What biologics (biological medications) are recommended for treating moderate to severe Crohn's disease or ulcerative colitis (UC)?

Biologics for Moderate to Severe Crohn's Disease and Ulcerative Colitis

For moderate to severe ulcerative colitis, use infliximab, adalimumab, golimumab, vedolizumab, tofacitinib, or ustekinumab over no treatment, with infliximab or vedolizumab preferred as first-line agents in biologic-naive patients. 1 For moderate to severe Crohn's disease, use infliximab, adalimumab, or ustekinumab as first-line biologics in biologic-naive patients, with these agents preferred over certolizumab pegol. 1

Ulcerative Colitis: Treatment Algorithm

First-Line Biologic Selection (Biologic-Naive Patients)

• Prefer infliximab or vedolizumab over adalimumab for induction of remission in biologic-naive patients with moderate-severe UC 1
• Adalimumab remains a reasonable alternative for patients who prioritize the convenience of self-administered subcutaneous injection and have less severe disease 1
• Avoid tofacitinib as first-line therapy in biologic-naive patients; FDA guidance restricts its use to patients who have failed or are intolerant to TNF antagonists 1
• Golimumab and ustekinumab are also approved options, though positioned after infliximab and vedolizumab based on comparative efficacy data 1

Second-Line Selection (After Infliximab Failure)

• For patients with primary non-response to infliximab, prefer ustekinumab or tofacitinib over vedolizumab or adalimumab for induction of remission 1
• This recommendation is based on conditional evidence but reflects superior efficacy in this specific population 1

Combination Therapy Considerations

• Combine TNF antagonists, vedolizumab, or ustekinumab with thiopurines or methotrexate rather than using biologic monotherapy for enhanced efficacy 1, 2
• Patients with less severe disease who prioritize safety may reasonably choose biologic monotherapy 1
• Early introduction of biologics with or without immunomodulators is preferred over gradual step-up after 5-ASA failure 1, 2

Crohn's Disease: Treatment Algorithm

First-Line Biologic Selection (Biologic-Naive Patients)

• Use infliximab, adalimumab, or ustekinumab over certolizumab pegol for induction of remission in biologic-naive patients 1
• Vedolizumab is suggested over certolizumab pegol but is positioned after the three preferred agents above 1
• In the head-to-head SEAVUE trial, ustekinumab and adalimumab showed equivalent efficacy (65% vs 61% clinical remission at week 52, p=0.42) in biologic-naive patients, confirming both as excellent first-line options 3

Second-Line Selection (After TNF Antagonist Failure)

• For primary non-response to anti-TNF therapy, use ustekinumab as the preferred agent 1
• Vedolizumab is also suggested over no treatment in this population 1
• For secondary non-response to infliximab, use adalimumab or ustekinumab as preferred options 1
• If adalimumab was the first-line agent, indirect evidence supports switching to infliximab as a second-line TNF antagonist 1

Combination Therapy for Crohn's Disease

• Combine infliximab with thiopurines over infliximab monotherapy in biologic-naive and immunomodulator-naive patients for both induction and maintenance 1
• Indirect evidence suggests combining infliximab or adalimumab with methotrexate may be more effective than monotherapy 1
• No recommendation exists for combining ustekinumab or vedolizumab with immunomodulators due to knowledge gaps 1
• Use biologic monotherapy over thiopurine monotherapy for induction of remission 1

Early Biologic Introduction

• Introduce biologics early (with or without immunomodulators) rather than delaying until after failure of mesalamine and/or corticosteroids 1
• This approach reduces risk of complications, hospitalization, and colectomy 2

Perianal Fistulizing Crohn's Disease

• Use infliximab over no treatment for induction and maintenance of fistula remission in patients with active perianal fistulas 1
• This is a strong recommendation with moderate quality evidence 1

Ustekinumab-Specific Efficacy Data

Crohn's Disease Performance

• In the UNITI-1 trial (TNF antagonist failures), ustekinumab achieved clinical response rates of 34.3% (130 mg) and 33.7% (6 mg/kg) versus 21.5% placebo at week 6 (p≤0.003) 4
• In the UNITI-2 trial (conventional therapy failures), response rates were 51.7% and 55.5% versus 28.7% placebo (p<0.001) 4
• Maintenance therapy with ustekinumab every 8 weeks achieved 53.1% remission at week 44 versus 35.9% placebo (p=0.005) 4
• Among TNF antagonist failures, 41% maintained remission at week 44 with ustekinumab maintenance 5

Ulcerative Colitis Performance

• Ustekinumab (6 mg/kg IV induction) achieved clinical remission in 34% of patients at week 8 in UC-1 trial 5
• Clinical response occurred in 58% of patients at week 8 5
• Maintenance therapy achieved 53% clinical remission at week 44 versus 36% placebo 5

Critical Pitfalls to Avoid

• Do not delay effective biologic therapy in moderate-severe disease, as this increases risk of complications and need for surgery 2
• Do not use thiopurine monotherapy for induction in active moderate-severe UC or CD 1
• Do not use methotrexate monotherapy for UC (oral or parenteral) 1
• Do not use tofacitinib as first-line therapy in UC without prior TNF antagonist failure per FDA guidance 1
• Do not continue 5-ASA therapy once remission is achieved with biologics and/or immunomodulators 1
• Do not use corticosteroids for maintenance of remission in CD 1

Biosimilars and Alternative Formulations

• Biosimilars of infliximab, adalimumab, and ustekinumab are equivalent to originator drugs 2
• Subcutaneous formulations of infliximab and vedolizumab have comparable efficacy to IV formulations 2