Alternatives to Infliximab in Inflammatory Bowel Disease
For ulcerative colitis with contraindication to infliximab, use ustekinumab or tofacitinib as first-line alternatives, with vedolizumab reserved for patients prioritizing safety over efficacy. 1
For Ulcerative Colitis
Primary Alternatives (Ranked by Efficacy)
Ustekinumab or Tofacitinib are the preferred alternatives when infliximab is contraindicated, particularly in patients who would have been infliximab-naïve 1. The AGA guidelines suggest these agents over vedolizumab or adalimumab based on network meta-analysis showing superior efficacy for induction of remission 1.
Vedolizumab represents a reasonable alternative for patients who place higher value on medication safety and lower value on relative efficacy, particularly those with less severe disease 1. This is especially relevant given the favorable safety profile of vedolizumab compared to TNF antagonists.
Adalimumab is classified as a "lower efficacy medication" compared to infliximab 2, but remains viable for patients who value the convenience of self-administered subcutaneous injections 2. Network meta-analysis demonstrated infliximab superiority over adalimumab (OR 2.10; 95% CI 1.16-3.79) 1.
Golimumab is another TNF antagonist option approved for ulcerative colitis 1, though it shares similar efficacy concerns as adalimumab when compared to infliximab.
For Crohn's Disease
Adalimumab is FDA-approved for Crohn's disease and represents the primary alternative TNF antagonist 1. It has demonstrated efficacy in randomized controlled trials specifically after infliximab failure 3.
Certolizumab pegol is approved for Crohn's disease and effective for both induction and maintenance of remission 1, 3.
Ustekinumab (IL-12/23 inhibitor) is approved for moderately to severely active Crohn's disease, particularly in patients with inadequate response or intolerance to TNF inhibitors 1.
Upadacitinib (JAK inhibitor) has been approved in some countries for adults with moderately to severely active Crohn's disease who have had inadequate response or intolerance to one or more TNF inhibitors 1.
Critical Contraindications to Consider
Avoid Specific Agents in Certain Contexts
IL-17 inhibitors (secukinumab, brodalumab) are absolutely contraindicated in patients with active IBD as they have been shown to exacerbate Crohn's disease in clinical trials 1. This is a strong recommendation based on evidence of disease worsening.
Etanercept is not approved for either Crohn's disease or ulcerative colitis and should not be used as an alternative 1.
NSAIDs should be avoided in patients with active IBD as they may precipitate de novo disease or exacerbate pre-existing IBD 1.
Safety Considerations for Alternative TNF Antagonists
If the contraindication to infliximab is related to class-wide TNF antagonist concerns (such as active tuberculosis, serious infections, hepatitis B reactivation, demyelinating disease, or heart failure), then all TNF antagonists including adalimumab, golimumab, and certolizumab should also be avoided 4, 5.
In such cases, switch to a different mechanism of action:
- Vedolizumab (anti-integrin) for both UC and CD 6
- Ustekinumab (IL-12/23 inhibitor) for both UC and CD 1
- Tofacitinib (JAK inhibitor) for UC only 1, 7
- Upadacitinib (JAK inhibitor) for CD 1
Special Populations
Patients with Concurrent Axial Spondyloarthritis
Monoclonal antibody TNF inhibitors (adalimumab, certolizumab, golimumab) are strongly recommended over other biologics or JAK inhibitors for patients with both axSpA and IBD 1. If TNF inhibitors are contraindicated in patients with axSpA and ulcerative colitis specifically, JAK inhibitors are conditionally recommended 1.
Patients with Recurrent Uveitis
Monoclonal antibody TNF inhibitors (adalimumab) are conditionally recommended over other biologics for patients with axSpA and recurrent/refractory uveitis 1. Etanercept should be avoided as it is less effective and may exacerbate uveitis 1.
Common Pitfalls to Avoid
Do not assume all TNF antagonists are interchangeable - infliximab has demonstrated superior efficacy to adalimumab in biologic-naïve UC patients 1, 2, though this difference may be less pronounced when drug concentrations are optimized 1.
Do not use tofacitinib as first-line therapy in biologic-naïve patients outside clinical trials - FDA labeling restricts use to post-TNF failure 7. Additionally, avoid high-dose maintenance (10 mg BID) due to increased thromboembolism and mortality risk 7.
Do not overlook the importance of combination therapy - combining TNF antagonists with immunomodulators (azathioprine, 6-mercaptopurine, or methotrexate) reduces antibody formation and improves treatment durability 8, 9, though this increases risk of hepatosplenic T-cell lymphoma, particularly in young males 4.
Screen for latent tuberculosis before initiating any TNF antagonist alternative 8, 9, as this is a class effect requiring monitoring across all TNF inhibitors.