CONSENSUS STATEMENT – Clinical Practice Guidelines for the Medical Management of Nonhospitalized Ulcerative Colitis: The Toronto Consensus
The consensus guidelines for the treatment of ambulatory patients with mild to severe active ulcerative colitis (UC) are summarized. The goal of therapy is complete remission defined as both symptomatic and endoscopic remission without corticosteroids. The consensus focused on five main drug classes, 5-aminosalicylate (ASA), corticosteroids, immunosuppressants, anti-tumor necrosis factor-alpha (TNF) therapies, and other therapies. Oral and rectal 5-ASAs are recommended first-line therapy for mild-to-moderate UC, with corticosteroid therapy for those who fail to achieve remission. Patients with moderate-to-severe UC should undergo a course of oral corticosteroids with transition to 5-ASA, thiopurines, anti-TNF therapy (with or without thiopurines or methotrexate), or vedolizumab maintenance therapy in those who successfully achieve symptomatic remission. For patients with corticosteroid-resistant/dependent UC, anti-TNF therapies or vedolizumab are recommended. Timely assessments of response and remission are critical to ensuring optimal outcomes.
Summary of Consensus Recommendations for the Medical Management of UC
Statements regarding 5-ASA
- In patients with mild to moderate active ulcerative proctitis, rectal 5-ASA, at a dosage of 1 g daily, is recommended as first-line therapy to induce symptomatic remission.
- In patients with mild to moderate active left-sided UC, 5-ASA enemas, at a dosage of at least 1 g daily, are recommended as an alternative first-line therapy to induce complete remission.
- In patients with mild to moderate active UC of any disease extent beyond proctitis, an oral 5-ASA preparation, at dosages between 2.0 and 4.8 g/day, is recommended as an alternative first-line therapy to induce complete remission.
- In patients with mild to moderate active UC of any disease extent beyond proctitis, the combination of a rectal and an oral 5-ASA preparation over oral 5-ASA alone is suggested as an alternative first-line therapy to induce complete remission.
- It is recommended that patients with UC be evaluated for lack of symptomatic response to oral/rectal 5-ASA induction therapy in 4 to 8 weeks to determine the need to modify therapy.
- In patients with oral or rectal 5-ASA–induced complete remission of mild to moderate active left-sided UC or proctitis, the same therapy shall be continued to maintain complete remission.
- In patients with oral 5-ASA–induced complete remission of mild to moderate active UC of any disease extent, continued oral therapy of at least 2 g/day is recommended to maintain complete remission.
- In selected 5-ASA–naive patients with UC who have achieved symptomatic remission on oral corticosteroids, an oral 5-ASA preparation of at least 2 g/day is recommended while being assessed for corticosteroid-free complete remission.
- In patients with UC who have failed to respond to oral 5-ASA, switching to another oral 5-ASA formulation to induce remission is not recommended.
- When using oral 5-ASA to induce or maintain complete remission of UC, once-daily dosing is preferred over more frequent dosing.
Statements regarding corticosteroids
- In patients with moderate to severe active UC, oral corticosteroids are recommended as first-line therapy to induce complete remission.
- In patients with mild to moderate active UC who fail to respond to 5-ASA therapy, oral corticosteroids are recommended as second-line therapy to induce complete remission.
- In patients with mild to moderate active left-sided UC or proctitis who fail to respond to rectal 5-ASA therapy, rectal corticosteroids are suggested as second-line therapy to induce complete remission.
- In patients with UC, oral corticosteroids are not recommended to maintain complete remission because they are ineffective for this indication and their prolonged use is associated with significant adverse effects.
- In patients with mild to moderate UC of any disease extent, oral budesonide MMX is suggested as an alternative first-line therapy to induce complete remission.
- It is recommended that patients with UC be evaluated for lack of symptomatic response to corticosteroid induction therapy within 2 weeks to determine the need to modify therapy.
Statements regarding immunosuppressants
- In patients with UC, the use of thiopurine monotherapy to induce complete remission is not recommended.
- In selected patients with UC who have achieved symptomatic remission on oral corticosteroids, thiopurine monotherapy is suggested as an option to maintain complete corticosteroid-free remission.
- In patients with UC, the use of methotrexate monotherapy is not recommended to induce or maintain complete remission.
Statements regarding anti-TNF therapy
- In patients with UC who fail to respond to thiopurines or corticosteroids, anti-TNF therapy is recommended to induce complete corticosteroid-free remission.
- Anti-TNF therapy should be combined with a thiopurine or methotrexate rather than used as monotherapy to induce complete remission.
- In patients with UC who are corticosteroid dependent, anti-TNF therapy is recommended to induce and maintain complete corticosteroid-free remission.
- It is recommend that patients with UC be evaluated for lack of symptomatic response to anti-TNF induction therapy in 8 to 12 weeks to determine the need to modify therapy.
- In patients with UC who respond to anti-TNF induction therapy, continued anti-TNF therapy is recommended to maintain complete remission.
- In patients with UC who have a suboptimal response to anti-TNF induction therapy, dose intensification is recommended to achieve complete remission.
- In patients with UC who lose response to anti-TNF maintenance therapy, optimizing dose is recommended to recapture complete remission.
- Dose optimization for patients with UC thjrough therapeutic drug monitoring is recommended.
Statements regarding other agents
- In patients with primary failure to an anti-TNF therapy, switching to vedolizumab is recommended over switching to another anti-TNF therapy to induce complete corticosteroid-free remission.
