Guselkumab/Golimumab Induction Safe and Effective for Ulcerative Colitis

Patients with ulcerative colitis treated with combination induction therapy with guselkumab plus golimumab followed by guselkumab monotherapy achieved higher rates of the several end points at week 38 as compared to either guselkumab or golimumab alone.

Brian G. Feagan, MD, Alimentiv, Inc.; Western University, London, ON, Canada

Brian G. Feagan, MD

The combination of induction guselkumab (Tremfya) and golimumab (Simponi) followed by guselkumab monotherapy maintenance led to clinical remissions and endoscopic improvement compared with either agent alone for patients with moderately to severely active ulcerative colitis (UC), according to findings from the phase 2a VEGA study presented at the American College of Gastroenterology (ACG) 2022 Annual Scientific Meeting in Charlotte, NC.

At week 38, the combination of golimumab and guselkumab with guselkumab monotherapy led to a clinical remission for 43.7% of patients (31 of 71). This was a 21.5 percentage point advantage over the TNF alpha antagonist golimumab alone for induction and maintenance, which elicited a clinical remission in 22.2% of patients (16 of 72; P = .006). Additionally, clinical remission rates were 12.7 percentage points greater with the combination than the IL-23 antagonist guselkumab alone for induction and maintenance, which elicited a 31.0% clinical remission rate (22 of 71; P = .109).

"Patients treated with combination induction therapy with guselkumab plus golimumab followed by guselkumab monotherapy achieved higher rates of the clinical remission, endoscopic improvment, and the composite end point of histologic remission and endoscopic improvement," lead author Brian G. Feagan, MD, Alimentiv, Inc.; Western University, London, ON, Canada, said during a presentation of the results. "The combination treatment paradigm evaluated in VEGA warrants further investigation."

The proof-of-concept VEGA study randomized 214 participants evenly across 3 treatment arms to receive 12 weeks of induction therapy followed by maintenance for up to 38 weeks. In the combination therapy arm (n = 71), induction consisted of guselkumab at 200 mg intravenously (IV) and golimumab at 200 mg subcutaneously (SC) at week 0. At weeks 2, 6, and 10 single-agent golimumab was given at 100 mg SC and then at weeks 4 and 8 guselkumab was given at 200 mg IV. This was followed by guselkumab at 100 mg SC every 8 weeks in the maintenance period.

In the golimumab monotherapy arm (n = 72), the agent was given SC at 200 mg on week 0 and then at 100 mg SC on weeks 2, 6, and 10. As maintenance it was given at 100 mg SC every 4 weeks. In the guselkumab monotherapy group (n = 71), the agent was given at 200 mg IV on weeks 0, 4, and 8 in the induction phase and 100 mg SC every 8 weeks in the maintenance period.

Across all patients, the mean age was 38.4 years and 54.2% were male. The mean UC duration at baseline was 4.9 years and the disease was limited to the left side of the colon for 57.9% of patients. The mean full Mayo score was 8.8 and the endoscopy subscore was 3 for 59.3% of patients. Nearly half (41.1%) of patients were on corticosteroids at baseline.

Following induction therapy at week 12, the clinical remission rate was 36.6% with the combination (26 of 71), which was a 14.5 percentage point advantage over single agent golimumab (22.2%; P = .058) and a 15.5 percentage point improvement guselkumab monotherapy (21.1%; P = .041).

By modified Mayo score at week 38, clinical remission was experienced by 47.9% of those in the combination induction and single-agent guselkumab maintenance group. This was a 16.9 percentage point increase over guselkumab monotherapy (31.0%; P = .033) and a 27.1-point increase of golimumab monotherapy (20.8%; P <.001). After induction, the modified Mayo clinical remission rates were 46.5% with the combination, which was a 22.5 percentage point increase over guselkumab monotherapy (23.9%; P = .005) and a 21.6 percentage change over golimumab monotherapy (25.0%; P = .007).

"This is the measure used by the FDA currently, and includes bleeding. Under this, the differences is more striking," said Feagan.

Symptomatic remission was similar through week 38 in the guselkumab monotherapy and the combination followed by guselkumab monotherapy arms, with 69% meeting this criteria. There were 59.7% of patients with symptomatic remission in the golimumab monotherapy arm.

At week 38, endoscopic improvement was experienced by 49.3% of patients treated with the combination followed by guselkumab monotherapy. This was a 16.9 percentage point advantage over single-agent guselkumab (32.4%; P =.033) and a 27.2 point change over golimumab (22.2%; P <.001). Following induction alone at week 12, endoscopic improvement was seen in 49.3% of patients with the combination, which was a 19.7 increase over guselkumab (29.6%; P = .016) and a 24.4-point increase over golimumab (25.0%; P = .003).

At 38 weeks, endoscopic normalization was experienced by 25.4% of patients in the combination group compared with 15.5% in the guselkumab arm (P = .134) and 6.9% in the golimumab group (P = .002). At week 12, endoscopic normalization was seen in 18.3% of those treated with the combination compared with 8.5% for guselkumab monotherapy (P = .084) and 9.7% with golimumab (P = .140).

At week 38, both histologic remission and endoscopic improvement was experienced by 42.3% of patients in the combination arm compared with 21.1% for guselkumab monotherapy (P = .005) and 13.9% for golimumab monotherapy (P <.001). At week 12, the combination elicited both a histologic remission and endoscopic improvement for 40.8% of patients compared with 26.8% with guselkumab alone (P = .077) and 15.3% with golimumab alone (P <.001).

Adverse events (AEs) of any cause or severity throughout the study were experienced by 76.4% of those in the golimumab arm, 64.8% of patients in the guselkumab arm, and 63.4% of those in the combination group. Serious AEs were seen in 5.6% of patients in each arm. Infections were seen in 31.9% of patients in the golimumab arm, 23.9% in the guselkumab group, and by 31.0% of those in the combination arm.

"We don't see striking differences between adverse events, any adverse event, or serious adverse events leading to discontinuation," noted Feagan.

Overall, 13.1% of patients had discontinued treatment prior to the full 34 weeks. This was numerically more common in the golimumab monotherapy arm (18.1%). The most common adverse event causing discontinuation was a worsening in UC, which occurred in 3.3% of patient. UC worsened for 4.2% of those in the golimumab monotherapy arm and for 5.6% of those in the combination arm. No patients in the guselkumab arm had a worsening of their disease.

The oral abstract, “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,” was presented at ACG 2022.

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