaanalyses (10,11,27,28) have evaluated the relationship between the use of aspirin ( 325 mg/day) and other nonaspirin, nonselective NSAIDs and the risk for clinically defined adverse GI events (Table 2). Exposure to NSAIDs has been associated with a fold increased risk of various GI adverse events in these various studies.

3 Measuring Quality in Arthritis Care: Analgesics 339 Table 2. Meta-analyses of nonselective NSAID use with GI endpoints* Author, year (ref.) Endpoint No. studies pooled GI risk OR or RR (95% CI) Ofman et al, 2002 (28) PUBs 16 placebo RCT 5.4 ( ) 9 cohort 2.7 ( ) 23 case-control 3.0 ( ) Bollini et al, 1992 (27) GI tract disease 34 studies (7 cohort and 27 case-control) 3.0 ( ) Gabriel et al, 1991 (10) GI AEs 16 studies (7 cohort and 9 case-control) 2.7 ( ) Hernandez-Diaz et al, 2000 (11) UGIB 18 studies (3 cohort and 15 case-control) 3.8 ( ) * NSAID nonsteroidal antiinflammatory drug; GI gastrointestinal; OR odds ratio; RR relative risk; 95% CI 95% confidence interval; PUBs perforations, ulcers, or GI bleeds; RCT randomized controlled trial. GI tract disease indicates hematemesis, melena, peptic ulcer, ulcer perforation, or death attributable to these outcomes (RR adjusted for study design and methodologic strength). GI AEs indicates bleeding, perforation, or other adverse GI events resulting in hospitalization or death. UGIB indicates bleeding, perforation, or other serious upper GI tract events resulting in hospitalization or visit to a specialist. GI risks of COX-2 selective NSAIDs. The GI risk associated with NSAID use is best assessed by studies of clinically relevant endpoints, such as perforations, ulcers, and GI bleeds (PUBs). Two large, multicenter studies (the Vioxx Gastrointestinal Outcomes Research [VIGOR] trial and the Celecoxib Long-term Arthritis Safety Study [CLASS]) (29,30) were designed specifically to compare the upper GI toxicity of COX-2 selective and nonselective NSAIDs using clinically relevant endpoints. Additionally, 2 pooled analyses have examined similar outcomes (31,32). In 3 of these studies, the incidence of clinically meaningful upper GI bleeding was lower among the COX- 2 selective agents than comparator NSAIDs for the primary study endpoints (29,31,32). In the CLASS trial, a reduction in upper GI ulcer complications (primary endpoint) was not statistically significant at 6 months (30) or at 1 year (33), but when combined with symptomatic gastroduodenal ulcers (secondary endpoint), a significant difference between celecoxib and pooled NSAIDs (diclofenac and ibuprofen) was reported at both time points (30,33). Results of these studies are summarized in Table 3. Neither the VIGOR trial nor the CLASS study contained a placebo control. However, Arthritis, Rheumatism and Aging Medical Information System epidemiologic data have estimated the annual hospitalization rate for GI complications in osteoarthritis and rheumatoid arthritis patients not taking NSAIDs as 0.29% and 0.19%, respectively (34). Additionally, retrospective cohort data of 100,000 Tennessee Medicaid recipients reported rates of hospitalization for upper GI hemorrhage of 0.42 per 100 person-years for current NSAID nonusers (35). Moreover, the standardized incidence rate of hospitalization for upper GI bleeding has been defined from a Danish population-based cohort as 0.2 per 100 patient-years for those aged 75 years without NSAID exposure (36). In addition to comparing the incidence of clinically relevant endpoints among COX-2 selective users to that of nonselective NSAID users (as shown in Table 3) and to historical placebo controls, pooled analyses by Langman et al (31) and Goldstein et al (32) included a placebo comparator (data not shown). Langman et al (31) compared the incidence of upper GI tract PUBs in patients receiving rofecoxib, ibuprofen, or placebo by pooling data from 4 double-blind, randomized, phase 2b/3 rofecoxib trials with placebo controls. The annualized incidence rates (per 100 patient-years) over 4 months of therapy were 2.7 for placebo and 2.5 for rofecoxib (P not significant). Goldstein et al pooled 10 multicenter, randomized controlled trials (RCTs) of celecoxib-treated patients with a placebo comparator (32). In this analysis, the annualized incidence (per 100 patient years) of upper GI ulcer complications (GI bleeding, perforation, and gastric outlet obstruction) in celecoxib-treated patients was 0.2 compared with an incidence rate of 0 in placebo-treated