After accounting for potential overlap between the PharMetrics and MarketScan populations, the 95% CI for the combined HR for composite cardiovascular events associated with TCZ use versus TNFi became slightly wider (combined HR 0.84 [95% CI 0.56C1.27 for 10% overlap and 0.55C1.28 for 20% overlap]). inhibitors (TNFi). Methods To examine comparative cardiovascular safety, we conducted a cohort study of RA patients who newly started TCZ or TNFi using claims data from Medicare, IMS PharMetrics, and MarketScan. All patients were required to have previously used a different TNFi, abatacept, or tofacitinib. The primary outcome measure was a composite cardiovascular end point of hospitalization for myocardial infarction or stroke. TCZ initiators were propensity score matched to TNFi initiators with a variable ratio of 1 1:3 within each database, controlling for 65 baseline characteristics. A fixed\effects model combined database\specific hazard ratios (HRs). Results We included 9,218 TCZ initiators propensity score matched to 18,810 TNFi initiators across all 3 databases. The mean age was 72 years in Medicare, 51 in PharMetrics, and 53 in MarketScan. Cardiovascular disease was present at baseline in 14.3% of TCZ initiators and 13.5% of TNFi initiators. During the study period (mean??SD 0.9??0.7 years; maximum 4.5 years), 125 composite cardiovascular events occurred, resulting in an incidence rate of 0.52 per 100 person\years for TCZ initiators and 0.59 per 100 person\years for TNFi initiators. The risk of cardiovascular events associated with TCZ use versus TNFi use was similar across all 3 databases, with a combined HR of 0.84 (95% confidence interval 0.56C1.26). Conclusion This multi\database population\based cohort study showed no evidence of an increased cardiovascular risk among RA patients who switched from a different biologic drug or tofacitinib to TCZ versus to a TNFi. Epidemiologic studies of SC 560 patients with rheumatoid arthritis (RA) have shown a 1.5C2.0 times increased risk of cardiovascular morbidity and mortality 1, 2. This excess cardiovascular risk is thought to be the result of not only traditional cardiovascular risk factors but also RA severity or active systemic inflammation 3, 4. The 2015 American College of Rheumatology guidelines for the treatment of RA recommend a treat\to\target strategy to better control disease activity in both early and established RA 5. Use of tumor necrosis factor inhibitors (TNFi) or other biologic agents is recommended for patients who have moderate\to\high disease activity while taking a traditional disease\modifying antirheumatic drug (DMARD) 5. Over the past decade, a number of studies have suggested potential cardiovascular benefits of using DMARDs in patients with RA 6. In particular, a number of cohort studies showed that treatment with TNFi may be associated with a decreased cardiovascular risk, probably related to a reduction in systemic inflammation 7, 8, 9, although some studies did SC 560 not find a beneficial effect on cardiovascular risk in patients receiving TNFi compared with patients receiving DMARDs 10, 11. Tocilizumab (TCZ), an interleukin\6 receptor antagonist, is an effective biologic agent that reduces inflammatory disease activity in RA. In several clinical trials in humans, elevations in serum lipid levels were noted among subjects receiving TCZ 12, 13, 14. In a head\to\head randomized controlled trial (RCT) of TCZ monotherapy versus adalimumab monotherapy in 325 patients with RA, TCZ was superior to adalimumab for the reduction of signs and symptoms of RA, but more patients in the TCZ group had increased low\density lipoprotein (LDL) cholesterol levels than in the adalimumab group 15, 16. Post hoc analyses of clinical trials and extension studies of TCZ suggest that RA disease activity, but not changes in lipid levels during treatment, may be independently associated with cardiovascular risk in RA patients treated with TCZ 17. Nonetheless, whether increases in lipid levels with TCZ treatment compared with treatment with other biologic agents leads to an excess cardiovascular risk has not been determined, although the ENTRACTE trial (ClinicalTrials.gov identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT01331837″,”term_id”:”NCT01331837″NCT01331837), a postmarketing open\label RCT that has just been completed, focused on evaluating the risk of cardiovascular events with TCZ versus etanercept in RA patients with elevated cardiovascular risk at baseline. The main objective of this study was to compare the risk of cardiovascular events, including myocardial infarction (MI) and stroke, in patients who newly started TCZ versus those who newly started TNFi in a multi\database population\based cohort of RA patients. The secondary aim was to compare the risk of other cardiovascular events, such as coronary revascularization, acute coronary syndrome (ACS), heart failure, and all\cause deaths, in TCZ initiators compared with TNFi initiators. PATIENTS AND METHODS Data sources We carried out a cohort study using data from 3 large US health care claims databases: Medicare (Parts A/B/D 2010C2013), IMS PharMetrics Plus SC 560 (2011C2014), and IgM Isotype Control antibody (FITC) Truven MarketScan (2011CJune 2015). Medicare is definitely a federally funded system and provides.
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- Abbreviations: CON, control; CANA, canagliflozin; AMPK, AMP-activated proteins kinase; ACC, acetyl-CoA carboxylase
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