Investigational drug therapies for coeliac disease – where to from here?

ABSTRACT

Introduction: Despite decades of research and a detailed knowledge of the immunopathological basis of coeliac disease (CD), adherence to a lifelong gluten-free diet (GFD) remains the single proven and available treatment. The increasing prevalence of CD combined with variable adherence to the GFD in a significant proportion of patients demands new therapeutic strategies.

Areas covered: Trial registries, clinicaltrials.gov, pharmaceutical company website searches as well as published data from PubMed and conference proceedings were used to extract the most recent outcomes for CD therapeutics. This article aims to review the available therapies from a pathophysiological approach, and propose future directions in this interesting yet largely unfulfilled area of research.

Expert opinion: Increasingly, the GFD is being challenged by its availability, palatability, practicality and now even efficacy in some populations. Whilst the causative antigens have been well described, it is clear that treatment based on the removal of these immunostimulatory peptides from the diet is far more complex than early experience in CD treatment implied. Despite burgeoning interest and research in experimental therapies for CD over the past twenty years, the only therapy showing promise as a true alternative to a GFD is that of the induction of tolerance via a vaccine.

KEYWORDS:

• Coeliac disease
• therapeutics
• refractory
• experimental

Article highlights

• Despite intense development of trial therapeutics in coeliac disease over many years, the GFD remains the sole approved and available treatment.

• Therapies inducing pre-digestion or targeting tight junctions display mixed results and are unlikely to provide a mainstay of therapy beyond inadvertent gluten exposure.

• Available immunosuppressant and immunomodulatory therapies display efficacy for refractory coeliac disease at the expense of tolerability and side-effect profiles that restrict broader use.

• Induction of immune tolerance via vaccination shows promise as a true alternative to the GFD.

This box summarizes key points contained in the article.

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.

Additional information

Funding

This paper was not funded.