Introduction
Bowel urgency is one of the symptoms that patients with Crohn’s disease (CD) frequently experience and consider most important to control. Bowel urgency often has a substantial negative impact on quality of life. The Urgency Numeric Rating Scale (NRS) is a single-item patient-reported outcome assessing severity of bowel urgency in the previous 24 hours on an 11-point scale (0–10), with higher scores indicating more severe bowel urgency. The Urgency NRS was initially developed to assess the urgency to have a bowel movement in ulcerative colitis due to lack of appropriate existing instruments.
Aims & Methods
This work aimed to evaluate the psychometric properties of the Urgency NRS in CD and to estimate thresholds for meaningful change and remission for bowel urgency. Pooled data from VIVID-1 (NCT03926130), a Phase 3, multicentre, randomised, placebo- and active-controlled study of mirikizumab in adults with moderately to severely active CD were analyzed. The measurement properties (reliability, validity, and responsiveness) of the Urgency NRS were evaluated using weekly average scores at Weeks 0 (Baseline), 4, 12, and 52, which were calculated by averaging the most recent 7 days in the 12 days prior to the visit. These analyses used other measures administered in VIVID-1, including the Patient Global Rating of Severity (PGRS), Patient Global Impression of Change (PGIC), Inflammatory Bowel Disease Questionnaire (IBDQ), and Crohn’s Disease Activity Index (CDAI). PGRS and PGIC were used as primary anchors to establish the Urgency NRS score thresholds for meaningful change and remission of bowel urgency. Data from VIVID-1 treatment arms were pooled for these analyses.
Results
The analysis population comprised 1065 adults (mean age 36.2 years [standard deviation: 13.0]; 55% male, 71% White). The Urgency NRS weekly average score decreased during the trial (from 6.6 at Baseline to 2.9 at Week 52), indicating a reduction in bowel urgency severity. Test-retest reliability was good for patients who were stable between Baseline and Week 4 based on the PGRS (intraclass correlation coefficient [ICC] 0.86) and the PGIC (ICC 0.78). At Weeks 12 and 52, the Urgency NRS showed moderate correlations (0.30≤ r <0.70) with the PGRS, IBDQ Bowel Symptom domain, IBDQ total score, and CDAI score; as expected, correlations with clinical and laboratory assessments were weak (r <0.30), demonstrating discriminant validity. The Urgency NRS could differentiate between groups of participants known to be distinct based on PGRS and IBDQ Bowel Symptom domain scores. Improvement in the Urgency NRS average score from Baseline to Weeks 12 and 52 was statistically significantly different between most PGRS change groups and PGIC groups, as well as groups based on IBDQ Bowel Symptom domain, IBDQ response and remission, and clinical response/remission by CDAI, indicating that the Urgency NRS was able to detect change. Anchor-based analysis indicated that clinically meaningful improvement could be represented by a 3–5-point reduction in the Urgency NRS score and that an Urgency NRS score of ≤2 could represent bowel urgency remission.
Conclusion
These results support the reliability, validity, responsiveness of the Urgency NRS and provide definitions of clinically meaningful improvement (reduction of 3–5 points in the Urgency NRS score) and remission of bowel urgency (Urgency NRS score of ≤2) in adults with moderately to severely active CD. These findings confirm the Urgency NRS as suitable for assessing treatment benefits in patients with CD during clinical trials.
Disclosure
MD reports being a consultant for AbbVie, Arena, BMS, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Gilead, Janssen, Merck, Pfizer, Prometheus Laboratories, Takeda, and UCB; and received research grants from Janssen, AbbVie, and Prometheus Laboratories. AV, SS, and FD are employees and shareholders of Eli Lilly and Company. XZ is an employee of Syneos Health, which received funding from Eli Lilly and Company in connection with this study. CC, LS, and AK are employees of Evidera, which received funding from Eli Lilly and Company in connection with this study. ST has received grants from AbbVie, BUHLMANN Diagnostics, ECCO, Eli Lilly and Company, Ferring Pharmaceuticals, International Organization for the Study of Inflammatory Bowel Disease, Janssen, Merck Sharp & Dohme, Norman Collison Foundation, Pfizer, Procter & Gamble, Schering-Plough, Takeda, UCB Pharma, Vifor Pharma, and Warner Chilcott; and reports other disclosures from Abacus Pharma, AbbVie, Actial Farmaceutica, ai4gi, Alcimed, Allergan, Amgen, Aptel, Arena Pharmaceuticals, Asahi Kasei Pharma, Aspen Pharmacare, Astellas, AstraZeneca, Atlantic Pharmaceuticals, Barco, Biocare Medical, Biogen, BL Pharma, Boehringer Ingelheim, Bristol Myers Squibb, BUHLMANN Diagnostics, Calcico Therapeutics, Celgene, Cellerix, Cerimon Pharmaceuticals, ChemoCentryx, Chiesi, Cisbio, Comcast, Coronado Biosciences, Cosmo Pharmaceuticals, Dr. Falk Pharma, Ducentis BioTherapeutics, Dynavax Technologies, Elan Pharma, Eli Lilly and Company, Enterome, Equillium, Ferring Pharmaceuticals, Galapagos NV, Genentech/Roche, Genzyme, Gilead Sciences, GlaxoSmithKline, Glenmark Pharmaceuticals, Grünenthal, GW Pharmaceuticals, Immunocore, Indigo Biosciences, Janssen, Lexicon Pharmaceuticals, Medarex, MedTrix, Merck, Merrimack Pharmaceuticals, Mestag Therapeutics, Millennium Pharmaceuticals, Neovacs, Novartis, Novo Nordisk, NPS Pharmaceuticals/Nycomed, Ocera Therapeutics, OPTIMA Pharma, Origin Pharma, Otsuka, Palau Pharma, Pentax Medical, Pfizer, PharmaVentures, Phesi, Phillips Pharma Group, Procter & Gamble, Pronota, Proximagen, Resolute Pharma, Robarts Clinical Trials, Sandoz, Santarus, Satisfai Health, Sensyne Health, Shire, Sigmoid Pharma, Sorriso Pharmaceuticals, Souffinez, SynDermix, Synthon, Takeda, Theravance Biopharma, TiGenix, Tillotts Pharma AG, Topivert, Trino Therapeutics with Wellcome Trust, TxCell SA, UCB Pharma, Vertex Pharma, VHsquared, Vifor Pharma, Warner Chilcott, and Zeria Pharmaceutical.