Rheumatoid Arthritis: Solomon DH

Ridker PM, Solomon DH. · No affiliation provided · Arthritis Rheum. · Pubmed #19404973 No free full text.

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Love T, Solomon DH. · No affiliation provided · Arthritis Res Ther. · Pubmed #18495048 links to  free full text

Abstract: The association between rheumatoid arthritis (RA) and malignancies has received increased attention in recent years. Reports suggesting that tumor necrosis factor blockers might elevate the risk of malignancy in RA patients have prompted researchers to look at the incidence of malignancies in all RA patients. In a recent issue of Arthritis Research & Therapy, Smitten and colleagues suggest that previous reports of a standardized incidence ratio close to one for malignancies in RA may reflect an increased risk for some site-specific malignancies and a reduced risk for others. Here we discuss these findings and suggest what issues could be addressed in future studies.

Solomon DH. · Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, MA 02120, USA. · J Manag Care Pharm. · Pubmed #17378700 links to  free full text

Abstract: OBJECTIVE: To describe the current knowledge on safety and effectiveness of the tumor necrosis factor (TNF)-alpha antagonists and identify current knowledge/ evidence gaps for study by the Agency for Healthcare Research and Quality (AHRQ) Effective Health Care Program. BACKGROUND: Evidence-based Practice Centers (EPCs) and the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) network of AHRQ's Effective Health Care Program will study the safety and effectiveness of biologic and nonbiologic disease-modifying antirheumatic drugs (e.g., TNF-alpha antagonists). The current knowledge of safety and effectiveness of TNF-alpha antagonists is reviewed. SUMMARY: Treatment of adult rheumatoid arthritis (RA) involves determining which agents are safe, effective, and cost effective for an individual. Each individual patient's health system may also play a role in which agents are chosen. Many agents are available for the management of RA, some with high cost and unknown safety. Section 1013 of the Medicare Modernization Act of 2003 authorizes AHRQ to study comparative effectiveness and safety of RA treatments through both EPCs and DEcIDE centers to develop scientific knowledge for RA management as well as through epidemiologic studies. Results will be compiled through a Clinical Decisions and Communications Science Center, then disseminated to all appropriate stakeholders, including patients, payers, and health care professionals. The current knowledge of safety and effectiveness of TNF-alpha antagonists in the treatment of RA is reviewed. Increased rates of serious infections, including Mycobacterium tuberculosis (MTB), or tuberculosis reactivation, may occur with the use of TNF-a antagonists. It is still unclear if RA increases the risk of developing cancer, or if use of TNF-alpha antagonists increases cancer risk. CONCLUSIONS: TNF-alpha antagonists are costly, yet effective treatments for early and late RA. Use of these agents provides rapid relief of RA symptoms and provides positive outcomes, defined as improvements in American College of Rheumatology 20, 50, 70 scores; Health Assessment Questionnaire ratings; activities of daily living; joint space narrowing; erosions; and acute-phase reactants. Reactivation of latent MTB or onset of other infections or cancers may occur in RA patients with TNF-alpha antagonists.

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.

Solomon DH, Katz JN, La Tourette AM, Coblyn JS. · Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02120, USA. · Arthritis Rheum. · Pubmed #15188323 links to  free full text

Abstract: OBJECTIVE: To assess the effectiveness of a multifaceted intervention to improve the management of glucocorticoid-induced osteoporosis (GIOP). METHODS: Of 21 rheumatologists, 11 were randomly assigned to a 3-part intervention consisting of a lecture and discussion regarding optimal management of GIOP, a confidential doctor-specific audit regarding management of GIOP, and a reminder mailing including concise pharmacologic recommendations. The remaining 10 rheumatologists received no special education. Patients with rheumatoid arthritis (RA) taking oral glucocorticoids seen in the 2 months after the intervention were followed for 6 months. Medical records were assessed to determine the proportion undergoing bone mineral density testing or receiving pharmacologic interventions for GIOP during the 6 months before and 6 months after the intervention. RESULTS: There were 373 patients with RA taking oral glucocorticoids whose records were assessed. Patients in both arms of the trial were similar with respect to age, sex, menopausal status, glucocorticoid dosage and duration, duration of RA, disease-modifying antirheumatic drug use, and the proportion with comorbid conditions. At baseline, there was no significant difference between the patients with respect to osteoporosis medication use (intervention 32% versus control 34%) or bone densitometry use (intervention 9% versus control 5%). After the intervention and a 6-month followup period, there were no differences in treatment (intervention 33% versus control 38%) or bone densitometry use (intervention 8% versus control 8%). Adjusting for patient and physician characteristics did not significantly change these results. CONCLUSION: A multifaceted intervention for GIOP, including doctor education, practice audit, and treatment suggestions, had no significant benefit on testing or treatment by rheumatologists over a 6-month followup period. Other intervention approaches need to be tested.

