Abstract Background Crohn’s disease significantly impairs health-related quality of life (HRQoL), even during remission. The double-blinded, randomised controlled STOP IT trial1 investigated outcomes following infliximab (IFX) withdrawal in patients in sustained clinical-biochemical-endoscopic remission, showing 48% relapse rate within 48 weeks of withdrawal, but did not assess HRQoL. This study evaluated longitudinal HRQoL trajectories to determine whether a decline in HRQoL is detectable prior to clinical relapse following discontinuation of biologics. Methods Post hoc analysis of STOP IT.1 Patients were followed for 48 weeks after randomisation with predefined study visits. HRQoL was assessed at each visit using Short Inflammatory Bowel Disease Questionnaire (SIBDQ) comprising 10 questions each scored from 1 (severe problem) to 7 (not a problem at all). Relapse was defined as CDAI ≥150 together with CDAI increase ≥70 above baseline over 2 consecutive weeks. For patients who experienced clinical relapse between scheduled visits, an early termination visit was conducted, and this SIBDQ measurement was defined as event time. Longitudinal changes in SIBDQ were analysed using linear mixed-effects models. A segmented regression restricted to patients who relapsed was used to estimate the inflection point at which HRQoL began to decline prior to relapse. Results One hundred patients with Crohn’s disease were included. Forty-six patients discontinued treatment (intervention group), and 22 (48%) had relapse within 48 weeks. In the control group where all 54 patients continued IFX therapy, none experienced a relapse. Baseline SIBDQ was comparable between patients who later experienced relapse and those who did not (median 61, IQR 56–65 vs. 61, 54–66; p = 0.98). At time of clinical relapse, SIBDQ was significantly lower among patients who relapsed (median 43, IQR 36-55 vs. 61, 54-65; p 0.001). In mixed-effects analyses, SIBDQ remained stable in patients who did not relapse (β = -0.01 -0.05 – 0.02; p = 0.51), whereas patients who relapsed showed a significantly decline over time (β = -0.46 -0.63 – -0.30; p 0.001). In segmented regression restricted to relapsing patients, an inflection point was identified 7 weeks prior to clinical relapse. SIBDQ remained stable until this time (β = 0.04, -0.18 – 0.26; p = 0.72) and thereafter sharply declined (β = -2.26 -2.90 − -1.61; p 0.001). Conclusion Significant HRQoL impairment presented 7 weeks prior to manifestation of clinical relapse in Crohn’s disease patients discontinuing IFX while in clinical-biologic-endoscopic remission, supporting SIBDQ as a practical, non-invasive tool for early detection of potential loss of disease control. References: 1Buhl S et al. NEJM Evidence 2022;1:EVIDoa2200061. Conflict of interest: Nissen, Mathilde Jepsen: No conflict of interest Gill, Prabhpreet: No conflict of interest Buhl, Sine: No conflict of interest Brynskov, Jørn: No conflict of interest Christensen, Katrine Risager: No conflict of interest Dorn-Rasmussen, Maria: No conflict of interest Thomsen, Ole Ostergaard: No conflict of interest Klausen, Tobias Wirenfeldt: No conflict of interest Dahlerup, Jens Frederik: No conflict of interest Sorensen, Heidi Gram: No conflict of interest Jahnsen, Jørgen: No conflict of interest Molazahi, Akbar: No conflict of interest Pedersen, Natalia: No conflict of interest Kjeldsen, Jens: No conflict of interest Almer, Sven: No conflict of interest Dahl, Eva: No conflict of interest Vind, Ida: No conflict of interest Cannon, Annett: No conflict of interest Marshall, Jan: No conflict of interest Sipponen, Tiana: No conflict of interest Agnholt, Jørgen Steen: No conflict of interest Kievit, Linda Hendrika Adriana: No conflict of interest Aure, Synnøve Louise: No conflict of interest Martinsen, Lars: No conflict of interest Meisner, Svetlana: No conflict of interest Møller Hansen, Jane: No conflict of interest Ainsworth, Mark Andrew: No conflict of interest Steenholdt, Casper: Lectures for Takeda, MSD and Janssen-Cilag research grant from Takeda.
Nissen et al. (Thu,) studied this question.