patients (P not significant). Other studies comparing COX-2 selective NSAIDs to nonselective NSAIDs and placebo have used endoscopically detected ulcerations (37 39) and commonly reported clinical and research-related GI adverse events (nonulcer dyspepsia and study discontinuation rates) (31,40 43) as surrogate endpoints of GI toxicity. These studies report nonsignificant trends toward more endoscopic ulcerations, nonulcer dyspepsia, and study discontinuation rates in COX-2 selective NSAID users compared with placebo. However, the relationship between endoscopic ulcers and clinically significant GI adverse events is not well established (34). In summary, investigations of COX-2 selective NSAIDs collectively suggest GI safety advantages over nonselective NSAIDs. However, based on secondary analyses of existing data, analysis of pooled RCT data, comparison with historical controls, data from endoscopic studies, and patient withdrawal rates, there appears to be a small GI risk for COX-2 users in comparison with nonusers. GI risks of low-dose aspirin. We identified 3 metaanalyses and 3 case-control studies that assessed the GI toxicities of low-dose aspirin. All but 1 of these studies demonstrated an increased risk of gastrointestinal bleeding with low-dose aspirin use (relative risk ranging from 1.5 to 3.2). These studies are summarized in Table 4. The CLASS study conducted a subgroup analysis evaluating the interaction of low-dose aspirin with celecoxib and nonselective NSAIDs on the incidence of upper GI ulcer complications and symptomatic gastroduodenal ulcers (30). In this study, low-dose aspirin use was found to negate the potential GI safety benefits of celecoxib use. Renal risks of nonselective NSAIDs. At least 8 casecontrol studies have reported an increased risk of both

4 340 Saag et al Table 3. RCTs and pooled analyses of COX-2 selective NSAIDs and clinically relevant GI endpoints* Annualized incidence of GI events (per 100 patient-years) Author, year (ref.) Subjects GI endpoint COX-2 agent Active comparator drug Randomized controlled trials Bombardier et al, 2000 (29) Silverstein et al, 2000 (30) 7,968 RA and OA patients NDA Lu, Reviewer (33) 8,076 RA patients Confirmed upper GI events Rofecoxib (50 mg/day) Naproxen (500 mg b.i.d.) ,968 RA and OA patients Pooled analyses Langman et al, 1999 (31) 5,435 OA patients Goldstein et al, 2000 (32) 11,008 RA and OA patients## Upper GI ulcer complications (primary) Celecoxib (400 mg b.i.d) Ibuprofen (800 mg t.i.d.) Symptomatic gastroduodenal ulcer (secondary) Diclofenac (75 mg b.i.d) 0.8 (primary) 1.5 (primary) 2.1 (secondary) 3.5 (secondary)# Upper GI ulcer complications (primary), Celecoxib (400 mg b.i.d) Ibuprofen (800 mg t.i.d.) Diclofenac (75 mg b.i.d.) Symptomatic gastroduodenal ulcer (secondary) 26-week crude rate: 0.28% (primary) 26-week crude rate: 0.50% (primary)** 52-week crude rate: 0.43% (primary) 52-week crude rate: 0.53% (primary) 1.05% (secondary) 1.56% (secondary) PUBs Rofecoxib ( mg/day) Ibuprofen (800 mg t.i.d.) Diclofenac (50 mg t.i.d.) Nabumetone (1,500 mg/day) UGI ulcer complications*** Celecoxib ( mg b.i.d) Naproxen (500 mg b.i.d.) Diclofenac (50 or 75 mg b.i.d.) Ibuprofen (800 mg t.i.d.) * RCT randomized controlled trial; COX-2 cyclooxygenase 2; NSAIDs nonsteroidal antiinflammatory drugs; GI gastrointestinal; RA rheumatoid arthritis; b.i.d. 2 times per day; OA osteoarthritis; t.i.d. 3 times per day; NDA new drug application; PUBs perforations, ulcers, or GI bleeds. Indicates gastroduodenal perforations or obstructions, upper GI bleeding, or symptomatic gastroduodenal ulcers. P versus rofecoxib. Indicates gastric or duodenal perforation, gastric outlet obstruction, or upper GI bleeding (primary analysis); endoscopic/radiographic evidence of a gastric or duodenal ulcer combined with upper GI ulcer complications (secondary analysis). Silverstein et al (30) and NDA (33) report data from the same study. NDA reports 52-week outcomes in addition to the 6-month outcomes reported by Silverstein et al (30). # P NS versus celecoxib (primary analysis); P 0.02 versus celecoxib (secondary analysis). ** P versus celecoxib. P 0.45 versus celecoxib. P 0.04 versus celecoxib. Pooled data from 8 double-blind, randomized phase 2b/3 rofecoxib trials. P value not reported (relative risk 0.5; 95% confidence interval ). ## Pooled analysis of 14 multicenter RCTs. *** Indicates bleeding, perforation, or gastric outlet obstruction. P versus celecoxib.

