Inflammatory bowel disease: long-term therapeutic challenges

ABSTRACT

Introduction: Long-term, sustained, remission is the ultimate goal of contemporary inflammatory bowel disease (IBD) therapy. Avoiding complications, surgery and malignancy, alongside minimizing the side effects of medications are vital. However, the reality of treatment involves patients losing response to therapy, or developing complications requiring cessation of medication. The reasons underlying this are numerous and include medication and host-related influences. Underpinning the response to medication, long-term outcomes and loss of response are individual etiological factors including the molecular cause of disease and individual pharmacogenomic influences.

Areas covered: In this review, we discuss the long-term outcome of IBD, with a focus on pediatric-onset illness and discuss the factors leading to loss of treatment response whilst briefly considering the future of personalized therapy as a strategy to improve long-term outcomes.

Expert opinion: Research findings are now moving toward clinical translation, including application of novel medications targeting new pathways. The integration of biological and multiomic data to predict disease outcome will provide personalized therapeutic management.

KEYWORDS:

• IBD
• Crohn’s disease
• ulcerative colitis
• personalized therapy
• outcome

Article highlights

• The long-term outcomes of IBD are extremely varied. Some patients will have quiescent disease, whereas some will have a severe course with multiple relapses.

• A significant number of patients will develop complications (such as strictures or fistulae) and require intestinal resections for disease refractory to medical management.

• Many patients will be primary non-responders to therapy, lose response to medication within a year of starting or find efficacy gradually reducing overtime.

• Whilst some patients may relapse or worsen whilst on a therapy, increasing dose, reducing dosing interval or commencement of concurrent therapy can rescue response in selected cases.

• Active patient monitoring, including drug levels, antibodies and regular assessment of disease activity (faecal calprotectin, endoscopy) are vital to promote disease monitoring to assess long-term response to treatment.

• The reasons underlying loss of response include medication side-effects, long-term sequelae of therapy such as malignancy or bone marrow suppression, and patient tolerance.

• Host-factors influencing loss of response relate to the molecular causes underpinning chronic inflammation, fluctuating activation of different immune pathways, microbial influences and the modifying effects of medicines.

• Pharmacogenomics will become increasingly important to prevent side effects and toxicity, and to promote medication-stewardship to ensure long-term remission.

• We are moving into an era of precision therapy where prediction of outcome and response to medication will shape personalised outcomes, improving long-term treatment response.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by Action Medical Research: Personal Fellowship to J.J. Ashton.