Search

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.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.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).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. [ABSTRACT FROM AUTHOR]

Concerns persist about a possible association between tumor necrosis factor α (TNFα) 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.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 ≥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).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.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. [ABSTRACT FROM AUTHOR]

To observe the long-term safety and efficacy of combination therapy with etanercept and methotrexate in patients with rheumatoid arthritis (RA), and to determine whether the addition of etanercept allowed reductions in methotrexate or corticosteroid dosages while maintaining a clinical response. Patients with RA who received methotrexate plus etanercept in a previous randomized, placebo-controlled trial were offered the opportunity to enroll in an open-label extension study for further evaluation of treatment with etanercept and methotrexate. Seventy-nine of the 89 patients in the original blinded study enrolled in the extension study, and 65 of these patients continue in the study. Patients have received etanercept therapy for up to 47 months (median 44 months). The types and rate of adverse events noted during the extension trial were similar to those observed in the controlled trial. At the 3-year assessment, 77% of the 57 patients available for evaluation met American College of Rheumatology 20% (ACR20) criteria for improvement in RA, 47% met the ACR50 criteria, and 23% met the ACR70 criteria. Of the 36 patients assessed at 3 years in the extension study, 30 (83%) were able to decrease their dosages of corticosteroids, and 20 (56%) were able to discontinue corticosteroid therapy. At 3 years, the dosage of methotrexate was decreased in 41 of 66 patients (62%), and methotrexate therapy was discontinued in 19 patients (29%). In this observational continuation study, the addition of etanercept to background methotrexate provided sustained clinical benefit over a median period of 44 months. With etanercept therapy, there were trends toward dosage reduction or discontinuation of methotrexate and corticosteroids, without apparent worsening of ACR response rates. Compared with the controlled trial, no increases in the rate of adverse events were observed. [ABSTRACT FROM AUTHOR]

Arthritis in the K/BxN mouse model results from pathogenic immunoglobulins that recognize glucose-6-phosphate isomerase (GPI), a glycolytic enzyme residing in the cytoplasm of all cells. Antibodies directed against GPI can, alone, transfer arthritis to healthy recipients. Previous experiments have revealed significant titers of anti-GPI antibodies in the serum of many patients with rheumatoid arthritis (RA). We evaluated the generality of these observations in cohorts of patients with 12 different arthritic and chronic autoimmune diseases and in population-matched healthy control subjects. Anti-GPI antibodies were assayed in 811 individual serum samples by enzyme-linked immunosorbent assay with 2 forms of GPI, recombinant and native. Results were confirmed by immunoblotting. Several patients had significantly elevated anti-GPI antibody titers, but without the prevalence or the specificity reported previously. Only 15% of RA patients had anti-GPI antibodies (range 12–29% in different cohorts), with a higher prevalence in patients with active disease. Psoriatic arthritis, undifferentiated arthritis, and spondylarthropathy patients also displayed anti-GPI antibodies at similar frequencies (12–25%). Similar titers were detected in a proportion (5–10%) of control subjects or patients with Crohn's disease or sarcoidosis. Very high titers were found in rare cases of RA and systemic lupus erythematosus. No disease-specific pattern of antibody positivity to GPI was apparent. While the antibody-mediated mechanism at play in the mouse model may exemplify a generic mechanism for some forms of arthritis in humans, GPI itself does not appear to be a target common to the majority of RA patients. [ABSTRACT FROM AUTHOR]