Hans Herfarth, MD, on Ulcerative Colitis in 2022

Two new oral medications have added to a significant extension of the therapeutic armamentarium for moderate to severe ulcerative colitis (UC), Hans Herfarth, MD, told the audience at the April 2 Advances in Inflammatory Bowel Diseases (AIBD) regional meeting in Raleigh, North Carolina.

“Now we have a choice of 11 drugs, including cyclosporine/tacrolimus and steroids,” he noted.

Dr Herfarth is a professor medicine at the University of North Carolina at Chapel Hill and leads the UNC Multidisciplinary Center for IBD Research and Treatment.

He discussed the importance of distinguishing between disease activity—the severity of symptoms at the time of assessment—and disease severity—"the assessment of disease course since diagnosis, which includes current disease activity, past failed therapies, steroid dependence, hospitalizations for active UC, and complications,” including cytomegalovirus (CMV) colitis and Clostridioides difficile infection.

Dr Herfarth reviewed the use of endoscopic severity grading using the Mayo score or the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) when determining the appropriate therapy for the patient. For a flare of disease that can be categorized as mild to moderate in terms of disease activity, the location is important, he noted. For proctitis, local 5-ASA administered by suppository is recommended. In the case of left-sided UC or pancolitis, topic 5-ASA (4 g by enema) plus oral 5-ASAs are indicated. Among patients who have required corticosteroids, a dosing of oral 5-ASA at 4.8 g/day have shown greater efficacy than a dose of 2.4 g daily, he added.

If patients treated according to these guidelines show no significant improvement after 7-14 days, Dr Herfarth suggested the next step is budesonide multimatrix (MMX) therapy or systemic corticosteroids plus oral 5-ASAs. In the case of proctitis, the addition of a topical steroid to the topical 5-ASA is an option.

When patients suffer a recurrence of UC after induction therapy with corticosteroids, Dr Herfarth stated, these patients should be treated according to the moderate/severe UC algorithm and considered steroid dependent. If remission is achieved, maintenance therapy with 5-ASAs is indicated for patients with proctitis (at 1 g/day or less frequent) or with left-sided or pancolitis (at ≥1.6 g/day.) Corticosteroids should not be used for maintenance therapy, he stressed.

Dr Herfarth discussed the real-world efficacy of nudesonide MMX. He referenced a study by Greenberg et al of 96 patients in a tertiary care center during the period 2013-2017, in which 55% of patients were treated with 5-ASAs, 18% with thiopurine, 17% with a biologic, and 8% received no therapy. These patients had a median disease duration of 12 years.

The indication for treatment with budesonide MMX was to prevent the need to treat with prednisone among 86% of patients, while among 14% of the patients budesonide MMX was chosen due to previous side effects of prednisone. The study indicated that among this cohort, 54% did not require a transition to prednisone after being treated with budesonide MMX. The key risk factors for those who did require the transition were male sex and an age at diagnosis of UC of 29 years or younger.

One of the newest therapies for UC is ozanimod, a first sphingosine-1-phosphate receptor agonist. Dr Herfarth reviewed data from a study of ozanimod’s efficacy for inducing remission in UC. Of all patients in the study, 18.0% achieved remission at week 10 vs 10.0% on placebo; 22.o% of patients naïve to biologics achieved remission vs 6.6 on placebo; among biologic-experienced patients, 10.0% achieved remission vs 4.6% of patients on placebo.

At week 52, 37.0% of all patients had achieved remission vs 18.5% of patients in the placebo group. Among bio-naïve patients, 40.9% were in remission vs 22.2 of those on placebo; and  28.9% of bio-experienced patients were in remission vs 10.1% of patients on placebo.

Upadacitinib, a JAK-inhibitor, showed significant results in two studies, Dr Herfarth explained. At week 8, 33.5% of patients in UACCOMPLISH had achieved remission, compared to 4.1% of patients in the placebo group. In UACHIEVE, 26.1% of patients treated with upadacitinib had reached remission vs 4.8% of those treated with placebo. Further, the extension trial of UACHIEVE demonstrated that at week 52, 42.0% of patients treated with upadacitinib at the 15

Dr Herfarth explained that the safest therapies to date are vedolizumab and ustekinumab, followed by anti-TNF monotherapy; thiopurine and ozanimod; combination therapy with thiopurine and anti-TNFs; cyclosporine; and the JAK inhibitors tofacitinib and upadacitinib.

He recommended positioning infliximab or vedolizumab for induction therapy among biological-naïve patients, with ozanimod or upadacitinib as possible options. For patients already exposed to an anti-TNF, upadacitinib, tofacitinib, and ustekinumab are good choices. Among patients already exposed to vedolizumab, Dr Herfarth said infliximab and ustekinumab are options, with ozanimod and upadacitinib offered as options. For patients at risk of adverse events and infection, or with cancer history, the best choices are vedolizumab and ustekinumab due to their excellent safety profiles.

“We have seen the significant extension of our therapeutic armamentarium for moderate-severe UC with 2 new oral drugs,” Dr Herfarth stated. “Based on guidelines from 2020 we have some guidance, but we need real-world studies to understand better the context of comparative efficacy and sequencing, and the search for biomarkers for success of specific drugs needs to be intensified.”

--Rebecca Mashaw

Herfarth, H. Ulcerative Colitis in 2022. Presented at: Advances in Inflammatory Bowel Diseases regional meeting. April 2, 2022. Raleigh, North Carolina.