Current Status, Challenges, and Future Directions in Crohn’s Disease

The treatment goal for patients with Crohn's disease (CD) has traditionally been aimed at symptomatic steroid-free clinical remission [...].

argue in their study that the complexity and heterogeneity of Crohn's disease are not currently reflected in conventional classification systems.The Montreal classification describes the phenotype but does not allow for the prediction of disease course [9].Novel approaches that aim to include serological markers and multi-omics approaches including genomics, transcriptomics, proteomics, epigenomics, metagenomics, metabolomics, lipidomics, and immunophenomics may, in the future, allow us to classify Crohn's disease in a manner that can be helpful for treatment decisions and disease course prediction.
Fibrosis is a common phenomenon in healing intestinal tissue and can lead to symptomatic stricturing of Crohn's disease.Thus far, there are no clinically meaningful predictors of strictures nor are there available treatment modalities to combat fibrosis.The advent of single-cell sequencing has led to significant advances in our understanding of the disease at the cellular level.Campbell et al. (Contribution 5) review the current understanding of the pathophysiology of fibrosis in Crohn's disease.They summarise current treatments and highlight how single-cell sequencing may be the key to developing effective therapies.
Many women with Crohn's disease are of childbearing age, and management of pregnancies in these women is often complex.While the management of IBD during pregnancy is often discussed in the literature, in their review article, Rosiou and Selinger (Contribution 6) focus on the management of obstetric considerations in pregnant women with Crohn's disease.Discussions of fertility in the disease course during pregnancy are followed by advice on risk factors for adverse maternal and fetal outcomes.The focus on delivery allows clinicians to advise their patients on the optimal mode of delivery.
Around the globe, there is an increasing prevalence of IBD, and in developed countries, this increase is predominantly driven by the long life expectancy of patients with IBD.Hence, we are seeing an increasing number of patients over 60 years of age in our IBD clinics.The risk of adverse health outcomes often potentially related to IBD treatment correlates better with biological than with chronological age.Fons et al. (Contribution 7) review frailty in IBD patients.They define frailty, examine its prevalence in IBD patients, and describe the outcomes associated with frailty.It is paramount that we shift away from basing treatment decisions on chronological age and instead focus on frailty.We should not deny fit older patients treatment based on their chronological age alone.
Crises can often prompt great innovations and changes in approach.The COVID-19 pandemic was certainly one of the biggest global crises to affect healthcare.Zhang et al. (Contribution 8) review the effects of the pandemic on patients with IBD.They review the risk of COVID-19 infection, the response to COVID-19 vaccines, and the treatment of COVID-19 in patients diagnosed with IBD.In addition, they reflect on positive changes brought about or at least accelerated by the pandemic.Telemedicine has provided patients with greater choice, reduced carbon emissions, and is generally favored by patients.Noninvasive monitoring with faecal calprotectin and bowel ultrasound can replace more invasive endoscopies in many scenarios.Point-of-care testing of faecal calprotectin in the patient's home may reduce the need for travel.Finally, subcutaneous versions of established biologics such as infliximab and vedolizumab allow for a reduction in travel and time spent on healthcare for patients.
Radiological imaging remains crucial in the assessment of small bowel or perianal Crohn's disease.While magnetic resonance imaging (MRI) offers a radiation-free method, computed tomography (CT) is an often-used radiation-exposure method.Yang et al. (Contribution 9) examine radiation exposure in a single-center cohort.Unsurprisingly, the rate of radiation exposure was higher for patients with Crohn's disease than for those diagnosed with ulcerative colitis.Nearly 7% of patients with Crohn's disease were classed as having experienced high radiation exposure.Therefore, clinicians need to focus on using MRI or small bowel ultrasound over CT and reserve the latter for emergency situations.
Anti-TNF medications are often recommended as a first-line choice of advanced therapy for Crohn's disease [3].However, many patients experience a loss of response [10], which necessitates second-line advanced therapies.Sharip et al. (Contribution 10) examine studies containing real-world evidence by examining the effectiveness of ustekinumab versus vedolizumab in this setting.They conclude that most studies find ustekinumab to be superior or at least non-inferior to vedolizumab, though many confounders remain despite best efforts by researchers to adjust for these factors.Lastly, the increasing use of JAK inhibitors in Crohn's disease patients highlights the need for further studies on second-line therapy.
In summary, the future for patients with Crohn's disease seems brighter due to increased choice of effective medication, new approaches to classifying disease and assessing disease effectively and safely, and the appropriate management of Crohn's disease through the different life phases of our patients.