Several new treatments including small molecules and biologics have been approved for the treatment of inflammatory bowel diseases in recent years. Clinicians and patients now have a wide variety of therapeutic options to choose from and these novel therapies provide several advantages including oral administration, lower immunogenicity, better selectivity and arguably better safety profiles. An increase in treatment options has increased the complexity of decision-making. Both patients and clinicians have had to become rapidly familiar with efficacy of new medications balanced against a range of pre-initiation requirements, dosing schedules and adverse event profiles.
To provide a simple guide to practising clinicians on recently approved and emerging therapies and address key challenges around treatment strategies such as optimal sequencing and timing of treatment.
We comprehensively searched the published literature and major conference abstracts to identify phase III placebo-controlled and active comparator trials for Crohn's disease and ulcerative colitis.
Data for recently approved therapies including selective Janus kinase inhibitors, sphingosine-1 receptor modulators and p19 interleukin (IL)-23 inhibitors have demonstrated improved patient outcomes in both Crohn's disease and ulcerative colitis. Further comparative head-to-head studies have improved our understanding of when and how to optimally use newer therapies, specifically for IL-23 inhibitors. Data for emerging treatment options and novel treatment strategies such as early effective treatment, combinations of treatments and implications for sequencing are continuing to transform IBD care continually.
Recently approved novel therapies have expanded the range of medical options available to treat IBD. However, further data from long-term extension studies, real-world studies and head-to-head trials are warranted to better inform the long-term safety and optimal sequencing of treatments for patients living with IBD.
The possibility of preventing inflammatory bowel disease (IBD) is becoming more plausible due to advances in understanding preclinical disease and successful prevention trials in other immune-mediated diseases, such as type 1 diabetes and rheumatoid arthritis. However, before that possibility becomes reality, several efforts need to occur in parallel and in a coordinated way.
To propose some critical steps necessary for advancing the field of IBD prediction and prevention.
We reviewed the current literature to identify the necessary steps toward a preventive strategy for IBD.
The first step should determine the most robust predictive biomarkers and validate them across independent cohorts, creating a multidimensional predictive tool. The second step is to gain a better understanding of the preferences of first-degree relatives and people at risk for IBD, informing the implementation of screening and preventive strategies. Third, these efforts should contribute to the development of high-risk clinics and establish the necessary networks for disease prevention trials.
Advancing the field of IBD prediction and prevention will require a multifaceted approach, integrating biomarker discovery, understanding patient preferences, and establishing infrastructure for a collaborative network to support the practical implementation of IBD prevention strategies.
Inflammatory bowel disease (IBD) follows a heterogenous disease course and predicting a patient's prognosis is challenging. There is a wide burden of illness in IBD and existing tools measure disease activity at a snapshot in time. Comprehensive assessment of IBD severity should incorporate disease activity, prognosis, and the impacts of disease on a patient. This review investigates the concept of disease severity in adults with IBD to highlight key components contributing to this.
To perform this narrative review, a Medline search was conducted for full-text articles available at 1st March 2024 using search terms which encompassed disease activity assessment, disease severity, prognosis, natural history of Crohn's disease (CD) and ulcerative colitis (UC), and the burden of IBD.
Current methods of disease assessment in IBD have evolved from a focus on the burden of symptoms to one that includes inflammatory targets, genetic, serological, and proteomic profiles, and assessments of quality-of-life (QoL), disability, and psychosocial health. Longitudinal studies of IBD suggest that the burden of illness is driven by disease phenotype, clinical markers of complicated disease course (previous intestinal resection, corticosteroid use, perianal disease in CD, recent hospitalisations in UC), gut inflammation, and the impact of IBD on the patient.
Disease severity in IBD can be difficult to conceptualise due to the multitude of factors that contribute to IBD outcomes. Measurement of IBD severity may better encapsulate the full burden of illness rather than gut inflammation alone at a single timepoint and may be associated with longitudinal outcomes.
There are a plethora of therapeutic options for the management of inflammatory bowel disease (IBD). Despite this, clinical outcomes with standard dosing often fall short of established targets. While efforts centre on developing novel therapies, there is an ongoing need to optimise the use of existing agents.
To focus on strategies to optimise response to biologic (monoclonal antibody) therapies in IBD, including use of therapeutic drug monitoring (TDM).
An extensive review of the published literature.
TDM is a strategy aimed at enhancing the effectiveness of drugs with variable exposure-response relationships by measuring serum concentrations of biologic therapies and detecting neutralising antibodies. Reactive TDM is performed when therapeutic goals have not been achieved. Tumour necrosis factor alpha (TNF) inhibitors are the treatment class most frequently associated with immunogenicity and loss of response. Immunogenicity can be reduced through avoidance of low serum drug concentrations by dose optimisation or use of concomitant immunomodulator therapy. Subtherapeutic dosing in the absence of antidrug antibodies is best managed by dose escalation or dose interval reduction. Persistent neutralising drug antibodies necessitate switching to an alternative therapy. Proactively ensuring adequate serum trough levels might help sustain treatment durability and prevent loss of response. Newer non-TNF inhibitors demonstrate less robust exposure-response relationships, and TDM may not prove as beneficial.
In the treat-to-target paradigm of IBD treatment, optimising treatment effect with dose optimisation, which may involve strategies including TDM, increases the likelihood of achieving clinical remission and may accomplish deeper levels of remission beyond symptom control.
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