Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis progression in pubertal lupus patients with higher C reactive protein

Stacy P. Ardoin, Laura Eve Schanberg, Christy I. Sandborg, Huiman X. Barnhart, Greg W. Evans, Eric Yow, Kelly L. Mieszkalski, Norman T. Ilowite, Anne Eberhard, Lisa F. Imundo, Yuki Kimura, Deborah Levy, Emily Von Scheven, Earl Silverman, Suzanne L. Bowyer, L. Punaro, Nora G. Singer, David D. Sherry, Deborah K. McCurdy, Marissa Klein-Gitelman & 9 others Carol Wallace, Richard M. Silver, Linda Wagner-Weiner, Gloria C. Higgins, Hermine I. Brunner, Lawrence Jung, Jennifer B. Soep, Ann M. Reed, Susan D. Thompson

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)557-566
Number of pages10
JournalAnnals of the Rheumatic Diseases
Volume73
Issue number3
DOIs
StatePublished - Mar 1 2014

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Pediatrics
C-Reactive Protein
Atherosclerosis
Systemic Lupus Erythematosus
LDL Cholesterol
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Secondary Prevention
Atorvastatin Calcium
Therapeutics
Placebos
Quality of Life
Outcome Assessment (Health Care)
Lipids
Research

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy

Cite this

Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis progression in pubertal lupus patients with higher C reactive protein. / Ardoin, Stacy P.; Schanberg, Laura Eve; Sandborg, Christy I.; Barnhart, Huiman X.; Evans, Greg W.; Yow, Eric; Mieszkalski, Kelly L.; Ilowite, Norman T.; Eberhard, Anne; Imundo, Lisa F.; Kimura, Yuki; Levy, Deborah; Von Scheven, Emily; Silverman, Earl; Bowyer, Suzanne L.; Punaro, L.; Singer, Nora G.; Sherry, David D.; McCurdy, Deborah K.; Klein-Gitelman, Marissa; Wallace, Carol; Silver, Richard M.; Wagner-Weiner, Linda; Higgins, Gloria C.; Brunner, Hermine I.; Jung, Lawrence; Soep, Jennifer B.; Reed, Ann M.; Thompson, Susan D.

In: Annals of the Rheumatic Diseases, Vol. 73, No. 3, 01.03.2014, p. 557-566.

Research output: Contribution to journalArticle

Ardoin, SP, Schanberg, LE, Sandborg, CI, Barnhart, HX, Evans, GW, Yow, E, Mieszkalski, KL, Ilowite, NT, Eberhard, A, Imundo, LF, Kimura, Y, Levy, D, Von Scheven, E, Silverman, E, Bowyer, SL, Punaro, L, Singer, NG, Sherry, DD, McCurdy, DK, Klein-Gitelman, M, Wallace, C, Silver, RM, Wagner-Weiner, L, Higgins, GC, Brunner, HI, Jung, L, Soep, JB, Reed, AM & Thompson, SD 2014, 'Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis progression in pubertal lupus patients with higher C reactive protein', Annals of the Rheumatic Diseases, vol. 73, no. 3, pp. 557-566. https://doi.org/10.1136/annrheumdis-2012-202315
Ardoin, Stacy P. ; Schanberg, Laura Eve ; Sandborg, Christy I. ; Barnhart, Huiman X. ; Evans, Greg W. ; Yow, Eric ; Mieszkalski, Kelly L. ; Ilowite, Norman T. ; Eberhard, Anne ; Imundo, Lisa F. ; Kimura, Yuki ; Levy, Deborah ; Von Scheven, Emily ; Silverman, Earl ; Bowyer, Suzanne L. ; Punaro, L. ; Singer, Nora G. ; Sherry, David D. ; McCurdy, Deborah K. ; Klein-Gitelman, Marissa ; Wallace, Carol ; Silver, Richard M. ; Wagner-Weiner, Linda ; Higgins, Gloria C. ; Brunner, Hermine I. ; Jung, Lawrence ; Soep, Jennifer B. ; Reed, Ann M. ; Thompson, Susan D. / Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis progression in pubertal lupus patients with higher C reactive protein. In: Annals of the Rheumatic Diseases. 2014 ; Vol. 73, No. 3. pp. 557-566.
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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.",
author = "Ardoin, {Stacy P.} and Schanberg, {Laura Eve} and Sandborg, {Christy I.} and Barnhart, {Huiman X.} and Evans, {Greg W.} and Eric Yow and Mieszkalski, {Kelly L.} and Ilowite, {Norman T.} and Anne Eberhard and Imundo, {Lisa F.} and Yuki Kimura and Deborah Levy and {Von Scheven}, Emily and Earl Silverman and Bowyer, {Suzanne L.} and L. Punaro and Singer, {Nora G.} and Sherry, {David D.} and McCurdy, {Deborah K.} and Marissa Klein-Gitelman and Carol Wallace and Silver, {Richard M.} and Linda Wagner-Weiner and Higgins, {Gloria C.} and Brunner, {Hermine I.} and Lawrence Jung and Soep, {Jennifer B.} and Reed, {Ann M.} and Thompson, {Susan D.}",
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TY - JOUR

T1 - Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis progression in pubertal lupus patients with higher C reactive protein

AU - Ardoin, Stacy P.

AU - Schanberg, Laura Eve

AU - Sandborg, Christy I.

AU - Barnhart, Huiman X.

AU - Evans, Greg W.

AU - Yow, Eric

AU - Mieszkalski, Kelly L.

AU - Ilowite, Norman T.

AU - Eberhard, Anne

AU - Imundo, Lisa F.

AU - Kimura, Yuki

AU - Levy, Deborah

AU - Von Scheven, Emily

AU - Silverman, Earl

AU - Bowyer, Suzanne L.

AU - Punaro, L.

AU - Singer, Nora G.

AU - Sherry, David D.

AU - McCurdy, Deborah K.

AU - Klein-Gitelman, Marissa

AU - Wallace, Carol

AU - Silver, Richard M.

AU - Wagner-Weiner, Linda

AU - Higgins, Gloria C.

AU - Brunner, Hermine I.

AU - Jung, Lawrence

AU - Soep, Jennifer B.

AU - Reed, Ann M.

AU - Thompson, Susan D.

PY - 2014/3/1

Y1 - 2014/3/1

N2 - 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.

AB - 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.

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U2 - 10.1136/annrheumdis-2012-202315

DO - 10.1136/annrheumdis-2012-202315

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JO - Annals of the Rheumatic Diseases

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