Expert spotlights advances in ulcerative colitis treatment

FDA approval of the IL-23 inhibitor guselkumab has expanded treatment options for patients with moderately to severely active ulcerative colitis, offering greater flexibility through subcutaneous administration, according to Kara De Felice, MD.

“It's been exciting getting a subcutaneous option for our patients with ulcerative colitis,” Dr. De Felice, a gastroenterologist at the University of Cincinnati Medical Center, said during the 2026 Crohn’s & Colitis Congress®, a partnership of AGA and the Crohn's & Colitis Foundation, held in Las Vegas.

Data supporting subcutaneous guselkumab were presented from the multicenter ASTRO treat-through-design trial at the 2025 Digestive Disease Week meeting. In the 12-week induction study, 395 patients with moderate-to-severe UC were randomized to receive subcutaneous guselkumab or placebo at weeks 0, 4 and 8, followed by maintenance therapy of either 200 mg every four weeks or 100 mg every eight weeks, or placebo.

The primary endpoint was clinical remission at week 12, with endoscopic improvement as a key secondary endpoint. At week 12, clinical remission was achieved in 26% of patients treated with guselkumab compared with 7% of those receiving placebo. Endoscopic improvement occurred in 36% of guselkumab-treated patients versus 12% in the placebo group (P < 0.001 for both comparisons).

Additional evidence came from QUASAR, randomized withdrawal design studies which evaluated guselkumab as both induction (intravenous) and maintenance (subcutaneous) therapy in UC. The induction study included 701 patients, with 421 receiving intravenous guselkumab 200 mg and 280 receiving placebo.

At week 12, clinical remission was observed in 23% of patients treated with intravenous guselkumab compared with 8% of those receiving placebo. Endoscopic improvement rates were 27% and 11%, respectively (P < 0.001 for both comparisons).

“Even though these studies were differently designed and we can’t make direct comparisons, I think that we can walk away saying that we have two good choices for our patients in clinic, either giving them subcutaneous or intravenous guselkumab for induction therapy,” Dr. De Felice said. “Reflecting on my experience, most patients are choosing to subcutaneous injections as it’s easier to arrange and they’re probably getting to drug faster instead of waiting to be set up in our infusion center.”

Dr. De Felice also highlighted emerging data supporting the use of Janus kinase (JAK) inhibitors in the inpatient management of acute severe UC.

She cited results from the Canadian TRIUMPH study, which evaluated 24 patients treated with tofacitinib 10 mg twice daily for intravenous steroid–refractory disease. By day 7, 58.3% of patients achieved a clinical response, with a mean time to response of 2.4 days. Responders also demonstrated a marked reduction in C-reactive protein within the first two days of treatment compared with nonresponders.

Further evidence was presented from the TACOS trial, which randomized 104 adults with acute severe UC to receive either tofacitinib 10 mg three times daily or placebo for seven days while continuing intravenous corticosteroids.

The primary endpoint was treatment response by day 7, defined as a reduction in the Lichtiger score of more than 3 points with a sustained score below 10 for two consecutive days without rescue therapy. A key secondary endpoint was the need for infliximab or colectomy within 90 days.

At day 7, response rates were 83.01% in the tofacitinib group compared with 58.82% in the placebo group (odds ratio, 3.42; P = 0.007). The need for rescue therapy by day 7 was lower in the tofacitinib arm (odds ratio, 0.27; P = 0.01).

“About six patients in the tofacitinib arm did require colectomy by month six, and one patient developed a dural venous sinus thrombosis,” said Dr. De Felice, who was not involved in the trial.

Sara Horst, MD, MPH, Professor of Medicine, Gastroenterology, Hepatology, & Nutrition and Vanderbilt University Medical Center, Nashville, who moderated the session, told GI & Hepatology News that she is increasingly using JAK inhibitors for acute severe UC. “The key for clinicians is to remember how devastating acute severe UC can be for patients and the high need for colectomy within six to 12 months,” she said. “Therefore, starting an advanced therapy as soon as possible is key to prevent adverse outcomes.”

Dr. De Felice concluded by discussing the potential role of laparoscopic appendicectomy in maintaining remission in UC. In the international, open-label ACCURE trial, 201 patients were randomized to appendicectomy plus standard medical therapy or standard medical therapy alone. At one year, relapse occurred in 36% of patients in the appendicectomy group compared with 56% in the standard care group (P = 0.005).

Adverse events were reported in 11% of patients who underwent appendicectomy and 10% of those in the control group. The most common adverse events were temporary self-limiting postoperative abdominal pain in the appendicectomy group (3%) and skin rash in the control group (3%). Serious adverse events occurred in two patients (2%) in the appendicectomy group and none in the control group. No deaths were reported.

“Appendicectomy is a viable and safe strategy for reducing the relapse rate in patients with UC compared to standard medical therapy alone,” Dr. De Felice said.

Dr. Horst cautioned that while the data are encouraging and suggest potential new options for patients, further evidence is needed. “Ideally, a high-quality placebo (aka sham surgery) randomized trial is needed to verify these results,” she said.

Dr. De Felice disclosed that she is an honorary speaker for AbbVie, Janssen and Pfizer and serves on AbbVie’s advisory board. Dr. Horst disclosed that she is a consultant to Johnson & Johnson, AbbVie, Takeda, Pfizer, and Biocon. She has also received educational grants from AbbVie and Takeda.