Many biologics that are currently US Food and Drug Administration (FDA) approved or under investigation for ulcerative colitis target TNF, α4β7, IL-12/IL-23, the S1P receptor, and JAK signaling. Due to their different mechanisms of action, both the therapeutic effects and the adverse events that are associated with each class of agent can vary, as can their long-term safety profiles.

We have a number of treatment options for patients with moderate to severe ulcerative colitis, each of which has their own efficacy and side-effect profiles. It is important to choose the right therapy for each patient and to understand each patient’s individual comorbidities, disease characteristics, and disease severity. Anti-TNF medications are quite effective at controlling inflammation but are associated with drug immunogenicity and other issues. Before recommending them, we need to screen for hepatitis B and tuberculosis exposure and to consider vaccination against infectious diseases. In my practice, that includes pneumococcal, influenza, and COVID-19 vaccines for adults. Recently, the Advisory Committee on Immunization Practices (ACIP) recommended that the shingles vaccine also be given to everyone aged 19 years and older receiving immunosuppressive therapy.

Importantly, anti-TNF therapies have been associated with rare complications that may occur when bowel inflammation is exceedingly well controlled. Probably the most common are psoriasiform eruptions on the scalp, hands, and feet. In most instances, we can treat these effects with topicals and maintain the patient’s anti-TNF therapy, but sometimes we need to switch classes of medication. Another rare paradoxical reaction is demyelination, so any new neurologic symptoms should be worked up. Drug-induced leukocytoclastic vasculitis can occur, as well as a drug-induced lupus reaction with a paradoxical increase in inflammatory joint symptoms. These reactions often require a change in class of therapy.

Vedolizumab is a gut-specific medication targeting α4β7 integrin to reduce colonic inflammation. It has a favorable safety profile and typically results in fewer infectious complications. In a meta-analysis of patients with ulcerative colitis, vedolizumab was associated with a nearly 32% lower risk of serious infection compared with anti-TNF medications. So, this is something that we want to consider, and, in my practice, it is often a first-line agent.

Ustekinumab is an anti–IL-12/IL-23 agent with an excellent safety profile. With this treatment, we have not seen significant malignancy risk or infectious complications, or many of the adverse events that are associated with anti-TNF therapies. Therefore, this class of agents is my first choice when someone receiving an anti-TNF therapy develops paradoxical psoriasis or psoriasiform eruption.

For S1P receptor modulators such as ozanimod and etrasimod, side effects include bradycardia, so we screen with an electrocardiogram to make sure that people with a heart block are excluded. Macular edema also has been reported, so we do not include anyone with history of that. We have patients with a risk factor such as diabetes undergo an ophthalmologic examination. Additionally, if necessary, varicella antibody titers and revaccination are recommended to ensure the prevention of primary varicella infection. Other recommendations include having a skin examination to ensure that there is no evidence of malignancy.

JAK inhibitors have demonstrated efficacy in ulcerative colitis, but there are safety considerations. For example, there is an increased risk of infections, so vaccination is recommended. There may also be an increased risk of major adverse cardiac events and deep vein thrombosis, based on the results from a study of patients with rheumatoid arthritis, so, right now, the FDA recommends the use of JAK inhibitors only after failing anti-TNF therapy.