Agreement between local and central reading of endoscopic disease activity in ulcerative colitis: results from the tofacitinib OCTAVE trials. Issue 11 (6th October 2021)

• Record Type: Journal Article
• Authors: Feagan, Brian G.; Khanna, Reena; Sandborn, William J.; Vermeire, Séverine; Reinisch, Walter; Su, Chinyu; Salese, Leonardo; Fan, Haiyun; Paulissen, Jerome; Woodworth, Deborah A.; Niezychowski, Wojciech; Sands, Bruce E.
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 54:Issue 11/12(2021)
• Page Start: 1442
• Page End: 1453
• Publication Date: 2021-10-06
• Subjects: endoscopy -- inflammatory bowel disease -- symptom score or index -- ulcerative colitis; Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.16626
• Languages: English
• ISSNs: 0269-2813

Abstract

Summary: 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. Abstract : What is the level of agreement, and what are the potential sources of disagreement, between local and central reading of endoscopic disease activity in ulcerative colitis?