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 disease,3 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,*

Challenges in IBD treatment

Professor Charlie Lees outlines the current challenges in IBD care

The challenge of controlling inflammation in UC

Indications of a poor prognosis, including relapse and colectomy, are:
  • 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
  • 51% risk of relapse within 1 year of diagnosis13
  • 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
  • Histologic healing may be a better predictor of time to relapse than macroscopic appearance12,17
  • Patients with histological normalisation are almost 7 times more likely to have relapse-free survival compared with those with histologically active disease18
  • Reduced histologic activity is associated with decreased risk of relapse, steroid use, colectomy, and hospitalisation18

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

* 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

Normal mucosa without features of chronicity.

Effective and early intervention is critical to limiting the 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 to have 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

While 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 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.7

Better control of inflammation helps reduce colorectal cancer risk.8

Optimal therapy can help patients achieve and maintain steroid-free remission

Achieving steroid-free remission is key to improving patient quality of life (QoL) and avoiding the complications of prolonged steroid use.15 Steroid-free remission is an established therapeutic target,22 and clinical guidelines recommend rapid introduction of effective therapies to improve patient outcomes.22–24

Corticosteroid use is associated with both short- and long-term toxicities, including mood disturbances, moon face/Cushingoid appearance, cataracts and insomnia, all of which can be distressing for patients.22,24,25

Steroids are not an appropriate option for the long-term maintenance of remission,3 and patients receiving oral steroid treatment are at increased risk of colectomy if they experience a moderate flare.22

Introducing highly effective treatments in
appropriate patients early in the disease
course is crucial for achieving deep remission
and avoiding disease complications.1

Achieving deep histological remission predicts a reduced need for steroids in patients with UC

Achieving rapid disease control is key, as requiring multiple courses of steroids early in the disease course is associated with poor outcomes, including colectomy.10

Adapted with permission from Bryant et al.26 Histology was scored using the Trulove and Richards’ index. Histological remission is defined as “no significant inflammation” and architectural changes in the absence of erosions, crypt abcesses, and neutrophilic infiltration. Endoscopic disease activity was measured using the Baron index.26

* Complete remission refers to both histological and endoscopic remission.

Histological remission and “complete” histological remission were virtually indistinguishable and are depicted by a single line.

Achieving rapid control of disease activity can improve QoL

UC is associated with a significant 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 actually 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.18,27

In addition to lower QoL, patients with UC may have diminished psychological functioning and wellbeing with poorer psychosocial outcomes during periods of active disease.28

Control of disease activity is an important determinant of QoL outcomes.28

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

Steroids and immunomodulator therapies are not associated with long-term improvements in
health-related QoL29

Despite this, there is evidence of prolonged corticosteroid use in patients with UC.22 Various analyses have shown:

Up to 24% of patients with UC received steroids for >3 months in a 12-month period.22

12% of patients with UC were treated with steroids for ≥6 months.22

15% of patients with IBD demonstrated steroid dependency or excess use of steroids.24,*

43% of patients with moderate-to-severe UC demonstrated steroid dependency or excess use of steroids.24,*

Evidence suggests that long-term, sustained improvements in health-related QoL may be achieved with more advanced therapies.29

Studies highlight the importance of optimising therapy to establish remission in patients with UC to alleviate the psychosocial stress of the disease.30

Recognition of high-risk disease features in UC and concordant therapeutic strategies are key to improving patient outcomes.10

Primary non-response to advanced therapies is ~30%, and loss of response after initially responding is ~50%.31

Achieving and sustaining remission remains a challenge and is achieved by fewer than one-third of treated patients.32

There is an unmet need for efficacious and well-tolerated therapies using novel mechanisms that can achieve early and sustained remission.15,32

* Steroid dependency and excess use defined in accordance with European Crohn’s and Colitis Organisation (ECCO) and UK guidelines.23


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