Insights into Ulcerative Rectocolitis
Ulcerative colitis is a relapsing and remitting disease that is increasing in incidence and prevalence. Treatment is aimed at achieving rapid resolution of symptoms, healing of the mucosa and improvement of the patient's quality of life. Drugs with 5-aminosalicylate acid remain the first-line treatment for mild to moderate disease. In case of suboptimal response to these drugs, escalation to immunosuppressive and biological drugs may be necessary. Importantly, despite the best medical therapy, surgery may be necessary in a percentage of patients. The future is likely to see a number of new treatment options for people with ulcerative colitis with the potential for a more personalised treatment approach.
Ulcerative colitis (UC) is a relapsing and remitting inflammatory bowel disease (IBD) characterised by inflammation of the mucosa that begins distally and may extend proximally to involve the entire colon. UC has a bimodal age distribution with a peak incidence in the second or third decade and a second peak between 50 and 80 years of age. The aetiology involves interactions between environment, immune system, gut microbiome and a genetic predisposition to the disease. Ulcerative colitis presents with bloody diarrhoea, frequency, abdominal pain, fatigue and faecal incontinence.
The Montreal classification groups patients with UC, according to their maximum extent of disease, into E1 or proctitis (disease limited to the rectum); E2 or left-sided disease (distal to splenic flexure); and E3 or extensive colitis (disease extends proximal to splenic flexure). Patients with left-sided disease or extensive colitis are associated with increased risks of drug use, colectomy and colorectal cancer. In addition to the extent of disease, the main risk factors for colorectal dysplasia/cancer in UC include duration of disease; endoscopically or histologically active inflammation; presence of a post-inflammatory stenosis or polyps; family history of colorectal cancer; and associated primary sclerosing cholangitis (a chronic inflammatory disease of the bile duct that affects 3-7% of UC patients). Other extra-intestinal manifestations of UC include, in order of frequency, anaemia, arthropathy (axial or peripheral), cutaneous (erythema nodosum or pyoderma gangrenosum) and ocular (anterior uveitis or episcleritis), most of which reflect UC disease activity, with the exception of ankylosing spondylitis and peripheral polyarthritis.
In 2015, the Selection Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative made recommendations on therapeutic targets in IBD that were subsequently updated in December 2020 in the SPIRIT consensus. In summary, this consensus agreed that UC treatment targets should address a composite of clinical and endoscopic outcomes (potentially with the use of surrogate measures of inflammation, such as faecal calprotectin), in addition to the ultimate goals of addressing the impact on a patient's life (health-related quality of life, disability, and faecal incontinence), preventing disease extension, surgery, permanent ostomy, and dysplasia or cancer.
The severity of the disease is measured by the evaluation of clinical and biochemical parameters. Endoscopically, the Endoscopic Ulcerative Colitis Severity Index (UCEIS) is the only validated scoring system to assess severity, however, the Mayo score is commonly used in clinical practice due to its simplicity in application.
The future
There are a number of therapeutic targets being explored in the treatment of ulcerative colitis in various clinical stages to include sphingosine-1-phosphate receptor modulators (such as ozanimod and etrasimod), JAK inhibitors (such as upadacitinib), anti-leukocyte integrins (such as etrolizumab and abrilumab), monoclonal antibodies (such as mirikizumab) and faecal microbiota transplantation. These will potentially offer new options for the medical treatment of ulcerative colitis, but currently remain at the clinical trial stage.
It is likely that head-to-head studies will allow us to position the biologics correctly. As we gain a better understanding of the biological mechanisms that drive UC, it may become possible to find the right drug for the right person at the right time, while ensuring that the patient's broader goals (impact on quality of life, psychological and dietary support) are addressed.
