Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
A Secondary Analysis of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Study Shows That Atorvastatin Therapy Reduces Progression of Carotid Intima Medial Thickening in Pubertal SLE Patients with Higher C Reactive Protein.
Ardoin1, Stacy P., Schanberg2, Laura E., Sandborg3, Christy I., Barnhart4, Huiman, Yow4, Eric, Evans5, Greg, Mieszkalski2, Kelly
Ohio State University, Columbus, OH
The Hospital for Sick Children, Toronto, ON
Pediatrics, Hackensack, NJ
Hospital for Sick Children, Toronto, ON
James Whitcomb Riley Hospital, Indianapolis, IN
Texas Scottish Rite Hospital, Dallas, TX
Director, Division of Rheumatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH
Children's Hospital of Philadelphia, Philadelphia, PA
Mattel Children's Hospital, University of California, Los Angeles, Los Angeles, CA
Children's Memorial Hospital, Chicago, IL
Childrens Hosp & Regional Med, Seattle, WA
Duke University Medical Center, Durham, NC
MUSC, Charleston, SC
University of Chicago Hospital, Chicago, IL
NATIONWIDE CHILDRENS HOSPITAL, Columbus, OH
Cincinnati Children's Hospital Medical Center, Cincinnati, OH
Stanford University, Palo Alto, CA
Duke Clinical Research Institute, Durham, NC
Children's Hospital Montefiore, Bronx, NY
UC San Francisco, San Francisco, CA
Cohen Children's Hospital Medical Center, New Hyde Park, NY
Childrens Hospital of New York, Columbia University Medical Center, New York, NY
APPLE assessed atorvastatin's efficacy in reducing carotid intimal medial thickening (CIMT) progression in pediatric SLE (pSLE). While the primary endpoint of reduced mean-mean common CIMT progression was not met, observed trends of near significance in several CIMT segments suggested atorvastatin may reduce CIMT progression. Secondary analyses were performed to determine whether treatment effect was consistent across subgroups defined by LDL, high-sensitivity c-reactive protein (hscrp), age, pubertal status, SLE duration and medication adherence.
APPLE is a randomized, placebo-controlled, multicenter trial randomizing 221 subjects with pSLE (age 1021 years) to 36 months of atorvastatin or placebo. CIMT was measured by standard protocol at 0, 12, 24 and 36 months. Fasting lipids and hscrp were measured centrally. Subgroups were defined as LDL < or >/= 110 mg/dL, hscrp < or >/= 1.5 mg/dL, age < or >/= 15.5 yrs, SLE duration < or 3 24 months, adherence < or >/= 75%. Prepubertal status was defined by self-reported Tanner stage < 4. An additional combined subgroup of post-pubertal subjects with hscrp 3 1.5 mg/dL vs. others was defined.
The statistical approach replicated primary APPLE efficacy analysis comparing CIMT progression rates between treatment groups based on test of interaction between treatment group and time in a longitudinal linear mixed effects model. Similar models were used to assess non-CIMT outcomes. Indicator variables were included for subgroup level as well as two- and three-way interactions between subgroup, treatment group and time between subgroup level, treatment group and time. All statistical analyses were 2-sided, and the level of significance for all analyses was 0.05.
Differences in treatment effects between hscrp subgroups were identified for mean-mean common (p=0.029) and mean-mean near wall (p=0.014). In both cases, the reduction in CIMT progression associated with atorvastatin assignment was more pronounced in the elevated hscrp subgroup. Similar differences were identified by pubertal status for mean-mean bifurcation (p=0.019) mean-max near wall (p=0.027) and mean-mean near wall (p=0.021), and by adherence for mean-mean far wall (p=0.035) and mean-mean near wall (p=0.028), where reduction in CIMT progression with atorvastatin assignment was more pronounced among post-pubertal or more adherent participants. No significant differences in treatment effects were observed between subgroups defined by LDL, age or SLE duration. The combined pubertal and high hscrp subgroup atorvastatin group had lower CIMT progression rates in five of 12 CIMT segments: mean-mean common (p=0.005), mean-mean (p=0.008), mean-mean bifurcation (p=0.023), mean-max near wall (p=0.029), and mean-mean near wall (p=0.002).
These exploratory results need to be confirmed and interpreted cautiously as multiple comparisons were performed. APPLE secondary analyses showed a trend of lower CIMT progression rates in the atorvastatin-treated pubertal and elevated hscrp subgroups, particularly in the combined pubertal subjects with high hscrp, suggesting that this subgroup may benefit from statin therapy.
To cite this abstract, please use the following information:
Ardoin, Stacy P., Schanberg, Laura E., Sandborg, Christy I., Barnhart, Huiman, Yow, Eric, Evans, Greg, et al; A Secondary Analysis of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Study Shows That Atorvastatin Therapy Reduces Progression of Carotid Intima Medial Thickening in Pubertal SLE Patients with Higher C Reactive Protein. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2015