5 Measuring Quality in Arthritis Care: Analgesics 341 Table 4. Meta-analyses and observational studies of low-dose aspirin use and gastrointestinal outcomes* Author, year (ref.) Study design n Dosage Endpoint GI risk OR or RR (95% CI) Derry and Loke, 2000 Meta-analysis 49,927 (8 studies mg GI bleeding 1.6 ( ) (78) pooled) Stalnikowicz-Darvasi, Meta-analysis 29,513 (9 studies mg GI bleeding 1.5 ( ) 1995 (79) pooled) Roderick et al, 1993 Meta-analysis (7 15 studies 300 mg versus All GI bleeding Nonsignificant difference (80) pooled) 300 mg Upper GI symptoms Withdrawal due to side effects for all endpoints Weil et al, 1995 (81) Case-control 3, mg Hospitalization with 3.2 ( ) peptic ulcer bleeding de Abajo et al, 2001 Case-control 13, mg Upper GI 2.0 ( ) (82) bleed/perforation Lanas et al, 2000 (83) Case-control 3, mg GI bleeding 2.4 ( ) *GI gastrointestinal; OR odds ratio; RR relative risk; 95% CI 95% confidence interval. acute and chronic renal dysfunction with use of nonselective NSAIDs. Risk and NSAID exposure definitions range substantially across populations studied. These are summarized in Table 5. In contrast, a large prospective cohort over a 14-year study period, the Physicians Health Study (n 11,032), found no associations between self-reported use of acetaminophen, aspirin, or other NSAIDs and elevated serum creatinine ( 1.5 mg/dl) or reduced creatinine clearance ( 55 ml/minute) (44). The results of this large cohort study are further substantiated by 2 additional cohort studies that did not identify any association between NSAID use and long-term renal adverse events (45,46). Renal risks of COX-2 selective NSAIDs. We identified 3 RCTs (47 49) that were designed to primarily assess the effect of COX-2 selective NSAIDs on physiologic measures of renal function. Each of these studies, examining both celecoxib and rofecoxib, demonstrated reductions in various parameters of renal function for the COX-2 selective NSAIDs assessed (Table 6). Despite the lack of a placebo comparator, both the CLASS and VIGOR trials provide ancillary data on renalassociated adverse events of celecoxib and rofecoxib compared with nonselective NSAIDs. CLASS patients taking comparator NSAIDs experienced more hypertension (n 90, 2.3%) and increased serum creatinine levels (n 48, 1.2%) compared with those using celecoxib (P 0.05 versus celecoxib for both outcomes) (30). The withdrawal rate due to renal-associated adverse events did not differ significantly between groups. The VIGOR trial reported a nonsignificant difference in the incidence of renal-associated adverse events between rofecoxib- (1.2%) and naproxen- (0.9%) treated patients (29). The discontinuation rate due to these adverse events was 0.2% in both groups. However, data on discontinuations due to hypertension-related adverse events presented to the Food and Drug Administration Arthritis Advisory Committee on February 8, 2001 ( briefing/ 3677b2_01_merck.pdf) identified a significantly greater incidence in patients taking rofecoxib (0.7%) than in those taking nonselective NSAIDs (0.1%) (P 0.001). Other RCTs with secondary renal outcomes (39,41 43,50) found no significant differences in the frequency of renal-associated adverse events (changes in blood pressure, incidence of hypertension, peripheral edema, or increases in serum creatinine levels) among patients receiving COX-2 selective NSAIDs, traditional NSAIDs, or placebo. Direct comparisons of blood pressure, sodium retention, and renal function were not conducted in these smaller studies. In summary, predominately observational study data using surrogate endpoints, and to a lesser extent RCT results, demonstrate increased risk of renal toxicity with nonselective and COX-2 selective NSAIDs. Hepatic risks of acetaminophen. This indicator was created and validated by the expert panel. Although routinely recommended as a first-line analgesic due to its safety profile (14,51), acetaminophen has been associated with hepatotoxicity in patients receiving very high doses (typically 10 gm/day) (52,53) or having risk factors, such as chronic alcoholism (52,54 57), fasting (58,59), or existing renal or cardiovascular disease (60). NSAID choice and GI prophylaxis in patients at higher GI risk. For the purpose of QIs 4 7, based on the many non-nsaid risk factors (summarized below), heightened risk for GI bleeding was defined as age 75 years, history of peptic ulcer disease, history of GI bleeding, or glucocorticoid use. Coumadin as a risk factor for GI bleeding is addressed separately in QI 8. QI 4: IF a patient is treated with a nonselective NSAID, AND the patient has risk factors for GI bleeding, THEN the patient should be treated concomitantly with either misoprostol or a proton pump inhibitor (PPI), BECAUSE these agents can reduce the risk of GI bleeding. QI 5: IF a patient is treated with a COX-2 selective NSAID AND the patient takes low-dose aspirin daily AND the patient has risk factors for GI bleeding, THEN the patient should be treated concomitantly with either misoprostol or a PPI, BECAUSE these agents can reduce the risk of GI bleeding. QI 6: IF a patient is treated with low-dose aspirin daily

