Agreement between local and central reading of endoscopic disease activity in ulcerative colitis: results from the tofacitinib OCTAVE trials

Brian G. Feagan, Reena Khanna, William J. Sandborn, Séverine Vermeire, Walter Reinisch, Chinyu Su, Leonardo Salese, Haiyun Fan, Jerome Paulissen, Deborah A. Woodworth, Wojciech Niezychowski, Bruce E. Sands

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4 Scopus citations

Abstract

Background: Endoscopy is routine in trials of ulcerative colitis therapies. Aim: To investigate agreement between central and local Mayo endoscopic subscore (MES) reads in the OCTAVE programme. Methods: Flexible sigmoidoscopy was performed in tofacitinib induction (OCTAVE Induction 1&2, NCT01465763 and NCT01458951), maintenance (OCTAVE Sustain, NCT01458574) and open-label, long-term extension (OCTAVE Open, NCT01470612) studies. Kappa statistics and Bowker's tests evaluated agreement/disagreement between centrally and locally read MES, with potential determinants of differences analysed by logistic regression. Results: Moderate-to-substantial agreement was observed between central and local reads at screening (77.1% agreement; kappa 0.62 [95% confidence interval 0.59-0.66]), OCTAVE Induction 1&2 week (Wk) 8 (63.8%; 0.62 [0.59-0.66]), OCTAVE Sustain Wk 52 (55.6%; 0.56 [0.50-0.62]) and for induction non-responders at OCTAVE Open month 2 (59.9%; 0.54 [0.48-0.60]). Where disagreements occurred, local reads were systematically lower than central reads at OCTAVE Induction 1&2 Wk 8, OCTAVE Sustain Wk 52 and OCTAVE Open month 2 (Bowker's P < 0.0001); this difference was not observed at screening (P = 0.0852). Using multivariable logistic regression, geographical region, C-reactive protein (Wk 8), partial Mayo score (Wk 8) and prior tumour necrosis factor antagonist failure were associated with disparity at OCTAVE Induction 1&2 Wk 8 (P < 0.05). In OCTAVE Induction 1&2 and OCTAVE Sustain, significantly higher proportions of patients endoscopic improvement, remission and endoscopic remission with tofacitinib vs placebo, using either central or local reads. Conclusion: Moderate-to-substantial agreement was observed between central and local endoscopic reads. Where disagreements occurred, local reads were systematically lower than central reads at most timepoints, suggesting potential bias. ClinicalTrials.gov identifier: NCT01465763, NCT01458951, NCT01458574, NCT01470612.

Original languageEnglish
Pages (from-to)1442-1453
Number of pages12
JournalAlimentary Pharmacology and Therapeutics
Volume54
Issue number11-12
DOIs
StatePublished - Dec 2021

Keywords

  • endoscopy
  • inflammatory bowel disease
  • symptom score or index
  • ulcerative colitis

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