Impact of Upadacitinib Induction and Maintenance Therapy on Health-related Quality of Life, Fatigue, and Work Productivity in Patients with Moderately-to-severely Active Crohn's Disease.
Ghosh, Subrata; Feagan, Brian G; Parra, Rogério Serafimet al.
2024 • In Journal of Crohn's and Colitis, 18 (11), p. 1804-1818
[en] BACKGROUND AND AIMS: Quality of life in patients with active Crohn's disease may be significantly reduced. We evaluated the effects of upadacitinib induction and maintenance therapy on fatigue, quality of life, and work productivity in the phase 3 trials U-EXCEL, U-EXCEED, and U-ENDURE. METHODS: Clinical responders to upadacitinib 45 mg in U-EXCEL and U-EXCEED induction trials were re-randomised 1:1:1 to upadacitinib 30 mg, 15 mg, or placebo for 52 weeks of maintenance in U-ENDURE. Clinically meaningful improvements in Inflammatory Bowel Disease Questionnaire [IBDQ] response, IBDQ remission, Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue], and Work Productivity and Activity Impairment were evaluated. Percentages of patients achieving clinically meaningful improvements were assessed at induction Weeks 4 and 12 and maintenance Week 52. CLINICAL REGISTRATION NUMBER: U-EXCEED induction trial [NCT03345836], U-EXCEL induction trial [NCT03345849], U-ENDURE maintenance trial [NCT03345823]. RESULTS: Analysis included 1021 and 502 patients assessed at induction and maintenance, respectively. In U-EXCEL, greater improvements [all p ≤ 0.001] in IBDQ response [71.0% vs 50.2%], IBDQ remission [44.2% vs 23.7%], and FACIT-Fatigue [42.0% vs 27.0%] were observed in upadacitinib-treated patients versus placebo at Week 4. Improvements in IBDQ response, IBDQ remission, and FACIT-Fatigue were similar or greater at Week 12. Clinically meaningful improvement in overall work impairment [52.1% vs 38.1%, p ≤ 0.05] was demonstrated at Week 12. Similar results were observed in U-EXCEED. Improvements were sustained through 52 weeks of upadacitinib maintenance treatment. CONCLUSIONS: In patients with active Crohn's disease, upadacitinib treatment relative to placebo significantly improved fatigue, quality of life, and work productivity as early as Week 4. These effects were sustained through 52 weeks of maintenance.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Ghosh, Subrata; College of Medicine and Health and APC Microbiome Ireland, University College Cork, Cork, Ireland.
Feagan, Brian G; Robarts Research Institute, Western University, London, ON, Canada. ; Alimentiv Inc., London, ON, Canada.
Parra, Rogério Serafim ; Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
Lopes, Susana; Centro Hospitalar e Universitário São João, Porto, Portugal.
Steinlauf, Adam; IBD Clinical Center, Mount Sinai Hospital, New York, NY, USA.
Kakuta, Yoichi ; Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Joshi, Namita; Health Economics & Outcomes Research, AbbVie Inc., North Chicago, IL, USA.
Lee, Wan-Ju; Health Economics & Outcomes Research, AbbVie Inc., North Chicago, IL, USA.
Lacerda, Ana P; Health Economics & Outcomes Research, AbbVie Inc., North Chicago, IL, USA.
Zhou, Qian; Health Economics & Outcomes Research, AbbVie Inc., North Chicago, IL, USA.
Xuan, Si; Health Economics & Outcomes Research, AbbVie Inc., North Chicago, IL, USA.
Kligys, Kristina; Health Economics & Outcomes Research, AbbVie Inc., North Chicago, IL, USA.
Shukla, Nidhi; Health Economics & Outcomes Research, AbbVie Inc., North Chicago, IL, USA.
Louis, Edouard ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Impact of Upadacitinib Induction and Maintenance Therapy on Health-related Quality of Life, Fatigue, and Work Productivity in Patients with Moderately-to-severely Active Crohn's Disease.
