Ulcerative Colitis

CLINICAL CARE PATHWAY

Make Diagnosis and Assess Inflammatory Status (1)

Assess Comorbidities and Diseaseand Therapy-Related Complications (2)

Stratify According to Colectomy Risk (3)

LOW-RISK PATIENT
HIGH-RISK PATIENT

Inductive and Maintenance Therapy (Low Risk) (4)

Identify Patient Requiring Hospitalization

OUTPATIENT
INPATIENT

Inductive and Maintenance Therapy (High Risk, Outpatient) (5)

Inductive and Maintenance Therapy (High Risk, Inpatient) (7)

Therapy for High-Risk Outpatient Not in Remission (6)

MAKE DIAGNOSIS AND ASSESS INFLAMMATORY STATUS (1)

Assess Symptoms/Signs1–3

  • Bloody diarrhea
  • Tenesmus
  • Urgency
  • Abdominal pain
  • Fever
  • Weight loss
  • Joint swelling/redness
  • Localized abdominal tenderness
  • Signs of anemia
  • Cutaneous signs
* In patients with severe colitis, flexible sigmoidoscopy is safer and preferred over colonoscopy.4, 5

Perform Lab Testing1, 3

  • CBC
  • CMP
  • CRP
  • ESR
  • C. difficile assay
  • Stool cultures

Perform Colonoscopy/ Sigmoidoscopy1, 4, 5*

Select Imaging Modalities (If Indicated)

ASSESS COMORBIDITIES AND DISEASE AND THERAPY-RELATED COMPLICATIONS (2)

Patient Engagement and Coping

Assess Patient Preferences, Belief Systems, Disease Knowledge, Depression, Psychosocial Support

Infection

Treat Infection (C. difficile, Other Bacteria, CMV, Parasites)

Aspirin or NSAIDs

Stop Aspirin or NSAIDs

Non-Compliance

Educate and Support Patient

Adverse Reaction to Medical Therapy

Modify Therapy

Thromboembolic Complications

Treat DVT/PE

Colorectal Cancer/Dysplasia*

Colectomy

Toxic Megacolon/ Fulminant Colitis

Consult Surgery

*Colectomy is recommended for: 1) endoscopically unresectable polypoid high-grade or low-grade dysplasia, 2) invisible high-grade dysplasia on random biopsies, and 3) invisible low-grade dysplasia on random biopsies if the dysplasia is found (a) at more than one site (multifocal dysplasia), (b) on more than one occasion (repetitive dysplasia), and/or (c) at the time of initial screening colonoscopy (prevalent dysplasia).6
STRATIFY ACCORDING TO COLECTOMY RISK (3)

Identify Patient at Low Risk for Colectomy

  • Limited anatomic extent
  • Mild endoscopic disease

Identify Patient at High Risk for Colectomy

  • Extensive colitis7–10
  • Deep ulcers11
  • Age <408
  • High CRP and ESR8, 12, 13
  • Steroid-requiring disease8, 9, 12, 14
  • History of hospitalization9
  • C. difficile infection15
  • CMV infection16
INDUCTIVE AND MAINTENANCE THERAPY (LOW-RISK) (4)

Inductive Therapy

  • Oral 5ASA17, 18 and/or
  • Rectal 5ASA18 and/or
  • Oral budesonide19 or prednisone20 and/or
  • Rectal steroids21, 22
    • Rectal 5ASA is first line therapy in distal UC23

Maintenance Therapy

  • Maintenance with oral 5ASA and/or rectal 5ASA17, 18, 24
  • Taper steroid over 60 days
REMISSION
NO REMISSION
RELAPSE

Inductive and Maintenance Therapy (High Risk, Outpatient) (5)

Inductive and Maintenance Therapy (High Risk, Outpatient) (5)

INDUCTIVE AND MAINTENANCE THERAPY (HIGH RISK, OUTPATIENT) (5)

Induction Therapy

Maintenance Therapy


  • Short course of steroids with initiation of thiopurine19, 20

    Options:
  • Thiopurine23,31 and taper steroids over 60 days
  • Anti-TNF, with or without thiopurine26,29,32
  • Vedolizumab, with or without thiopurine or methotrexate30
REMISSION

  • Anti-TNF with or without thiopurine25–29 *,**

Continue anti-TNF, with or without thiopurine26, 29, 32


  • Vedolizumab, with or without immunodulator30 ***

Continue vedolizumab, with or without immunomodulator30

NO REMISSION
RELAPSE

Therapy for High-Risk Outpatient Not in Remission (6)

