Management and Treatment of Crohn’s Disease

Introduction: Crohn’s disease is a type of inflammatory bowel disease and is defined by transmural inflammation that can exist anywhere between from the mouth to anus. It is associated with diarrhoea and bleeding but also more systemic features such as mouth ulcers, abdominal pain, nausea and vomiting, loss of appetite, weight loss, malnutrition, loss of energy and anaemia. Compared to ulcerative colitis, Crohn’s disease can appear more subtly. Disease can be complicated by fistulae (connecting tracts between the bowel and other organs or skin surface), strictures (narrowing), or abscesses/ collections.1 Disease mainly affects the ileal, ileocolonic, or colonic regions.1 Treatment approaches in recent years have focused on a treat to target approach in order to avoid complications and digestive damage in the long run.2

Complications include

• Intestinal obstruction
• Malignancy
• Immunomodulator-associated sepsis1

Extraintestinal manifestations include

• Liver disease
• Metabolic bone disease
• Kidney stones

Pathophysiology

Crohn’s disease is thought to develop due to an interaction of genetic, environmental and immune factors and is complex in its aetiology similar to other chronic illnesses such as diabetes or multiple sclerosis with multiple susceptible genotypes (> 200 genetic SNP mutations associated) and a myriad of possible triggers.3

Intestinal macrophages, neutrophils, and helper T-cells (TH-1, TH-17) are the primary mediators of the inflammatory cascade in the gastrointestinal tract.4, 5 Ileocaecal damage has been identified in particular, which has resulted in anemia in the form of fecal bleeding and reduced capacity to absorb vitamin B12.

Crohn’s also starts from the superficial mucosal layer and creates ulcers from the inflammation and spreads into deeper layers. If detected early, endoscopic findings can identify hyperemia and edema in the inflamed mucosal layers. Skip lesions form from these deep ulcers as well.6

Epidemiology

In Ireland, approximately 40,000 people were diagnosed with inflammatory bowel disease according to a study published in January 2024. Severity was noted to vary to an unknown extent.7 It has equal gender distribution and a peak incidence in early adulthood/adolescence and again in middle age demographics.

Throughout the world, the rates of Crohn’s disease vary, likely related to genetic predisposition and industrialization. In the United States, Crohn’s disease mainly affects people in rural or urban areas, and northern Europeans and people of Jewish descent also contribute to high incidence rates.8 Meanwhile, prevalence in Asians, Africans, and South Americans living in North America is low.8 However, there is emerging data that reveals rising incidence rates in industrialized areas throughout Asia, Africa, and Australasia.9

Current Treatments/Management

Medical management

Treatment algorithms for Crohn’s disease are vast because of varied disease location. Severity and complications at outset. Therefore, more refined and individualised approaches need to be taken for each patient so that they are cared for appropriately.

Mild to moderate disease would sometimes warrant the use of corticosteroids to stabilize the disease. However, chronic use is not advised because of potential side effects emerging such as osteoporosis, osteonecrosis, and adrenal insufficiency.1

For more severe staging of Crohn’s, TNF-alpha inhibitors like infliximab and adalimumab are commonly used to lower the inflammatory response. These are known to be more effective than immunomodulators such as azathioprine. However, combination therapies using infliximab and azathioprine still prove to be more effective than administering each approach individually.1

Methotrexate continues to be used as another medication for Crohn’s disease especially in the paediatric population, but it is also commonly known to lead to hepatotoxicity, especially if taken at doses higher than what is prescribed.10

Other classes of biologic agent are also effective and used widely for treatment of Crohn’s disease. These include IL-12 or IL-23 inhibitors (such as ustekinumab or risankizumab), JAK inhibitors (such as tofacitibnib or upaticitinib), anti-integrin antibodies (such as vedolizumab) and sphingolipid (such as ozanimod or etrasimod).

Surgical Treatment

Complications involving strictures, bowel obstructions, or malignancies are some primary justifications for why ileorectal strictureplasty and surgical resection would be necessary. The emergence or potential of fistulating disease and risk of bleeding and perforation would also contribute to justification for either option.11 Perianal disease often requires management of septic complications or drainage procedures and occasionally diversion ileostomy and with severe Crohn’s colitis refractory to medical treatment colectomy can be required.

Long-term Monitoring

After remission, according to STRIDE2 consensus guidelines, patients are advised to check their biomarkers (CRP and fecal calprotectin) with their providers every 6 to 12 months to measure the level of effectiveness in therapeutic response. However, upon newly developed Crohn’s disease or recurrence, then the American Gastroenterology Association recommends that patients check their biomarkers every 2 to 4 months. Patients should also have routine endoscopies or imaging to check on the status of their remission.12

Dietary Management

Patients who are anaemic with ileal disease often benefit greatly by adding vitamin B12 supplements to their diet to account for their fecal blood loss.10 Weight maintenance and diet trigger avoidance during flares are also important aspects of dietary management. In paediatrics in particular and also in difficult to manage penetrating disease, exclusive or partial enteral nutrition can be used to treat the disease as an elemental diet.

Psychological Support

As with any chronic disease, Crohn’s disease can be difficult for patients to navigate and cope with. It greatly affects quality of life parameters and can be challenging on an everyday basis. Ultimately, IBD patients have higher levels of anxiety and depression. Psychological support from IBD nurses and clinical psychologists is an important part of the overall multidisciplinary treatment provided to Crohn’s patients.

Current Research/Novel Therapies

Endoscopic procedures are improving in their capacity to identify the recurrence of Crohn’s disease. A POCER postoperative index was used in the context of ulcer size and anastomosis, meaning that this was used to measure the severity of Crohn’s with regards to the level of anastomotic recurrence.13 This is a newly defined index, which warrants further investigation before its use can be generalised.13

Another important therapy that is emerging in clinical importance is the use of the Lemann index. Like the POCER postoperative index, the Lemann index is also focused on the progression of Crohn’s disease and the assessment of damage to any impacted areas of the bowel. More specifically, the latter index also has a grading system ranging between 0 to 3 (least to most severe), and it measures the inflammatory damage to all parts of the bowel.14 Studies have been conducted to relate the use of the Lemann index to a patient’s quality of life. The general outcome is that the Lemann index and quality of life have significant negative correlation.14, 15 Therefore, the viability of using this index is validated as an additional tool for Crohn’s disease assessment in clinical trials. However, with additional studies, there should be great prospects to incorporate the Lemann index into clinical practice and personalise the treatments that are given to IBD patients to ensure more effective and efficient recovery.

Combination therapies are still being explored with deeper research into infliximab and methotrexate uses targeted towards geriatric and pediatric populations alike. New monoclonal antibodies are being considered to broaden the options for Crohn’s disease.16 The dashboard approach of looking at potential genetic predisposition, immune activation factors and environmental triggers are also continuing to be researched in an effort to provide better overall therapeutic strategies for this challenging condition.

Written by Dr Orlaith Kelly, Consultant Gastroenterologist & Ronald Chia, Blackrock Health

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