Petagna L, Antonelli A, Ganini C, et al. Pathophysiology of Crohn's disease inflammation and recurrence. Biol Direct 2020;15:23.
Turner D, Ricciuto A, Lewis A, et al.; International Organization for the Study of IBD. STRIDE-II: an update on the selecting therapeutic targets in inflammatory bowel disease [STRIDE] initiative of the International Organization for the Study of IBD [IOIBD]: Determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology 2021;160:1570-83.
Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE. ACG clinical guideline: management of Crohn's disease in adults. Am J Gastroenterol 2018;113:481-517.
Gomollon F, Dignass A, Annese V, et al.; ECCO. Third European evidence-based consensus on the diagnosis and management of Crohn's disease 2016. Part 1: diagnosis and medical management. J Crohns Colitis 2017;11:3-25.
Ben-Horin S, Chowers Y. Review article: loss of response to anti-TNF treatments in Crohn's disease. Aliment Pharmacol Ther 2011;33:987-95.
Billioud V, Sandborn WJ, Peyrin-Biroulet L. Loss of response and need for adalimumab dose intensification in Crohn's disease: a systematic review. Am J Gastroenterol 2011;106:674-84.
Peyrin-Biroulet L, Danese S, Argollo M, et al. Loss of response to vedolizumab and ability of dose intensification to restore response in patients with Crohn's disease or ulcerative colitis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2019;17:838-46.e2.
Larsson K, Loof L, Ronnblom A, Nordin K. Quality of life for patients with exacerbation in inflammatory bowel disease and how they cope with disease activity. J Psychosom Res 2008;64:139-48.
Williet N, Sarter H, Gower-Rousseau C, et al. Patient-reported outcomes in a French Nationwide Survey of Inflammatory Bowel Disease Patients. J Crohns Colitis 2017;11:165-74.
Bernstein CN, Hitchon CA, Walld R, et al. Increased burden of psychiatric disorders in inflammatory bowel disease. Inflamm Bowel Dis 2019;25:360-8.
Chan W, Shim HH, Lim MS, et al. Symptoms of anxiety and depression are independently associated with inflammatory bowel disease-related disability. Dig Liver Dis 2017;49:1314-9.
Feagan BG, Reilly MC, Gerlier L, Brabant Y, Brown M, Schreiber S. Clinical trial: the effects of certolizumab pegol therapy on work productivity in patients with moderate-to-severe Crohn's disease in the PRECiSE 2 study. Aliment Pharmacol Ther 2010;31:1276-85.
Kappelman MD, Long MD, Martin C, et al. Evaluation of the patient-reported outcomes measurement information system in a large cohort of patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2014;12:1315-23.e2.
Knowles SR, Graff LA, Wilding H, Hewitt C, Keefer L, Mikocka-Walus A. Quality of life in inflammatory bowel disease: a systematic review and meta-analyses-part I. Inflamm Bowel Dis 2018;24:742-51.
Lonnfors S, Vermeire S, Greco M, Hommes D, Bell C, Avedano L. IBD and health-related quality of life: discovering the true impact. J Crohns Colitis 2014;8:1281-6.
Ding Z, Muser E, Izanec J, Lukanova R, Kershaw J, Roughley A. Work-related productivity loss and associated indirect costs in patients with Crohn's disease or Ulcerative Colitis in the United States. Crohns Colitis 360 2022;4:otac023.
Farrell D, McCarthy G, Savage E. Self-reported symptom burden in individuals with inflammatory bowel disease. J Crohns Colitis 2016;10:315-22.
Vogelaar L, van't Spijker A, van Tilburg AJ, Kuipers EJ, Timman R, van der Woude CJ. Determinants of fatigue in Crohn's disease patients. Eur J Gastroenterol Hepatol 2013;25:246-51.
Borren NZ, van der Woude CJ, Ananthakrishnan AN. Fatigue in IBD: epidemiology, pathophysiology and management. Nat Rev Gastroenterol Hepatol 2019;16:247-59.
van Gennep S, Gielen ME, Rietdijk ST, et al. Work productivity loss is determined by fatigue and reduced quality of life in employed inflammatory bowel disease patients: a prospective multicentre cohort study. Eur J Gastroenterol Hepatol 2021;33:e594-602.
