title: Open-label tofacitinib and double-blind atorvastatin in rheumatoid arthritis patients: a randomised study.
abstract: OBJECTIVE
  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. (Pfizer protocol A3921109).
authors.affiliation: Glasgow Biomedical Research Centre, University of Glasgow, , Glasgow, UK.
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Lee
authors.forename: David
authors.initials: D
authors.lastname: Mandel
authors.forename: Yeong-Wook
authors.initials: YW
authors.lastname: Song
authors.forename: Carol A
authors.initials: CA
authors.lastname: Connell
authors.forename: Zhen
authors.initials: Z
authors.lastname: Luo
authors.forename: M Julia
authors.initials: MJ
authors.lastname: Brosnan
authors.forename: Andrea
authors.initials: A
authors.lastname: Zuckerman
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Zwillich
authors.forename: John D
authors.initials: JD
authors.lastname: Bradley
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D000069059:Atorvastatin; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D010919:Placebos; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D010880:Piperidines; D010919:Placebos; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D000069059:Atorvastatin
keywords: Lipids; Rheumatoid Arthritis; Treatment