Solomon DH, Warsi A, Brown-Stevenson T, Farrell M, Gauthier S, Mikels D, Lee TH. · Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. · J Rheumatol. · Pubmed #11838857 No free full text.

Abstract: OBJECTIVE: Studies have suggested that the Arthritis Self-Management Program (ASMP) course is effective at reducing arthritis pain and health care costs in volunteer participants. There have been no reports of trials of the ASMP in the context of primary care physicians' practices, where the potential for spreading the program may be greatest. We conducted a randomized controlled trial of the ASMP course in a large primary care physician network. METHODS: Patients with osteoarthritis, rheumatoid arthritis, or fibromyalgia were recruited for the study. Subjects in the intervention practices received the 6 week course and those in the control practices received only the ASMP book, without course. Disability, pain, self-efficacy, mental health, and satisfaction were measured using validated instruments at baseline and at 4 months. RESULTS: One hundred thirteen patients were recruited for the ASMP course (intervention) and completed baseline and 4 month followup questionnaires. Eighty-four percent completed at least 4 of 6 classes. Seventy-four patients received the ASMP manual (controls) and completed both questionnaires. Patients in the intervention and control groups had similar baseline pain (p = 0.94), self-efficacy to control pain (p = 0.90), mental health (p = 0.10), and vitality scores (p = 0.21), but those in the intervention arm had slightly less disability (p = 0.04). At 4 months, there was no significant improvement from baseline in any endpoint and no difference between patients in the intervention and control groups (all p > 0.2). Patient satisfaction with arthritis care and outcomes was no different for intervention and control patients (all p > 0.3). All types of health care resource use were similar at baseline and followup for both intervention and control groups (all p > 0.2). CONCLUSION: While the ASMP course has been found to be effective in other patient groups, there were no significant clinical benefits noted at 4 months in patients recruited from primary care practices.

Solomon DH, Finkelstein JS, Shadick N, LeBoff MS, Winalski CS, Stedman M, Glass R, Brookhart MA, Weinblatt ME, Gravallese EM. · Brigham and Women's Hospital, Division of Rheumatology, Boston, Massachusetts 02115, USA. · Arthritis Rheum. · Pubmed #19479876 No free full text.

Abstract: OBJECTIVE: Among rheumatoid arthritis (RA) patients who have had the disease for 10 years, more than half have focal erosions, and the risk of fracture is doubled. However, there is little information about the potential relationship between focal erosions and bone mineral density (BMD). The aim of this study was to determine whether lower BMD is associated with higher erosion scores among patients with RA. METHODS: We enrolled 163 postmenopausal women with RA, none of whom were taking osteoporosis medications. Patients underwent dual x-ray absorptiometry at the hip and spine and hand radiography, and completed a questionnaire. The hand radiographs were scored using the Sharp method, and the relationship between BMD and erosions was measured using Spearman's correlation coefficients and adjusted linear regression models. RESULTS: Patients had an average disease duration of 13.7 years, and almost all were taking a disease-modifying antirheumatic drug. Sixty-three percent were rheumatoid factor (RF) positive. The median modified Health Assessment Questionnaire score was 0.7, and the average Disease Activity Score in 28 joints was 3.8. The erosion score was significantly correlated with total hip BMD (r=-0.33, P<0.0001), but not with lumbar spine BMD (r=-0.09, P=0.27). Hip BMD was significantly lower in RF-positive patients versus RF-negative patients (P=0.02). In multivariable models that included age, body mass index, and cumulative oral glucocorticoid dose, neither total hip BMD nor lumbar spine BMD was significantly associated with focal erosions. CONCLUSION: Our results suggest that hip BMD is associated with focal erosions among postmenopausal women with RA, but that this association disappears after multivariable adjustment. While BMD and erosions may be correlated with bone manifestations of RA, their relationship is complex and influenced by other disease-related factors.

Stoll ML, Solomon DH, Batra KL, Simard JF, Karlson EW, Dellaripa PF, Weinblatt ME, Glass R, Shadick NA. · Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA. · J Clin Rheumatol. · Pubmed #19455057 No free full text.

