| Highlights |
• The goals of treatment are to achieve rapid improvement in symptoms and cure the disease at the mucosal level, while restoring the patient’s overall quality of life. • 5-aminosalicylic acid ( 5 -ASA) represents the main therapy for mild to moderately active ulcerative colitis (UC). • In patients with UC with an inadequate response to 5-ASA, immunosuppressive or biological treatments are indicated. • Surgical options include retransit options such as an ileoanal pouch or, rarely, an ileorectal anastomosis or a permanent ileostomy. • The future will see a variety of new treatments with trials that will allow us to position UC therapeutics correctly. |
Ulcerative colitis (UC) is a relapsing-remitting inflammatory bowel disease (IBD) characterized by mucosal inflammation that begins distally and can extend proximally to affect the entire colon.
UC has a bimodal age distribution with a peak incidence in the second or third decades and a second peak between 50 and 80 years of age. The etiology involves interactions between the environment, the immune system, the gut microbiome, and a genetic predisposition. This disease presents with bloody diarrhea, frequency, abdominal pain, fatigue, and fecal incontinence.
The Montreal classification groups patients with UC, according to the maximum extension of the disease into:
- E1 or proctitis (disease limited to the rectum).
- E2 or left-sided disease (distal to the splenic flexure).
- E3 or extensive colitis (disease extends proximal to the splenic flexure).
Patients with left-sided disease or extensive colitis are associated with increased risks of medication use, colectomy, and colorectal cancer.
Other extraintestinal manifestations of UC include anemia, arthropathy (axial or peripheral), cutaneous (erythema nodosum or pyoderma gangrenosum) and ocular (anterior uveitis or episcleritis) manifestations, most of which reflect disease activity, except ankylosing spondylitis. and peripheral polyarthritis
| Determination of the severity at the presentation of the disease |
Disease severity is measured by evaluating clinical and biochemical parameters, as shown by the modified Truelove and Witts criteria (Table 1). Endoscopically, the Mayo score is commonly used in clinical practice due to its simplicity in application.
TABLE 1. MODIFIED TRUELOVE AND WITTS CRITERIA
| Parameter | Mild | Moderate | Severe |
| Bloody stools per day (n) | <4 | 4–6 | > 6 |
| Pulse (beats per minute) | <90 | ≤90 | > 90 |
| Temperature (°C) | <37.5 | 37.5–37.8 | >37.8 |
| Hemoglobin (g/dl) | > 11.5 | 11.5–10.5 | <10.5 |
| TSE (mm/h) (or CRP, mg/l) | <20 (normal) | 20–30 (<30) | > 30 (>30) |
CRP = C-reactive protein; ESR = erythrocyte sedimentation rate.
| Medical treatment |
5-aminosalicylic acid (5-ASA) drugs represent the standard treatment for patients with mild to moderate disease activity.
In patients with mild to moderate UC proctitis, 5-ASA suppositories are considered first-line therapy, rather than oral 5-ASA monotherapy and rectal corticosteroids. In case of a suboptimal response, the next step should be the addition of oral 5-ASA therapy. If the response remains incomplete, it is recommended to add a corticosteroid suppository and/or optimize oral 5-ASA dosing.
5-ASAs are well tolerated. Renal failure is a rare and unpredictable adverse event, so renal function should be monitored periodically after initiation of treatment with these drugs.
Prednisolone should be restricted to patients with moderate to severe UC of any extent of disease or those who do not respond to standard therapy. Alternatively, for cases of mild to moderate UC, budesonide may be indicated.
Thiopurines, such as azathioprine and mercaptopurine, have been used to maintain steroid-free remission. Adverse effects reported include nausea (8%), hepatotoxicity (4%), myelotoxicity (4%), pancreatitis (4%), non-melanoma skin cancers, and lymphomas.
Biologics have progressively changed the therapeutic landscape of UC. Anti-tumor necrosis factor (TNF) drugs include intravenous infliximab originator and biosimilars, subcutaneous adalimumab originator and biosimilars, and subcutaneous golimumab. These drugs are preferred in patients with extraintestinal manifestations of IBD, such as type 1 IBD-associated arthropathy, ankylosing spondylitis, and pyoderma gangrenosum.
Vedolizumab inhibits α4β7 integrin, which decreases leukocyte migration from the circulation to the intestinal wall. Such a selective intestinal pathway may explain the relative long-term safety of the drug.
Ustekinumab inhibits the p40 subunit of interleukins 12 and 23; One study showed that 15.5% receiving ustekinumab achieved clinical remission at 8 weeks compared to 5.3% receiving placebo.
Tofacitinib is an oral Janus kinase (JAK) inhibitor that showed improvement in clinical/endoscopic outcomes. Adverse events include an increased risk of herpes zoster infection (warranting appropriate vaccination) and an increased risk of venous thromboembolism (VTE).
| Tracking and Monitoring |
Clinical parameters should be re-evaluated every 3 months during the active phase. Once symptoms resolve, clinical reviews should be performed every 6 to 12 months. Colonoscopies should be performed every 1 to 5 years to investigate suspicious outbreaks and ensure surveillance for colorectal dysplasia.
| Acute severe ulcerative colitis and surgical treatment |
In the case of severe acute ulcerative colitis (according to Truelove and Witts), the mainstay of treatment is intravenous steroids . For those who do not respond, cyclosporine or infliximab can be used as rescue therapy, with studies showing no difference in effectiveness.
The timing of surgical intervention in a patient with UC is multifactorial and must take into account the severity of the disease and quality of life. In terms of acute severe ulcerative colitis that has not responded to medical treatment, a colectomy can be a life-saving procedure. For these patients who are offered surgery, subtotal colectomy is the operation of choice.
| The future |
There are a number of therapeutic targets being explored in the treatment of UC in various clinical phases to include sphingosine-1-phosphate receptor modulators (such as ozanimod and etrasimod), JAK inhibitors (such as upadacitinib), anti-leukocyte integrins (such as such as etrolizumab and aprilumab), monoclonal antibodies (such as mirikizumab) and fecal microbiota transplantation.
As we gain a better understanding of the biological mechanisms that drive this pathology, it will be possible to find the right drug for the right person at the right time, while ensuring that the patient’s broader goals are met.
