Adults with Moderately to Severely Active Ulcerative Colitis Maintain Higher Remission Rates with Guselkumab, Golimumab Combination Therapy

The VEGA study is the first randomized, controlled trial to evaluate the efficacy and safety of combination therapy with an interleukin (IL)-23p19 subunit antagonist (guselkumab) and a tumor necrosis factor-alpha (TNFα) antagonist (golimumab) in UC.

Adults with moderately to severely active ulcerative colitis (UC) who received 12 weeks of combination induction therapy with guselkumab and golimumab, followed by a transition to guselkumab alone for maintenance, achieved a clinical remission rate of 47.9% at week 38, according to data from an ongoing analysis of a phase 2a clinical trial .

The VEGA study is the first randomized, controlled trial to evaluate the efficacy and safety of combination therapy with an interleukin (IL)-23p19 subunit antagonist (guselkumab) and a tumor necrosis factor-alpha (TNFα) antagonist (golimumab) in UC.

“Exploring combinations of advanced therapies is an important step in continuing to innovate for the many patients living with ulcerative colitis,” said Bruce E. Sands, MD, MS, chief of the Dr. Henry D. Janowitz Division of Gastroenterology at Mount Sinai, professor of Medicine at the Icahn School of Medicine at Mount Sinai, and VEGA steering committee member, in a press release. “These new data from the VEGA trial build upon and affirm our initial 12-week findings showing the potential clinical benefit of combining guselkumab and golimumab in treating adults with moderately to severely active ulcerative colitis.”

In the VEGA study, patients with moderately to severely active UC were randomized to receive combination therapy with guselkumab and golimumab, guselkumab monotherapy, or golimumab monotherapy. After endpoints were evaluated at week 12, patients in the monotherapy groups continued their initially assigned treatment, whereas patients randomized to the combination therapy group transitioned to guselkumab alone as a maintenance therapy.

Clinical remission was assessed based on the modified Mayo score and the total Mayo score. Investigators assessed symptomatic remission, endoscopic improvement, endoscopic remission, histologic remission, and composite histologic-endoscopic endposting at week 38 in an exploratory analysis, with safety evaluated through week 50.

The study showed that 47.9% of patients administered the guselkumab and golimumab combination followed by maintenance treatment with guselkumab achieved clinical remission at week 38 versus 31% and 20.8% of patients who received guselkumab or golimumab alone, respectively.

At week 38, patients in the combination therapy followed by guselkumab cohort showed greater endoscopic improvement and higher composite histologic-endoscopic endpoint vs patients administered guselkumab or golimumab alone. Further, endoscopic and histologic remission were higher in patients in the combination therapy followed by guselkumab cohort vs patients administered golimumab monotherapy.

The cohorts of patients administered the combination therapy followed by guselkumab maintenance treatment and patients administered guselkumab monotherapy achieved the same rate of symptomatic remission of 69% at week 38, which was greater than the golimumab monotherapy group of 59.7%.

The rates of adverse events (AEs) were comparable through week 50 of the study. Further, the combination therapy followed by guselkumab, guselkumab alone, and golimumab alone groups had AE rates of 63.4%, 64.8%, and 76.4%, respectively, and infection rates of 31.0%, 23.9%, and 31.9%, respectively.

All the groups had the same rates of serious AEs at 5.6% and the same serious infection rates of 2.8%. Overall, 13.1% of patients discontinued their treatment prior to the final dose of study intervention.

“The 38-week VEGA data suggest the potential that guselkumab and golimumab combination therapy has in patients with moderately to severely active ulcerative colitis for whom previous conventional treatments have inadequately managed their disease or improved their well-being,” said Jan Wehkamp, MD, PhD, vice president of Gastroenterology Disease Area Leader, Janssen Research & Development, LLC, in a press release. “We thank the patients who participated in the VEGA study, as their contribution helps us get closer to our goal of developing therapies that will bring meaningful improvements to patients with ulcerative colitis.”

REFERENCE

Results of Novel Clinical Study of Guselkumab and Golimumab Combination Therapy Show Adults with Moderately to Severely Active Ulcerative Colitis Maintained Higher Rates of Clinical, Histologic, and Endoscopic Remission at Week 38. Johnson and Johnson. October 10, 2022. Accessed October 12, 2022. https://www.jnj.com/results-of-novel-clinical-study-of-guselkumab-and-golimumab-combination-therapy-show-adults-with-moderately-to-severely-active-ulcerative-colitis-maintained-higher-rates-of-clinical-histologic-and-endoscopic-remission-at-week-38