Rheumatoid Arthritis: Hochberg MC

Hochberg MC. · Division of Rheumatology and Clinical Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA. · Arthritis Res Ther. · Pubmed #12716445 links to  free full text

Abstract: Cyclooxygenase (COX)-2 selective inhibitors have been shown to have comparable efficacy to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Large outcome studies have shown that patients with OA and RA not taking low-dose aspirin have fewer symptomatic and complicated upper GI events when treated with COX-2 selective inhibitors than with nonselective NSAIDs. When used in recommended dosages, there is no convincing evidence that patients treated with COX-2 selective inhibitors have an increased incidence of cardiovascular thrombotic events, including non-fatal myocardial infarction, than patients treated with either placebo or nonselective NSAIDs other than naproxen. Co-therapy with low-dose aspirin is recommended in patients with OA and RA at increased risk for cardiovascular events; the need for gastroprotective therapy in such patients is controversial.

Lipsky PE, Abramson SB, Breedveld FC, Brook P, Burmester R, Buttgereit F, Cannon GW, Catella-Lawson F, Crofford LJ, Doherty M, Dougados M, DuBois RN, Froelich J, Garcia Rodriguez LA, Gibofsky A, Hernandez-Diaz S, Hochberg MC, Krause A, Liang MH, Machold K, Peloso PM, Raisz LG, Schayes B, Scheiman JM, Simon LS, Smolen J. · No affiliation provided · J Rheumatol. · Pubmed #10852251 No free full text.

This publication has no abstract.

Towheed TE, Hochberg MC, Shea BJ, Wells G. · Queen's University, Medicine and of Community Health and Epidemiology, Etherington Hall-Room 2066, Kingston, Ontario, Canada, K7L 3N6. · Cochrane Database Syst Rev. · Pubmed #17636642 No free full text.

Abstract: BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used as a pharmacologic treatment to relieve pain for patients with OA of the hip. However, these agents are associated with significant toxicity, particularly in the elderly population (age > 65 years). OBJECTIVES: To review all randomized trials of analgesics and anti-inflammatory therapy in osteoarthritis (OA) of the hip. To determine which non-steroidal, anti-inflammatory drug (NSAID) is the most effective, and which NSAID is the most toxic. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register and MEDLINE up to August 1994. Reference lists of all trials were also manually searched. SELECTION CRITERIA: All randomized controlled trials comparing non-steroidal anti-inflammatory drugs (NSAIDs) and/or analgesics in patients with Osteoarthritis. The trials selected for inclusion were identified by one reviewer (TT) and rechecked by a second (MH). DATA COLLECTION AND ANALYSIS: Qualitative assessments were performed using a quality scoring system designed for NSAID trials in rheumatoid arthritis. Both the design and analysis aspects of the trials were evaluated, each aspect being rated on a scale of 0 to 8. A quantitative method, which calculates the ratio of improvement produced by one NSAID to that produced by another, was used to rate the relative efficacy of different NSAIDs with respect to pain relief. Toxicity comparisons were made according to the reviewer findings. All quality assessments were carried out independently by two reviewers (TT, BS). All data abstraction was carried out by one reviewer (TT) and rechecked by two other reviewers (BS, GW). A consensus was reached on discrepancies. MAIN RESULTS: Forty-three trials were identified, and of these, 39 evaluated NSAIDs, while four evaluated only analgesics. The median design and analysis scores were two and four respectively. Six NSAIDs were included in at least five trials. Of these, indomethacin was rated more effective in five of its seven comparisons, but more toxic in seven of 12 comparisons. Only five of the 29 (17%) NSAID comparisons found statistically significant differences in efficacy. Of the 43 RCTs identified only 17 had statistical data available for future pooling for this meta-analysis. In the case where data was missing, authors of the trials will be contacted for inclusion of data in future reviews. AUTHORS' CONCLUSIONS: NSAID trials in patients with OA of the hip appear to be weakened by the lack of standardization of case definition of OA, and also by the lack of standardization of outcome assessments. No clear recommendations for the choice of specific NSAID therapy in hip OA can be offered at this time based on this analysis.

Hochberg MC. · Division of Rheumatology and Clinical Immunology, University of Maryland School of Medicine, 10 S. Pine St., MSTF 8-34, Baltimore, Maryland 21201, USA. · Curr Top Med Chem. · Pubmed #15974939 No free full text.

