Induction vs Maintenance Therapy in Patients With Ulcerative Colitis

Maia Kayal, MD: In a network meta-analysis where multiple biologics and small molecules were compared, upadacitinib across the board was the best at inducing clinical remission in patients with moderate to severe ulcerative colitis. However, we are limited in that we can’t use upadacitinib as first-line therapy as the FDA has restricted it to patients who have previously failed anti-TNF [tumor necrosis factor] therapy. However, it’s very reassuring to have these data, and to know that we can still treat our patients who have not responded to adalimumab or infliximab.

We typically divide treatment regiments into an induction phase and a maintenance phase. The induction phase is targeted to get as much of the drug into the patient as possible to rapidly eliminate the symptoms of inflammation and the severity of the disease. In the maintenance phase, we typically rely on the drug to maintain the remission that was induced in the initial induction phase. Different biologics and small molecules have different regimens for induction and maintenance. This can include either rapid dose optimization in the first couple of weeks, and then a dose decrease during maintenance, or it includes a change in frequency from induction to maintenance. For example, with infliximab, the initial induction doses are 3 and are given within 6 weeks of each other. In the maintenance phase, infliximab then shifts to dosing every 8 weeks. When approaching induction versus maintenance, the question that I like to ask myself is, how can I get the most out of this drug that I’m using for a patient with moderate to severe ulcerative colitis? The answer typically is during induction. You want to maximize induction dosing for patients with moderate to severe ulcerative colitis so that they can make it into the maintenance phase.

What does that translate into? That translates into early optimization of medication by using objective markers, such as C-reactive protein, fecal calprotectin, and in some cases even using therapeutic drug monitoring. For example, in a patient who is on upadacitinib, who has not responded to the standard 8 weeks of induction, we might consider doing an additional 8 weeks of induction. There have been data that support that extending induction can capture an additional 50% of patients who did not respond to the initial induction phase. In patients with infliximab who lose response after the second dose, there are some data to support bringing the patients in earlier for that third induction dose to optimize the amount of drug in the patient. This correlates directly with the severity of inflammation. Patients who have more severe disease might need more drug up front, and that’s why maximizing your induction is key to getting into maintenance of remission.

The presence of comorbidities has a significant impact on the treatment decisions and should be one of the first questions you ask yourself as a provider when deciding what the treatment approach should be. For patients with cardiac conduction abnormalities or a baseline history of macular edema, we stay away from ozanimod, as clinical trial data have shown a low incidence of bradycardia and macular edema in the safety risk profiles. For patients who have a history of thrombosis, we stay away from the Janus kinase inhibitors, as rheumatologic literature suggests an increased risk of thrombosis in that patient population. For patients who have significant extraintestinal manifestations, such as arthritis, arthralgia, ankylosing spondylitis, the use of anti-TNF agents is excellent. There have been data to support the use of ustekinumab and Janus kinase inhibitors for that patient population as well. For patients who have skin manifestations, the use of ustekinumab is an excellent option as that has been used for skin conditions for multiple years prior to approval for ulcerative colitis.

Transcript Edited for Clarity