Do Quality of Life, Disease Activity, and Flares Differ by Race in Ulcerative Colitis Over Time?

Crohn’s disease (CD) patients often suffer severe symptoms that impair their quality of life. A sample of 39 CD patients who were assessed using well validated measures of disease activity and disease-specific quality of life is reported. Twenty-six of these patients were reassessed an average of four months after the initial assessment to determine the impact of changes in disease activity on quality of life. For the total sample (n=39) disease activity did not predict quality of life for any of the scales of the Inflammatory Bowel Disease Questionnaire (IBDQ) (r<0.13 for each). Thus, examining fluctuations in disease activity between patients did not demonstrate a disease activity-quality of life relationship. In contrast, changes in disease activity within the same individuals over time (the repeat assessment sample, n=26) were correlated with changes in quality of life; increases in disease activity predicted decreases in quality of life on the IBDQ bowel symptoms subscale (r=-0.463, P<0.01) and the IBDQ systemic symptoms subscale (r=0.44, P<0.05). The 10 patients with the largest decrease in disease activity over time (mean decrease of 43.54 points using the Dutch Activity Index) had significant improvement in quality of life on the bowel and systemic subscales. In contrast, the nine patients with the largest increase in disease activity over time (mean increase of 20.57 points using the Dutch Activity Index) had significant reduction in quality of life on the bowel and systemic symptoms subscales. These differences between extreme groups were significant for both the bowel symptoms (P<0.05) and systemic symptoms (P<0.05) subscales. The authors conclude that changes in disease activity affect some important aspects of quality of life: aspects related to disease-specific (bowel symptoms) and nondisease-specific (systemic symptoms) physical symptoms. Importantly, disease activity was not able to predict the emotional and social aspects of IBD-related quality of life. This suggests that nondisease factors need to be considered when working with CD patients. Future research should evaluate the role of psychological intervention in improving quality of life for patients with reduced well-being, particularly in areas of emotional and social functioning.

Download Full-text

A randomised, placebo-controlled study of RIPK1 inhibitor GSK2982772 in patients with active ulcerative colitis

BMJ Open Gastroenterology ◽

10.1136/bmjgast-2021-000680 ◽

2021 ◽

Vol 8 (1) ◽

pp. e000680

Author(s):

Kathy Weisel ◽

Nicola Scott ◽

Scott Berger ◽

Susanne Wang ◽

Kurt Brown ◽

...

Keyword(s):

Quality Of Life ◽

Ulcerative Colitis ◽

Disease Activity ◽

Controlled Study ◽

Experimental Medicine ◽

Open Label ◽

Double Blind ◽

Treatment Groups ◽

To Receive

ObjectiveTumour necrosis factor signalling via the receptor-interacting protein kinase 1 (RIPK1) pathway regulates colonic inflammation suggesting that RIPK1 inhibition may be a potential therapeutic target in ulcerative colitis (UC). This phase IIa, randomised, double-blind experimental medicine study investigated the safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of the RIPK1 inhibitor GSK2982772 in patients with active UC.DesignIn part A, prior to a protocol amendment, one patient was randomised to receive GSK2982772 60 mg twice daily for 42 days. After the amendment, patients were randomised 2:1 to receive GSK2982772 60 mg or placebo three times daily for 42 days. In part B, all patients switched to open-label GSK2982772 60 mg three times daily for 42 days. Safety, PK, PD biomarkers, histological disease activity, clinical efficacy and quality of life were assessed at days 43 and 85.ResultsThirty-six patients were randomised (n=12, placebo/open-label GSK2982772; n=24, GSK2982772/open-label GSK2982772). Most adverse events were mild, with headache reported the most frequently across groups (placebo/open-label GSK2982772, n=2 (17%); GSK2982772/open-label GSK2982772, n=8 (33%)). GSK2982772 was well distributed into colonic tissue, with generally higher concentrations in colonic biopsy samples versus plasma. No apparent differences between treatment groups were observed for PD, histological disease activity, clinical disease activity or quality-of-life measures. At screening, all patients had Mayo endoscopic scores of 2 or 3. At day 43, no patients in the placebo/open-label GSK2982772 group achieved Mayo endoscopic scores of 0 or 1 vs 3/24 (13%) for GSK2982772/open-label GSK2982772. At day 85, 1/9 (11%) achieved scores of 0 or one for placebo/open-label GSK2982772 vs 3/22 (14%) for GSK2982772/open-label GSK2982772.ConclusionGSK2982772 was generally well tolerated, with no treatment-related safety concerns identified. However, no significant differences in efficacy were observed between treatment groups, suggesting that GSK2982772 as monotherapy is not a promising treatment for patients with active UC.Trial registration numberNCT02903966.

Download Full-text