Guselkumab plus golimumab promising combination for ulcerative colitis

The combination of guselkumab and golimumab resulted in improved clinical outcomes in participants with active ulcerative colitis (UC) compared with either guselkumab or golimumab monotherapy in a phase 2 study. Moreover, the safety profiles were similar across treatment groups. Further trials are warranted to evaluate the safety and efficacy of this promising combination regimen in patients with UC.

Preclinical data from a murine model of acute colitis has suggested that the combination therapy of guselkumab, an IL-23 inhibitor, and golimumab, a TNF inhibitor, may lead to improved outcomes in patients with UC [1]. A phase 2, proof-of-concept study (NCT03662542) was conducted to assess the efficacy and safety of guselkumab plus golimumab compared with guselkumab or golimumab monotherapy in participants with moderately to severely active UC [2]. Participants (n=214) were randomised 1:1:1 to golimumab monotherapy (subcutaneous 200 mg at week 0, 100 mg at weeks 2, 6, and 10), guselkumab monotherapy (intravenous 200 mg at weeks 0, 4, and 8), or a combination of these 2 regimens (200 mg guselkumab intravenous plus 200 mg golimumab subcutaneous at week 0, 100 mg golimumab subcutaneous at weeks 2, 6, and 10, 200 mg guselkumab intravenous at week 4 and 8). The primary outcome was the clinical response^a at week 12. Prof. Bruce Sands (Mount Sinai School of Medicine, NY, USA) presented the results.

At week 12, the combination therapy significantly outperformed golimumab monotherapy (83.1% vs 61.1%; P=0.003) but not guselkumab monotherapy (83.1% vs 74.6%; P=0.215) regarding clinical response rates (see Figure). Clinical remission^b was significantly higher in the combination therapy arm (36.6%) compared with guselkumab alone (21.1%; P=0.041), and borderline significant compared with golimumab alone (22.2%; P=0.058). Furthermore, endoscopic improvement^c significantly favoured the combination therapy over the monotherapy arms (P=0.003 for combination vs golimumab; P=0.016 for combination vs guselkumab) whereas for histologic remission^d the combination therapy was only significantly higher than golimumab monotherapy (P=0.003).

Figure: Clinical response of guselkumab, golimumab, or the combination at week 12 [2]



 

 

 

 

 

 

The safety profiles of the 3 treatment regimens were similar. Adverse events (AEs) occurred in 52.8%, 43.7%, and 40.8% of the participants in the golimumab, guselkumab, and combination therapy arm, respectively. Corresponding proportions of serious AEs were 1.4%, 2.8%, and 1.4%. The proportion of infections did not differ between the treatment conditions, with 14.1% of the participants in the golimumab or combination therapy arm and 22.2% of the participants in the golimumab arm displaying an infection. No deaths, malignancies, or opportunistic infections were observed at week 12.

“Combination induction treatment with guselkumab plus golimumab resulted in greater proportions of patients achieving a clinical response, clinical remission, endoscopic improvement and normalisation, and the composite endpoint of histologic remission and endoscopic improvement at week 1,” concluded Prof. Sands. “Further study of this combination therapy is warranted.”

a. Clinical response is defined as a decrease in the Mayo score ≥30% and ≥3 points, with either a decrease in rectal bleeding subscore ≥1 or rectal bleeding subscore of 0 or 1.

b. Clinical remission is defined as a stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on endoscopy, where the stool frequency subscore has not increased from baseline.

c. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy.

d. Histologic remission is defined as absence of neutrophils of the mucosa, no crypts destruction, and no erosion, ulcerations, or granulation tissues according to the Geboes grading system.

1. Perrigoue J, et al. In silico evaluation and pre-clinical efficacy of anti-TNF and anti-IL-23 combination therapy in Inflammatory Bowel Disease. P328, ECCO 2022, 16–19 February.
2. Sands BE, et al. Efficacy and safety of combination induction therapy with guselkumab and golimumab in participants with moderately-to-severely active Ulcerative Colitis: Results through week 12 of a phase 2a randomized, double-blind, active-controlled, parallel-group, multicenter, proof-of-concept study. OP36, ECCO 2022, 16–19 February.

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Posted on 12 April 20228 April 2024