title: Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis progression in pubertal lupus patients with higher C reactive protein.
abstract: OBJECTIVE
  Participants in the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) trial were randomised to placebo or atorvastatin for 36 months. The primary endpoint, reduced carotid intima medial thickness (CIMT) progression, was not met but atorvastatin-treated participants showed a trend of slower CIMT progression. Post-hoc analyses were performed to assess subgroup benefit from atorvastatin therapy.
  
  
  METHODS
  Subgroups were prespecified and defined by age (> or ≤15.5 years), systemic lupus erythematosus (SLE) duration (> or ≤24 months), pubertal status (Tanner score≥4 as post-pubertal or <4 as pre-pubertal), low density lipoprotein cholesterol (LDL) (≥ or <110 mg/dl) and high-sensitivity C reactive protein (hsCRP) (≥ or <1.5 mg/l). A combined subgroup (post-pubertal and hsCRP≥1.5 mg/l) was compared to all others. Longitudinal linear mixed-effects models were developed using 12 CIMT and other secondary APPLE outcomes (lipids, hsCRP, disease activity and damage, and quality of life). Three way interaction effects were assessed for models.
  
  
  RESULTS
  Significant interaction effects with trends of less CIMT progression in atorvastatin-treated participants were observed in pubertal (3 CIMT segments), high hsCRP (2 CIMT segments), and the combined high hsCRP and pubertal group (5 CIMT segments). No significant treatment effect trends were observed across subgroups defined by age, SLE duration, LDL for CIMT or other outcome measures.
  
  
  CONCLUSIONS
  Pubertal status and higher hsCRP were linked to lower CIMT progression in atorvastatin-treated subjects, with most consistent decreases in CIMT progression in the combined pubertal and high hsCRP group. While secondary analyses must be interpreted cautiously, results suggest further research is needed to determine whether pubertal lupus patients with high CRP benefit from statin therapy.
  
  
  BACKGROUND
  Clinical Trials.gov Identifier: NCT00065806.
authors: Department of Medicine, Nationwide Children's Hospital, Ohio State University, , Columbus, Ohio, USA.
authors: Stacy P
authors: SP
authors: Ardoin
authors: Laura Eve
authors: LE
authors: Schanberg
authors: Christy I
authors: CI
authors: Sandborg
authors: Huiman X
authors: HX
authors: Barnhart
authors: Greg W
authors: GW
authors: Evans
authors: Eric
authors: E
authors: Yow
authors: Kelly L
authors: KL
authors: Mieszkalski
authors: Norman T
authors: NT
authors: Ilowite
authors: Anne
authors: A
authors: Eberhard
authors: Lisa F
authors: LF
authors: Imundo
authors: Yuki
authors: Y
authors: Kimura
authors: Deborah
authors: D
authors: Levy
authors: Emily
authors: E
authors: von Scheven
authors: Earl
authors: E
authors: Silverman
authors: Suzanne L
authors: SL
authors: Bowyer
authors: L
authors: L
authors: Punaro
authors: Nora G
authors: NG
authors: Singer
authors: David D
authors: DD
authors: Sherry
authors: Deborah K
authors: DK
authors: McCurdy
authors: Marissa
authors: M
authors: Klein-Gitelman
authors: Carol
authors: C
authors: Wallace
authors: Richard M
authors: RM
authors: Silver
authors: Linda
authors: L
authors: Wagner-Weiner
authors: Gloria C
authors: GC
authors: Higgins
authors: Hermine I
authors: HI
authors: Brunner
authors: Lawrence
authors: L
authors: Jung
authors: Jennifer B
authors: JB
authors: Soep
authors: Ann M
authors: AM
authors: Reed
authors: Susan D
authors: SD
authors: Thompson
mesh_terms: D000293:Adolescent; D000367:Age Factors; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D008078:Cholesterol, LDL / Q000097:blood; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D011446:Prospective Studies; D011627:Puberty; D011758:Pyrroles / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D002097:C-Reactive Protein; D000069059:Atorvastatin
keywords: Atherosclerosis; Autoimmune Diseases; Systemic Lupus Erythematosus