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Becker MC, Wang TH, Wisniewski L, Wolski K, Libby P, Lüscher TF, Borer JS, Mascette AM, Husni ME, Solomon DH, Graham DY, Yeomans ND, Krum H, Ruschitzka F, Lincoff AM, Nissen SE, Anonymous00079. · Department of Cardiology, Cleveland Clinic Foundation, OH 44195, USA. · Am Heart J. · Pubmed #19332185 No free full text.

Abstract: BACKGROUND: Pain management in patients with osteoarthritis or rheumatoid arthritis often requires long-term use of nonsteroidal antiinflammatory drugs (NSAIDs). However, the relative cardiovascular safety of these therapies remains uncertain. METHODS: The Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen (PRECISION) trial will evaluate the cardiovascular safety of celecoxib, ibuprofen, and naproxen. Approximately 20,000 patients with symptomatic osteoarthritis or rheumatoid arthritis at high risk for, or with, established cardiovascular disease will be randomized in this double-blind, triple dummy, multinational, multicenter study. The primary end point is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The trial will continue until 762 primary events occur with at least 18 months follow-up. Noninferiority of any of the regimens will require a 97.5% upper CI of the hazard ratio (HR) < or =1.33 and point estimate < or =1.12 for both intent-to-treat (ITT) and modified ITT populations. CONCLUSION: PRECISION, the first study of patients with high cardiovascular risk chronically treated with a cyclooxygenase-2 selective inhibitor or nonselective NSAID, will define the relative cardiovascular safety profile of celecoxib, ibuprofen, and naproxen and provide data to help guide NSAID use for pain management for this population.

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.

Agarwal SK, Glass RJ, Shadick NA, Coblyn JS, Anderson RJ, Maher NE, Weinblatt ME, Solomon DH. · Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. · J Rheumatol. · Pubmed #18634159 No free full text.

Abstract: OBJECTIVE: Tumor necrosis factor-alpha (TNF) inhibitors have transformed management of rheumatoid arthritis (RA); however, many patients discontinue TNF inhibitors. Our goal was to determine the discontinuation rate of TNF inhibitors and identify predictors associated with discontinuation. METHODS: Enrollees in the Brigham RA Sequential Study (BRASS) formed the eligible cohort. Patients reporting use of a TNF inhibitor with at least 6 months of followup were followed until reporting TNF inhibitor discontinuation or their last study visit if they continued therapy. Potential predictor variables, including demographic and clinical data assessed at baseline and 6 months prior to study endpoint, were identified using a Cox proportional regression. RESULTS: Among 961 patients in BRASS, 503 were using a TNF inhibitor with at least 6 months of followup in BRASS (mean length of followup 39 mo, SD 13). Two hundred ten patients (42%) reported discontinuation of TNF inhibitor. Higher physician global scores (hazard ratio 1.27, 95% CI 1.18-1.38) and RA Disease Activity Index scores (HR 1.13, 95% CI 1.05-1.22) 6 months prior to stopping the TNF inhibitor and higher number of TNF inhibitors used previously (HR 1.30, 95% CI 1.03-1.66) were associated with discontinuation of TNF inhibitor. Prior use of synthetic disease modifying antirheumatic drugs (HR 0.50, 95% CI 0.34-0.72) and more years of cumulative methotrexate use (HR 0.24, 95% CI 0.12-0.47) were inversely associated with discontinuation of TNF inhibitor. CONCLUSION: These data demonstrate that a significant number of patients with RA discontinue TNF inhibitors. Several easily characterized clinical variables have a modest predictive association with reduced probability of TNF inhibitor discontinuation.

Agnew-Blais JC, Coblyn JS, Katz JN, Anderson RJ, Mehta J, Solomon DH. · Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Ann Rheum Dis. · Pubmed #18511547 No free full text.

Abstract: OBJECTIVES: The objective of this study was twofold: (1) to determine how best to measure adherence with time-dependent quality indicators (QIs) related to laboratory monitoring, and (2) to assess the accuracy and efficiency of gathering QI adherence information from an electronic medical record (EMR). METHODS: A random sample of 100 patients were selected who had at least three visits with the diagnosis of rheumatoid arthritis (RA) at Brigham and Women's Hospital Arthritis Center in 2005. Using the EMR, it was determined whether patients had been prescribed a disease-modifying antirheumatic drug (DMARD) (QI #1) and if patients starting therapy received appropriate baseline laboratory testing (QI #2). For patients consistently prescribed a DMARD, adherence with follow-up testing (QI #3) was calculated using three different methods, the Calendar, Interval and Rolling Interval METHOD: . RESULTS: It was found that 97% of patients were prescribed a DMARD (QI #1) and baseline tests were completed in 50% of patients (QI #2). For follow-up testing (QI #3), mean adherence was 60% for the Calendar Method, 35% for the Interval Method, and 48% for the Rolling Interval Method. Using the Rolling Interval Method, adherence rates were similar across drug and laboratory testing type. CONCLUSIONS: Results for adherence with laboratory testing QIs for DMARD use differed depending on how the QIs were measured, suggesting that care must be taken in clearly defining methods. While EMRs will provide important opportunities for measuring adherence with QIs, they also present challenges that must be examined before widespread adoption of these data collection methods.