6 342 Saag et al Table 5. Case-control studies of nonselective NSAIDs, analgesics, and acute and chronic renal toxicity* Number of subjects Author, year (ref.) Cases Controls Exposure definition Renal risk OR (95% CI) Acute effects Griffin et al, 2000 (6) Perez Gutthann et al, 1996 (7) Evans et al, 1995 (84) Chronic effects Perneger et al, 1994 (8) Sandler et al, 1991 (9) Morlans et al, 1990 (85) Pommer et al, 1989 (86) Murray et al, 1983 (87) 1,799 Tennessee Medicaid enrollees hospitalized with community acquired ARF 28 Canadian health plan members hospitalized for ARF 207 Scottish patients hospitalized with a diagnostic code for ARF 716 ESRD patients identified form the US Mid-Atlantic Renal Coalition 554 US patients hospitalized with chronic renal disease 340 Spanish ESRD patients on a hemodialysis program 517 German ESRD patients under going renal replacement therapy 527 US ESRD patients on hemodialysis 9,899 randomly selected population controls 1,997 health plan members with 1 NSAID prescription 1,238 community and 411 hospital ageand sex-matched controls 361 randomly selected community controls 516 randomly selected community controls Nonaspirin NSAID prescription overlapping index date NSAID prescription within 30 days before index date 1 oral NSAID prescription within 90 days prior to index date 5,000 NSAID pills in lifetime 360 days of consecutive NSAID use 673 hospital controls 30 days of nonnarcotic analgesics taken every other day before the first renal disease symptoms 517 sex-, age-, and nationality-matched hospital controls 1,047 sex-, age-, and race-matched hospital controls 15 analgesic doses per month for 1 year 30 days of analgesic use 1.6 ( ) 4.1 ( ) 2.2 ( ) versus community controls 1.8 ( ) versus hospital controls 8.8 ( ) 2.1 ( ) 2.9 ( ) 2.4 ( ) for any analgesic use 2.7 ( ) for combination analgesics 1.1 ( ) for overall analgesic exposure * NSAIDs nonsteroidal antiinflammatory drugs; OR odds ratio; 95% CI 95% confidence interval; ARF acute renal failure; ESRD end stage renal disease. Hospitalized patients with a discharge diagnosis indicating newly diagnosed chronic renal dysfunction. Including aspirin, pyrazolones, phenacetin, or any combination of the 3. Includes phenacetin, acetaminophen, aspirin, metamizole, phenazones, or others (not defined). Includes aspirin, acetaminophen, or phenacetin (either alone or in combination with other drugs).

7 Measuring Quality in Arthritis Care: Analgesics 343 Table 6. Randomized controlled trials of COX-2 selective NSAIDs and renal function* Author, year (ref.) Drug Study duration n Renal function measure Swan et al, 2000 (47) Rofecoxib (250 mg) Single dose 15 2 Glomerular filtration rate 2 Creatinine clearance 2 Urinary sodium excretion 2 Urinary potassium excretion Rofecoxib (12.5 mg/day) 2 weeks 60 2 Glomerular filtration rate Rofecoxib (25 mg/day) 2 Glomerular filtration rate Catella-Lawson et al, 1999 (49) Rofecoxib (50 mg t.i.d.) 2 weeks 36 2 Urinary sodium excretion Celecoxib (200 mg b.i.d.) 2 Urinary sodium excretion Rossat et al, 1999 (48) Celecoxib (400 mg b.i.d.) 7 days 40 2 Glomerular filtration rate 2 Effective renal plasma flow * COX-2 Cyclooxygenase 2; NSAIDs nonsteroidal antiinflammatory drugs; 2 decreased; t.i.d. 3 times per day; b.i.d. 2 times per day. P 0.05 for all measures. Versus placebo. Versus baseline. AND the patient has 2 or more risk factors for GI bleeding, THEN the patient should be treated concomitantly with either misoprostol or a PPI, BECAUSE these agents can reduce the risk of GI bleeding. QI 7: IF a patient who is NOT treated with low-dose aspirin has risk factors for GI bleeding and is prescribed an NSAID, THEN the patient should receive EITHER a nonselective NSAID plus a gastroprotective agent (PPI or misoprostol) OR a COX-2 selective NSAID BECAUSE these agents can reduce the risk of GI bleeding. QI 8: IF a patient who takes coumadin is prescribed an NSAID, THEN the NSAID should be either COX-2 selective or a nonacetylated salicylate BECAUSE these agents can reduce the risk of GI bleeding. GI toxicity risk factors for NSAID users. A variety of factors may predispose NSAID users to GI adverse events. Advanced age, history of GI adverse events, and concomitant therapy with either anticoagulants or glucocorticoids have been linked to an increased GI risk. Studies that have defined the risk of various factors for GI adverse events are described in Table 7. Although this literature search did not identify any formal investigations of potential risk factors of GI events in COX-2 selective NSAID users, secondary descriptive analyses of RCTs have identified similar risk factors to that of nonselective agents (32). GI prophylaxis for nonselective NSAID users. The protective effects of misoprostol and histamine-2 (H 2 ) receptor antagonists on the incidence of endoscopically determined gastric and duodenal ulcers and clinically relevant GI adverse events have been examined in both a metaanalysis and the Misoprostol Ulcer Complication Study Outcomes Safety Assessment (MUCOSA) study (12,61). These studies have reported a significant protective effect of misoprostol cotherapy compared with placebo in patients taking nonselective NSAIDs on the incidence of both gastric and