OR WAIT null SECS
The rate of adverse events was lower in the combination group than it was in patients in the guselkumab or golimumab monotherapy groups at week 50.
The combination therapy of guselkumab and golimumab is more efficacious than either treatment alone as a monotherapy for patients with ulcerative colitis.1
A team, led by Brian G. Feagan, MD, Western University, assessed guselkumab and golimumab combination therapy as a treatment for patients with ulcerative colitis compared to either monotherapy alone.
While new monoclonal antibodies and oral therapies have improved care for patients with ulcerative colitis, clinical remission rates continue to be low and new approaches to treatment could be needed.
In the randomized, double-blind, controlled, proof-of-concept study, the investigators examined patients with ulcerative colitis at 54 hospitals, academic medical centers, and private practices in 9 countries. Each participant had a confirmed diagnosis of ulcerative colitis for at least 3 months prior to screening and moderately to severely active ulcerative colitis defined as a Mayo score of 6-12 with a centrally-read baseline endoscopy subscore of 2 or higher.
Each participant was randomly assigned to either a combination therapy of subcutaneous golimumab 200 mg at week 0, subcutaneous golimumab 100 mg at weeks 2, 6, and 10 and intravenous guselkumab 200 mg at weeks 0, 4, and 8, followed by subcutaneous guselkumab monotherapy 100 mg every 8 weeks for 32 weeks or golimumab monotherapy which was subcutaneous golimumab 200 mg at week 0 followed by subcutaneous golimumab 100 mg at week 2 and every 4 weeks thereafter for 34 weeks, or guselkumab monotherapy, which was intravenous guselkumab 200 mg at weeks 0, 4, and 8, followed by subcutaneous guselkumab 100 mg every 8 weeks thereafter for 32 weeks. The mean age was 38.4 years.
The investigators sought a primary endpoint of clinical response at week 12, defined as a ≥30% decrease from baseline in the full Mayo score and a ≥3 points absolute reduction with either a decrease in rectal bleeding score of ≥1 point or a rectal bleeding score of 0 or 1.
The team analyzed efficacy of the treatments for all patients who received 1 done up to week 38 and analyzed safety up to week 50.
There were 358 patients screened between Nov. 20, 2018 and Nov. 15, 2021, of which 214 were randomly assigned either combination therapy (n = 71), golimumab monotherapy (n = 72), or guselkumab monotherapy (n = 71).
The results show 83% (n = 59) of patients in the combination group achieved clinical response. The response rate was much higher than the golimumab monotherapy group, where 61% (n = 44; adjusted treatment difference 22.1%; 80% confidence interval [CI]12.9-31.3; nominal P = 0.0032) achieved a clinical response and the guselkumab monotherapy group, where 75% (n = 53; adjusted treatment difference, 8.5%; 80% CI, –0.2 to 17.1; nominal P = 0.2155).
At week 50, 63% (n = 45) of the combination group had at least 1 adverse event reported, compared to 76% (n = 55) of the golimumab monotherapy group and 65% (n = 46) of the guselkumab monotherapy group.
The most common adverse events in the entire patient population were ulcerative colitis, upper respiratory tract infections, headache, anemia, nasopharyngitis, neutropenia, and pyrexia. There were no deaths, malignancies, or cases of tuberculosis reported during the combination induction period.
However, there was 1 case of tuberculosis in the combination group and 1 case of colon adenocarcinoma after week 12 in the guselkumab monotherapy group. There were also a death in the combination therapy due to a poisoning and 1 death in the guselkumab monotherapy group because of COVID-19.
“Data from this proof-of-concept study suggest that combination therapy with guselkumab and golimumab might be more effective for ulcerative colitis than therapy with either drug alone,” the authors wrote. “These findings require confirmation in larger trials.”
Feagan BG, Sands BE, Sandborn WJ, et al. Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (Vega): A randomised, double-blind, controlled, phase 2, proof-of-concept trial. The Lancet Gastroenterology & Hepatology. 2023. doi:10.1016/s2468-1253(22)00427-7