Rheumatoid Arthritis: Avorn J

Cabral D, Katz JN, Weinblatt ME, Ting G, Avorn J, Solomon DH. · Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Arthritis Rheum. · Pubmed #15696560 links to  free full text

Abstract: OBJECTIVE: To develop a set of indicators for assessing the severity of rheumatoid arthritis (RA) through medical records. METHODS: A list of 47 potential indicators of RA was reviewed by an expert Delphi panel of 6 rheumatologists. The Delphi method is a formal approach for gathering expert opinion. The 47 potential indicators included items from the following 5 categories: radiologic and laboratory findings, clinical and functional status measures, extraarticular manifestations, prior surgical history, and medications. The panelists rated the potential indicators' relationship to RA disease severity. Each panelist rated each indicator on a scale of 0-6, in which 0 indicated no relationship at all with severe RA and 6 indicated a perfect relationship with severe RA. After a baseline set of ratings, a literature review was distributed to the panelists along with the panel's initial mean ratings and the ranges. The panelists then met to discuss the literature and rerate all indicators. RESULTS: After repeat ratings and review of relevant literature, the panel rated 28 of 47 (60%) potential indicators as having a strong or very strong relationship to severe RA. These 28 indicators were drawn from all 5 categories of potential indicators. There was agreement among the panelists on ratings for 41 of 47 indicators. Agreement was defined as a range of scores among the panelists </=3. CONCLUSION: A Delphi panel of rheumatologists agreed that data generally available in medical records may serve as potential indicators of severe RA.

Solomon DH, Avorn J. · Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. · Curr Opin Rheumatol. · Pubmed #12598798 No free full text.

Abstract: Pharmacoepidemiology is the branch of epidemiology that focuses on medications and their outcomes, including both adverse events and intended consequences. Such studies have become more prominent in rheumatology as the number of new medications has grown and prescribing databases have become more available. In the past year, the potential cardiovascular complications associated with selective COX-2 inhibitors have become an important concern. A number of pooled analyses suggest the possibility of an increased risk of acute myocardial infarction, and studies of naproxen have found a possible protective effect. Accumulating evidence supports the contention that early initiation of disease modifying antirheumatid drug therapy improves outcomes of patients with rheumatoid arthritis. Open-label extensions of biologic therapies found continued benefits extending several years with the TNF-alpha antagonists, but concerns have arisen regarding tuberculosis and central nervous system demyelination with these agents. Data continue to be published quantifying the risk of osteoporosis associated with glucocorticoids, and the association between biphosphonate therapy and upper gastrointestinal events appears to be less of a concern that originally described.

Ting G, Schneeweiss S, Scranton R, Katz JN, Weinblatt ME, Young M, Avorn J, Solomon DH. · Department of Medicine, Division of Pharmacoepidemiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02120, USA. · Arthritis Res Ther. · Pubmed #18717997 links to  free full text

Abstract: INTRODUCTION: Health care utilisation ('claims') databases contain information about millions of patients and are an important source of information for a variety of study types. However, they typically do not contain information about disease severity. The goal of the present study was to develop a health care claims index for rheumatoid arthritis (RA) severity using a previously developed medical records-based index for RA severity (RA medical records-based index of severity [RARBIS]). METHODS: The study population consisted of 120 patients from the Veteran's Administration (VA) Health System. We previously demonstrated the construct validity of the RARBIS and established its convergent validity with the Disease Activity Score (DAS28). Potential claims-based indicators were entered into a linear regression model as independent variables and the RARBIS as the dependent variable. The claims-based index for RA severity (CIRAS) was created using the coefficients from models with the highest coefficient of determination (R2) values selected by automated modelling procedures. To compare our claims-based index with our medical records-based index, we examined the correlation between the CIRAS and the RARBIS using Spearman non-parametric tests. RESULTS: The forward selection models yielded the highest model R2 for both the RARBIS with medications (R2 = 0.31) and the RARBIS without medications (R2 = 0.26). Components of the CIRAS included tests for inflammatory markers, number of chemistry panels and platelet counts ordered, rheumatoid factor, the number of rehabilitation and rheumatology visits, and Felty's syndrome diagnosis. The CIRAS demonstrated moderate correlations with the RARBIS with medication and the RARBIS without medication sub-scales. CONCLUSION: We developed the CIRAS that showed moderate correlations with a previously validated records-based index of severity. The CIRAS may serve as a potentially important tool in adjusting for RA severity in pharmacoepidemiology studies of RA treatment and complications using health care utilisation data.

