What is the next step in biologic therapy for ulcerative colitis patients who have failed mesalamine?

Biologic Selection for Ulcerative Colitis Patients After Mesalamine Failure

For patients with ulcerative colitis who have failed mesalamine therapy, the first-line biologic therapy should be either infliximab or vedolizumab rather than adalimumab due to their superior efficacy in inducing remission. 1

Initial Biologic Selection Algorithm

For Biologic-Naïve Patients:

• Infliximab or vedolizumab are preferred first-line biologic agents due to their superior efficacy in inducing remission compared to adalimumab 1
• Consider combination therapy with a thiopurine (azathioprine or mercaptopurine) or methotrexate rather than biologic monotherapy to improve efficacy, particularly with infliximab 1
• Patients who place higher value on the convenience of self-administration may reasonably choose adalimumab despite its lower comparative efficacy 1
• Tofacitinib should only be used after failure of or intolerance to TNF-α antagonists per FDA recommendations, not as first-line therapy 1

For Patients Previously Exposed to Infliximab:

• In patients with primary non-response to infliximab, use ustekinumab or tofacitinib rather than vedolizumab or adalimumab 1
• For secondary loss of response to an anti-TNF agent, switching to a biologic with a different mechanism of action (vedolizumab or ustekinumab) is associated with better treatment persistence than cycling to another anti-TNF agent 2

Rationale for Early Biologic Therapy

The American Gastroenterological Association (AGA) suggests early use of biologic agents with or without immunomodulator therapy rather than gradual step-up therapy after mesalamine failure for patients with moderate-to-severe ulcerative colitis 1. This recommendation is based on:

• Biologic monotherapy (TNF-α antagonists, vedolizumab, or ustekinumab) or tofacitinib is more effective than thiopurine monotherapy for induction of remission 1
• Delaying effective treatment may increase risk of UC-related complications, hospitalization, colectomy, and reduced quality of life 1
• Early anti-TNF therapy is typically initiated in patients with more severe disease, though earlier treatment alone does not necessarily prevent hospitalization or colectomy 3

Combination Therapy Considerations

• Combining TNF-α antagonists, vedolizumab, or ustekinumab with thiopurines or methotrexate is suggested over biologic monotherapy 1
• The UC-SUCCESS trial demonstrated that combination of infliximab and thiopurines was superior to thiopurine monotherapy for achieving corticosteroid-free remission 1
• Patients with less severe disease who prioritize safety over efficacy may reasonably choose biologic monotherapy 1

Management After Initiating Biologics

• Once remission is achieved with biologic agents and/or immunomodulators or tofacitinib, discontinue mesalamine as it provides no additional benefit 1
• Thiopurine monotherapy is not recommended for induction of remission but may be considered for maintenance of remission 1
• Methotrexate monotherapy is not recommended for either induction or maintenance of remission 1

Special Considerations

• For hospitalized patients with acute severe ulcerative colitis refractory to intravenous corticosteroids, infliximab or cyclosporine are recommended rescue therapies 1
• Therapeutic drug monitoring should be considered to optimize biologic dosing, particularly with infliximab which has higher immunogenicity compared to newer agents 1
• Patients with moderate-to-severe UC who place higher value on safety of mesalamine therapy may choose gradual step therapy, particularly those with less severe disease 1

Common Pitfalls to Avoid

• Delaying biologic therapy in patients with moderate-to-severe disease who have failed mesalamine 1
• Continuing mesalamine after achieving remission with biologics and/or immunomodulators, as this provides no additional benefit 1
• Using thiopurine monotherapy for induction of remission 1
• Using tofacitinib as first-line therapy in biologic-naïve patients, as FDA recommendations specify its use only after failure of or intolerance to TNF-α antagonists 1
• Cycling to another anti-TNF agent after failure of the first one, as switching to a different mechanism of action shows better persistence 2