Abstract: COX-2 selective inhibitors were developed in order to provide similar efficacy to traditional nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) but with improved upper gastrointestinal safety. This paper presents an overview of randomized clinical trials demonstrating the efficacy of COX-2 selective inhibitors for the treatment of patients with arthritis, particularly osteoarthritis and rheumatoid arthritis. In osteoarthritis and rheumatoid arthritis, COX-2 selective inhibitors have been shown to be more effective than placebo and similarly effective as standard doses of nonselective NSAIDs. There are currently few randomized clinical trials comparing the efficacy of the 2 first-generation COX-2 selective inhibitors, celecoxib and rofecoxib, in osteoarthritis. Of 4 head-to-head studies comparing the 2 agents, 3 indicated similar efficacy, while the other demonstrated superiority of rofecoxib at a dose of 25 mg qd compared with celecoxib at a dose of 200 mg qd. There are no clinical trials comparing the efficacy of different agents for treatment of patients with rheumatoid arthritis. Some studies have also demonstrated efficacy for COX-2 selective inhibitors in patients with ankylosing spondylitis and gout. In aggregate, these data show that COX-2 selective inhibitors provide effective relief of pain in patients with osteoarthritis and rheumatoid arthritis, with efficacy that is similar to traditional NSAIDs. Cost-effectiveness and cost-utility studies suggest, however, that their use should be limited to patients at high risk of serious upper gastrointestinal side effects, including complicated ulcers.

Hochberg MC, Lebwohl MG, Plevy SE, Hobbs KF, Yocum DE. · Division of Rheumatology and Clinical Immunology, University of Maryland School of Medicine, Baltimore 21201, USA. · Semin Arthritis Rheum. · Pubmed #15942917 No free full text.

Abstract: OBJECTIVE: To review the benefits and risks associated with the use of the tumor necrosis factor (TNF)-blockers in various indications (eg, rheumatoid arthritis [RA], Crohn's disease [CD], psoriasis). METHODS: The members of the consensus panel were selected based on their expertise. Centocor, Inc provided an educational grant to the Center for Health Care Education to facilitate the consensus panel. Peer-reviewed articles discussing clinical studies and clinical experiences with TNF-blockers form the basis of this review. Emerging data that have not been peer-reviewed are also included. RESULTS: The TNF-blockers infliximab, etanercept, and adalimumab are all approved for treatment of RA. All 3 are effective, and there are currently no published data from head-to-head clinical trials to support using 1 agent over another. Preliminary data from small, retrospective studies indicate that switching among agents to overcome inadequate efficacy or poor tolerability is beneficial in some patients. The only TNF-blocker currently approved for the induction and maintenance of remission in CD is infliximab. Preliminary data indicate that etanercept and infliximab are effective in treating psoriasis. Some risks associated with TNF-blockers have become apparent, including congestive heart failure, demyelinating diseases, and systemic lupus erythematosus, but in most cases can be identified and managed. Several of these risks (eg, lymphoma and serious infections) are associated with either the condition per se or the concomitant medication use. Simple screening procedures help manage the risk of tuberculosis infection; however, it is recommended that physicians and patients be alert to the development of any new infection so that appropriate treatment may be initiated promptly. Rare infusion reactions, particularly with infliximab, may also be effectively managed. CONCLUSION: TNF-blockers are effective and may be safely used for short- and long-term management of RA or CD. TNF-blockers also show efficacy in other emerging indications.

Hochberg MC, Tracy JK, Hawkins-Holt M, Flores RH. · Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201 USA. · Ann Rheum Dis. · Pubmed #14532140 links to  free full text

Abstract: OBJECTIVE: To determine, using the method of adjusted indirect comparisons, whether there are differences in efficacy of tumour necrosis factor (TNF alpha) blocking agents, as measured by the rate ratios for American College of Rheumatology (ACR) 20, 50, and 70 responses, in patients with rheumatoid arthritis with an incomplete response to methotrexate. METHODS: A systematic review was performed to identify placebo controlled trials of 24-30 weeks' duration of combination therapy that used a step-up approach with the addition of TNF alpha blocking agents to methotrexate. The method of "adjusted indirect comparisons" was used to compare results across trials to determine the relative risk for an ACR20 or 50 response. RESULTS: Placebo controlled trials for adalimumab, etanercept, and infliximab provided data on ACR20 and 50 responses. Both the similarity of demographic and disease characteristics of patients at entry, and the homogeneity of response rates in the placebo groups across trials, suggested that comparing results across trials was valid. The relative risk for obtaining an ACR20 and 50 response derived from the adjusted indirect comparisons of the TNF alpha blocking agents did not significantly differ from unity. CONCLUSION: The analysis showed that the three currently marketed TNF alpha blocking agents have similarly efficacy when added to methotrexate in the treatment of patients with rheumatoid arthritis with active disease.

