The Effect of TNF-alpha Blocking Therapy on Lipid Levels in Rheumatoid Arthritis: A Meta-Analysis Alper M. van Sijl, MD,* ,†,‡ Mike J.L. Peters, MD, PhD, ‡ Dirk L. Knol, PhD, § Riekie H.C. de Vet, PhD, § Naveed Sattar, PhD, FRCP, ¶ Ben A.C. Dijkmans, MD, PhD,* ,† Yvo M. Smulders, MD, PhD, ‡ and Michael T. Nurmohamed, MD, PhD* ,†,‡ Objectives: Changes in the lipid profile have been described in patients with rheumatoid arthritis (RA) following therapy with tumor necrosis factor (TNF)-alpha blocking agents. However, thus far, results have been inconsistent. Therefore, we investigated changes in lipid levels after TNF- alpha blocking therapy using meta-analysis of published data. Methods: The literature was searched to identify studies assessing changes in total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol, triglycerides, athero- genic index (ie, TC/HDLc ratio), and apolipoprotein levels in response to TNF-alpha blocking ther- apy. Weighted mean levels of lipids at different time points and subsequent changes in these lipid levels between these time points were calculated with multivariate linear mixed models. Results: Data were available on TC in 15 studies encompassing 766 RA patients and on HDLc in 14 studies encompassing 736 RA patients. TC increased significantly (maximum increase of 10%) and HDLc increased significantly in the first 2 to 6 weeks of therapy (maximum increase of 7%), after which it remained more or less stable. The atherogenic index did not significantly change over time. There was too limited information to evaluate changes in other lipids and apolipoproteins. Conclusions: TNF-alpha blocking therapy has a modest effect on TC and HDLc levels in RA patients with no significant overall effect on the atherogenic index. Whether TNF-alpha blocking effects on qualitative lipid changes (structure and function) are more relevant to their presumed vascular benefits requires further study. © 2011 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 41:393-400 Keywords: arthritis, rheumatoid, meta-analysis, cholesterol, HDL-cholesterol, TNF-alpha blocking therapy T here is strong evidence that rheumatoid arthritis (RA) is associated with an increased risk for car- diovascular (CV) morbidity and mortality relative to the general population (1). While there are several po- tential reasons for the higher CV risk in RA, inflam- mation is considered to play a crucial role (2,3). In- flammation accelerates atherosclerosis directly, but also via effects on conventional and novel CV risk factors, *Department of Rheumatology, VU University Medical Center, Amsterdam, the Netherlands. †Department of Rheumatology, Jan van Breemen Research Institute, Amsterdam, the Netherlands. ‡Department of Internal Medicine and Institute for Cardiovascular Research (ICaR), VU University Medical Center, Amsterdam, the Netherlands. §Department of Epidemiology and Biostatistics, EMGO-Institute for Health Care Research, VU University Medical Center, Amsterdam, the Netherlands. ¶Department of Metabolic Diseases, University of Glasgow, Glasgow, United Kingdom. The authors declare that there are no competing interests. However, the Depart- ments of Rheumatology of the VU Medical Centre and Jan van Breemen Research Institute have both received funds for educational and research purposes from Pfizer, Abbott, UCB, MSD, BMS, and Roche. However, they had no involve- ment in the study design, in the collection, analysis, and interpretation of the data, in the writing of the report, or in the decision to submit the paper for publi- cation. NS has received research and lecture grants from Roche; MN has received speaking grants, ad-hoc consultancy grants, and congress support from Pfizer, Abbott, UCB, MSD, BMS, and Roche. Address reprint requests to Michael T. Nurmohamed, MD, PhD, Departments of Internal Medicine and Rheumatology, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, the Netherlands. E-mail: mt.nurmohamed@vumc.nl RA 393 0049-0172/11/$-see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.semarthrit.2011.04.003