Effect of different imputation approaches on the evaluation of radiographic progression in patients with psoriatic arthritis

Results of the RAPID-PsA 24-week phase III double-blind randomised placebo-controlled study of certolizumab pegol

D. Van Der Heijde, R. Fleischmann, J. Wollenhaupt, Atulya (Atul) Deodhar, D. Kielar, F. Woltering, C. Stach, B. Hoepken, T. Arledge, P. J. Mease

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Abstract

Objectives To report the effect of different imputation methodologies on the assessment of radiographic progression in clinical trials. Methods The 216-week RAPID-psoriatic arthritis (PsA) (NCT01087788) trial of certolizumab pegol (CZP) in patients with active PsA was double-blind and placebocontrolled until week 24. A primary end point was change from baseline in modified Total Sharp Score(s) (mTSS). Prespecified imputation methodology in patients with fewer than two analysable mTSS used minimum observed baseline score for missing baseline values and maximum observed week 24 score for missing week 24 values. Post hoc analyses used alternative methods of imputation in patients with fewer than two analysable mTSS. mTSS non-progressors were defined as patients with ≤0 ( predefined) or ≤0.5 (post hoc) change in mTSS from baseline to week 24. Baseline mTSS and C-reactive protein levels as predictors of radiographic progression were investigated. Results 409 patients were randomised. Baseline demographics were similar between groups. Prespecified imputation analysis inappropriately overestimated radiographic progression (least squares mean placebo, 28.9; CZP, 18.3; p≥0.05). Multiple post hoc analyses demonstrated that CZP inhibited radiographic progression compared with placebo, particularly in patients with high baseline mTSS and C-reactive protein levels. mTSS non-progression rate was higher in CZP than placebo groups in all analyses. Conclusions Inappropriate prespecified imputation methodology resulted in an unrealistic assessment of progression in all arms. Methodologies for imputing missing radiographic data can greatly affect assessment and reporting of mTSS progression.

Original languageEnglish (US)
Pages (from-to)233-237
Number of pages5
JournalAnnals of the Rheumatic Diseases
Volume73
Issue number1
DOIs
StatePublished - Jan 2014

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Psoriatic Arthritis
Placebos
C-Reactive Protein
Least-Squares Analysis
Certolizumab Pegol
Demography
Clinical Trials

ASJC Scopus subject areas

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

Cite this

Effect of different imputation approaches on the evaluation of radiographic progression in patients with psoriatic arthritis : Results of the RAPID-PsA 24-week phase III double-blind randomised placebo-controlled study of certolizumab pegol. / Van Der Heijde, D.; Fleischmann, R.; Wollenhaupt, J.; Deodhar, Atulya (Atul); Kielar, D.; Woltering, F.; Stach, C.; Hoepken, B.; Arledge, T.; Mease, P. J.

In: Annals of the Rheumatic Diseases, Vol. 73, No. 1, 01.2014, p. 233-237.

Research output: Contribution to journalArticle

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abstract = "Objectives To report the effect of different imputation methodologies on the assessment of radiographic progression in clinical trials. Methods The 216-week RAPID-psoriatic arthritis (PsA) (NCT01087788) trial of certolizumab pegol (CZP) in patients with active PsA was double-blind and placebocontrolled until week 24. A primary end point was change from baseline in modified Total Sharp Score(s) (mTSS). Prespecified imputation methodology in patients with fewer than two analysable mTSS used minimum observed baseline score for missing baseline values and maximum observed week 24 score for missing week 24 values. Post hoc analyses used alternative methods of imputation in patients with fewer than two analysable mTSS. mTSS non-progressors were defined as patients with ≤0 ( predefined) or ≤0.5 (post hoc) change in mTSS from baseline to week 24. Baseline mTSS and C-reactive protein levels as predictors of radiographic progression were investigated. Results 409 patients were randomised. Baseline demographics were similar between groups. Prespecified imputation analysis inappropriately overestimated radiographic progression (least squares mean placebo, 28.9; CZP, 18.3; p≥0.05). Multiple post hoc analyses demonstrated that CZP inhibited radiographic progression compared with placebo, particularly in patients with high baseline mTSS and C-reactive protein levels. mTSS non-progression rate was higher in CZP than placebo groups in all analyses. Conclusions Inappropriate prespecified imputation methodology resulted in an unrealistic assessment of progression in all arms. Methodologies for imputing missing radiographic data can greatly affect assessment and reporting of mTSS progression.",
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