Hochberg MC. · Department of Medicine and Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. · Semin Arthritis Rheum. · Pubmed #12528069 No free full text.

Abstract: The cyclooxygenase (COX)-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs; coxibs) were developed in order to reduce upper gastrointestinal (GI) side effects associated with traditional nonselective NSAIDs. This article presents an overview of clinical trials showing the efficacy of coxibs for the treatment of patients with arthritis. In osteoarthritis trials, coxibs were more effective than placebo and similarly effective compared with standard doses of traditional NSAIDs. Some studies lasted up to a year and showed effectiveness of coxibs for long-term treatment of patients with osteoarthritis. There are currently few adequately powered trials comparing the efficacy of the 2 first-generation coxibs, celecoxib and rofecoxib. Of 2 head-to-head studies comparing the 2 agents, 1 indicated similar efficacy, whereas the other showed the superiority of rofecoxib at a dose of 25 mg daily compared with celecoxib at a dose of 200 mg daily. In studies enrolling patients with rheumatoid arthritis, coxibs also have shown efficacy superior to that of placebo and similar to that of traditional NSAIDs. There are no clinical trials comparing the efficacy of different coxibs for treatment of patients with rheumatoid arthritis. In endoscopic studies, the GI safety and tolerability profile of coxibs has been consistently superior to that of traditional NSAIDs. In large clinical outcome trials, at least 1 of the coxibs, rofecoxib, significantly reduced the risk of confirmed complicated upper GI events compared with the conventional NSAID naproxen. Both rofecoxib and celecoxib reduced the risk of confirmed clinical upper GI events compared with the nonselective NSAIDs naproxen and ibuprofen in patients with osteoarthritis and rheumatoid arthritis not taking low-dose aspirin. Therefore, coxibs provide effective relief of pain from osteoarthritis and rheumatoid arthritis, with efficacy that is comparable to traditional NSAIDs, but with a significantly lower incidence of GI complications.

Hochberg MC. · Division of Rheumatology and Clinical Immunology, University of Maryland Medical Center, Baltimore, MD, USA. · Semin Arthritis Rheum. · Pubmed #12528068 No free full text.

This publication has no abstract.

Hochberg MC. · University of Maryland School of Medicine, Baltimore, USA. · Am J Manag Care. · Pubmed #12458820 links to  free full text

Abstract: The development of cyclooxygenase (COX)-2-selective inhibitors represents a major advance in the management of chronic pain and inflammation that may satisfy an unmet medical need for agents with improved gastrointestinal (GI) safety. This article is a review of the pharmacology, clinical efficacy, and safety of COX-2-selective inhibitors in the managed healthcare setting. The efficacy of COX-2-selective inhibitors in relieving chronic pain from osteoarthritis and rheumatoid arthritis is comparable to that of traditional nonsteroidal anti-inflammatory drugs (NSAIDs). However, the occurrence of GI complications may be less frequent in patients who receive COX-2-selective inhibitors than in patients receiving traditional NSAIDs. Thus, the use of COX-2-selective inhibitors for the management of chronic pain may reduce overall costs and provide an alternative with an improved safety profile compared with traditional NSAIDs.

Simon LS, Smolen JS, Abramson SB, Appel G, Bombardier C, Brater DC, Breedveld FC, Brune K, Burmester GR, Crofford LJ, Dougados M, DuBois RN, Fitzgerald GA, Frishman W, García Rodríguez LA, Hochberg MC, Kalden JR, Laine L, Langman MJ, Prescott SM, van de Putte LB, Whelton A, White WB, Willaims GH. · Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. · J Rheumatol. · Pubmed #12136912 No free full text.

This publication has no abstract.

