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SAT0281 Impact of Imputation Methodology on Radiographic Progression Outcomes in the Rapid-Psa Study Of Certolizumab Pegol In Patients With Psoriatic Arthritis
  1. D. van der Heijde1,
  2. R. Fleischmann2,
  3. J. Wollenhaupt3,
  4. A. Deodhar4,
  5. D. Kielar5,
  6. F. Woltering6,
  7. C. Stach6,
  8. B. Hoepken6,
  9. T. Arledge7,
  10. P. J. Mease8
  1. 1Department of Rheumatology, Leiden University Medical Centre, Leiden, Netherlands
  2. 2University of Texas SW Medical Center, Dallas, United States
  3. 3Schoen Klinik, Hamburg, Germany
  4. 4Oregon Health & Science University, Portland, United States
  5. 5UCB Pharma, Brussels, Belgium
  6. 6UCB Pharma, Monheim, Germany
  7. 7UCB Pharma, Raleigh
  8. 8Swedish Medical Center and University of Washington, Seattle, United States

Abstract

Background RAPID-PsA (NCT01087788) investigates the efficacy and safety of certolizumab pegol (CZP) in psoriatic arthritis (PsA).1

Objectives To analyse radiographic progression in PsA patients (pts) in the RAPID-PsA study using different imputation methods and assess the treatment effect of CZP in pts with and without identified baseline (BL) risk factors for progression.

Methods The ongoing 158-week (wk) RAPID-PsA trial recruited pts with active PsA who failed ≥1 DMARD. Pts were randomized 1:1:1 to placebo (PBO), CZP 400mg Q4W or 200mg Q2W following loading dose. Data was evaluated in the Randomized Set. Radiographic progression analyses were assessed at Wk24 using the modified Total Sharp Score (mTSS, primary end point). The pre-specified imputation for change from baseline (CFB) in mTSS for pts with <2 analyzable X-rays used minimum observed BL score (0) and maximum observed Wk24 score (365.5) for missing values. Post-hoc analyses used alternative methods of imputation for pts with <2 analyzable X-rays including no imputation, imputation with the median, or mean CFB mTSS. The same post-hoc imputation approach was used to calculate % non-progressors at Wk24 (mTSS ≤0.5). Inhibition of radiographic progression was also analyzed according to BL mTSS (≤ or > median) and BL CRP levels (≤ or >15mg/L).

Results 409pts were randomized. BL demographics were similar between groups. The pre-specified imputation analysis implausibly overestimated radiographic progression in all arms including PBO (Table). Post-hoc conventional analyses showed that CZP inhibited radiographic progression compared to PBO (Table). Pts with mTSS ≤6 (median score) or CRP ≤15mg/L at BL showed little radiographic progression in both the CZP and PBO groups. CZP (combined dose arm) decreased radiographic progression, vs PBO, in pts with BL mTSS >6 (0.08 vs 0.54, p<0.01) or CRP >15mg/L (0.08 vs 0.51, p<0.05). Higher BL mTSS and elevated CRP were also associated with a higher rate of non-progression in CZP vs PBO groups (95.1 vs 74.1 and 96.2 vs 78.3 for BL mTSS >6 and CRP >15mg/L, respectively).

Conclusions Pre-specified imputation overestimated radiographic progression in all treatment arms including PBO. Conventional imputation methods showed that CZP inhibited radiographic progression in PsA pts, particularly in pts with identified higher risk of progression.

References

  1. Mease P. Ann Rheum Dis 2012;71(Suppl3):150

Acknowledgements The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma.

Disclosure of Interest D. van der Heijde Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli Lilly, GSK, Janssen, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB Pharma, Vertex, Consultant for: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli Lilly, GSK, Janssen, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB Pharma, Vertex, Employee of: Imaging Rheumatology bv., R. Fleischmann Grant/research support from: Genetech Inc, Roche, Abbott, Amgen, UCB Pharma, Pfizer, BMS, Lilly, Sanofi-Aventis, Lexicon, MSD, Novartis, BiogenIdec, Astellas, AstraZeneca, Janssen, Consultant for: Roche, Abbott, Amgen, UCB Pharma, Pfizer, BMS, Lilly, Sanofi-Aventis, Lexicon, Novartis, Astellas, AstraZeneca, Janssen, HGS, J. Wollenhaupt Grant/research support from: UCB Pharma, Consultant for: UCB Pharma, A. Deodhar Grant/research support from: UCB Pharma, Abbott, Amgen, Janssen, Novartis, Consultant for: UCB Pharma, Abbott, Speakers bureau: Abbott, Novartis, D. Kielar Shareholder of: UCB Pharma, Employee of: UCB Pharma, F. Woltering Shareholder of: UCB Pharma, Employee of: UCB Pharma, C. Stach Shareholder of: UCB Pharma, Employee of: UCB Pharma, B. Hoepken Shareholder of: UCB Pharma, Employee of: UCB Pharma, T. Arledge Shareholder of: UCB Pharma, Employee of: UCB Pharma, P. Mease Grant/research support from: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Consultant for: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma

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