What are the stepwise management strategies for Crohn's disease (CD) and Ulcerative Colitis (UC)?

From the Guidelines

The management of Crohn's disease and ulcerative colitis should follow a stepwise approach, prioritizing the use of biologic agents such as infliximab, adalimumab, golimumab, vedolizumab, and tofacitinib for moderate to severe disease, as recommended by the AGA clinical practice guidelines 1.

Stepwise Approach

The stepwise approach typically starts with:

• 5-aminosalicylates (5-ASAs) such as mesalamine (2.4-4.8g daily) for mild to moderate ulcerative colitis, though these are less effective in Crohn's disease.
• Corticosteroids like prednisone (40-60mg daily with taper over 8-12 weeks) for disease flares in both conditions.

Biologic Agents

For moderate to severe disease or those failing conventional therapy, biologic agents are employed, including:

• Anti-TNF drugs (infliximab, adalimumab, golimumab)
• Anti-integrin therapies (vedolizumab)
• IL-12/23 inhibitors (ustekinumab)
• JAK inhibitors (tofacitinib for UC)

Combination Therapy

Combination therapy with an immunomodulator plus biologic often provides superior outcomes, as suggested by the ECCO guidelines on therapeutics in Crohn's disease 1.

Surgery

Surgery is reserved for complications or medically refractory disease, with colectomy being curative for ulcerative colitis but not for Crohn's disease.

Biomarker-Based Monitoring

A biomarker- and symptom-based monitoring strategy is suggested for patients with UC in symptomatic remission, using fecal calprotectin <150 mg/g, normal fecal lactoferrin, or normal CRP to rule out active inflammation and avoid routine endoscopic assessment of disease activity, as recommended by the AGA clinical practice guideline on the role of biomarkers for the management of ulcerative colitis 1.

From the FDA Drug Label

HUMIRA is a tumor necrosis factor (TNF) blocker indicated for: Crohn’s Disease (CD) (1.5): treatment of moderately to severely active Crohn’s disease in adults and pediatric patients 6 years of age and older. Ulcerative Colitis (UC) (1. 6): treatment of moderately to severely active ulcerative colitis in adults and pediatric patients 5 years of age and older.

ENTYVIO is indicated in adults for the treatment of: moderately to severely active ulcerative colitis (UC). moderately to severely active Crohn's disease (CD).

The management of Crohn's disease and ulcerative colitis can be done using a stepwise approach.

• Step 1: Treatment with aminosalicylates or corticosteroids for mild to moderate disease.
• Step 2: Addition of immunomodulators such as azathioprine or mercaptopurine for moderate to severe disease.
• Step 3: Introduction of biologics such as adalimumab 2 or vedolizumab 3 for moderately to severely active disease that does not respond to previous treatments. It is essential to note that the specific treatment approach may vary depending on the individual patient's condition and response to therapy. Key considerations include:
• Disease severity: Treatment should be tailored to the severity of the disease.
• Patient response: Treatment should be adjusted based on the patient's response to therapy.
• Safety profile: The safety profile of each medication should be considered when making treatment decisions.

From the Research

Management of Ulcerative Colitis

• The primary goal of managing ulcerative colitis (UC) is to induce and maintain clinical remission, as well as screen for complications of the disease 4.
• Mesalamine, a 5-aminosalicylic acid compound, is considered the first-line therapy for inducing and maintaining clinical remission in patients with mild-to-moderate UC 4, 5.
• For patients who are refractory to mesalamine or have more severe disease, other treatment options include steroids, azathioprine/mercaptopurine, cyclosporine, or infliximab 4.
• The use of once-daily formulations of mesalamine, such as MMX mesalamine, has been shown to effectively induce and maintain clinical remission in patients with active mild-to-moderate UC 4.

Management of Crohn's Disease

• Mesalamine derivatives have been shown to be beneficial in the treatment of Crohn's disease, although sulfasalazine is likely not effective in maintaining remission 6.
• Other mesalamine formulations have been shown to have some prophylactic activity after inducing remissions and for patients with disease of the ileum who have undergone surgical resection 6.

Stepwise Approach to Management

• The management of UC and Crohn's disease typically involves a stepwise approach, starting with mild treatments and progressing to more aggressive therapies as needed 7, 8.
• Traditional therapeutic agents such as 5-aminosalicylates, sulfasalazine, corticosteroids, and immunomodulatory drugs have remained the gold standard for decades, but novel formulations and dosage regimens have changed their sequences in the medical management of UC 7.
• Emerging therapies, including biologics and small molecules, are being developed and have shown promise in the treatment of UC 7, 8.