Schnitzer TJ, Hochberg MC. · Office of Clinical Research and Training, Northwestern University School of Medicine, Chicago, IL 60611, USA. · Cleve Clin J Med. · Pubmed #12086290 links to  free full text

Abstract: Therapy with nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) has long been the cornerstone of pharmacologic management of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Many patients with OA or RA, however, are at increased risk of developing clinically significant adverse events associated with NSAID therapy, particularly upper gastrointestinal (GI) complications including symptomatic and complicated ulcers. The introduction of cyclooxygenase (COX)-2-selective inhibitors (coxibs) represents a major advance in the pharmacologic approach to the signs and symptoms of arthritis. In addition to the first two members of this class, celecoxib and rofecoxib, other coxibs have been introduced or are in development (valdecoxib, etoricoxib). In numerous clinical trials, coxibs have been shown to be as effective as nonselective NSAIDs in relieving pain and inflammation associated with OA and RA, and notably, with a significantly lower risk of NSAID-type adverse events. The use of coxibs to treat OA and RA is recommended as first-line therapy when symptoms of pain and inflammation are present in patients vulnerable to potential NSAID-associated GI toxicity.

Hochberg MC, Tracy JK, Flores RH. · Department of Medicine, University of Maryland School of Medicine, Baltimore 21201, USA. · Ann Rheum Dis. · Pubmed #11890654 links to  free full text

This publication has no abstract.

Abramson SB, Furst DE, Hochberg MC, Patrono C. · Department of Rheumatology/Medicine, Hospital for Joint Surgery/NYU School of Medicine, New York, NY, USA. · Clin Exp Rheumatol. · Pubmed #11695257 No free full text.

This publication has no abstract.

Hochberg MC. · University of Maryland, Baltimore, Maryland, USA. · Clin Exp Rheumatol. · Pubmed #11695246 No free full text.

Abstract: The cyclooxygenase (COX)-2 selective inhibitors celecoxib and rofecoxib have been found to be more effective than placebo and comparably effective to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of patients with osteoarthritis and rheumatoid arthritis. Two large outcome studies, the Celecoxib Long-term Arthritis Safety Study (CLASS) and Vioxx Gastrointestinal Outcomes Research (VIGOR) trial, were conducted to test the hypothesis that patients receiving a COX-2 selective inhibitor would have significantly fewer clinically important upper gastrointestinal events than patients taking nonselective NSAIDs. This article critically reviews the design and results of these trials. Both trials found that arthritis patients not taking low-dose aspirin (325 mg/day or less) who were randomized to receive COX-2 selective inhibitors had significantly fewer symptomatic and complicated ulcers than patients randomized to nonselective NSAIDs. A significant risk reduction was not demonstrated, however, in patients in the CLASS trial who were taking low-dose aspirin, itself an independent risk factor for the endpoint. These data validate the COX-2 hypothesis and support recommendations that a COX-2 selective inhibitor should be used in the treatment of patients at increased risk for symptomatic and complicated ulcers. Further studies are needed to determine whether COX-2 selective inhibitors are safer than nonselective NSAIDs when used in patients receiving low-dose aspirin. The COX-2 selective inhibitors have a similar profile of renal adverse events to nonselective NSAIDs. The increased rate of cardiovascular thromboembolic adverse events among patients randomized to rofecoxib compared to those randomized to naproxen in the VIGOR trial is consistent with the lack of an anti-platelet effect for this COX-2 selective inhibitor. This emphasizes the need for the use of low-dose aspirin in patients at risk for such events, especially myocardial infarction.

Hochberg MC. · Division of Rheumatology and Clinical Immunology, University of Maryland, Baltimore 21201, USA. · Scand J Rheumatol Suppl. · Pubmed #10668521 No free full text.

Abstract: Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation, joint destruction, progressive disability, and premature death. Patients at risk for poor prognoses can be identified by a variety of prognostic indicators. These include sociodemographic factors (e.g., older age, female sex), clinical indicators (e.g., higher joint counts), laboratory variables (e.g., higher erythrocyte sedimentation rate, high rheumatoid factor titer), and radiographic indicators (e.g., the presence of bone erosions). Patients with a poor prognosis, as evidenced by the presence of one or more indicators of poor outcome, should be treated promptly and aggressively with disease-modifying antirheumatic drugs (DMARDs) or combination DMARD therapy to limit or prevent further disease progression. Limiting the severity of RA with early and aggressive treatment is the best way to minimize the dire consequences of untreated or inadequately treated disease.

Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, Day R, Ferraz MB, Hawkey CJ, Hochberg MC, Kvien TK, Schnitzer TJ, Anonymous00004. · Institute for Work and Health, Mount Sinai Hospital, and the University Health Network, Toronto, ON, Canada. · N Engl J Med. · Pubmed #11087881 links to  free full text

Abstract: BACKGROUND: Each year, clinical upper gastrointestinal events occur in 2 to 4 percent of patients who are taking nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We assessed whether rofecoxib, a selective inhibitor of cyclooxygenase-2, would be associated with a lower incidence of clinically important upper gastrointestinal events than is the nonselective NSAID naproxen among patients with rheumatoid arthritis. METHODS: We randomly assigned 8076 patients who were at least 50 years of age (or at least 40 years of age and receiving long-term glucocorticoid therapy) and who had rheumatoid arthritis to receive either 50 mg of rofecoxib daily or 500 mg of naproxen twice daily. The primary end point was confirmed clinical upper gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcers). RESULTS: Rofecoxib and naproxen had similar efficacy against rheumatoid arthritis. During a median follow-up of 9.0 months, 2.1 confirmed gastrointestinal events per 100 patient-years occurred with rofecoxib, as compared with 4.5 per 100 patient-years with naproxen (relative risk, 0.5; 95 percent confidence interval, 0.3 to 0.6; P<0.001). The respective rates of complicated confirmed events (perforation, obstruction, and severe upper gastrointestinal bleeding) were 0.6 per 100 patient-years and 1.4 per 100 patient-years (relative risk, 0.4; 95 percent confidence interval, 0.2 to 0.8; P=0.005). The incidence of myocardial infarction was lower among patients in the naproxen group than among those in the rofecoxib group (0.1 percent vs. 0.4 percent; relative risk, 0.2; 95 percent confidence interval, 0.1 to 0.7); the overall mortality rate and the rate of death from cardiovascular causes were similar in the two groups. CONCLUSIONS: In patients with rheumatoid arthritis, treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2, is associated with significantly fewer clinically important upper gastrointestinal events than treatment with naproxen, a nonselective inhibitor.

Smitten AL, Simon TA, Hochberg MC, Suissa S. · Duke University School of Medicine, Duke South, Durham, NC, 27710 USA. · Arthritis Res Ther. · Pubmed #18433475 links to  free full text

Abstract: INTRODUCTION: The risk of malignancies in patients with rheumatoid arthritis (RA) has raised some concern, particularly with immunosuppressive approaches to disease management. METHODS: We conducted a systematic review of the literature and meta-analysis characterizing the associated risk of overall malignancy and four site-specific malignancies (lymphoma, lung, colorectal, and breast cancer) in patients with RA. A Medline search from 1990 to 2007 was conducted using specified search terms and predefined inclusion criteria for identification of relevant observational studies that provide estimates of relative risk of malignancy associated with RA. Study-specific estimates of the relative risk, as measured by standardized incidence ratios (SIRs) and estimated in comparison with the general population, were combined using a random effects model. RESULTS: A total of 21 publications were identified, of which 13 reported the SIR for overall malignancy, 14 for lymphoma, 10 for colorectal, 12 for lung, and 9 for breast cancer. Compared with the general population, the overall SIR estimates suggest that RA patients have approximately a two-fold increase in lymphoma risk (SIR 2.08, 95% confidence interval [CI] 1.80 to 2.39) and greater risk of Hodgkin than non-Hodgkin lymphoma. The risk of lung cancer was also increased with an SIR of 1.63 (95% CI 1.43 to 1.87). In contrast, a decrease in risk was observed for colorectal (SIR 0.77, 95% CI 0.65 to 0.90) and breast (SIR 0.84, 95% CI 0.79 to 0.90) cancer. The SIR for overall malignancy was 1.05 (95% CI 1.01 to 1.09). CONCLUSION: Patients with RA appear to be at higher risk of lymphoma and lung cancer and potentially decreased risk for colorectal and breast cancer compared with the general population.

Smitten AL, Choi HK, Hochberg MC, Suissa S, Simon TA, Testa MA, Chan KA. · Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA. · J Rheumatol. · Pubmed #18260176 No free full text.

