Association Between Proposed Definitions of Clinical Remission/Response and Well-Being in Patients With Crohn's Disease

Abstract

Background and aims: Patient-reported outcomes are recommended endpoints in Crohn's disease [CD] trials. The association between patient-reported general well-being relative to symptoms of diarrhoea and abdominal pain [AP] in patients with moderate to severe CD was explored.

Methods: Patients from three randomized, placebo-controlled, double-blind adalimumab or upadacitinib studies with average daily very soft/liquid stool frequency [SF] ≥4 and/or AP score ≥2 at baseline were included. Using electronic diaries, patients reported general well-being [seven-point Likert scale; 1 = worst; 7 = best] in item 10 of the Inflammatory Bowel Disease Questionnaire [IBDQ]. Changes in well-being and clinical outcomes of SF and AP from baseline to week 12 or 16, and the relationship between well-being and clinical outcomes were evaluated using cumulative distribution function and probability density function curves.

Results: In total, 858 patients with CD were included [adalimumab, n = 695; upadacitinib, n = 163]. Patients who achieved clinical remission [SF ≤2.8, AP score ≤1.0, neither worse than baseline] were more likely than those not in clinical remission to report IBDQ item 10 response in the 6-7 group category but not IBDQ categories ≤5. Higher IBDQ score for item 10 [6-7] was associated with lower SF and AP score. Greater point increases in IBDQ item 10 were associated with a greater percentage decrease in clinical parameters; a ≥25-30% decrease in SF or AP was associated with a ≥1-point improvement in IBDQ.

Conclusions: An association between improvements in patient-reported general well-being and clinical remission/response was observed using outcomes of SF and AP, supporting the clinical remission/response endpoint definitions used in clinical studies of CD. Clinical Trial Registrations [ClinicalTrials.gov]: NCT00077779 [CHARM]; NCT00348283 [EXTEND]; NCT02365649 [CELEST].

Keywords: Stool frequency; abdominal pain; patient-reported outcomes.

© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.

Figures

Figure 1.

CDF and PDF of average daily very soft and liquid stool frequency [A] and abdominal pain score [B] by the grouped IBDQ item 10 response category at week 12 [adalimumab] and at week 16 [upadacitinib]. CDF, cumulative distribution function; IBDQ, Inflammatory Bowel Disease Questionnaire; PDF, probability density function.

Figure 2.

CDF and PDF of percentage change from baseline in average daily very soft and liquid stool frequency [A] and abdominal pain score [B] by the grouped IBDQ item 10 response category at week 12 [adalimumab] and at week 16 [upadacitinib]. CDF, cumulative distribution function; IBDQ, Inflammatory Bowel Disease Questionnaire; PDF, probability density function.