The potential for medical therapies to address fistulizing Crohn’s disease: a state-of-the-art review

ABSTRACT

Introduction

Crohn’s disease (CD) is a chronic, relapsing immune mediated disease, which is one of the two major types of inflammatory bowel disease (IBD). Fistulizing CD, pose a significant clinical challenge for physicians. Effective management of fistulizing CD requires a multidisciplinary approach, involving a gastroenterologist and a G.I surgeon, while tailoring treatment to each patient’s unique risk factors, clinical representations, and preferences.

Areas covered

This comprehensive review explores the intricacies of fistulizing CD including its manifestations, types, impact on quality of life, management strategies and novel therapies under investigation.

Expert opinion

Antibiotics are often used as first-line therapy to treat symptoms. Biologics that selectively target TNF-α, such infliximab (IFX), have shown high efficacy in randomized controlled trials. However, more than 50% of patients lose response to IFX, prompting them to explore alternative strategies. Current options include adalimumab and certolizumab pegol combination therapies, as well as small molecule drugs targeting Janus kinases such as Upadacitinib. Furthermore, a promising treatment for complex fistulas are mesenchymal stem cells such as Darvadstrocel (Alofisel) an allogeneic stem cell-based therapy. However, surgical interventions are necessary for complex cases or intra-abdominal complications. Setons and LIFT procedures are the most common surgical options.

KEYWORDS:

• Crohn’s disease
• Fistulas
• Infliximab
• Adalimumab
• Biologics therapy

Disclaimer

As a service to authors and researchers we are providing this version of an accepted manuscript (AM). Copyediting, typesetting, and review of the resulting proofs will be undertaken on this manuscript before final publication of the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal relate to these versions also.

ARTICLE HIGHLIGHTS

• Fistulizing Crohn’s disease (CD) represents a complex clinical condition and a challenging aspect in the treatment of CD. It poses substantial morbidity and mortality risks to patients, along with creating a significant economic burden on healthcare systems.

• Fistulizing CD patients endure both physical treatment side effects and social-emotional challenges, significantly impacting their overall quality of life.

• Effectively managing fistulizing CD requires a comprehensive, multidisciplinary strategy that integrates both medical and surgical interventions to achieve optimal outcomes.

• The current medical therapies for the management of include Antibiotics, Biologics preferably Infliximab, adalimumab and certolizumab pegol, small molecules like Upadacitinib.

• Therapeutic approaches involving mesenchymal stem cells have demonstrated promising outcomes in treating complicated perianal fistulas

Declaration of interest

MS has received Speaker/advisory board fees from Abbvie, Hikma, Ferring, Janssen, Acino, Pfizer, Sandoz, and Takeda. PLL has been a speaker and/or advisory board member for AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Fresenius Kabi, Gilead, Janssen, Eli Lilly, Merck, Organon, Pendopharm, Pfizer, Roche, Sandoz, and Takeda, they have also received unrestricted research grants from AbbVie, Gilead and Pfizer. TB has received speaker, consultant and research support from Abbvie, Alimentiv, BMS, CSF Vifor, Eli Lilly, Ferring, Fresenius Kabi, Gilead, Iterative scope, Janssen, Merck, Pendopharm, Pentax, Pfizer, Roche, Sandoz, Sanofi, Takeda, Viatris. The authors have no other 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.

Reviewers Disclosure

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

Additional information

Funding

This paper was not funded.