duodenal ulcers; these studies have also reported a protective effect of H 2 -receptor antagonists in the prevention of duodenal ulcers alone (Table 8). The aforementioned metaanalysis and MUCOSA trial both focused solely upon primary prevention of NSAIDrelated gastric and duodenal ulceration through cotherapy with GI prophylactic agents. The Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-Associated Ulcer Treatment (62) and the Omeprazole Versus Misoprostol for NSAID-Induced Ulcer Management (OMNIUM) (63) studies examined the healing effects of misoprostol, PPIs, and H 2 -receptor antagonists on secondary prevention of endoscopically confirmed ulcers and erosions in patients receiving NSAID therapy. Both studies enrolled patients who required continuous NSAID therapy and had either endoscopic ulcers or 10 gastric or duodenal erosions at baseline. In each trail, those patients achieving treatment success (absence of endoscopically determined ulcers and the presence of 5 erosions in the stomach or duodenum) were rerandomized to a treatment arm and monitored for the maintenance of gastric and duodenal integrity over an additional 6 months of continued cotherapy. Of note, the OMNIUM trial utilized a placebo control during this maintenance phase. As noted in Table 9, greater than two-thirds of all patients achieved treatment success, irrespective of treatment arm. The patients randomized to omeprazole treatment had the highest rate of healing. Of those in the maintenance phase, at least half of all patients remained ulcer-free across each treatment arm. GI toxicity and prophylaxis of COX-2 selective NSAIDs with low-dose aspirin use. Our literature review did not identify any studies that evaluated with the prophylactic use of cytoprotective agents in NSAID users taking concomitant low-dose aspirin. However, no significant difference was observed in the frequency of upper GI complications between the celecoxib and nonselective NSAID groups among 581 patients who were taking concomitant low-dose aspirin in the CLASS study. Thus, the interaction of celecoxib with low-dose aspirin may negate the potential GI safety benefits of celecoxib. There is no comparable data from large RCTs with other COX-2 selective NSAIDs. Of note, aspirin cotherapy has become increasingly prevalent due to concerns of an increased risk of myocardial infarction seen in patients randomized to rofecoxib compared with those receiving naproxen in the VIGOR study (naproxen relative risk 0.2, 95% confidence interval ) (29). GI prophylaxis for aspirin. The literature regarding concomitant misoprostol or PPI therapy in individuals taking aspirin (including doses 325 mg daily) has been primarily restricted a number of small, placebo-controlled trials

8 344 Saag et al Table 7. Meta-analyses, clinical trials, and observational studies of nonselective NSAIDs and risk factors for gastrointestinal adverse events* Author, year (ref.) Study design GI endpoints Sample Risk factor GI risk OR or RR (95% CI) Gabriel et al, 1991 (10) Hernandez-Diaz and Rodriguez, 2000 (11) Silverstein et al, 1995 (12) Singh et al, 1996 (13) Shorr et al, 1993 (73) Garcia Rodriguez and Jick, 1994 (72) Piper et al, 1991 (88) Hernandez-Diaz and Rodriguez, 2001 (89) Meta-analysis Meta-analysis Randomized, placebocontrolled trial Prospective cohort Retrospective cohort Case-control Case control Case-control Bleeds, perforations, or other GI events resulting in hospitalization or death Subsequent or unspecified GI event Bleeds, perforations, or other GI events resulting in hospitalization or visit to a specialist Perforations, gastric outlet obstructions, or bleeds Risk of hospitalization or death due to NSAID-induced GI events Hospitalization for hemorrhagic peptic ulcers Upper GI bleeds or perforations Hospitalization for gastric or duodenal ulcer Upper GI complications 8 studies pooled Age ( ) Not reported Concomitant corticosteroid use 1.8 ( ) 10 studies pooled History of GI AEs 4.8 ( ) 7 studies pooled Age 80 years 9.2 ( ) 12 studies pooled History of ulcer 5.9 ( ) 8,843 RA patients Age 75 years 2.5 ( ) History of peptic 2.3 ( ) ulcer History of GI bleeding 2.6 ( ) 1,921 RA patients Advancing age 1.0 ( ) Previous NSAID 1.6 ( ) GI side effect Prednisone use 1.8 ( ) 2,203 personyears Anticoagulant 12.7 ( ) of oral use anticoagulant (Medicaid enrollees) 1,457 cases, 10,000 controls 1,415 cases, 7,063 controls (Medicaid enrollees) 2,105 cases, 11,500 controls Anticoagulant use Concomitant corticosteroid use Concomitant oral steroid use 6.4 ( ) 4.4 ( ) 8.9 ( ) * NSAIDs Nonsteroidal antiinflammatory drugs; GI gastrointestinal; OR odds ratio; RR relative risk; 95% CI 95% confidence interval; AEs adverse events; RA rheumatoid arthritis. (64 71). These studies confirmed a reduction in endoscopically measured gastroduodenal ulcers and erosions in patients receiving one of these cytoprotective agents. Coumadin and NSAID use. This indicator was created and validated by the expert panel. The concomitant use of anticoagulants (such as coumadin) and nonselective NSAIDs has been associated with an increased risk of clinically relevant upper GI adverse events in both cohort and case-control studies (72,73). These