Solomon DH, Glynn RJ, Rothman KJ, Schneeweiss S, Setoguchi S, Mogun H, Avorn J, Stürmer T. · Brigham and Women's Hospital, 1620 Tremont Street, Boston, MA 02120, USA. · Arthritis Rheum. · Pubmed #18668605 No free full text.

Abstract: OBJECTIVE: To explore the extent to which clinical characteristics influence the association between cyclooxygenase 2 inhibitors (coxibs) and/or nonselective nonsteroidal antiinflammatory drugs (NSAIDs) and increased cardiovascular disease (CVD) risk in specific patient subgroups. There is substantial concern regarding the potential cardiovascular adverse effects of selective coxibs and nonselective NSAIDs, but many patients with arthritis experience important clinical benefits from these agents. METHODS: The study population consisted of Medicare beneficiaries also eligible for a drug benefits program for older adults during the years 1999-2004. We calculated the relative risk (RR) for CVD events (myocardial infarction [MI], stroke, congestive heart failure, and cardiovascular death) among users of coxibs or nonselective NSAIDs in the prior 6 months compared with nonusers. We assessed biologic interaction between these medication exposures and important patient characteristics. RESULTS: In the primary cohort, we identified 76,082 new users of coxibs, 53,014 new users of nonselective NSAIDs, and 46,558 nonusers. Compared with nonusers, the adjusted RR of CVD events for new users of each agent increased for rofecoxib (RR 1.22, 95% confidence interval [95% CI] 1.14, 1.30) and decreased for naproxen (RR 0.79, 95% CI 0.67, 0.93). Several patient characteristics were found to increase the risk of CVD events among users of some agents in both the primary and secondary cohorts, including age >/=80 years, hypertension, prior MI, prior CVD, rheumatoid arthritis, chronic renal disease, and chronic obstructive pulmonary disease. Rofecoxib and ibuprofen appeared to confer an increased risk in multiple patient subgroups. CONCLUSION: Many nonselective NSAIDs and coxibs are not associated with an increased risk of CVD events. However, several patient characteristics identify important subgroups that may be at an increased risk when using specific agents.

Setoguchi S, Schneeweiss S, Avorn J, Katz JN, Weinblatt ME, Levin R, Solomon DH. · Divisions of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard MedicalSchool, Boston, MA 02130, USA. <> · Am Heart J. · Pubmed #18657665 No free full text.

Abstract: BACKGROUND: Clinical trials have shown that tumor necrosis factor-alpha antagonists (TNFAs) confer little benefit, and some may cause potential harm in advanced heart failure (HF). Although TNFAs had significant benefits in treating rheumatoid arthritis (RA), little is known whether the drugs pose an increased risk of HF in older patients with RA. METHODS: A cohort study was conducted using data from Medicare and drug benefit programs in 2 states (1994-2004). We identified patients with RA aged > or =65 who received TNFA or methotrexate (MTX). The cohort was divided into patients with and without previous HF. We considered demographic variables, cardiovascular risk factors, RA severity-related measures, and other comorbidities. The primary end point was hospitalization with HF. We used stratified Cox proportional hazards regression to estimate the adjusted effect of TNFAs on HF hospitalization. RESULTS: The cohort consisted of 1,002 TNFA users and 5,593 MTX users. There were 59 HF admissions during 1,680 person-years of TNFA use and 227 HF admissions during 10,623 person-years of MTX use. Comparing TNFA with MTX users, the adjusted hazard ratio for HF hospitalization was 1.70 (95% confidence interval 1.07-2.69). We found similar results in patients with and without previous HF. Among patients with previous HF, the adjusted hazard ratio for death was 4.19 (95% confidence interval 1.48-11.89). CONCLUSIONS: TNFAs may increase the risk of both first hospitalization and exacerbation of HF in elderly patients with RA. The potential for residual confounding in our study cannot be ruled out; larger and more detailed studies are needed to confirm the findings.

