FRI0137 Effects of tofacitinib on lipid biomarkers in patients with active rheumatoid arthritis

Background Tofacitinib is a novel, oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). Administration of tofacitinib to RA patients (pts) is associated with increases in lipid moieties. However, active RA is in turn associated with altered lipid parameters. Objectives To explore changes in biomarkers relevant to lipid biochemistry and cardiovascular (CV) risk in pts treated with tofacitinib or placebo. Methods CV biomarkers were evaluated in blood samples reserved during two Phase 2 studies (NCT00413660; NCT00550446) and one Phase 3 study (NCT00853385) of tofacitinib in pts with an inadequate response to methotrexate (MTX) or traditional disease-modifying antirheumatic drugs (DMARDs). Analyses were conducted at baseline and Month 3 in pts receiving tofacitinib 5 and 10 mg twice daily (BID) as monotherapy or with background MTX, or placebo. Mean changes at Month 3 were analysed using ANOVA. To investigate the impact of outliers, trimmed analyses were also performed whereby extreme values (lower and upper percentiles) were removed in 1% increments, and ANOVA repeated for each. Results Tofacitinib increased the activity of lecithin-cholesterol acyltransferase (LCAT) and paraoxonase, and reduced serum amyloid A (SAA) and high-density lipoprotein (HDL)-associated SAA levels. No significant changes were observed in lipoprotein (a) (Lp[a]), cholesteryl ester transfer protein (CETP), or lipoprotein-associated phospholipase A 2 (Lp PLA2) levels in both full (Table 1) and trimmed analyses. Conclusions Tofacitinib induced increases in LCAT and paraoxonase and decreases in SAA and HDL-associated SAA, implicating JAK-dependent pathways in structural and functional modifications of lipoprotein particles, thereby suggesting a potential for reduction in CV risk in pts treated with tofacitinib. Consequences on vascular co-morbidity require further investigation. Disclosure of Interest I. McInnes Grant/research support from: Pfizer Inc, Speakers bureau: Pfizer Inc, I. Kaplan Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, M. Boy Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. Riese Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, A. Zuckerman Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Gruben Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, M. Brosnan Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Zwillich Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Bradley Shareholder of: Pfizer Inc, Employee of: Pfizer Inc