For patients with ulcerative colitis, combined induction treatment with guselkumab and golimumab was more effective at inducing a clinical response, clinical remission and endoscopic improvement after 12 weeks than either drug alone, according to a study presented at the 2022 annual meeting of the European Crohn’s and Colitis Organisation.
“This study is the first of its kind and opens you to the possibilities of the power of combining many different sorts of therapies to achieve better results,” said investigator Bruce Sands, MD, MS, a gastroenterologist and the Dr. Burrill B. Crohn Professor of Medicine at Mount Sinai Health System, in New York City. “But I think we’ll have to really study them carefully to understand which combinations will be safe and effective.”
Guselkumab (Tremfya, Janssen) is an interleukin-23 p19 subunit antagonist approved for use in patients with plaque psoriasis and psoriatic arthritis that is being studied as a treatment for inflammatory bowel disease, including ulcerative colitis (UC) and Crohn’s disease. Golimumab (Simponi Aria, Janssen) is a tumor necrosis factor–alpha (TNF-alpha) antagonist that is approved for treating UC. The study, known as VEGA, was a phase 2a multicenter, randomized, double-blind, active-controlled, parallel-group, proof-of-concept clinical trial.
The researchers recruited 214 patients naive to TNF-alpha antagonists and refractory to or intolerant of immunomodulators and/or corticosteroids. In the study (abstract OP36), 71 patients received guselkumab (200 mg IV at weeks 0, 4 and 8), 72 patients received golimumab (200 mg subcutaneously at week 0 and then 100 mg at weeks 2, 6 and 10) and 71 patients received combination treatment (200 mg of guselkumab and 200 mg of golimumab at week 0 and then 100 mg of golimumab at weeks 2, 6 and 10, and 200 mg of guselkumab at weeks 4 and 8).
After 12 weeks, the researchers found that 83.1% of the patients who received the combination therapy achieved a clinical response—the study’s primary end point—compared with 74.6% of patients who received only guselkumab and 61.1% of patients who received only golimumab. In addition, 36.6% of patients who were given the combination treatment achieved clinical remission, compared with 21.1% of the guselkumab group and 22.2% of the golimumab group.
The secondary outcome, endoscopic improvement, was particularly exciting, Dr. Sands told Gastroenterology & Endoscopy News. In the study, 49.3% of the patients who received the combined treatment showed endoscopic improvement, compared with 29.6% of those who received guselkumab alone and 25.0% of the patients who received only golimumab. “We just have seen very few things that can achieve that level of efficacy” in endoscopic improvement, Dr. Sands said.
Rates of adverse events were similar in all three treatment groups. One patient who received the combination therapy had a serious infection with influenza and sepsis. Through week 12, no deaths, malignancies or cases of tuberculosis were reported.
Although the initial findings are promising, the researchers cannot determine all the outcomes from this small and short study, Dr. Sands noted. The next step would be to study this combination therapy compared with monotherapy in a one-year, dose-ranging study (called DUET-UC), he said.
It will be interesting to see if this combined therapy approach would benefit the sickest UC patients, including those who have failed standard therapy, commented Arun Swaminath, MD, the director of Northwell Health’s Inflammatory Bowel Diseases Program and the chief of gastroenterology at Lenox Hill Hospital, in New York City. “That’s the group many of us, I would imagine, are hungry to be able to treat with this type of approach,” he said.
A cost analysis also would be important, to see if the price of the combined treatment is worth the benefits, including avoiding hospitalization and surgery, Dr. Swaminath said. He also noted that risks associated with the combined treatment may not become apparent until after patients have been on the therapy for longer than 12 weeks.
Nevertheless, exploring the efficacy and safety of combined therapies that interfere with these specific inflammatory pathways is important, particularly when it comes to expanding treatment options for UC patients who don’t do well on a single therapy, Dr. Swaminath said. “Something like this is really critical for all of us to understand if we’re actually on the right track.”