Abstract: OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) are at increased risk of hospitalized infection and whether the risk varies by RA treatment. METHODS: A retrospective cohort study was conducted using data from a medical and pharmacy claims managed-care database from 1999 to 2006. A total of 24,530 patients were included in the RA cohort; a random sample of non-RA patients served as a comparison cohort (n = 500,000). Rates of hospitalized infection were compared between the cohorts. A nested case-control analysis was performed within the RA cohort to assess the effect of current RA medication use on hospitalized infection risk. RESULTS: A total of 1,993 patients with RA and 11,977 non-RA patients experienced a hospitalized infection. The rate of first hospitalized infection was higher in the RA cohort [adjusted hazard ratio = 2.03; 95% confidence interval (CI) 1.93-2.13]. In the case-control analysis, the current use of biological disease modifying antirheumatic drugs (DMARD) was associated with slightly increased risk of hospitalized infection [rate ratio (RR) = 1.21; 95% CI 1.02-1.43]. Methotrexate and hydroxychloroquine were associated with decreased risk. Oral corticosteroid use increased risk (RR = 1.92; 95% CI 1.67-2.21), and there was a dose-related effect [< or = 5 mg/day: RR = 1.32 (95% CI 1.06-1.63), 6-10 mg/day: RR = 1.94 (95% CI 1.53-2.46), > 10 mg/day: RR = 2.98 (95% CI 2.41-3.69)]. CONCLUSION: These data confirm that individuals with RA are at increased risk of hospitalized infection compared to those without RA. Oral corticosteroid use was associated with a dose-related increase. Biological DMARD use was associated with slightly elevated risk; however, this may reflect confounding and channeling bias.

Hochberg MC, Johnston SS, John AK. · Division of Rheumatology and Clinical Immunology, University of Maryland School of Medicine, 10 South Pine Street, MSTF 8-34 Baltimore, MD 21201, USA. · Curr Med Res Opin. · Pubmed #18179735 No free full text.

Abstract: OBJECTIVE: To evaluate the incidence and prevalence of extra-articular (ExRA) and systemic (SysM) manifestations in a cohort of newly-diagnosed patients with rheumatoid arthritis (RA) in the United States. PATIENTS AND METHODS: Retrospective analysis using inpatient, outpatient, and pharmacy claims data contained in the Thomson Healthcare MarketScan research databases. Patients >or= 18 years of age with a diagnosis of RA (ICD-9-CM 714.0x) on three non-diagnostic claims on different days between January 1, 1999 and September 30, 2006, and at least 12 months of continuous enrollment prior to, and at least 2 years following diagnosis were included in the analysis. Thirty ExRA/SysM, classified into six groups (cardiovascular, blood, mucosa, pulmonary, other, and non-specific), were evaluated. Patients were followed until in-hospital death, disenrollment, or study end. RESULTS: A total of 16,752 patients were included (mean age 59.8 +/- 13.5 years; 72.0% female), and were followed up for a mean of 3.9 +/- 1.4 years. ExRA/SysM were experienced by 47.5% of patients, with cardiovascular (27.2%) the most common. The most frequent individual ExRA/SysM was 'other CVD' (17.2%). Female sex was associated with a reduced risk of cardiovascular ExRA/SysM (HR, 0.66; 95% CI, 0.61-0.72), and an increase in mucosa ExRA/SysM (HR, 2.55; 95% CI, 2.03-3.19). Prior treatment with methotrexate (MTX) was associated with significantly reduced risks of cardiovascular (HR 0.65; 95% CI, 0.59-0.72) and blood system (HR 0.71; 95% CI, 0.61-0.82) ExRA/SysM. Other significant associations were also evident: age, comorbidity as measured by CCI and CDS, and geographic region were associated with increased risks for some ExRA/SysM, while prior NSAID treatment and the presence of diabetes were associated with a lower risk for some ExRA/SysM. CONCLUSION: ExRA/SysM develop in approximately 47% of patients with RA within a few years of diagnosis. Prior treatment with some therapies used in RA management were associated with a reduced risk of developing some ExRA/SysM, while several demographic factors and the presence of comorbidities also affected the risk of developing ExRA/SysM. This analysis was restricted to patients with employer- or government-funded health insurance, while several potential predictors of ExRA/SysM could not be controlled for in the multivariate analysis, as they could not be measured using claims data. Hence, these results may not be generalizable to other groups of patients with RA.

Smitten AL, Choi HK, Hochberg MC, Suissa S, Simon TA, Testa MA, Chan KA. · Harvard School of Public Health, Boston, Massachusetts 02115, USA. · Arthritis Rheum. · Pubmed #18050184 links to  free full text

