Introduction
Bowel urgency is increasingly recognized as a common and impactful symptom in patients with Ulcerative Colitis (UC)1. However, there are limited data exploring the relationship of bowel urgency with work productivity. We examined the relative association of bowel urgency clinically meaningful improvement (CMI) and bowel urgency remission with Work Productivity and Activity Impairment (WPAI) scores in the presence of rectal bleeding (RB) remission and stool frequency (SF) remission as potential confounding variables using data from LUCENT-1 (NCT03518086) and LUCENT-2 (NCT03524092) phase 3 trials.
Aims & Methods
Bowel urgency severity was assessed using the Urgency Numeric Rating Scale (UNRS; 0=no urgency to 10=worst possible urgency). Bowel urgency CMI is a ≥3-point decrease and bowel urgency remission is a UNRS score of 0 or 12. WPAI scores (absenteeism, presenteeism, and work productivity loss in employed patients, and activity impairment in all patients) were measured using a 6-item questionnaire; higher scores indicate greater impairment and less productivity. Mediation analyses were performed to separately examine the relative association between the direct effect of bowel urgency CMI and bowel urgency remission (predictor) and WPAI scores while adjusting for the potential confounding effects of RB remission and SF remission (mediator). Analyses were treatment agnostic and combined patients from mirikizumab and placebo groups from LUCENT-1 (N=1162) and LUCENT-2 (N=544) trials.
Results
At week (W)12 and W52, the direct effect of bowel urgency remission accounted for 43%–49% and 27%–57% of the improvement in all WPAI domain scores except absenteeism, respectively. The association values greater than 100% at W12 and W52 (153% and 148%, respectively) reflect the critical importance of SF remission in the improvement of absenteeism score. Bowel urgency CMI resulted in the largest proportion of improvement in WPAI domain scores (except absenteeism) at W12 (71%–74%) and W52 (66%–78%). Bowel urgency CMI accounted for 68% and 239% of the improvement in absenteeism scores at W12 and W52, respectively. At W52, 750% of the effect was mediated by RB remission.
Conclusion
Improvement in work productivity and regular activities were primarily ascribed to bowel urgency remission or bowel urgency CMI relative to RB remission and SF remission in patients with moderately-to-severely active UC. These findings suggest that bowel urgency is a critical and independent symptom that considerably impacts patients’ productivity.
References
- Dubinsky MC, et al. Crohn's & Colitis 360. Volume 4, Issue 3, July 2022;7(4):3.
- Dubinsky MC, et al. J Patient Rep Outcomes. 2022;6(1):114.
Disclosure
Bruce Sands: Consulting: Amgen, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Boehringer-Ingelheim, Boston Pharmaceuticals, Calibr, Celltrion Healthcare, ClostraBio, Entera, Evommune, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Inotrem, Innovation Therapeutics, Ironwood Pharmaceuticals, Kaleido, Kallyope, Lilly, Miro Bio, Morphic Therapeutics, MRM Health, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Q32 Bio, Surrozen, Teva, TLL Pharmaceutical, USWM Enterprises, VielaBio; consulting, speaking, research funding: Bristol Myers Squibb; consulting, speaking, grant/research support: Janssen; consulting, speaking: Abivax, Pfizer, Takeda
Brian Feagan: Consulting: AbbVie, AbolerIS, AgomAB Therapeutics, Allianthera, Amgen, AnaptysBio, Applied Molecular Transport Inc., Arena Pharma, Avir, Azora Therapeutics, BioJamp, Biora Therapeutics, Boehringer-Ingelheim, Boston Pharma, Boxer, Celgene/BMS, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1, Everest Clinical Research Corp., Lilly, Equillium, Ermium, Ferring, First Wave, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Glenmark, Gossamer Pharma, GSK, Hoffmann-LaRoche, Hot Spot Therapeutics, Index Pharma, Imhotex, ImmunExt, Immunic Therapeutics, Intact Therapeutics, JAKAcademy, Janssen, Japan Tobacco Inc., Kaleido Biosciences, Landos Biopharma, Leadiant, L.E.K. Consulting, LifeSci Capital, Lument AB, Millennium, MiroBio, Morphic Therapeutics, Mylan, OM Pharma, Origo BioPharma, Orphagen, Otsuka, Pandion Therapeutics, Pfizer, Prometheus Therapeutics and Diagnostics, Play to Know AG, Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, RedHill, Biopharma, REDX, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen Inc., Takeda, Teva, Thelium, Theravance, Tigenix, Tillotts, UCB Pharma, VHSquared Ltd., Viatris, Ysios, Ysopia, Zealand Pharma; speakers bureau: AbbVie, Janssen, Takeda. Scientific advisory board member: AbbVie, Amgen, Boehringer-Ingelheim, Celgene/BMS Genentech/Roche, Janssen, Novartis, Origo BioPharma, Pfizer, Prometheus, Takeda,Tillotts Pharma, Teva, Progenity, Index, Ecor1Capital, Morphic, GSK; stock shareholder: Gossamer Pharma.
Employment: Western University, Alimentiv Inc.
Stefan Schreiber: Consulting and personal fees: AbbVie, Arena, BMS, Biogen, Celltrion, Celgene, Falk, Ferring, Fresenius, Galapagos/Gilead, HIKMA, IMAB, Janssen, Lilly, MSD, Mylan, Pfizer, Protagonist, Provention Bio, Takeda, and Theravance.
Vipul Jairath: Consulting/advisory board fees: AbbVie, Alimentiv Inc., Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, BMS, Celltrion, Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Sandoz, Second Genome, Sorriso pharmaceuticals, Takeda, Teva, Topivert, Ventyx, Vividion. Speaker’s fees: Abbvie, Ferring, BMS, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi.
Alessandro Armuzzi: Consulting/advisory board fees: AbbVie, Allergan, Amgen, Arena, Biogen, Boehringer-Ingelheim, BMS, Celgene, Celltrion, Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda.
Speaker’s fees: AbbVie, Amgen, Arena, Biogen, BMS, Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Tigenix.
Research grants: MSD, Takeda, Pfizer, Biogen.
Theresa Hunter Gibble: Employment and stockholder: Eli Lilly and Company
Anthony Keohane: Employment and stockholder: Eli Lilly and Company
William J Eastman: Employment and stockholder: Eli Lilly and Company
Kristina A Traxler: Employment and stockholder: Eli Lilly and Company