Schmajuk G, Schneeweiss S, Katz JN, Weinblatt ME, Setoguchi S, Avorn J, Levin R, Solomon DH. · Stanford University, Palo Alto, California, USA. · Arthritis Rheum. · Pubmed #17665462 links to  free full text

Abstract: OBJECTIVE: The National Committee on Quality Assurance has determined that all patients with rheumatoid arthritis (RA) should be treated with disease-modifying antirheumatic drugs (DMARDs). Our objective was to determine the rate and predictors of DMARD use in a cohort of elderly patients with RA. METHODS: We analyzed health care utilization data for 5,864 Medicare beneficiaries with RA who also participated in a state-run pharmaceutical benefit program in Pennsylvania. Patients with RA were defined as those with at least 3 diagnoses of RA (International Classification of Diseases, Ninth Revision code 714.xx) at least 1 week apart who were enrolled in these programs for at least 12 months during 1995-2004. Multivariate logistic regression was used to assess predictors of synthetic or biologic DMARD use in the 12 months after cohort entry. RESULTS: Thirty percent of patients filled a DMARD prescription during 12 months of followup. Frequency of DMARD use increased steadily over time: 24% received DMARDs in 1996 compared with 43% in 2003 (P for trend <0.001). Of patients with at least 1 rheumatologist visit, 41% received a DMARD in 1996 compared with 70% in 2003 (P < 0.001). After the introduction of biologic DMARDs in 1998, 6% of all patients with RA received a biologic, including 12% who saw a rheumatologist. Patients ages 75-84 were 52% less likely to receive DMARDs (95% confidence interval [95% CI] 46-58%) and patients ages >or=85 were 74% less likely (95% CI 69-79%) compared with patients ages 65-74. CONCLUSION: In this cohort of patients in the community with full prescription drug coverage, most patients diagnosed with RA did not receive a DMARD during the 12 months after cohort entry. Older patients and those not seeing a rheumatologist were less likely to receive a DMARD and may provide a target for quality improvement interventions.

Schneeweiss S, Setoguchi S, Weinblatt ME, Katz JN, Avorn J, Sax PE, Levin R, Solomon DH. · Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02120, USA. · Arthritis Rheum. · Pubmed #17530704 links to  free full text

Abstract: OBJECTIVE: To assess the association between the initiation of anti-tumor necrosis factor alpha (anti-TNFalpha) therapy and the risk of serious bacterial infections in routine care. METHODS: This was a cohort study of patients with rheumatoid arthritis (RA) in whom specific disease-modifying antirheumatic drugs (DMARDs) were initiated. Patients were Medicare beneficiaries ages 65 years and older (mean age 76.5 years) who were concurrently enrolled in the Pharmaceutical Assistance Contract for the Elderly provided by the state of Pennsylvania. A total of 15,597 RA patients in whom a DMARD was initiated between January 1, 1995 and December 31, 2003 were identified using linked data on all prescription drug dispensings, physician services, and hospitalizations. Initiation of anti-TNFalpha therapy, cytotoxic agents other than methotrexate (MTX), noncytotoxic agents, and glucocorticoids was compared with initiation of MTX. The main outcome measure was serious bacterial infections that required hospitalization. RESULTS: The incidence of serious bacterial infections was, on average, 2.2 per 100 patient-years in this population (95% confidence interval [95% CI] 2.0-2.4). Glucocorticoid use doubled the rate of serious bacterial infections as compared with MTX use, independent of previous DMARD use (rate ratio [RR] 2.1 [95% CI 1.5-3.1]), with a clear dose-response relationship for dosages >5 mg/day (for < or = 5 mg/day, RR 1.34; for 6-9 mg/day, RR 1.53; for 10-19 mg/day, RR 2.97; and for > or = 20 mg/day, RR 5.48 [P for trend < 0.0001]). Adjusted models showed no increase in the rate of serious infections among initiators of anti-TNFalpha therapy (RR 1.0 [95% CI 0.6-1.7]) or other DMARDs as compared with initiators of MTX. CONCLUSION: In a large cohort of patients with RA, we found no increase in serious bacterial infections among users of anti-TNFalpha therapy compared with users of MTX. Glucocorticoid use was associated with a dose-dependent increase in such infections.

