Colon to Rectum
Lancet Gastroenterol Hepatol. 2023;8(4):307–20
Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA): A randomized, double-blind, controlled, phase 2, proof-of-concept trial
Background: Despite the introduction of new monoclonal antibodies and oral therapies for the treatment of ulcerative colitis, clinical remission rates remain low, underscoring the need for innovative treatment approaches. The authors assessed whether guselkumab plus golimumab com-bination therapy was more effective for ulcerative colitis than either monotherapy.
Methods: They did a randomized, double-blind, controlled, proof-of-concept trial at 54 hospitals, academic medical centers, or private practices in 9 countries. Eligible adults (aged ≥ 18 to 65 years) had a confirmed diagnosis of ulcerative colitis at least 3 months before screening and moder-ately-to-severely active ulcerative colitis (Mayo score 6–12) with a centrally-read baseline endoscopy subscore of 2 or higher. Patients were ran-domly assigned (1:1:1) using a computer-generated randomization schedule to combination therapy (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), golimumab monotherapy (subcutaneous golimumab 200 mg at week 0 fol-lowed by subcutaneous golimumab 100 mg at week 2 and every 4 weeks thereafter for 34 weeks), or guselkumab monotherapy (intravenous guselkumab 200 mg at weeks 0, 4, and 8, followed by subcutaneous guselkumab 100 mg every 8 weeks thereafter for 32 weeks). The primary end point was 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). Efficacy was analyzed in the modified inten-tion-to-treat population up to week 38, which included all randomly assigned patients who received at least 1 (partial or complete) study inter-vention dose. Safety was analyzed up to week 50, according to study intervention received among all patients who received at least 1 (partial or complete) dose of study intervention.
Findings: Between November 20, 2018, and November 15, 2021, 358 patients were screened for eligibility, of whom 214 patients were ran-domly assigned to combination therapy (n = 71), golimumab monotherapy (n = 72), or guselkumab monotherapy (n = 71). Of the 214 patients included, 98 (46%) were women and 116 (54%) were men and the mean age was 38.4 ± 12.0 years. At week 12, 59 of 71 patients (83%) in the combination therapy group had achieved clinical response compared with 44 of 72 patients (61%) in the golimumab monotherapy group (ad-justed treatment difference 22.1% [80% confidence interval [CI]: 12.9–31.3]; nominal p = 0.0032) and 53 of 71 patients (75%) in the guselku-mab monotherapy group (adjusted treatment difference 8.5% [80% CI: -0.2–17.1; nominal p = 0.2155). At week 50, 45 of 71 patients (63%) in the combination therapy group, 55 of 72 patients (76%) in the golimumab monotherapy group, and 46 of 71 patients (65%) in the guselkumab monotherapy group had reported at least 1 adverse event. The most common adverse events were ulcerative colitis, upper respiratory tract infection, headache, anemia, nasopharyngitis, neutropenia, and pyrexia. No deaths, malignancies, or cases of tuberculosis were reported during the combination induction period. One case of tuberculosis was reported in the combination therapy group and 1 case of colon adenocarcinoma was reported in the guselkumab monotherapy group; both occurred after week 12. Two deaths were reported after the final dose of study inter-vention (poisoning in the combination therapy group and COVID-19 in the guselkumab monotherapy group).
Interpretation: Data from this proof-of-concept study suggest that combination therapy with guselkumab and golimumab might be more effec-tive for ulcerative colitis than therapy with either drug alone. These findings require confirmation in larger trials.