Open-label tofacitinib and double-blind atorvastatin in rheumatoid arthritis patients: a randomised study*
- Iain B McInnes1,
- Ho-Youn Kim2,
- Sang-Heon Lee3,
- David Mandel4,
- Yeong-Wook Song5,
- Carol A Connell6,
- Zhen Luo7,
- M Julia Brosnan6,
- Andrea Zuckerman6,
- Samuel H Zwillich6,
- John D Bradley6
- 1Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, UK
- 2Division of Rheumatology, Department of Internal Medicine, Rheumatism Research Center, The Catholic University of Korea, Seoul, Republic of Korea
- 3Division of Rheumatology, Konkuk University School of Medicine, Seoul, Republic of Korea
- 4Rheumatology and Osteoporosis Practice, Mayfield Village, Ohio, USA
- 5Department of Internal Medicine, Division of Rheumatology, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea
- 6Medicines Development, Pfizer Inc, Groton, Connecticut, USA
- 7Pfizer Inc, Shanghai, China
- Correspondence to Dr Iain B McInnes, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow, G12 8QQ, UK;
- Received 31 July 2012
- Revised 14 January 2013
- Accepted 14 February 2013
- Published Online First 12 March 2013
Objectives To evaluate the efficacy and safety of atorvastatin versus placebo in modifying lipids in patients with rheumatoid arthritis (RA) receiving the oral Janus kinase inhibitor, tofacitinib.
Methods A randomised, placebo controlled, multicentre phase 2 study, open-label for tofacitinib and blinded for atorvastatin. Patients received tofacitinib 10 mg twice daily for 12 weeks; at week 6, patients were randomly assigned 1:1 to receive oral atorvastatin 10 mg once daily or placebo for 6 weeks. Main outcome measures were lipid moieties, American College of Rheumatology (ACR) response rates, disease activity score in 28 joint counts and safety.
Results 111 patients meeting ACR 1987 RA criteria with active disease were enrolled. Tofacitinib-induced elevation of mean total, low-density lipoprotein (LDL) and high-density lipoprotein-cholesterol, triglycerides and apolipoprotein A-1 concentrations were sustained in placebo recipients to week 12; atorvastatin added at week 6 significantly reduced tofacitinib-associated increases in total and LDL-cholesterol, triglycerides and apolipoprotein B to below week 0 levels. Co-administration of atorvastatin resulted in a significant reduction of LDL-cholesterol versus placebo (primary endpoint; p<0.0001); from week 6 to week 12 the least squares mean reduction was 35.3% with atorvastatin, versus 5.8% increase with placebo. ACR responses were observed with tofacitinib; numerically greater rates were seen with atorvastatin versus placebo. Adverse events were consistent with phase 3 studies.
Conclusions Tofacitinib-associated elevated total and LDL-cholesterol and triglycerides were rapidly and significantly reduced by atorvastatin. Further investigation is required to explore the significance of reductions in RA disease activity in patients receiving tofacitinib and atorvastatin.