Solomon DH, Avorn J, Katz JN, Weinblatt ME, Setoguchi S, Levin R, Schneeweiss S. · Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02120, USA. · Arthritis Rheum. · Pubmed #17136752 links to  free full text

Abstract: OBJECTIVE: The risk of cardiovascular disease (CVD) is increased in patients with rheumatoid arthritis (RA), most likely because of increased systemic inflammation. Prior research suggests that immunosuppressive medications may reduce the risk of CVD among RA patients. This study was undertaken to investigate the effects of various immunosuppressive medications on the risk of cardiovascular events among a group of older patients with RA. METHODS: In this nested case-control study, the source cohort was derived from Medicare beneficiaries receiving a drug benefit from the state of Pennsylvania. These individuals were required to have been diagnosed as having RA on at least 2 visits and to have filled a prescription for an immunosuppressive agent. Cases were defined as those patients who were hospitalized for a cardiovascular event such as myocardial infarction or stroke, and 10 control subjects were matched to each case by age, sex, and calendar year of the index date (the time of the first cardiovascular event in each case). Current use of an immunosuppressive medication was defined as having filled a prescription for these agents within the 90 days prior to the index date. Multivariate logistic regression models that included important covariates were assessed to determine the risk of cardiovascular events associated with immunosuppressive agents and their combinations. RESULTS: Among the study cohort, we identified 3,501 RA patients who fulfilled our eligibility criteria. During followup of this cohort, 946 patients were hospitalized for a cardiovascular event. Although the 95% confidence intervals (95% CIs) were wide in adjusted risk regression models with methotrexate (MTX) monotherapy as the reference group, biologic immunosuppressive agents showed neither protective nor deleterious effects (with biologics monotherapy, odds ratio [OR] 1.0, 95% CI 0.5-1.9; with biologics plus MTX combination therapy, OR 0.8, 95% CI 0.3-2.0; and with biologics plus other immunosuppressive agents, OR 1.2, 95% CI 0.7-2.2). Monotherapy with oral glucocorticoids was associated with an increased risk of cardiovascular events (OR 1.5, 95% CI 1.1-2.1), and a similar trend in the direction of risk was seen with glucocorticoid combination therapy (OR 1.3, 95% CI 0.8-2.0). Cytotoxic immunosuppressive agents other than MTX (azathioprine, cyclosporine, and leflunomide) were also associated with an increased risk of cardiovascular events (with both monotherapy and combination treatment, OR 1.8, 95% CI 1.1-3.0). CONCLUSION: When compared with RA patients receiving MTX monotherapy, those receiving biologic immunosuppressive agents had neither an increased nor decreased risk of experiencing a cardiovascular event, whereas use of oral glucocorticoids and cytotoxic immunosuppressive agents was associated with significant increases in the risk of cardiovascular events.

Setoguchi S, Solomon DH, Weinblatt ME, Katz JN, Avorn J, Glynn RJ, Cook EF, Carney G, Schneeweiss S. · Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02130, USA. · Arthritis Rheum. · Pubmed #16947774 links to  free full text

Abstract: OBJECTIVE: Concerns persist about a possible association between tumor necrosis factor alpha (TNFalpha) antagonist treatment and development of cancers in patients with rheumatoid arthritis (RA). This study was undertaken to estimate the association between treatment with biologic disease-modifying antirheumatic drugs (DMARDs) and development of cancer in patients with RA. METHODS: We conducted a cohort study pooling administrative databases from 2 US states and 1 Canadian province. A cohort of patients who had received a diagnosis of RA on > or =1 occasion and had been prescribed DMARDs was identified. We categorized patients with a prescription for a biologic DMARD as biologic DMARD users, and those with a prescription for methotrexate (MTX) but no biologic DMARD as MTX users. We used time-varying propensity scores to adjust for the large number of possible confounders and stratified proportional hazards regression to estimate the effects of biologic DMARDs on cancer. The primary end points were hematologic malignancies (lymphoma, multiple myeloma, and leukemia) and common solid tumors (colorectal, lung, stomach, breast, prostate, uterine, ovarian, urinary tract/bladder, and melanoma). RESULTS: The pooled cohort included 1,152 biologic DMARD users and 7,306 MTX users. We identified 11 hematologic malignancies and 46 solid tumors during 2,940 person-years of biologic DMARD use, and 88 hematologic malignancies and 558 solid tumors during 30,300 person-years of MTX use. Comparing biologic DMARD users with MTX users, the propensity score-adjusted pooled hazard ratio was 1.37 (95% confidence interval 0.71-2.65) for hematologic malignancies and 0.91 (95% confidence interval 0.65-1.26) for solid tumors. CONCLUSION: Our results indicate that users of biologic agents are unlikely to have a substantial increase in the risk of hematologic malignancies and solid tumors as compared with MTX users. Despite the use of large combined data sets, studying the effect of an infrequent exposure (biologic DMARDs) on rare diseases (hematologic malignancies) remains a challenge.

