Concomitant Use of Statins in Tocilizumab-Treated Patients with Rheumatoid Arthritis: A Post Hoc Analysis

Abstract

IntroductionPatients with rheumatoid arthritis (RA) have decreased survival because of increased cardiovascular risk compared with the general population, and treatment with tocilizumab (TCZ) has been shown to increase lipid levels; however, the relationship between lipids and cardiovascular risk is unknown. This post hoc analysis expanded on previously reported 24-week results by characterizing statin use and subsequent changes in lipid parameters in patients with RA treated with intravenous or subcutaneous TCZ (TCZ-IV or TCZ-SC) over 2 years of treatment.MethodsData were collected from patients with moderate to severe active RA who received ≥1 dose of the study drug in seven international, randomized, double-blind, controlled phase 3 and 4 clinical trials of TCZ-IV or TCZ-SC. Lipid levels and safety events were assessed over 2 years of treatment. Data were summarized for all pooled treatment groups of the intention-to-treat populations in the TCZ-IV and TCZ-SC studies, and results were stratified by concomitant statin use.ResultsData from this descriptive, retrospective, pooled analysis indicated that statins can stabilize lipid levels without a clinically significant increase in adverse events. Approximately 30% of patients in the TCZ treatment arms who never received a statin demonstrated a shift in low-density-lipoprotein cholesterol (LDL-C) from <130 mg/dl at baseline to ≥130 mg/dl at 2 years. However, despite the increased potential cardiovascular risk, <15% of patients with LDL-C ≥100 mg/dl and <35% of patients with a total cholesterol:high-density-lipoprotein cholesterol ratio >5 at 2 years were receiving concomitant statins.ConclusionConcomitant statin use attenuated TCZ-mediated lipid increases; however, a large proportion of TCZ-treated patients potentially at risk of cardiovascular disease were untreated. These findings highlight the need for better understanding of potential risk associated with TCZ-mediated lipid elevations as well as implementation of RA-specific guidelines on the recognition and management of elevated risk of cardiovascular events in patients with RA.FundingF. Hoffmann-La Roche, Ltd.Electronic supplementary materialThe online version of this article (doi:10.1007/s40744-016-0049-8) contains supplementary material, which is available to authorized users.

Immune modulatory effects of statins

“…Multiple preclinical and clinical studies have analysed the impact of different statins on RA . Statins are given to patients with RA because of their increased risk for cardiovascular complications .…”

“…A cohort study that included patients with a diagnosis of hyperlipidaemia who started statin intake showed that the connection between lowering low‐density lipoprotein cholesterol and cardiovascular events in RA was comparable to the association found in matched general controls . Another study analysed the effect of statins in patients treated for RA with tocilizumab . The rationale was that treatment with tocilizumab increases lipid levels.…”

“…The rationale was that treatment with tocilizumab increases lipid levels. The authors reported that concomitant statin use reduced tocilizumab‐mediated lipid increases . A randomized, placebo‐controlled, multi‐centre phase II study, on a combination of tofacitinib and atorvastatin showed that tofacitinib‐associated elevated low‐density lipoprotein cholesterol was reduced by atorvastatin .…”

“…Multiple preclinical and clinical studies have analysed the impact of different statins on RA. [21][22][23] Statins are given to patients with RA because of their increased risk for cardiovascular complications. 24 A cohort study that included patients with a diagnosis of hyperlipidaemia who started statin intake showed that the connection between lowering low-density lipoprotein cholesterol and cardiovascular events in RA was comparable to the association found in matched general controls.…”

“…24 Another study analysed the effect of statins in patients treated for RA with tocilizumab. 22 The rationale was that treatment with tocilizumab increases lipid levels. The authors reported that concomitant statin use reduced tocilizumab-mediated lipid increases.…”