VEGA: Guselkumab plus golimumab achieved higher clinical remission rates in UC
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CHARLOTTE, N.C. — Guselkumab in combination with golimumab induced greater rates of clinical remission compared with monotherapy among patients with moderate to severely active ulcerative colitis.
VEGA phase 2a proof-of-concept week 12 data showed dual blockade of interleukin (IL)-23 and tumor necrosis factor induced clinical response, clinical remission, endoscopic improvement and composite histologic-endoscopic outcomes more effectively than monotherapy alone, Brian G. Feagan, MD, senior scientific director of Alimentiv Inc. and gastroenterologist at Western University, reported at the ACG Annual Scientific Meeting.
“The induction phase of VEGA, which was reported out earlier this year, showed clearly that combination of golimumab and guselkumab was superior to either golimumab alone or guselkumab alone for induction at week 12 in patients with moderately to severely active ulcerative colitis,” Bruce E. Sands, MD, MS, chief of the Dr. Henry D. Janowitz division of gastroenterology at the Icahn School of Medicine at Mount Sinai, told Healio.
Following these results, Feagan and colleagues aimed to assess the safety and efficacy of combined guselkumab (Tremfya, Janssen) and golimumab (Simponi, Janssen) induction therapy among 214 patients with UC. They noted enrolled patients were naive to TNF-alpha agonists and either refractory or intolerant to conventional therapy.
Patients received either IV guselkumab 200 mg at weeks 0, 4 and 8 followed by subcutaneous guselkumab 100 mg every 8 weeks (n = 71); subcutaneous golimumab 200 mg at week 0 followed by subcutaneous golimumab 100 mg at week 2 and ever 4 weeks thereafter (n = 72); or combined IV guselkumab 200 mg IV with subcutaneous golimumab 200 mg therapy at week 0, subcutaneous golimumab 100 mg at week 2,week 6 and week 10 with IV guselkumab 200 mg at week 4 and week 8 followed by subcutaneous guselkumab 100 mg ever 8 weeks thereafter (n=71). After week 12 follow-up, patients in the monotherapy group continued the same treatment regimen while patients in the combination group transition to maintenance treatment with guselkumab through 38 weeks.
Researchers assessed clinical, endoscopic, histologic and composite histologic-endoscopic outcomes as well as safety through the patient’s final visit. They noted 13.1% of patients discontinued prior to week 34.
According to study results, patients in the combination group had greater rates of clinical remission (42.7%) compared with either the guselkumab (31%) or golimumab (22.2%) monotherapy groups. Similarly, the combination group also saw greater rates of clinical remission by modified Mayo score components (47.9% vs. 31% vs. 20.8%, respectively), endoscopic improvement (49.3% vs. 32.4% vs. 22.2%), endoscopic normalization (25.4% vs. 15.5% vs. 6.9%), histologic remission (50.7% vs. 40.8% vs. 25%) and composite histologic-endoscopic endpoints (improvement: 42.3% vs. 21.1% vs. 13.9%; normalization: 23.9% vs. 12.7% vs. 5.6%).
“We found that, while there was additive benefit of combination therapy by week 12, that benefit continued out through week 38 in the combination induction followed by guselkumab monotherapy group compared with the guselkumab or golimumab monotherapy groups out to week 38,” Sands added. “Very significant improvements in the overall efficacy at week 38. Furthermore, we had an extension of the safety data showing no significant safety issues in comparing all the three groups to each other.”
Monotherapy group analysis further revealed greater rates of clinical, endoscopic and histologic outcomes among patients dosed with guselkumab vs. golimumab.
“Patients treated with combination induction therapy with guselkumab plus golimumab followed by guselkumab monotherapy achieved higher rates of clinical remission, endoscopic improvement and the composite endpoint of histologic remission and endoscopic improvement,” Feagan concluded. “Adverse event rates were similar across the treatment groups. Further investigation and phase 2 trials are underway.”
Sands added that these results are suggestive of a new ‘avenue of treatment.’
“At this point, we're not advocating the combination of anti-TNF and anti-IL-23 for patients in our offices, but it does suggest a new avenue of treatment that may be more effective in the future,” he said. “We really have to wait for confirmatory phase three studies before we adopt this in clinical practice.”
Perspective
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Benjamin L. Cohen, MD
We are in an era of increasing new drug development for treatment of ulcerative colitis. However, there appears to be a therapeutic ceiling with most new treatments that we have yet to break. Part of the problem may be that there are multiple inflammatory pathways driving disease and necessitating a combination biologic approach to treatment.
Interleukin (IL)-23 inhibitors hold promise as a combination agent due to their efficacy and relative safety. The VEGA trial presented at ACG was a phase 2a proof-of-concept study in which dual blockade of IL-23 with guselkumab and tumor necrosis factor with golimumab for 12 weeks was compared against induction with either agent alone for treatment of moderate to severe UC. Patients were then maintained on monotherapy with their original induction agent or guselkumab if they had been randomized to induction with combination therapy through 38 weeks.
Patients randomized to a combination biologic induction regimen had higher rates of 38-week clinical remission, endoscopic improvement, endoscopic normalization and histologic remission compared with either monotherapy group without a signal for increased adverse events. While only proof-of-concept results, the VEGA trial has supported the launch of the DUET UC and Crohn’s disease trials, which are larger phase 2b programs to evaluate the efficacy and safety of induction and maintenance combination therapy with guselkumab and golimumab for both UC and CD, respectively.
To crack the therapeutic ceiling, new paradigms for treatment must be utilized, including combination biologics, biomarker driven treatment selection and other personalized approaches to management. Hopefully, these results will open the door to more novel studies using our expanding treatment armamentarium.
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Feagan BG, et al. Abstract S716: Induction combination therapy with guselkumab and golimumab followed by
guselkumab monotherapy maintenance: Results of the phase 2a randomized, double-blind, proof-of-concept VEGA study. Presented at: ACG Annual Scientific Meeting; Oct. 21-26, 2022; Charlotte (hybrid meeting).
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