Solomon DH, Goodson NJ, Katz JN, Weinblatt ME, Avorn J, Setoguchi S, Canning C, Schneeweiss S. · Division of Pharmacoepidemiology, Brigham and Women's Hospital, 1620 Tremont Street, Suite 3030, Boston, MA 02120, USA. · Ann Rheum Dis. · Pubmed #16793844 No free full text.

Abstract: BACKGROUND: Although it is known that rheumatoid arthritis is associated with an increased risk of cardiovascular disease (CVD), the pattern of this risk is not clear. This study investigated the relative risk of myocardial infarction, stroke and CVD mortality in adults with rheumatoid arthritis compared with adults without rheumatoid arthritis across age groups, sex and prior CVD event status. METHODS: We conducted a cohort study among all residents aged >or=18 years residing in British Columbia between 1999 and 2003. Residents who had visited the doctor at least thrice for rheumatoid arthritis (International Classification of Disease = 714) were considered to have rheumatoid arthritis. A non-rheumatoid arthritis cohort was matched to the rheumatoid arthritis cohort by age, sex and start of follow-up. The primary composite end point was a hospital admission for myocardial infarction, stroke or CVD mortality. RESULTS: 25 385 adults who had at least three diagnoses for rheumatoid arthritis during the study period were identified. During the 5-year study period, 375 patients with rheumatoid arthritis had a hospital admission for myocardial infarction, 363 had a hospitalisation for stroke, 437 died from cardiovascular causes and 1042 had one of these outcomes. The rate ratio for a CVD event in patients with rheumatoid arthritis was 1.6 (95% confidence interval (CI) 1.5 to 1.7), and the rate difference was 5.7 (95% CI 4.9 to 6.4) per 1000 person-years. The rate ratio decreased with age, from 3.3 in patients aged 18-39 years to 1.6 in those aged >or=75 years. However, the rate difference was 1.2 per 1000 person-years in the youngest age group and increased to 19.7 per 1000 person-years in those aged >or=75 years. Among patients with a prior CVD event, the rate ratios and rate differences were not increased in rheumatoid arthritis. CONCLUSIONS: This study confirms that rheumatoid arthritis is a risk factor for CVD events and shows that the rate ratio for CVD events among subjects with rheumatoid arthritis is highest in young adults and those without known prior CVD events. However, in absolute terms, the difference in event rates is highest in older adults.

Sato M, Schneeweiss S, Scranton R, Katz JN, Weinblatt ME, Avorn J, Ting G, Shadick NA, Solomon DH. · Division of Pharmacoepidemiology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA 02120, USA. · Arthritis Res Ther. · Pubmed #16542499 links to  free full text

