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SAT0214 Statistical Evalution of Joint Damage Prgression in Patients with Rheumatoid Arthritis Treated with Infliximab or Biosimilar Infliximab (CT-P13) Anti-TNF Therapy: A Role of Sensitivity Analysis for Missing Data Evaluating Similarity
  1. S.J. Lee1,
  2. D.H. Yoo2,
  3. W. Park3,
  4. U. Müller-Ladner4,
  5. T.N. Pyo1
  1. 1CELLTRION Inc., Incheon
  2. 2Hanyang Univ. Hospital
  3. 3Inha Univ. Hospital, Seoul, Korea, Republic Of
  4. 4Justus-Liebig-University of Giessen, Kerckhoff-Klinik, Bad Nauheim, Germany

Abstract

Background Biosimilar infliximab (CT-P13) was the first monoclonal antibody biosimilar of innovator infliximab (INX) approved by the European Medicines Agency. In the PLANETRA study (1), patients with rheumatoid arthritis received 3 mg/kg of CT-P13 (n=302) or INX (n=304) every 8 weeks and were evaluated for joint damage at baseline and at week 54. The joint damage progression (JDP) was determined using the total Sharp score (TSS) in combination with erosion and joint space narrowing (JSN) (2).

Objectives To investigate the similarity of JDP between CT-P13 and INX using TSS, erosion and JSN based on data with two different missing data imputations and without imputation.

Methods Each radiograph was randomly assigned to two qualified experienced independent readers without the information of the time point of the radiograph images. The two readers scored the images for both time points while remaining blinded. The mean values of two quantified scores were used. Two different missing data imputation methods were used. The first method (Method A) is based on Analysis of Covariance (ANCOVA) with covariates, treatment group, CRP at baseline (CRP ≤2 mg/dL or >2 mg/dL), region (European Union (EU) or non-EU), and joint damage score at baseline. The predicted values from the ANCOVA were used for the missing values. The second method (Method B) is a simple linear extrapolation of the scores on the real time scale. Here, mean, standard deviation, median and range were calculated for each method and 95% confidence intervals (CI) of the JDP between the treatment groups were evaluated along with p-values from t-test. Every individual radiographic score per treatment group was plotted against its cumulative probability for each imputation method and without imputation.

Results In the PLANETRA study, the changes of radiographic scores from baseline to week 54 were 1.3±9.3 and 0.7±7.0 for CT-P13 and INX, respectively, when ANCOVA was used for all-randomized patients. In addition, there was no statistical significant difference between CT-P13 and INX (p=0.3171). These results match the ATTRACT study (3), in which infliximab-treated subjects demonstrated also no significant change in the mean radiographic score when baseline scores were compared with those at 54 weeks, with a p-value of 0.43. Particularly, in 3mg/kg every 8 weeks group in the ATTRACT study, the total radiographic score increase from baseline was also 1.3±6.0. The figure shows similarity of TSS between CT-P13 and INX using the probability plot. There was no impact of the choice of imputation (Method A, B or no missing data imputation) on the results.

Conclusions In this comparison of JDP during CT-P13 and INX treatment, CT-P13 shows comparable results, which supports the robust similarity either with missing data imputations or with data excluding missing data. The obtained JDP from PLANETRA study also supports the historical data of the early INX trials.

References

  1. Yoo DH, et al. ARD 2013; 72: 1613-1620.

  2. Van der Heijde DM, et al. Arthritis Rheum 2005; 52: 49-60.

  3. Maini R, et al. Lancet 1999; 354: 1932-1939.

Disclosure of Interest S. J. Lee Employee of: CELLTRION Inc., D. H. Yoo Consultant for: CELLTRION Inc., W. Park Consultant for: CELLTRION Inc., U. Müller-Ladner Speakers bureau: CELLTRION Inc., T. N. Pyo Employee of: CELLTRION Inc.

DOI 10.1136/annrheumdis-2014-eular.3461

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