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

Golimumab is a TNF-α antagonist that is FDA approved for the treatment of adult patients with moderately to severely active UC who have demonstrated corticosteroid dependence or who have had an inadequate response to or failed to tolerate oral aminosalicylates, oral corticosteroids, azathioprine, or 6-mercaptopurine.¹ The indication for golimumab includes the induction and maintenance of clinical response, improvement of endoscopic appearance of the mucosa during induction, induction of clinical remission, and achieving and sustaining clinical remission in induction responders. Guselkumab, an IL-23p19 subunit antagonist, is FDA approved for the treatment of plaque psoriasis and psoriatic arthritis, and is currently under investigation in IBD.² The phase 2a VEGA study was designed to compare combination induction therapy with guselkumab plus golimumab followed by guselkumab for maintenance treatment, or either guselkumab or golimumab alone for induction and maintenance treatment, in patients with moderately to severely active UC.³

A total of 214 patients with moderately to severely active UC were enrolled. All patients were naive to TNF-α, IL-12/23, and IL-23p19 antagonists and had an inadequate response or intolerance to conventional therapy (immunosuppressants and/or corticosteroids). Additionally, immunosuppressants must have been discontinued prior to randomization and corticosteroids (up to a dose of prednisone of 20 mg/day or equivalent) were permitted with mandatory tapering beginning at week 6. Patients were randomized 1:1:1 to the 3 treatment arms.

Patients treated with combination induction therapy consisting of guselkumab plus golimumab followed by guselkumab maintenance monotherapy achieved higher rates of several endpoints at week 38 compared with either guselkumab or golimumab alone. Rates of clinical remission (Figure 7) at week 12 after induction therapy (defined as a Mayo score ≤2 with no individual subscore >1) were 36.6% in the combination arm compared with 21.1% with guselkumab alone (P=.041 compared with the combination) and 22.2% with golimumab alone (P=.058 compared with the combination). By week 38, clinical remission rates were 43.7% in the combination and guselkumab maintenance arm, compared with 31.0% with guselkumab alone (P=.109 compared with the combination) and 22.2% with golimumab alone (P=.006 compared with the combination). Using the modified Mayo score (Mayo SFS of 0 or 1 and not increased from baseline, an RBS of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy), the week 38 rates of clinical remission were 47.9% with the combination compared with 31.0% with guselkumab alone (P=.033 compared with the combination) and 20.8% with golimumab alone (P<.001 compared with the combination). Symptomatic remission rates (Mayo SFS of 0 or 1 andnot increased from baseline, and an RBS of 0) at week 38 were similar across the treatment arms: 69.0% with the combination vs 69.0% with guselkumab alone and 59.7% with golimumab alone.

Figure 7.

Rates of clinical remission with a combination of guselkumab plus golimumab as induction therapy followed by guselkumab maintenance monotherapy, or golimumab or guselkumab alone as both induction and maintenance therapy in the VEGA study. COMBO, combination of golimumab plus guselkumab; GOL, golimumab; GUS, guselkumab. Adapted from Feagan BG, et al. ACG abstract 40. Am J Gastroenterology. 2022;117(suppl 105).³

Endoscopic improvement was defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. Rates of endoscopic improvement were also higher with the combination than with the monotherapy arms. At week 12, the rates of endoscopic improvement were 49.3% in the combination arm compared with 29.6% with guselkumab alone (P=.016 compared with the combination) and 25.0% with golimumab alone (P=.003 compared with the combination). These rates at week 38 were 49.3%, 32.4% (P=.033), and 22.2% (P<.001), respectively. Endoscopic normalization was defined as an endoscopy score of 0, and at week 12 the rates were 18.3% with the combination vs 8.5% with guselkumab alone (P=.084 compared with the combination) and 9.7% with golimumab alone (P=.140 compared with the combination). These rates at week 38 were 25.4%, 15.5% (P=.134), and 6.9% (P=.002), respectively.

Similar improvements were observed for patients who achieved a composite endpoint of endoscopic improvement and histologic remission (absence of neutrophils from the mucosa [both lamina propria and epithelium], no crypt destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes grading system) and endoscopic improvement.

Adverse event rates were comparable among the treatment groups, although more patients in the combination arm (9.9%) compared with either the guselkumab (1.4%) or the golimumab (5.6%) monotherapy arms discontinued treatment owing to an adverse event. The rates of infection were 31.0%, 23.9%, and 31.9% in the combination, guselkumab-alone, and golimumab-alone arms, respectively. Two patients in each arm (2.8% of each arm) experienced a serious infection.