Abstract: The objective of this work was to assess the convergent validity of a previously developed rheumatoid arthritis medical records-based index of severity (RARBIS) by comparing it with the 28-joint Disease Activity Score (DAS28). This study was conducted in subjects within the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS). We selected 100 patients with rheumatoid arthritis (RA) from the BRASS with DAS28 scores equally distributed in four quartiles. The medical records were reviewed to calculate the RARBIS, which includes indicators from the following categories: prior surgical history, radiologic and laboratory findings, clinical and functional status, and extra-articular manifestations. The Spearman correlation between the RARBIS and the DAS28 was assessed in the total study population and in relevant subgroups. We re-weighted on subscales and recalculated the RARBIS score. This was performed based on findings of correlations between the DAS28 and subscales; and also the result from a multiple linear regression with the DAS28 (as a dependent variable) and five subscales (as independent variables). The mean RARBIS was 4.36 (range 0-11). Among the total study cohort, the RARBIS was moderately correlated with the DAS28 (r = 0.41, 95% confidence interval [CI] 0.23-0.56). In subgroup analyses, including age, gender, rheumatoid factor status, and disease duration, we found no statistically significant differences in the correlations. After re-weighting, the correlation between the RARBIS and the DAS28 was somewhat improved (r = 0.48, 95% CI 0.31-0.62). In conclusion, the RARBIS correlated moderately well with the DAS28 in this population. The RARBIS has both face and convergent validity for patients with RA and relevant subgroups and may have application for medical records studies in patients with RA.

Solomon DH, Avorn J, Wang PS, Vaillant G, Cabral D, Mogun H, Stürmer T. · Brigham and Women's Hospital, Harvard Medical School, 1620 Tremont Street, Ste, 3030, Boston, MA 02120, USA. · Arthritis Rheum. · Pubmed #16463409 links to  free full text

Abstract: OBJECTIVE: To examine patterns of chronic opioid use in selected groups with arthritis and low back pain and compare them with patterns among persons with ischemic heart disease. METHODS: The study database consisted of Medicare beneficiaries who were enrolled in a drug benefit program for low-to-moderate income Pennsylvania residents. We identified selected patients who had a diagnosis of rheumatoid arthritis, osteoarthritis, chronic low back pain, or ischemic heart disease since 1995. Chronic opioid use, defined as at least six 30-day prescriptions in a year, was the endpoint of interest. We examined the proportion of patients meeting this definition during the period 1996-2001 and determined predictors based on multivariable Cox proportional hazards models. RESULTS: Four percent of subjects with rheumatoid arthritis used opioids chronically in 2001, compared with <1% in each of the other groups. There was no increase in the chronic use of opioids over the 6-year study period. Low-potency opioids were the most commonly prescribed preparations for chronic users from all patient groups. The prior use of medicines for psychiatric illness, including benzodiazepines or barbiturates, was associated with chronic prescription opioid use across all diagnoses. However, subjects with a prior diagnosis of psychiatric illness were less likely to receive chronic opioids. CONCLUSION: Chronic opioid use is relatively uncommon, even among older individuals with arthritis or low back pain. The proportion of these individuals receiving such medicines has not increased in the late 1990s. There seems to be a complex relationship between psychiatric medication use, psychiatric diagnoses, and the use of chronic opioids among these individuals.

Solomon DH, Schneeweiss S, Levin R, Avorn J. · Division of Pharmacoepidemiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02120, USA. · Hypertension. · Pubmed #15226279 links to  free full text

Abstract: There is controversy whether cyclooxygenase-2 (COX-2) specific inhibitors are associated with elevations in blood pressure requiring treatment in typical clinical practice. We examined the risk of new onset hypertension in a retrospective case-control study involving 17 844 subjects aged > or =65 years from 2 US states. Multivariable logistic models were examined to assess the relative risk of new onset hypertension requiring treatment in patients who used celecoxib or rofecoxib compared with patients taking either the other COX-2 specific inhibitor, a nonspecific NSAID, or no NSAID. During the 1999 to 2000 study period, 3915 patients were diagnosed and began treatment for hypertension; 4 controls were selected for every case. In no model was celecoxib significantly associated with the development of hypertension. Rofecoxib users were at a significantly increased relative risk of new onset hypertension compared with patients taking celecoxib (odds ratio [OR] 1.6; 95% confidence interval [CI], 1.2 to 2.1), taking a nonspecific NSAID (OR 1.4; 95% CI, 1.1 to 1.9), or taking no NSAID (OR 1.6; 95% CI, 1.3 to 2.0). There were no clear dosage or duration effects. In patients with a history of chronic renal disease, liver disease, or congestive heart failure, the relative risk of new onset hypertension was twice as high in those taking rofecoxib compared with celecoxib (OR 2.1; 95% CI, 1.0 to 4.3). In this retrospective case-control study of patients aged > or =65 years, rofecoxib use was associated with an increased relative risk of new onset hypertension; this was not seen in patients taking celecoxib.

