Combination biologic therapy for ulcerative colitis

Abstract

In The Lancet Gastroenterology & Hepatology, Brian Feagan and colleagues report the results of VEGA, the first randomised, controlled trial investigating the efficacy and safety of short-term combination therapy with biologics in patients with moderate-to-severe ulcerative colitis. 1 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. Lancet Gastroenterol Hepatol. 2023; (published online Feb 1.)https://doi.org/10.1016/S2468-1253(22)00427-7 Google Scholar Patients were randomly assigned (1:1:1) to receive anti-tumour necrosis factor (TNF) inhibitor golimumab, interleukin (IL)-23p19 inhibitor guselkumab, or combined therapy with both golimumab and guselkumab, referred to as combined therapy hereafter. The primary endpoint of the trial was clinical response at week 12. At week 12, 59 (83%) of 71 patients in the combination therapy group had achieved clinical response compared with 44 (61%) of 72 patients in the golimumab monotherapy group (adjusted treatment difference 22·1% [80% CI 12·9 to 31·3]; nominal p=0·0032) and 53 (75%) of 71 patients in the guselkumab monotherapy group (adjusted treatment difference 8·5% [–0·2 to 17·1; nominal p=0·2155). However, the prespecified criterion for significance (the superiority of combination therapy to both monotherapy groups for the primary endpoint at the two-sided significance level of 0·2) was not met. The fact that the primary endpoint of the trial was not met does not detract from the importance of the study findings: twice as many patients in the combination therapy group achieved the more stringent endpoint of clinical remission when compared with either monotherapy group. At weeks 12 and 38, the proportion of patients who met other objective endpoints, including endoscopic, histological, and composite histological-endoscopic endpoints was numerically higher in the combination therapy group than either monotherapy. 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 trialData 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. These findings require confirmation in larger trials. Full-Text PDF