studies are summarized in Table 7. Although validated by the panel process, our literature search did not identify any studies evaluating a decreased risk of GI bleeding when either a COX-2 selective or nonacetylated salicylate is substituted for a nonselective NSAID. Side effect monitoring practices for NSAIDs. The final 2 QIs deal with side effect monitoring. QI 9: IF a patient is treated with daily NSAIDs (selective or nonselective) and has risk factors for GI bleeding, THEN a complete blood count should be performed at baseline and during the first year after initiating therapy BECAUSE monitoring NSAID therapy can reduce the incidence and severity of associated adverse events. QI 10: IF a patient is treated with daily NSAIDs (selective or nonselective) and has risk factors for developing renal insufficiency, THEN a serum creatinine should be assessed at baseline and at least once in the first year following the initiation of therapy BECAUSE monitoring NSAID therapy can reduce the incidence and severity of associated adverse events. For the purpose of QI 9, GI risk factors include age 75 years, peptic ulcer disease, GI bleeding, current coumadin use, or glucocorticoid use. For QI 10, renal insufficiency risk factors include age 75 years, diabetes mellitus, hypertension, angiotensin-converting enzyme inhibitor or diuretic use. Our literature search did not identify any experimental or observational evidence on the efficacy of drug monitor-

9 Measuring Quality in Arthritis Care: Analgesics 345 Table 8. Meta-analysis and clinical trial of misoprostol and histamine-receptor antagonists and the incidence of gastric and duodenal ulcers among patients treated with nonselective NSAIDs* Risk reduction with cytoprotective agent OR (95% CI) Author, year (ref.) Study design n Outcome Misoprostol H 2 receptor antagonist Koch et al, 1996 (61) Meta-analysis (24 studies pooled) 4,325 RA and OA patients; 680 healthy subjects Gastric ulcers 0.29 ( ) 0.86 ( ) Duodenal ulcers 0.28 ( ) 0.38 ( ) Silverstein et al, 1995 (12) RCT 8,843 RA patients UGI AE 0.6 ( ) * NSAIDs nonsteroidal antiinflammatory drugs; OR odds ratio; 95% CI 95% confidence interval; RA rheumatoid arthritis; OA osteoarthritis; RCT randomized, placebo-controlled trial. All comparisons versus placebo. Endoscopically determined ulcers. UGI AE upper gastrointestinal adverse event (perforation, gastric outlet obstruction, or GI bleeding). ing to improve outcomes for analgesic users. Despite the absence of empirical data, a number of prior expert groups have recommended monitoring for GI and renal adverse events in patients taking NSAIDs, particularly those at increased risk (14 18). A summary of these recommendations and alternate approaches for NSAID-treated patients is included in Table 10. DISCUSSION Although analgesics are among the most commonly used classes of therapeutics in the United States, their popularity and efficacy are offset by the risks of drug-related adverse events. There is a large body of evidence associating nonselective, and to a lesser extent low-dose aspirin and COX-2 selective NSAIDs, with GI risks. Evidence also implicates NSAIDs and acetaminophen with renal and hepatic adverse events, respectively. Based on a review of the evidence we have performed and by subsequent expert consensus, 10 indicators are presented that were judged to be valid measures of the quality of care for analgesic use in the treatment of musculoskeletal disorders. These indicators were divided into 3 categories: 1) informing patients about the risks of analgesic use, 2) NSAID choice and GI prophylaxis in patients at higher risk of GI side effect, and 3) side effect monitoring. Knowledge of involved risks may help patients and providers make better decisions leading to improved identification of adverse effects (74 76). However, 75% of regular NSAID users are not informed about potential drugrelated GI complications (34). This finding suggests issues with patient informed consent, but also highlights a pa- Table 9. Randomized clinical trials of omeprazole, ranitidine, and misoprostol and prevalent and recurring gastric and duodenal ulcers* Author, year (ref.) Population Cytoprotective agent GI outcome Success rate, % Gastric ulcer healing rate, % Duodenal ulcer healing rate, % Remission at 6 months Yoemans et al, 1998 (62) Hawkey et al, 1998 (63) 541 patients with ulcers or 10 erosions in stomach or duodenum 935 patients with ulcers or 10 erosions in stomach or duodenum Omeprazole (20 mg/day) Omeprazole (40 mg/day) Ranitidine (150 mg b.i.d.) Omeprazole (20 mg/day) Omeprazole (40 mg/day) Misoprostol (200 mg q.i.d.) Misoprostol (200 mg b.i.d.) Placebo # ** 73** *GI gastrointestinal; b.i.d. twice daily; q.i.d. 4 times daily. Success rate absence of ulcers and 5 erosions in stomach or duodenum. Remission absence of a relapse of lesions, dyspeptic symptoms, and adverse events leading to the discontinuation of treatment. P for comparisons with ranitidine. P 0.03 for comparison with ranitidine. # P for comparison with misoprostol. ** P for comparison with misoprostol. P for comparison with misoprostol. Placebo in maintenance phase only. P for comparison with omeprazole and misoprostol.

