Inflammatory Bowel Diseases最新文献

Background: Mucosal healing in ulcerative colitis (UC) is believed to follow a proximal-to-distal pattern. We evaluated colonic healing distribution in patients with moderate-to-severe UC receiving adalimumab.

Methods: Patients from the SERENE UC (Study of a Novel Approach to Induction and Maintenance Dosing with Adalimumab in Patients with Moderate to Severe Ulcerative Colitis) trial with full colonoscopies and segmental biopsies at screening, weeks 8, and 52 were included for endoscopic and histologic analyses if baseline Mayo endoscopic subscore (MES) or Robarts Histopathology Index (RHI) score, respectively, was >0 in the ascending, transverse, and/or descending colon. Data were analyzed using a mixed model for repeated measures to account for clustering of segments within a patient.

Results: Endoscopic and histologic analyses comprised 76 and 79 patients, respectively. Score reductions were significantly greater vs the rectum in the ascending (week 8: MES, mean -0.78 [95% confidence interval (CI), -1.03 to -0.52]; RHI, mean -4.70 [95% CI, -6.92 to -2.49]; week 52: MES, mean -0.63 [95% CI, -0.91 to -0.35]; RHI, mean -2.39 [95% CI, -4.64 to -0.15]), transverse (week 8: MES, mean -0.69 [95% CI, -0.94 to -0.43]; RHI, mean -3.57 [95% CI, -5.62 to -1.51]; week 52: MES, mean -0.64 [95% CI, -0.89 to -0.38]; RHI, mean -2.88 [95% CI, -4.99 to -0.77]), and descending colon (week 8: MES, mean -0.40 [95% CI, -0.67 to -0.13]; RHI, mean -2.55 [95% CI, -4.94 to -0.16]; week 52: MES, mean -0.52 [95% CI, -0.70 to -0.34]; RHI, mean -3.47 [95% CI, -5.37 to -1.56]). Endoscopic improvement/remission and histologic remission were significantly more likely in the ascending and transverse colon than the rectum.

Conclusions: Our findings demonstrate that endoscopic and histologic healing is more challenging in the rectum compared with proximal colonic segments.

Background: With modest rates of endoscopic remission to anti-TNF biologics in children with moderate-to-severe Crohn's disease (CD), there is a critical need to develop noninvasive biomarkers associated with anti-TNF response. We performed a comprehensive proteomic evaluation to identify peripheral-blood candidate biomarkers for anti-TNF response.

Methods: The ENvISION study enrolled patients (2-19 years old) with CD prior to starting infliximab or adalimumab with outcomes prospectively monitored at Month 3 (M3) and Month 12 (M12). The SomaScan® (Somalogic, Boulder, CO, 7322 analytes) was performed prior to anti-TNF treatment (baseline) at M3 and M12. Endoscopic remission was assessed at M12 (simple endoscopic score-CD < 3).

Results: Eighty patients with CD were enrolled with the CD Core Proteome developed from 61 prednisone-naive CD and 30 healthy controls. We identified 2999 differentially abundant proteins, 1403 with lower abundance and 1596 with higher abundance (FDR < 0.05). The CD Core Proteome was then compared across the three timepoints (baseline, M3 and M12) and we found that at both M3 and M12, the Core Proteome dysregulation retains strong identity with the baseline protein signal (β = .7, P < .001; β = .63, P < .001, respectively). Although the proteome exhibits change over time, it does not revert to a control-like state; rather, it transitions to a distinct "treated CD" proteome. In an exploratory investigation of the change in (delta) protein abundance from baseline to M3, we identified 132 proteins nominally associated with M12 endoscopic remission (P < .01). Using elastic net regression, we identified a three-protein panel (IRF1, NEUROG1, and APOA5) associated with M12 endoscopic remission (AUROC 0.94, 95% CI 0.88-1.0).

Conclusions: In an exploratory investigation, we identified a CD Core Proteome and three-protein panel whose early changes were associated with M12 endoscopic remission, supporting their use as early pharmacodynamic response markers following external validation.

Background: Evidence for the clinical importance of changes in health-related quality of life (HRQoL) over time in unselected patients with ulcerative colitis (UC) and Crohn's disease (CD) is limited. We aimed to describe HRQoL trajectories, determine clinically meaningful HRQoL improvement, and identify factors associated with such improvement during the first 3 years after diagnosis.

Methods: Adults with UC and CD from a population-based inception cohort completed the Inflammatory Bowel Disease Questionnaire (IBDQ) and the 36-Item Short Form Survey (SF-36) at inclusion and at the 1-year and 3-year follow-ups. HRQoL trajectories were estimated using linear mixed-effects models. Clinically meaningful improvement was defined using established minimal clinically important difference (MCID) thresholds (IBDQ ≥16; SF-36 physical and mental component summary scores ≥3). Associations between prespecified variables and MCID achievement at follow-up were assessed using multivariable logistic regression.

Results: Among 1016 patients (UC: 68%; CD: 32%), IBDQ and SF-36 physical and mental component summary scores improved at both follow-ups, and approximately half of the patients achieved the corresponding MCID thresholds. HRQoL scores remained below general Norwegian population norms, and trajectories were similar for UC and CD. Symptomatic remission was consistently associated with higher odds of clinically meaningful HRQoL improvement, whereas depressive symptoms, substantial fatigue, and irritable bowel-like symptoms were associated with lower odds. Endoscopic remission, biologic therapy, and bowel surgery during the first year were not significantly associated with clinically meaningful improvement.

Conclusions: Clinically meaningful HRQoL improvement was achieved by about half of the patients and was consistently associated with lower symptom and psychosocial burden.