Exploring UC

Unmet Needs

Introduction

Controlling inflammation in UC-reducing the risk of relapse

Patients with UC experience a relapsing and remitting course of disease, with a 5-year risk of surgery of ~12% and the potential for irreversible structural damage and disability.1–3

Approximately 15% of patients have an initial presentation of severe disease3 and ~30% of patients demonstrate extensive disease at diagnosis.4

In the UK, many people with UC live with symptoms for years before being diagnosed.5,*

*Data are from a population-based case–control study using the Clinical Practice Research Datalink to compare 19,555 cases of IBD diagnosed between 1998 and 2016 with 78,114 matched controls.5

Indications of a poor prognosis, including relapse and colectomy, include:

• Younger age at diagnosis6

• Moderate-to-severe disease at diagnosis6

• Presentation of extensive disease at diagnosis6

• Evidence of deep ulceration on endoscopy3,6

• Long-standing disease7,8

• Persistent inflammation9

• Early requirement for steroids10,11

Patients with persistent inflammation and uncontrolled disease are at greater risk of relapse, increased steroid use, disease complications and surgery.9,11,12


The risk of relapse is significant in UC

• There is a 51% risk of relapse within 1 year of diagnosis13

• There is a 70–80% chance of relapse after 1 year in patients with clinically active disease14

• The frequent need for steroids to manage relapses and control inflammation is associated with poor outcomes10,11

During the early stages of UC, relapses are associated with accelerating disease.15

Patients with better mucosal healing experience fewer relapses16

  • Histological healing may be a better predictor of time to relapse than macroscopic appearance17
  • Patients with histological normalisation are almost seven times more likely to achieve relapse-free survival compared with those with histologically active disease18
  • Reduced histological activity is associated with decreased risk of relapse, steroid use, colectomy and hospitalisation18

Normal mucosa without features of chronicity.

Rapid, sustained and early control of inflammation has the potential to improve the disease course.2,15,19

Early intervention

Effective and early intervention is critical to limiting damage in UC
UC: a disease with structural and functional consequences19

  • Evidence supports the existence of transmural chronic inflammation and fibrotic changes that may affect colonic motility and anorectal function in UC20
  • Deep ulcerations are a risk factor for aggressive and complicated disease; these endoscopic findings are associated with poor outcomes3,6

Recognition of the damage and disability associated with inflammation in UC supports the concept of timely, effective management having an impact on the course of disease.1

Notably, patients who need treatment with steroids are more likely to have structural damage and anorectal dysfunction.19

The risk of colorectal cancer                                                                                                                                                                         

Although early intervention with effective therapies may have contributed to an overall decline in the incidence of colorectal cancer, the risk remains elevated in some patients with UC.11

Patients with UC at higher risk of dysplasia and colorectal cancer include those with:

  • Long-standing disease7,8
  • Persistent histological activity (chronic mucosal inflammation assessed macroscopically and microscopically independently contributes to cancer risk)11,21
  • Extensive colitis11

Colorectal cancer risk is driven by the extent, duration and severity of colonic inflammation.8

Better control of inflammation helps reduce colorectal cancer risk.8

QoL

Achieving rapid control of disease activity can improve QoL

UC is associated with a substantial impact on health-related QoL.15

Patients identify achieving rapid control of disease activity as an important aim for their therapy.15 Patients with severe UC prioritise rapid symptom resolution over long-term control.15

Rapidly resolving inflammation can have an early impact on patient-reported outcomes, reduce steroid use and restore patient QoL.18,22

In addition to lower QoL, patients with UC may have diminished psychological functioning and well-being, with poorer psychosocial outcomes during periods of active disease.23

Control of disease activity is an important determinant of QoL outcomes.23

Additional therapeutic options that provide rapid onset of clinical effect and reduce disease activity would be of value in moderate-to-severe UC.15

REFERENCES: 1. Gonczi L, Bessissow T and Lakatos PL. World J Gastroenterol 2019;25(41):6172–6189. 2. Torres J, Billioud V, Sachar DB, et al. Inflamm Bowel Dis 2012;18(7):1356–1363. 3. Ungaro R, Mehandru S, Allen PB, et al. Lancet 2017;389(10080):1756–1770. 4. Vegh Z, Burisch J, Pedersen N, et al. J Crohns Colitis 2015;9(9):747–753. 5. Blackwell J, Saxena S, Jayasooriya N, et al. J Crohns Colitis 2020:1–9. 6. Reinisch W, Reinink AR and Higgins PD. Clin Gastroenterol Hepatol 2015;13(4):635–642. 7. Choi CH, Rutter MD, Askari A, et al. Am J Gastroenterol 2015;110(7):1022–1034. 8. Beaugerie L and Itzkowitz SH. N Engl J Med 2015;372(15):1441–1452. 9. Colombel JF, Rutgeerts P, Reinisch W, et al. Gastroenterology 2011;141(4):1194–1201. 10. Mosli M, Alfaer S, Almalaki T, et al. Eur J Gastroenterol Hepatol 2019;31(1):80–85. 11. Torres J, Caprioli F, Katsanos KH, et al. J Crohns Colitis 2016;10(12):1385–1394. 12. Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Am J Gastroenterol 2015;110(9):1324–1338. 13. Wanderås MH, Moum BA, Høivik ML and Hovde Ø. World J Gastrointest Pharmacol Ther 2016;7(2):235–241. 14. Sairenji T, Collins KL and Evans DV. Prim Care 2017;44(4):673–692. 15. Danese S, Allez M, van Bodegraven AA, et al. Dig Dis 2019;37(4):266–283. 16. Barreiro-de Acosta M, Vallejo N, de la Iglesia D, et al. J Crohns Colitis 2016;10(1):13–19. 17. Peyrin-Biroulet L, Bressenot A and Kampman W. Clin Gastroenterol Hepatol 2014;12(6):929–34.e2. 18. Christensen B, Hanauer SB, Erlich J, et al. Clin Gastroenterol Hepatol 2017;15(10):1557–1564.e1. 19. Massinha P, Portela F, Campos S, et al. GE Port J Gastroenterol 2018;25(2):74–79. 20. Colombel JF, Shin A and Gibson PR. Clin Gastroenterol Hepatol 2019;17(3):380–390.e1. 21. Beaugerie L and Sokol H. World J Gastroenterol 2012;18(29):3806–3813. 22. Armuzzi A, Tarallo M, Lucas J, et al. BMC Gastroenterol 2020;20(1):18. 23. Lix LM, Graff LA, Walker JR, et al. Inflamm Bowel Dis 2008;14(11):1575–1584.

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