Therapy for High-Risk Outpatient Not in Remission (6)

* Combination therapy with a thiopurine is more efficacious than anti-TNF monotherapy25 and should be considered, especially in patients who have failed one or more anti-TNF agents.
** Extrapolating from data in Crohn’s disease, methotrexate may be used instead of thiopurines to decrease anti-TNF immunogenicity.33,34
*** Extrapolating from data with anti-TNF agents, thiopurines and methotrexate may be used to decrease vedolizumab immunogenicity
THERAPY FOR HIGH-RISK OUTPATIENT NOT IN REMISSION (6)

    Options:
  • Anti-TNF +/- thiopurine*,**
  • Vedolizumab +/- immunomodulator***

  • Thiopurine (optimize 6TGN concentrations)
  • Proctocolectomy

Failure to Respond to Prednisone

Failure to Maintain SteroidInduced Remission on Thiopurine

OR
(6A)
(6B)

Anti-TNF With or Without Thiopurine

Vedolizumab With or Without Immunomodulator

Subtherapeutic 6TGN

(>230 pmol 6-TGN/8×108 RBCs)

Therapeutic 6TGN

(>230 pmol 6-TGN/8×108 RBCs)

Increase Dose and Recheck Metabolites◊

Switch to Anti-TNF or Vedolizumab

Loss of Response to Anti-TNF

Loss of Response to Vedolizumab

(6C)
(6D)

Subtherapeutic Level No or Low Ab

Subtherapeutic Level High Ab

Therapeutic Level

Increase Dose to 300 mg Every 4 Weeks36

NON-RESPONSE

  • Increase dose and/or decrease interval
  • Consider adding immunomodulator35

  • Switch within class

  • Switch to vedolizumab with or without immunomodulator

Switch to Anti-TNF With or Without Thiopurine

* Combination therapy with a thiopurine is more efficacious than anti-TNF monotherapy25 and should be considered, especially in patients who have failed one or more anti-TNF agents.
** Extrapolating from data in Crohn’s disease, methotrexate may be used instead of thiopurines to decrease anti-TNF immunogenicity.33,34
*** Extrapolating from data with anti-TNF agents, thiopurines and methotrexate may be used to decrease vedolizumab immunogenicity.
◊ The addition of allopurinol (while decreasing the thiopurine dose to 1/4 of the previous dose) may be considered at centers with experience with this approach and recognizing the risks of severe myelosuppression and infection.
INDUCTIVE AND MAINTENANCE THERAPY (HIGH RISK, INPATIENT) (7)

Inductive Therapy*

    Options:
  • IV steroids3, 5, 23, 37
  • Infliximab
  • IV cyclosporine36
IV STEROIDS
INFLIXIMAB

    IV steroid-induced remission maintenance options:
  • Thiopurine
  • Anti-TNF, with or without Thiopurine**, ✖
  • Vedolizumab, with or without immunomodulator✚

    IV steroid failure options:
  • Infliximab5, 23, 39–41
  • Cyclosporine5, 23, 40–42
  • Colectomy5, 23

    Infiximab-induced remission maintenance:
  • Infliximab with or without Thiopurine5,**, ✖

    Infliximab failure✦
  • Colectomy5, 23
IV CYCLOSPORINE

    IV Cyclosporin-induced remission maintenance options:
  • Start thiopurine5
  • Anti-TNF, with or without Thiopurine**, ★
  • Vedoluzimab, with or without immunomodulator✚

    IV cyclosporine failure✦
  • Colectomy5, 23
* All hospitalized patients should receive prophylaxis for venous thromboembolism.5, 43–44
** Combination therapy with a thiopurine is more efficacious than anti-TNF monotherapy25 and should be considered, especially in patients who have failed one or more anti-TNF agents.
✖ Extrapolating from data in Crohn’s disease, methotrexate may be used instead of thiopurines to decrease anti-TNF immunogenicity.33, 34
✚ Extrapolating from data with anti-TNF agents, thiopurines and methotrexate may be used to decrease vedolizumab immunogenicity.
✦ Sequential rescue therapy (IFX-CSA or CSA-IFX) may be considered for select patients only in centers with experience with this approach and recognizing the risks of severe infection and death.23


Clinical care pathways are formulated by an expert physician panel through the review of existing clinical practice guidelines and systematic reviews. For pathway decisions points where no guidelines or systematic reviews exist, recommendations are made based on review of the available data. The clinical care pathways are not created using the GRADE methodology.

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