Solomon DH, Schneeweiss S, Glynn RJ, Levin R, Avorn J. · Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. · Am J Med. · Pubmed #14693324 No free full text.

Abstract: BACKGROUND: Little is known about which factors influence the widespread use of selective cyclooxygenase (COX)-2 inhibitors. We examined the relative effects of patient risk factors for gastrointestinal toxicity, other patient characteristics, and physician prescribing preferences on the decision to prescribe a selective COX-2 inhibitor. METHODS: We retrospectively studied a cohort of 28,190 Medicare beneficiaries who were continuously enrolled in a large, state-run pharmacy benefits program that reimbursed for selective COX-2 inhibitors and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) without restrictions. Half of the study sample filled a prescription for a selective COX-2 inhibitor and the other half for a nonselective NSAID. Multivariable logistic regression models were developed to predict COX-2 inhibitor use. RESULTS: Seventeen percent of patients using a COX-2 inhibitor had no identifiable risk factor for NSAID-associated gastrointestinal toxicity, compared with 23% of those using a nonselective NSAID. Established risk factors (age > or =75 years, history of gastrointestinal hemorrhage or peptic ulcer disease, or concomitant warfarin or oral glucocorticoid use) were all significant predictors of COX-2 inhibitor use, but a multivariable model including only these risk factors discriminated poorly between the two patient groups (C statistic = 0.55). Adding other patient clinical and demographic characteristics to the model somewhat improved this association (C statistic = 0.66); however, when physician prescribing preference was included, the model had excellent ability to discriminate between the two treatment groups (C statistic = 0.83). CONCLUSION: Established risk factors for NSAID-associated gastrointestinal toxicity were poor predictors of who was prescribed a selective COX-2 inhibitor; in contrast, physician prescribing preference was an important determinant.

Bérard A, Solomon DH, Avorn J. · Brigham and Womenś Hospital, Division of Pharmacoepidemiology and Pharmacoeconomics, and Harvard Medical School, Boston, MA 02115, USA. · J Rheumatol. · Pubmed #10914846 No free full text.

Abstract: OBJECTIVE: Treatment strategies for rheumatoid arthritis (RA) are rapidly evolving, but few data exist on current prescribing patterns in distinct populations of patients and physicians. We described patterns of drug use for RA in a large population including use of nonsteroidal antiinflammatory drugs (NSAID), disease modifying antirheumatic drugs (DMARD), and corticosteroids. METHODS: We identified a cohort of 10,262 New Jersey Medicaid/Medicare/PAAD (Pharmacy Assistance for the Aged and the Disabled) beneficiaries with at least one episode of care for RA between January 1, 1992, and January 1, 1995, and at least one episode of care after December 31, 1995. All patients were present for the entire study period and thus constituted a closed cohort. All filled prescriptions, hospitalizations, nursing home care, and physician visits during 1995 were analyzed. RESULTS: The cohort was 67 years old on average, 82% female, and 63% white; 63% were enrolled in Medicaid and 9% were in a nursing home at the beginning of followup. During the study year, 68% of patients filled at least one prescription for any of the drug groups studied. The most frequently prescribed medication was an NSAID (57%), followed by corticosteroids (23%) and DMARD (13%). Thirty-nine percent of patients used only NSAID, 2% only DMARD, and 6% only corticosteroid. Patients taking NSAID used them on average for 3 months during the study year, corticosteroids for 4 months, and DMARD for over 7 months. During the study year, one-third of DMARD users stopped all DMARD therapy. One-third of prednisone users were taking doses higher than 10 mg/day. CONCLUSION: While our RA cohort was older than would be expected, they represent a typical Medicare and Medicaid or PAAD population. In this cohort of patients with a diagnosis of RA cared for by either general practitioners or rheumatologists, NSAID were the most commonly prescribed medication, with substantially lower rates of use for DMARD and corticosteroids. Drug discontinuation and medication switching were common.

Solomon DH, Glynn RJ, Avorn J. · No affiliation provided · Lancet. · Pubmed #12114070 No free full text.

This publication has no abstract.