Regueiro M, Hunter T, Lukanova R, et al. Burden of fatigue among patients with ulcerative colitis and Crohn's disease: results from a global survey of patients and gastroenterologists. Adv Ther 2023;40:474-88.
Romberg-Camps MJ, Bol Y, Dagnelie PC, et al. Fatigue and health-related quality of life in inflammatory bowel disease: results from a population-based study in the Netherlands: the IBD-South Limburg cohort. Inflamm Bowel Dis 2010;16:2137-47.
Varma A, Weinstein J, Seabury J, et al. Patient-reported impact of symptoms in Crohn's disease. Am J Gastroenterol 2022;117:2033-45.
Louis E, Siegel CA, James B, Heidenreich S, Krucien N, Ghosh S. Patients with inflammatory bowel disease have heterogeneous treatment preferences that are largely determined by the avoidance of abdominal pain and side effects [P-POWER IBD Study]. J Crohns Colitis 2023;17:231-9.
Loftus EV Jr, Panes J, Lacerda AP, et al. Upadacitinib induction and maintenance therapy for Crohn's disease. N Engl J Med 2023;388:1966-80.
Irvine EJ, Feagan B, Rochon J, et al. Quality of life: a valid and reliable measure of therapeutic efficacy in the treatment of inflammatory bowel disease. Canadian Crohn's Relapse Prevention Trial Study Group. Gastroenterology 1994;106:287-96.
Irvine EJ. Development and subsequent refinement of the inflammatory bowel disease questionnaire: a quality-of-life instrument for adult patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1999;28:S23-7.
Williet N, Sandborn WJ, Peyrin-Biroulet L. Patient-reported outcomes as primary end points in clinical trials of inflammatory bowel disease. Clin Gastroenterol Hepatol 2014;12:1246-56.e6.
Tinsley A, Macklin EA, Korzenik JR, Sands BE. Validation of the functional assessment of chronic illness therapy-fatigue [FACIT-F] in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2011;34:1328-36.
Chandran V, Bhella S, Schentag C, Gladman DD. Functional assessment of chronic illness therapy-fatigue scale is valid in patients with psoriatic arthritis. Ann Rheum Dis 2007;66:936-9.
Loftus EV Jr, Ananthakrishnan AN, Lee WJ, et al. Content validity and psychometric evaluation of the functional assessment of chronic illness therapy-fatigue [FACIT-Fatigue] in patients with Crohn's disease and ulcerative colitis. PharmacoEcon Open 2023;7:823-40.
Ware JE Jr. SF-36 health survey update. Spine [Phila Pa 1976] 2000;25:3130-9.
Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey [SF-36]. I. Conceptual framework and item selection. Med Care 1992;30:473-83.
Maruish ME. User's Manual for the SF-36v2 Health Survey. Johnston, RI: QualityMetric; 2011.
Coteur G, Feagan B, Keininger DL, Kosinski M. Evaluation of the meaningfulness of health-related quality of life improvements as assessed by the SF-36 and the EQ-5D VAS in patients with active Crohn's disease. Aliment Pharmacol Ther 2009;29:1032-41.
Rabin R, de Charro F. EQ-5D: a measure of health status from the EuroQol Group. Ann Med 2001;33:337-43.
Janssen MF, Pickard AS, Golicki D, et al. Measurement properties of the EQ-5D-5L compared to the EQ-5D-3L across eight patient groups: a multi-country study. Qual Life Res 2013;22:1717-27.
Peyrin-Biroulet L, Ghosh S, Lee SD, et al. Effect of risankizumab on health-related quality of life in patients with Crohn's disease: results from phase 3 MOTIVATE, ADVANCE and FORTIFY clinical trials. Aliment Pharmacol Ther 2023;57:496-508.
Reilly MC, Gerlier L, Brabant Y, Brown M. Validity, reliability, and responsiveness of the work productivity and activity impairment questionnaire in Crohn's disease. Clin Ther 2008;30:393-404.