Abstract: OBJECTIVE: To determine whether the incidence of herpes zoster is elevated in patients with rheumatoid arthritis (RA) and whether herpes zoster is associated with use of disease-modifying antirheumatic drugs (DMARDs) in patients with RA. METHODS: Two retrospective cohort studies were conducted using data from a US integrated managed care database (PharMetrics claims database) from 1998-2002 and the UK General Practice Research Database (GPRD) between 1990-2001. Rates of herpes zoster among patients with RA and randomly sampled non-RA patients were compared. A nested case-control analysis was performed within each RA cohort to examine the effect of current treatment on herpes zoster risk. RESULTS: A total of 122,272 patients with RA from the PharMetrics database and 38,621 from the GPRD were included. The adjusted hazard ratios of herpes zoster for patients with RA compared with non-RA patients were 1.91 (95% confidence interval [95% CI] 1.80-2.03) in the PharMetrics database and 1.65 (95% CI 1.57-1.75) in the GPRD. In the PharMetrics database, current use of biologic DMARDs alone was associated with herpes zoster (odds ratio [OR] 1.54, 95% CI 1.04-2.29), as was current use of traditional DMARDs alone (OR 1.37, 95% CI 1.18-1.59). In the GPRD, current use of traditional DMARDs was associated with herpes zoster (OR 1.27, 95% CI 1.10-1.48). In both data sources, use of oral corticosteroids was associated with herpes zoster regardless of concomitant therapies. CONCLUSION: Data from 2 large databases suggested that patients with RA are at increased risk of herpes zoster. Among patients with RA, DMARDs and/or use of oral corticosteroids appeared to be associated with herpes zoster.

Pradhan EK, Baumgarten M, Langenberg P, Handwerger B, Gilpin AK, Magyari T, Hochberg MC, Berman BM. · The University of Maryland School of Medicine, Baltimore, MD, USA. · Arthritis Rheum. · Pubmed #17907231 links to  free full text

Abstract: OBJECTIVE: To assess the effect of a meditation training program, Mindfulness-Based Stress Reduction (MBSR), on depressive symptoms, psychological status, and disease activity in patients with rheumatoid arthritis (RA) through a randomized, waitlist-controlled pilot study. METHODS: Participants were randomized to either an MBSR group, where they attended an 8-week course and 4-month maintenance program, or to a waitlist control group, where they attended all assessment visits and received MBSR free of charge after study end. Participants received usual care from their rheumatologists throughout the trial. Self-report questionnaires were used to evaluate depressive symptoms, psychological distress, well-being, and mindfulness. Evaluation of RA disease activity (by Disease Activity Score in 28 joints) included examination by a physician masked to treatment status. Adjusted means and mean changes in outcomes were estimated in mixed model repeated measures analyses. RESULTS: Sixty-three participants were randomized: 31 to MBSR and 32 to control. At 2 months, there were no statistically significant differences between groups in any outcomes. At 6 months, there was significant improvement in psychological distress and well-being (P = 0.04 and P = 0.03, respectively), and marginally significant improvement in depressive symptoms and mindfulness (P = 0.08 and P = 0.09, respectively). There was a 35% reduction in psychological distress among those treated. The intervention had no impact on RA disease activity. CONCLUSION: An 8-week MBSR class was not associated with change in depressive symptoms or other outcomes at 2-month followup. Significant improvements in psychological distress and well-being were observed following MBSR plus a 4-month program of continued reinforcement. Mindfulness meditation may complement medical disease management by improving psychological distress and strengthening well-being in patients with RA.

Weisman MH, Gano AD, Gabriel SE, Hochberg MC, Kavanaugh A, Ofman JJ, Prashker M, Suarez-Almazor ME, Yelin E, Nakelsky SD, Croft JD, Anonymous00394. · Evidence-Based Medicine Working Groups in Rheumatology, Beverly Hills, CA, USA. · J Rheumatol. · Pubmed #12913929 No free full text.

Abstract: OBJECTIVE: To describe and compare the relative attributes (reliability, ease of use, applicability, and relevance) of different assessment tools for economic analyses as they pertain to rheumatoid arthritis (RA) literature. METHODS: An expert panel, comprising rheumatology researchers and clinicians, operationalized 2 economic appraisal instruments and applied them to 11 articles used for analysis. Each expert reviewed 3 articles, with each article independently reviewed by a pair of experts. A summary score for each article per appraisal instrument was calculated by dividing the number of items that received a "positive" response by the total number of items in the appraisal instrument. RESULTS: Scores for each article were similar across reviewers and appraisal instruments. CONCLUSION: There is a need for a more comprehensive approach for evaluating this rapidly growing body of economic literature that is not only valid and reliable, but also easy to apply and understand. Although consistency between reviewers was good on both guidelines, inter-guideline discrepancies were noted and reviewers reported some difficulty in using the operationalized format.

