A Future Beyond Long-Term Corticosteroid Use in Ulcerative Colitis

The European Crohn’s and Colitis Organisation’s (ECCO) annual meeting is a premier event for professionals involved in research and caring of patients with inflammatory bowel disease (IBD). With the ECCO meeting kicking off today, I wanted to take the opportunity to share how #MyCompany is moving beyond traditional therapies to redefine immune treatment and investigate novel pathways in ulcerative colitis (UC) – strategies which are bringing us closer to our goal of full remission for patients. 

IBDs such as Crohn’s disease (CD) and UC affect more than five million people worldwide. (1) Both diseases can begin at any age, but most patients are young and experience symptoms before the age of 30. These chronic, life-long, immune-mediated conditions cause symptoms that can include loose and urgent bowel movements, persistent diarrhea, abdominal pain, bloody stool, loss of appetite, weight loss, and fatigue. (2) In patients with UC, these symptoms are caused by inflammation and ulcers along the lining of the large intestine and rectum that produce pus and mucus due to a dysregulated immune response. (3) These symptoms, with an unpredictable and recurrent course, can have a devastating impact on patients’ lives – including physical, psychological, sexual and social aspects.

While corticosteroids can be very effective in managing the symptoms of UC in the short-term, they do not provide long-lasting remission or prevent flares of the disease. (1) In addition, the risks of side effects limit their use as a long-term treatment option. People living with UC urgently need better and more sophisticated medicines that reduce the impact of the disease and allow them to achieve remission.

How are corticosteroids currently used in the treatment of UC?

With UC, the goals of treatment are to quickly relieve symptoms and better regulate the immune system to help patients achieve and sustain long-term remission. A range of behavior modifications such as adjustments to diet and nutrition, combined with quick-acting medications such as immunosuppressants and corticosteroids may be applied. (4) In about 30% of patients, surgical removal of the damaged portions of the intestinal tract may be required. (5)

While not part of the primary medication regimen used to treat UC, corticosteroids are frequently prescribed to treat acute flares, as they are fast acting with broad anti-inflammatory activity. However, they are not effective in preventing the progression of disease, and their long-term use is associated with debilitating side effects such as elevated blood sugar levels, sleep disturbances, weight gain, and changed in mood (6). In addition, corticosteroids leave individuals more susceptible to infections, including serious and rare ones. (6) The risk and severity of these side effects is directly related to increased dose and duration of corticosteroid treatment. (7)

There is clear evidence that the long-term use of corticosteroids is not conducive to long-term remission in UC patients. Within the first five years of their diagnosis, one in eight individuals living with UC will demonstrate an inability to withdraw their use without return of symptoms, resulting in corticosteroid dependence. (6) In addition, misuse of corticosteroids is an important limitation of current UC therapy. One study found that 91% of dependency or excess use of corticosteroids prescribed in primary care was likely avoidable. (6) Specific groups of patients, especially elderly people with IBD – the very group in whom chronic use should be minimized or avoided – appear to be at an increased risk of corticosteroid dependency. (6) Because of these risks, the decision to initiate treatment with corticosteroids should always be made carefully and alternate suitable options should be considered where possible.

What does the future of UC treatment look like?

The future of UC treatment should focus on eliminating repeated or chronic dosing with corticosteroids by using effective and targeted medications, so that patients living with the disease are not compounding their burden with the substantial challenges of side effects and dependency. Chronic conditions like UC require therapies that target the underlying pathways that are dysregulated and remain safe and effective over the long term – not just those that offer quick and symptomatic relief.

Our Immunology teams at Janssen are working to develop effective medications that offer the potential to achieve long lasting symptomatic remission, and that may also potentially eliminate prolonged treatment with corticosteroids. In this process, we are continuing to investigate the origins of IBDs, which are linked to damage of the intestinal epithelial barrier, to inform the development of more precise therapies. We are also extending our research to explore how immune system balance can be restored in a damaged gut, either by building or protecting a healthy epithelial barrier defense or by promoting a healthy microbiome. (8)

Every UC and CD patient should be able to live a very productive life with minimal impact from disease or worries about medication side effects. I am incredibly excited to be part of the Janssen team that aspires to build this exciting future with novel research to improve the standard of care for UC patients who need it.

#ECCO2021 #UlcerativeColitis #Immunology #jnj #janssen

Since we’re on LinkedIn, I invite you to explore our career opportunities in immunology at Janssen: https://bit.ly/2WKDJLd 

References:

1.      The Facts About Inflammatory Bowel Diseases. Crohn's & Colitis Foundation of America. Retrieved June 2021. https://www.crohnscolitisfoundation.org/sites/default/files/2019-02/Updated%20IBD%20Factbook.pdf

2.      Signs and Symptoms of Ulcerative Colitis. Crohn’s & Colitis Foundation. Retrieved June 2021. https://www.crohnscolitisfoundation.org/what-is-ulcerative-colitis/symptoms

3.      What is Ulcerative Colitis? Crohn’s & Colitis Foundation. Retrieved June 2021. https://www.crohnscolitisfoundation.org/what-is-ulcerative-colitis

4.      Ulcerative Colitis Treatment Options. Crohn’s & Colitis Foundation. Retrieved June 2021.  https://www.crohnscolitisfoundation.org/what-is-ulcerative-colitis/treatment-options

5.      Hefti, M., et al. Severity of inflammation as a predictor of colectomy in patients with chronic ulcerative colitis. Dis Colon Rectum. 2009;52(2):193-197. doi:10.1007/DCR.0b013e31819ad456

6.      Blackwell, J., Selinger, C., Raine, T., Parkes, G., Smith, M. A., & Pollok, R. (2020). Steroid use and misuse: a key performance indicator in the management of IBD. Frontline Gastroenterology, 12(3), 207–213. https://doi.org/10.1136/flgastro-2019-101288

7.      Fact Sheet: Corticosteroids. Crohn’s & Colitis Foundation. Retrieved June 2021.  https://www.crohnscolitisfoundation.org/sites/default/files/legacy/corticosteroids.pdf

8.      Brown, Jessica. Have IBD? Read About the Next Frontier in Disease Research That Taps Into the Microbiome. Johnson & Johnson, December 2, 2019. Accessed June 2021. https://www.jnj.com/innovation/next-frontier-ibd-research-gut-microbiome-treatments