- In patients with secondary failure to an anti-TNF therapy, switching to another anti-TNF therapy or vedolizumab is recommended based on therapeutic drug monitoring results to induce complete corticosteroid-free remission.
- In patients with moderate to severe active UC who fail to respond to corticosteroids, thiopurines, or anti-TNF therapies, vedolizumab is recommended to induce complete corticosteroid-free remission.
- Patients with UC shall be evaluated for lack of symptomatic response to vedolizumab induction therapy in 8 to 14 weeks to determine the need to modify therapy.
- In patients with UC who respond to vedolizumab, continued vedolizumab therapy is recommended to maintain complete corticosteroid- free remission.
- Fecal microbial transplant to induce or maintain complete remission in patients with UC is not recommended outside the setting of a clinical trial.
- In patients with UC, probiotics to induce or maintain complete remission outside the setting of a clinical trial are not recommended.
Definitions of Treatment Failure
- 5-ASA failure: Inability of the patient to achieve and maintain complete corticosteroid-free remission despite optimal treatment with oral, rectal, or combination 5-ASA therapy
- Thiopurine failure: Inability of the patient to maintain corticosteroid-free complete remission despite dose optimization
- Biologic failure:
- Primary failure: Inability of the patient to achieve corticosteroid-free complete remission despite dose optimization
- Secondary failure: Inability of the patient to maintain corticosteroid-free complete remission after achieving a symptomatic response
Factors to Consider in a Comprehensive Assessment of Disease Impact
- High disease activity (in acute setting)
- Frequency of hospitalization
- Need for surgery
- Inability to work or participate in leisure activities
- Failure to respond to medication
Defining Remission and Response in Patients With UC
- Complete remission: Both symptomatic remission and endoscopic healing as defined below
- Endoscopic healing: Normal mucosa, vascular blurring, or chronic changes (eg, inflammatory polyps, scarring) without friability
- Symptomatic remission: Normal stool frequency ( 3/day) and no blood in the stool
- Symptomatic response: Meaningful improvement in symptoms as judged by both the patient and physician in the absence of remission; response should not be considered a desirable final outcome but is useful to assess early response to treatment
Definitions of UC
- Disease Extent
- The extent of endoscopic disease was categorized as
- proctitis (distal to the rectosigmoid junction or within 18 cm of the anal verge)
- left-sided colitis (extending anywhere from the sigmoid to the splenic flexure), or
- extensive colitis (extending beyond the splenic flexure).
- The extent of endoscopic disease was categorized as
- Disease Activity
- Disease activity is best determined by clinical symptoms and an objective assessment of disease activity through endoscopy. Yet is often necessary to make clinical decisions based on symptoms alone. Ideally, a formal scoring tool such as the Mayo score or a similar disease activity score should be used to determine disease activity in patients with UC. The Mayo score includes 4 measures: stool frequency, rectal bleeding, endoscopic findings, and the physician’s global assessment. Although such a scoring system is desirable for accurate and consistent assessment of disease activity, it is often necessary to make management decisions in the absence of endoscopic information while considering the subjective aspects of disease presentation not captured by the full Mayo score. In such circumstances, the partial Mayo score (which omits the endoscopic subscore) can be informative.
Mayo Score: Measuring Disease Activity in UC
Stool frequency
- 0 – Normal number of stools for this patient
- 1 – 1–2 stools more than normal
- 2 – 3–4 stools more than normal
- 3 – 5 or more stools more than normal
Rectal bleeding
- 0 – No blood seen
- 1 – Streaks of blood with stool less than half the time
- 2 – Obvious blood with stool most of the time or more
- 3 – Blood passed alone
Findings on flexible proctosigmoidoscopy
- 0 – Normal or inactive disease
- 1 – Mild disease (erythema, decreased vascular pattern, mild friability)
- 2 – Moderate disease (marked erythema, absent vascular pattern, friability, erosions)
- 3 – Severe disease (spontaneous bleeding, ulceration)
Physician’s global assessment
- 0 – Normal (there are no symptoms of colitis, the patient feels well, and the flexible proctosigmoidoscopy score is 0) (stool frequency = 0; rectal bleeding = 0; patient’s functional assessment = 0; flexible proctosigmoidoscopy findings = 0)
- 1 – Mild disease (mild symptoms and proctoscopic findings that were mildly abnormal) (the subscores should be mostly 1: stool frequency = 0 or 1; rectal bleeding = 0 or 1; patient’s functional assessment = 0 or 1; flexible proctosigmoidoscopy findings = 0 or 1)
- 2 – Moderate disease (more serious abnormalities and proctosigmoidoscopic and symptom scores of 1 or 2) (the subscores should be mostly 2: stool frequency = 1 or 2; rectal bleeding = 1 or 2; patient’s functional assessment = 1 or 2; flexible proctosigmoidoscopy findings = 1 or 2)
- 3 – Severe disease (the proctosigmoidoscopic and symptom scores are 2 to 3 and the patient probably requires corticosteroid therapy and possibly hospitalization) (the subscores should be mostly 3: stool frequency = 2 or 3; rectal bleeding = 2 or 3; patient’s functional assessment = 2 or 3; flexible proctosigmoidoscopy findings = 2 or 3)
Patient’s functional assessment
- 0 – Generally well
- 1 – Fair
- 2 – Poor
- 3 – Terrible
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