Rasch EK, Hirsch R, Paulose-Ram R, Hochberg MC. · National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Maryland 20782, USA. · Arthritis Rheum. · Pubmed #12687533 links to  free full text

Abstract: OBJECTIVE: To determine prevalence estimates for rheumatoid arthritis (RA) in noninstitutionalized older adults in the US. Prevalence estimates were compared using 3 different classification methods based on current classification criteria for RA. METHODS: Data from the Third National Health and Nutrition Examination Survey (NHANES-III) were used to generate prevalence estimates by 3 classification methods in persons 60 years of age and older (n = 5,302). Method 1 applied the "n of k" rule, such that subjects who met 3 of 6 of the American College of Rheumatology (ACR) 1987 criteria were classified as having RA (data from hand radiographs were not available). In method 2, the ACR classification tree algorithm was applied. For method 3, medication data were used to augment case identification via method 2. Population prevalence estimates and 95% confidence intervals (95% CIs) were determined using the 3 methods on data stratified by sex, race/ethnicity, age, and education. RESULTS: Overall prevalence estimates using the 3 classification methods were 2.03% (95% CI 1.30-2.76), 2.15% (95% CI 1.43-2.87), and 2.34% (95% CI 1.66-3.02), respectively. The prevalence of RA was generally greater in the following groups: women, Mexican Americans, respondents with less education, and respondents who were 70 years of age and older. CONCLUSION: The prevalence of RA in persons 60 years of age and older is approximately 2%, representing the proportion of the US elderly population who will most likely require medical intervention because of disease activity. Different classification methods yielded similar prevalence estimates, although detection of RA was enhanced by incorporation of data on use of prescription medications, an important consideration in large population surveys.

Astin JA, Beckner W, Soeken K, Hochberg MC, Berman B. · University of Maryland School of Medicine, Baltimore, USA. · Arthritis Rheum. · Pubmed #12115160 links to  free full text

Abstract: OBJECTIVE: To carry out a systematic review of the literature examining the efficacy of psychological interventions (e.g., relaxation, biofeedback, cognitive-behavioral therapy) in the treatment of rheumatoid arthritis (RA).METHODS: Studies that met the following criteria were included: random assignment, wait-list or usual care control condition; publication in peer-reviewed journals; treatment that included some psychological component beyond simply providing education information; and separate data provided for patients with RA if subjects with conditions other than RA were included. Two investigators independently extracted data on study design, sample size and characteristics, type of intervention, type of control, direction and nature of the outcome(s).RESULTS: Twenty-five trials met the inclusion criteria. Methodologic quality was assessed, and effect sizes were calculated for 6 outcomes. Significant pooled effect sizes were found postintervention for pain (0.22), functional disability (0.27), psychological status (0.15), coping (0.46), and self efficacy (0.35). At followup (averaging 8.5 months), significant pooled effect sizes were observed for tender joints (0.33), psychological status (0.30), and coping (0.52). No clear or consistent patterns emerged when effect sizes for different types of treatment and control conditions were compared, or when higher quality trials were compared to lower quality ones. Findings do, however, suggest that these psychological interventions may be more effective for patients who have had the illness for shorter duration.CONCLUSIONS: Despite some methodologic flaws in the literature, psychological interventions may be important adjunctive therapies in the medical management of RA.

Ling SM, Fried LP, Garrett E, Hirsch R, Guralnik JM, Hochberg MC. · Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · J Rheumatol. · Pubmed #10852259 No free full text.

Abstract: OBJECTIVE: To determine the accuracy of self-report of physician diagnosed rheumatoid arthritis (RA) in moderately to severely disabled older women. METHODS: A total of 1002 participants in the Women's Health and Aging Study were included. These women were > or =65 years old, had an average of 4 chronic illnesses, and represented the one-third most disabled women living in the community. Self-report of a physician's diagnosis of RA was compared to cases of "definite" RA that were adjudicated using an algorithm modeled on the American College of Rheumatology criteria for RA. RESULTS: The sensitivity of self-report of physician diagnosed RA was 77%, with 90.6% specificity and 99% negative predictive value, kappa = 0.46. The positive predictive value was 34% and likely reflected the low prevalence of RA in this sample (3.1%). Five of the 6 women who did not correctly report RA were under the care of a rheumatologist. CONCLUSION: The accuracy of self-report of a physician's diagnosis of RA in this sample of disabled women with multiple chronic illnesses matched that observed in the general adult population of previous studies. Accuracy was enhanced by including report of receiving care by a rheumatologist.