10 346 Saag et al Table 10. Consensus statements on NSAID and analgesic safety and monitoring recommendation* Consensus groups (ref.) Informing patients about risk Alternate approaches in NSAID-treated patients at high GI risk Side effect monitoring practices American College of Rheumatology (17 20) Canadian Consensus Conferences (15,16) National Kidney Foundation (14) North of England Evidence Based Guideline Development Project (21) US Preventative Services Task Force (22) International COX-2 Study Group (23) American College of Gastroenterology (24) Cautious use of acetaminophen in patients with existing liver disease and avoidance in patients with history of chronic alcohol abuse. Discuss safety with patients requiring NSAIDs (including COX-2). Over-the-counter label warning of renal risks Discuss risk and side effects of NSAIDs with patients before treatment Discuss GI risk of aspirin in those taking for coronary heart prophylaxis Low-dose prednisone Nonacetylated salicylate COX-2 selective NSAID Nonselective NSAID with misoprostol or PPI COX-2 selective NSAID Nonselective NSAID with misoprostol or PPI GI: CBC at baseline and yearly Renal: Creatinine at baseline; serial measurement of creatinine may be required (weekly for at least 3 weeks in patients receiving concomitant ACE inhibitors or diuretics) Renal: Baseline creatinine clearance and electrolyte concentrations Renal: Monitor renal function in patients with preexisting volume disease or volume depletion Paracetamol Low-dose ibuprofen Co-codamol Lower NSAID dose COX-2 selective or nonselective NSAID with misoprostol or PPI in users taking low-dose aspirin Nonselective NSAID with misoprostol or PPI Renal: At-risk patients (preexisting cardiac, renal, or hepatic disease) should be monitored (including COX-2) * NSAID Nonsteroidal antiinflammatory drug; GI gastrointestinal; CBC complete blood count; COX-2 cyclooxygenase 2; PPI proton pump inhibitor; ACE angiotensin-converting enzyme. No evidence of cost-effectiveness of NSAID plus GI prophylaxis in osteoarthritis patients. tient population at greater risk of drug-related complications because harbingers of potential complications may not be recognized. Through numerous metaanalyses and observational studies, important patient characteristics associated with increased risk of NSAID adverse events have been identified (10 13). The toxicity burden may be lessened in highrisk groups by prudent use of GI prophylaxis and/or COX- 2 selective NSAIDs. Laboratory monitoring for GI bleeding and renal damage has the potential for early identification of significant side effects and could therefore improve patient outcomes (77). This is particularly relevant for NSAID-induced GI complication because the minority of users experience early warning symptoms (13). It should be noted that the indicators selected by our process are not comprehensive and do not necessarily represent recommendations for optimal care, but instead they should be construed as minimally acceptable standards. For example, guidelines from the American College of Rheumatology recommend that renal monitoring is needed weekly for the first few weeks in patients coprescribed NSAIDs with angiotensin converting inhibitors or diuretics (18), yet the panel validated a much less stringent quality indicator for this situation. In summary, we propose 10 validated processes of care indicators. These indicators developed by literature review and finalized by an expert panel process can serve as a basis to compare the quality of analgesic use provided by different health care providers and health care delivery systems. REFERENCES 1. Baum C, Kennedy DL, Forbes MB. Utilization of nonsteroidal antiinflammatory drugs. Arthritis Rheum 1985;28: Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA 2002;287: Holt WS Jr, Mazzuca SA. Prescribing behaviors of family physicians in the treatment of osteoarthritis. Fam Med 1992; 24: Ward MM, Fries JF. Trends in antirheumatic medication use among patients with rheumatoid arthritis, J Rheumatol 1998;25: Berard A, Solomon DH, Avorn J. Patterns of drug use in rheumatoid arthritis. J Rheumatol 2000;27: Griffin MR, Yared A, Ray WA. Nonsteroidal antiinflammatory drugs and acute renal failure in elderly persons. Am J Epidemiol 2000;151: Perez Gutthann S, Garcia Rodriguez LA, Raiford DS, Duque Oliart A, Ris Romeu J. Nonsteroidal anti-inflammatory drugs

11 Measuring Quality in Arthritis Care: Analgesics 347 and the risk of hospitalization for acute renal failure. Arch Intern Med 1996;156: Perneger TV, Whelton PK, Klag MJ. Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs. N Engl J Med 1994;331: Sandler DP, Burr FR, Weinberg CR. Nonsteroidal anti-inflammatory drugs and the risk for chronic renal disease. Ann Intern Med 1991;115: Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs: a meta-analysis. Ann Intern Med 1991;115: Hernandez-Diaz S, Rodriguez LA. Association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal tract bleeding/perforation: an overview of epidemiologic studies published in the 1990s. Arch Intern Med 2000;160: Silverstein FE, Graham DY, Senior JR, Davies HW, Struthers BJ, Bittman RM, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 1995;123: Singh G, Ramey DR, Morfeld D, Shi H, Hatoum HT, Fries JF. Gastrointestinal tract complications of nonsteroidal anti-inflammatory drug treatment in rheumatoid arthritis: a prospective observational cohort study. Arch Intern Med 1996;156: Henrich WL, Agodoa LE, Barrett B, Bennett WM, Blantz RC, Buckalew VM Jr, et al. Analgesics and the kidney: summary and recommendations to the Scientific Advisory Board of the National Kidney Foundation from an Ad Hoc Committee of the National Kidney Foundation. Am J Kidney Dis 1996;27: Tannenbaum H, Davis P, Russell AS, Atkinson MH, Maksymowych W, Huang SH, et al, Canadian NSAID Consensus Participants. An evidence-based approach to prescribing NSAIDs in musculoskeletal disease: a Canadian consensus. CMAJ 1996;155: Tannenbaum H, Peloso PM, Russell AS, Marlow B. An evidence-based approach to prescribing NSAIDs in the treatment of osteoarthritis and rheumatoid arthritis: the second Canadian consensus conference. Can J Clin Pharmacol 2000;7 Suppl A:4A 16A. 17. