What is the diagnosis and treatment for Ulcerative Colitis (UC)?

From the Guidelines

The diagnosis and treatment of Ulcerative Colitis (UC) should be guided by the most recent and highest quality evidence, which recommends a step-up approach starting with 5-aminosalicylates (5-ASAs) like mesalamine for mild to moderate disease, and corticosteroids for more severe cases, with biologic agents reserved for moderate to severe disease that doesn't respond to conventional therapy 1.

Diagnosis

The diagnosis of UC involves a combination of clinical evaluation, endoscopy, and histology. It is essential to consider differential diagnoses, such as infection, proximal constipation, Crohn's disease, co-existent irritable bowel syndrome, and rectal prolapse/solitary rectal ulcer, especially when there is an incomplete response to treatment or a flare 1.

Treatment

The treatment of UC typically involves medications to reduce inflammation and manage symptoms.

• First-line therapy often includes 5-ASAs like mesalamine (doses range from 2-4.8g daily) for mild to moderate disease, with once-daily dosing being as effective as divided doses 1.
• For more severe cases, corticosteroids such as prednisone may be used for acute flares, with systemic corticosteroids being appropriate in patients with moderate to severe activity and in those with mild activity who do not respond to mesalamine 1.
• Immunomodulators like azathioprine or 6-mercaptopurine are used for maintenance therapy in steroid-dependent patients.
• Biologic agents, including anti-TNF drugs, anti-integrins, and JAK inhibitors, are reserved for moderate to severe disease that doesn't respond to conventional therapy.

Management

Patients with UC should maintain regular follow-up appointments, undergo periodic colonoscopies for cancer surveillance, and report worsening symptoms promptly. Lifestyle modifications, including stress management, avoiding trigger foods, and smoking cessation, can help manage symptoms alongside medical therapy. In cases of incomplete response to treatment or flare, it is essential to ensure adherence, enquire if patients require advice on use of therapy, and consider sigmoidoscopy or colonoscopy to exclude more extensive ulcerative colitis 1.

Hospital Admission

Hospital admission is indicated for patients who are systemically unwell or suspected to have acute severe colitis, with intensive treatment being necessary for severe extensive colitis 1.

Alternative Therapies

There is some evidence for a therapeutic benefit of probiotics, particularly VSL#3, when added to standard therapy to induce remission, although the evidence is not yet conclusive 1. Faecal transplantation (FT) has shown promise in inducing remission in active UC, with more patients reaching remission with FT than with water enema in one trial, although additional studies are warranted to define the best protocol and ensure safety 1. Helminth therapy and phosphatidylcholine have also been investigated, but there is currently insufficient evidence to support their use in UC 1.

From the FDA Drug Label

ENTYVIO is indicated in adults for the treatment of: moderately to severely active ulcerative colitis (UC). The safety and effectiveness of HUMIRA have been established for: ... the treatment of moderately to severely active ulcerative colitis in pediatric patients 5 years of age and older.

The diagnosis of Ulcerative Colitis (UC) is not explicitly stated in the provided drug labels. The treatment for UC includes:

• Vedolizumab (ENTYVIO) for moderately to severely active UC in adults 2
• Adalimumab (HUMIRA) for moderately to severely active UC in pediatric patients 5 years of age and older 3

From the Research

Diagnosis of Ulcerative Colitis (UC)

• The diagnosis of UC is made by combining the clinical picture, tissue biopsy, and the endoscopic appearance of mucosal ulceration, friable, edematous, erythematous granular appearing mucus 4.
• The disease is diagnosed on the basis of clinical parameters and endoscopic-histologic evaluation 5.

Treatment of Ulcerative Colitis (UC)

• The approach to therapy of UC has been dependent on the severity of symptoms, with frontline therapy being salicylate-based sulfasalazine 4.
• Mesalamine, a 5-aminosalicylic acid (5-ASA) compound, is the first-line therapy to induce and maintain clinical remission in patients with mild-to-moderate UC 6, 5, 7.
• For patients with distal and left-sided disease, the use of rectal preparations is effective, and most patients respond to 5-ASA suppositories or topical steroids such as budesonide suppositories or hydrocortisone foam 5.
• In case of low- to moderate-grade inflammation, 5-ASA preparations should be implemented, and for severe disease, treatment with steroids is required 5.
• For patients with moderately active ulcerative colitis, mesalamine has response rates between 40%-70% and remission rates of 15%-20% 4.
• The optimal dosages for mild-moderate distal active disease and for maintenance therapy are 4.8 g/day and 2.4 g/day, respectively 4.
• Patients with moderately active ulcerative colitis treated with 4.8 g/d of mesalamine are significantly more likely to achieve overall improvement at week 6 compared to patients treated with 2.4 g/d 4.
• MMX mesalamine, an oral once-daily tablet formulation of mesalamine, effectively induces and maintains clinical remission in patients with active mild-to-moderate UC 6.
• The use of once-daily formulations has led to intense interest in whether simplified pill regimens can improve patient adherence to mesalamine therapy 6.
• In the era of biologics, aminosalicylates remain the first-line therapy in patients with mild UC and have to be considered in case of moderate UC, given their favorable risk-benefit profile 7.
• High-dose 5-ASA therapy may be a valuable option for patients with moderately active disease, and physicians should weigh the pros and cons of this strategy in selected patients 7.

Treatment Patterns in Clinical Practice

• Oral 5-ASAs and systemic steroids are the mainstay of treatment in patients with new-onset ulcerative colitis 8.
• In patients with new-onset ulcerative proctitis, mesalazine suppositories are the most commonly used treatment, followed by oral 5-ASAs and combination therapy 8.
• Few patients receive maintenance therapy, and there is limited use of antimetabolites and biological agents 8.