Goodson NJ, Brookhart AM, Symmons DP, Silman AJ, Solomon DH. · Academic Rheumatology Unit, University Hospital Aintree, Liverpool University, Lower Lane, Liverpool, L9 7AL, UK. · Ann Rheum Dis. · Pubmed #18408253 links to  free full text

Abstract: OBJECTIVES: There is controversy about the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on cardiovascular disease (CVD) mortality. The aim of this study was to explore associations between NSAID use and mortality in patients with inflammatory polyarthritis (IP). SUBJECTS AND METHODS: A total of 923 patients with new onset (IP), recruited to the UK Norfolk Arthritis Register (NOAR) between 1990-1994, were followed up to the end of 2004. Current medication was recorded annually for the first 6 years and then every 2-3 years. Rheumatoid factor (RF) and C-reactive protein (CRP) were measured. Logistic regression was used to calculate all cause and CVD mortality odds ratios (OR) for NSAID use at baseline and during follow-up, adjusting for gender and time-varying covariates: RF, CRP, joint counts, smoking, steroid use, DMARD use and other medication use. RESULTS: By 2004 there were 203 deaths, 85 due to CVD. At baseline, NSAIDs were used by 66% of patients. In final multivariate models, baseline NSAID use was inversely associated with all cause mortality (adjusted OR 0.62, 95% CI 0.45 to 0.84) and CVD mortality (adjusted OR 0.54, 95% CI 0.34 to 0.86). Interval NSAID use had weaker mortality associations: all cause mortality (adjusted OR 0.72, 95% CI 0.52 to 1.00), CVD mortality (adjusted hazard ratio (HR) 0.66, 95% CI 0.40 to 1.08). CONCLUSION: No excess CVD or all cause mortality was observed in NSAID users in this cohort of patients with IP. This is at variance with the literature relating to NSAID use in the general population. It is unclear whether this represents unmeasured confounders influencing a doctor's decision to avoid NSAIDs in the treatment of IP.

Kinjo M, Setoguchi S, Solomon DH. · Teine Keijinkai Hospital, Teine-ku Sapporo city, Japan. · J Rheumatol. · Pubmed #17896806 No free full text.

Abstract: OBJECTIVE: Several studies suggest that bone mineral density (BMD) is reduced in rheumatoid arthritis (RA). However, it is unclear whether this relationship holds in a representative community-based typical RA population. We examined the relationship between BMD and RA in a representative US population-based sample from the Third National Health and Nutrition Examination Survey (NHANES III: 1988-1994). METHODS: We selected subjects over age 60 with RA from NHANES III using previously described methods. Femoral neck BMD (FN-BMD) measured by dual-energy x-ray absorptiometry was compared for the RA (n = 106) and non-RA cohorts (n = 4,277). Multivariable linear regression models included known risk factors for osteoporosis. Further adjusted analyses compared the BMD among subgroups of patients with RA, such as those taking methotrexate (MTX), those with positive rheumatoid factor (RF), and those with elevated C-reactive protein (CRP). RESULTS: Patients with RA more frequently reported poor health, a history of falling, cognitive impairment, early menopause, a history of chronic obstructive lung disease, higher total calcium intake, and thiazide use than the non-RA subjects (all p < 0.05). Adjusted FN-BMD was similar between the patients with RA (0.71 g/cm2) and non-RA subjects (0.72 g/cm2; p = 0.5). Among patients with RA, reduced BMD tended to be seen with MTX use (0.60 g/cm2, p = 0.07), CRP above 1 mg/dl (0.66 g/cm2, p = 0.09), and positive RF in female patients (0.68 g/cm2, p = 0.056). However, none of these findings reached statistical significance. CONCLUSIONS: Among a US population-based representative sample, FN-BMD was similar in RA and non-RA patients. Several characteristics of patients with RA may be associated with reduced BMD.

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.