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 update. Arthritis Rheum 2002; 46: American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Guidelines for the management of rheumatoid arthritis. Arthritis Rheum 1996;39: Hochberg MC, Altman RD, Brandt KD, Clark BM, Dieppe PA, Griffin MR, et al. Guidelines for the medical management of osteoarthritis. Part I. Osteoarthritis of the hip. Arthritis Rheum 1995;38: Hochberg MC, Altman RD, Brandt KD, Clark BM, Dieppe PA, Griffin MR, et al. Guidelines for the medical management of osteoarthritis. Part II. Osteoarthritis of the knee. Arthritis Rheum 1995;38: Eccles M, Freemantle N, Mason J, The North of England Non-Steroidal Anti-Inflammatory Drug Guideline Development Group. North of England evidence based guideline development project: summary guideline for non-steroidal antiinflammatory drugs versus basic analgesia in treating the pain of degenerative arthritis. BMJ 1998;317: U.S. Preventive Services Task Force. Aspirin for the primary prevention of cardiovascular events: recommendation and rationale. Ann Intern Med 2002;136: Simon LS, Smolen JS, Abramson SB, Appel G, Bombardier C, Brater DC, et al. Controversies in COX-2 selective inhibition. J Rheumatol 2002;29: Lanza FL, Members of the Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology. A guideline for the treatment and prevention of NSAID-induced ulcers. Am J Gastroenterol 1998;93: MacLean CH, Saag KG, Solomon DH, Morton SC, Sampsel S, Klippel JH. Measuring Quality in Arthritis Care: Methods for Developing the Arthritis Foundation s Quality Indicator Set. Arthritis Rheum 2004;51: Shekelle PG, MacLean CH, Morton SC, Wenger NS. Assessing care of vulnerable elders: methods for developing quality indicators. Ann Intern Med 2001;135: Bollini P, Garcia Rodriguez LA, Perez Gutthann S, Walker AM. The impact of research quality and study design on epidemiologic estimates of the effect of nonsteroidal antiinflammatory drugs on upper gastrointestinal tract disease. Arch Intern Med 1992;152: Ofman JJ, MacLean CH, Straus WL, Morton SC, Berger ML, Roth EA, et al. A metaanalysis of severe upper gastrointestinal complications of nonsteroidal antiinflammatory drugs. J Rheumatol 2002;29: Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al, VIGOR Study Group. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med 2000;343: Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, et al, Celecoxib Long-term Arthritis Safety Study. Gastrointestinal toxicity with celecoxib vs nonsteroidal antiinflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. JAMA 2000;284: Langman MJ, Jensen DM, Watson DJ, Harper SE, Zhao PL, Quan H, et al. Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs. JAMA 1999;282: Goldstein JL, Silverstein FE, Agrawal NM, Hubbard RC, Kaiser J, Maurath CJ, et al. Reduced risk of upper gastrointestinal ulcer complications with celecoxib, a novel COX-2 inhibitor. Am J Gastroenterol 2000;95: Lu H. Statistical Reviewer Briefing Document for the Advisory Committee. Accessed January 15, URL: www. fda.gov/ohrms/dockets/ac/01/briefing/3677b1_04_stats.doc. 34. Singh G, Triadafilopoulos G. Epidemiology of NSAID induced gastrointestinal complications. J Rheumatol 1999;26 Suppl 56: Smalley WE, Ray WA, Daugherty JR, Griffin MR. Nonsteroidal anti-inflammatory drugs and the incidence of hospitalizations for peptic ulcer disease in elderly persons. Am J Epidemiol 1995;141: Hallas J, Lauritsen J, Villadsen HD, Gram LF. Nonsteroidal anti-inflammatory drugs and upper gastrointestinal bleeding, identifying high-risk groups by excess risk estimates. Scand J Gastroenterol 1995;30: Laine L, Harper S, Simon T, Bath R, Johanson J, Schwartz H, et al, Rofecoxib Osteoarthritis Endoscopy Study Group. A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis. Gastroenterology 1999;117: Hawkey C, Laine L, Simon T, Beaulieu A, Maldonado-Cocco J, Acevedo E, et al, The Rofecoxib Osteoarthritis Endoscopy Multinational Study Group. Comparison of the effect of rofecoxib (a cyclooxygenase 2 inhibitor), ibuprofen, and placebo on the gastroduodenal mucosa of patients with osteoarthritis: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2000;43: Simon LS, Weaver AL, Graham DY, Kivitz AJ, Lipsky PE, Hubbard RC, et al. Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized controlled trial. JAMA 1999;282: Watson DJ, Harper SE, Zhao PL, Quan H, Bolognese JA, Simon TJ. Gastrointestinal tolerability of the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib compared with nonselective COX-1 and COX-2 inhibitors in osteoarthritis. Arch Intern Med 2000;160: Day R, Morrison B, Luza A, Castaneda O, Strusberg A, Nahir M, et al, Rofecoxib/Ibuprofen Comparator Study Group. A randomized trial of the efficacy and tolerability of the COX-2

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