Sandborn WJ, Reilly MC, Brown MCJ, Brabant Y, Gerlier L. Minimally important difference for WPAI-CD scores: defining relevant impact on work productiviity in active Crohn's disease. Am J Gastroenterol 2007;102:S472.
Gregor JC, McDonald JW, Klar N, et al. An evaluation of utility measurement in Crohn's disease. Inflamm Bowel Dis 1997;3:265-76.
Salaffi F, De Angelis R, Stancati A, Grassi W, Pain MA. Prevalence IGs. Health-related quality of life in multiple musculoskeletal conditions: a cross-sectional population based epidemiological study. II. The MAPPING study. Clin Exp Rheumatol 2005;23:829-39.
Salaffi F, Sarzi-Puttini P, Girolimetti R, Atzeni F, Gasparini S, Grassi W. Health-related quality of life in fibromyalgia patients: a comparison with rheumatoid arthritis patients and the general population using the SF-36 health survey. Clin Exp Rheumatol 2009;27:S67-74.
Montan I, Löwe B, Cella D, Mehnert A, Hinz A. General population norms for the functional assessment of chronic illness therapy [FACIT]-Fatigue scale. Value Health 2018;21:1313-21.
Jiang R, Janssen MFB, Pickard AS. US population norms for the EQ-5D-5L and comparison of norms from face-to-face and online samples. Qual Life Res 2021;30:803-16.
Baker KF, Isaacs JD. Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn's disease and ulcerative colitis? Ann Rheum Dis 2018;77:175-87.
Radi G, Simonetti O, Rizzetto G, Diotallevi F, Molinelli E, Offidani A. Baricitinib: the first JAK inhibitor approved in Europe for the treatment of moderate to severe atopic dermatitis in adult patients. Healthcare [Basel] 2021;9:1575.
Czuber-Dochan W, Norton C, Bassett P, et al. Development and psychometric testing of inflammatory bowel disease fatigue [IBD-F] patient self-assessment scale. J Crohns Colitis 2014;8:1398-406.
Czuber-Dochan W, Norton C, Bredin F, Darvell M, Nathan I, Terry H. Healthcare professionals' perceptions of fatigue experienced by people with IBD. J Crohns Colitis 2014;8:835-44.
Rochelle TL, Fidler H. The importance of illness perceptions, quality of life and psychological status in patients with ulcerative colitis and Crohn's disease. J Health Psychol 2013;18:972-83.
van Langenberg DR, Papandony MC, Gibson PR. Sleep and physical activity measured by accelerometry in Crohn's disease. Aliment Pharmacol Ther 2015;41:991-1004.
Knowles SR, Wilson J, Wilkinson A, et al. Psychological well-being and quality of life in Crohn's disease patients with an ostomy: a preliminary investigation. J Wound Ostomy Continence Nurs 2013;40:623-9.
Loftus EV Jr, Guerin A, Yu AP, Wu EQ, Yang M, Chao J, Mulani PM. Increased risks of developing anxiety and depression in young patients with Crohn's disease. Am J Gastroenterol 2011;106:1670-7.
Mahadev S, Young JM, Selby W, Solomon MJ. Self-reported depressive symptoms and suicidal feelings in perianal Crohn's disease. Colorectal Dis 2012;14:331-5.
Zhang M, Hong L, Zhang T, et al. Illness perceptions and stress: mediators between disease severity and psychological well-being and quality of life among patients with Crohn's disease. Patient Prefer Adherence 2016;10:2387-96.
Camara RJ, Lukas PS, Begre S, Pittet V, von Kanel R; Swiss Inflammatory Bowel Disease Cohort Study Group. Effects of social support on the clinical course of Crohn's disease. Inflamm Bowel Dis 2011;17:1277-86.
Yarlas A, Rubin DT, Panés J, et al. Burden of ulcerative colitis on functioning and well-being: A systematic literature review of the SF-36® health survey. J Crohns Colitis 2018;12:600-9.