Shadick NA, Heller JE, Weinblatt ME, Maher NE, Cui J, Ginsburg G, Coblyn J, Anderson R, Solomon DH, Roubenoff R, Parker A. · Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. · Ann Rheum Dis. · Pubmed #17491100 No free full text.

Abstract: BACKGROUND: Certain sequences present in the hypervariable region of human leucocyte antigen (HLA)-DRB1 known as the shared epitope (SE) are hypothesised to increase the risk of rheumatoid arthritis (RA), whereas alleles encoding aspartic acid at position 70 (D70 alleles) may have a protective effect. METHODS: Patient HLA-DRB1 serotypes were assessed and the genotypes encoding the SE motif or the putatively protective D70 motif identified in a large RA cohort. Logistic regression was used to analyse associations of genotype with presence of disease, comorbidities and disease severity, and association between genotype and change in disease activity over time. RESULTS: The 689 patients enrolled had a mean (SD) age of 57.9 (13.7) years and mean (SD) disease duration of 15.3 (12.7) years. In a comparison with 482 ethnicity matched population-based controls, the D70 sequence exerted a strong protective effect (OR = 0.52, p<0.001) that remained significant when the SE at the same locus was accounted for (OR = 0.72, 95% CI 0.60 to 0.86, p<0.001). The SE assessed on all HLA-DRB1 serotypic backgrounds except DR1 was associated with RA susceptibility (additive OR = 2.43, p<0.001). Associations were found between SE and serum levels of rheumatoid factor (p<0.001, with correlation of 0.18) and anti-cyclic citrullinated peptide antibodies (p<0.001, with correlation of 0.25) but not with serum C-reactive protein. CONCLUSION: The D70 allele has a significant protective effect that is mitigated but still significant when the risk effect of the SE at the same locus is taken into account. The presence of the SE on DR4 is associated with greater RA susceptibility and certain disease-activity measures.

Solomon DH, Stedman M, Licari A, Weinblatt ME, Maher N, Shadick N. · Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Arthritis Rheum. · Pubmed #17330299 links to  free full text

Abstract: OBJECTIVE: With the growth in patient registries in rheumatic disease research, it is important to validate the collected information. We examined the convergent validity of self-reported medication use for rheumatoid arthritis (RA). METHODS: In the setting of the Brigham Rheumatoid Arthritis Sequential Study (BRASS), a large registry of patients with RA, we examined the agreement between patients' self-report of current and past RA medication use and information from medical records. For a sample of patients in BRASS, these 2 sources of information were compared using the kappa statistic as well as the percent agreement. RESULTS: The 91 patients selected for assessment were typical of a prevalent RA cohort: >80% were women and the mean disease duration was 16 years. The agreement for current medication use was excellent, ranging from 0.71 for sulfasalazine to 0.96 for methotrexate. However, for past medication use agreement was lower, ranging from 0.13 for methotrexate to 0.74 for aurothioglucose. The weighted kappa for cumulative oral glucocorticoid dose was 0.67. CONCLUSION: Self-report of current medication use and cumulative oral glucocorticoid dose appears to have moderate to excellent validity. However, self-report of past medication use may not be valid.

Solomon DH, Katz JN, Cabral D, Patrick AR, Bukowski JF, Coblyn JS. · Division of Pharmacoepidemiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02120, USA. · Arthritis Rheum. · Pubmed #17139663 links to  free full text

Abstract: OBJECTIVE: Osteoporosis in patients with rheumatoid arthritis (RA) is increasingly recognized as a major comorbidity. We examined past management patterns for glucocorticoid-induced osteoporosis and attempted to improve care through an educational intervention. The goal was to examine the frequency of osteoporosis management in patients with RA treated at a large academic rheumatology practice. METHODS: We performed a structured chart review on randomly selected patients seen during 2004 for RA. Osteoporosis management was defined as a bone mineral density test or receipt of a medication for osteoporosis in the prior 24 months. The frequency of osteoporosis management among our study group was assessed. We also examined how glucocorticoid dosage affected osteoporosis management in adjusted models. RESULTS: We reviewed the records for 193 patients, 99 had not used glucocorticoids in the prior 24 months, and 94 had used them. Of the total study population, 48% had received a bone mineral density test or medication for osteoporosis. Some form of osteoporosis management was present for 64% of patients taking > or =5 mg prednisone for > or =3 months compared with 38% for patients taking none (P = 0.002). Predictors of osteoporosis management included older age, female sex, glucocorticoid dosage, and prior osteoporosis diagnosis or fracture. CONCLUSION: The frequency of osteoporosis management appears to have increased compared with a prior chart review.

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.