Can Ustekinumab (Stelara) be used to treat both Crohn's disease and Ulcerative Colitis (UC)?

Ustekinumab for Crohn's Disease and Ulcerative Colitis

Yes, ustekinumab is FDA-approved and strongly recommended for both Crohn's disease and ulcerative colitis, with high-quality evidence supporting its use for induction and maintenance of remission in both conditions. 1, 2

FDA-Approved Indications

Ustekinumab (Stelara) is approved for both inflammatory bowel disease subtypes:

• Crohn's Disease: Approved for moderate to severe disease in both anti-TNF naïve and anti-TNF experienced patients 1, 2
• Ulcerative Colitis: Approved for moderate to severe disease with demonstrated efficacy in clinical trials 1, 2
• The pharmacokinetics are similar between Crohn's disease and ulcerative colitis patients, with clearance of 0.19 L/day and median terminal half-life of approximately 19 days in both populations 1, 2

Guideline Recommendations

Crohn's Disease

The British Society of Gastroenterology provides a strong recommendation (GRADE: strong recommendation, high-quality evidence, 97.7% agreement) that ustekinumab can be used for induction and maintenance of remission in Crohn's disease, both in anti-TNF naïve patients and those where anti-TNF treatment fails. 3

• In the UNITI-1 trial (anti-TNF failure patients), clinical response at week 8 was 37.8% with ustekinumab 6 mg/kg versus 20.2% with placebo (p<0.001) 3
• In the UNITI-2 trial (anti-TNF naïve patients), clinical response at week 8 was 57.9% with ustekinumab 6 mg/kg versus 32.1% with placebo (p<0.001) 3
• For maintenance therapy, 53.1% of responders treated with 90 mg subcutaneously every 8 weeks remained in remission at 44 weeks versus 35.9% on placebo (p=0.005) 3
• In anti-TNF refractory patients specifically, 41.1% achieved remission at week 44 with ustekinumab versus 26.2% with placebo 3

The American Gastroenterological Association (2024) recommends ustekinumab for TNF-antagonist-naïve CD patients, though infliximab and risankizumab are now favored over ustekinumab based on more recent comparative data. 3

Ulcerative Colitis

Ustekinumab is approved and effective for ulcerative colitis, though it ranks lower in the treatment hierarchy compared to other biologics:

• The 2024 Gastroenterology guidelines indicate that in biologic-naïve UC patients, infliximab is superior to ustekinumab 3
• For TNF-antagonist exposed UC patients, ustekinumab is superior to vedolizumab or tofacitinib 3
• However, upadacitinib is superior to ustekinumab in TNF-antagonist exposed UC patients 3
• A positive relationship exists between ustekinumab exposure and rates of clinical remission, clinical response, and endoscopic improvement in UC 1, 2

Dosing Regimen

The dosing differs between Crohn's disease and ulcerative colitis:

Induction Dosing

• Weight-based IV induction: Approximately 6 mg/kg administered intravenously 3, 4
• Mean peak serum concentration: 125.2 ± 33.6 mcg/mL in Crohn's disease and 129.1 ± 27.6 mcg/mL in ulcerative colitis 1, 2

Maintenance Dosing

• 90 mg subcutaneously every 8 weeks starting at Week 8 3, 1, 2
• Steady-state trough concentrations: 2.5 ± 2.1 mcg/mL in Crohn's disease and 3.3 ± 2.3 mcg/mL in ulcerative colitis 1, 2
• No apparent accumulation occurs with every 8-week dosing 1, 2

Treatment Positioning

When to Use Ustekinumab

For Crohn's Disease:

• First-line biologic option in anti-TNF naïve patients (though infliximab and risankizumab are now preferred based on 2024 data) 3, 4
• Strongly recommended after anti-TNF failure (primary or secondary loss of response) 3, 4
• After vedolizumab failure in patients who have not responded to anti-TNF therapy 4

For Ulcerative Colitis:

• Preferred over vedolizumab or tofacitinib in TNF-antagonist exposed patients 3
• Not first-line in biologic-naïve patients (infliximab is superior) 3

Dose Escalation Strategies

Loss of response occurs at a rate of 21% per person-year in Crohn's disease patients who initially respond to ustekinumab. 5

• 58% of secondary non-responders regain clinical response after dose escalation (interval reduction or IV reinduction) 5
• Dose escalation is required in approximately 25% of primary responders per person-year 5
• IV maintenance therapy can be effective when subcutaneous dosing loses efficacy, with 64.3% achieving clinical remission at 52 weeks and ustekinumab serum levels quadrupling 6
• In ulcerative colitis, 35% of patients may require dose escalation, with 58% regaining symptomatic remission after escalation 5

Safety Profile

Ustekinumab has a favorable safety profile:

• Low rate of antibody formation (under 5%) 4
• No clinically significant drug interactions with CYP450 substrates 2
• Clearance not impacted by concomitant corticosteroids, immunomodulators (azathioprine, 6-MP, methotrexate), NSAIDs, or prior TNF blocker exposure 1, 2
• Rare immediate infusion reactions can occur with IV administration 7
• Avoid live vaccines during treatment 4

Combination Therapy

There is no evidence to support routine use of thiopurines or methotrexate with ustekinumab compared with ustekinumab monotherapy in either Crohn's disease or ulcerative colitis. 3

• This contrasts with anti-TNF therapy where combination therapy is recommended 3
• Serum ustekinumab concentrations are not impacted by concomitant use of immunomodulators 1, 2

Clinical Monitoring

For Crohn's disease:

• Evaluate response between 6-10 weeks after initiation 8
• Regular monitoring with objective markers (endoscopy, CRP, fecal calprotectin) is crucial 8

For ulcerative colitis:

• Monitor for clinical remission, clinical response, and endoscopic improvement 1, 2
• Response rates approach a plateau at exposures associated with the recommended maintenance dosing regimen 1, 2