VEGAUC · Treatment strategy
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
Feagan BG, et al.
Lancet Gastroenterol Hepatol 2023 · PMID 36738762 (PubMed, opens in a new tab) · doi 10.1016/S2468-1253(22)00427-7 (full paper, opens in a new tab)
| Outcome | Combination | Monotherapy | Estimate (confidence interval) | P |
|---|---|---|---|---|
| vs golimumab, Clinical response, week 12 (primary) | 59/71 (83%) | 44/72 (61%) | +22.1 (80% CI 12.9–31.3) | Nominal P=0.0032 |
| vs guselkumab, Clinical response, week 12 (primary) | 59/71 (83%) | 53/71 (75%) | +8.5 (80% CI −0.2 to 17.1) | Nominal P=0.2155 |
Even with the narrower 80% intervals, the comparison with guselkumab alone crosses zero.
Source: Feagan 2023, abstract. P values are nominal.
Structured abstract
BackgroundRemission rates with single advanced therapies in UC remain low. VEGA tested whether combining two biologics with different targets, an anti-TNF and an anti-IL-23 antibody, works better than either alone.
MethodsPhase 2 (2a), randomised (1:1:1), double-blind, controlled proof-of-concept trial (54 sites, 9 countries). 214 patients. Primary endpoint: Clinical response at week 12 (full Mayo score down ≥30% and ≥3 points, with rectal bleeding down ≥1 or a score of 0–1).
ResultsPrimary result. 83% (59/71) with combination vs 61% (44/72) with golimumab (adjusted difference 22.1%, 80% CI 12.9–31.3; nominal P=0.0032) and 75% (53/71) with guselkumab (8.5%, 80% CI −0.2 to 17.1; nominal P=0.2155)
Take-homeCombining an anti-TNF with an IL-23 antibody for induction outperformed golimumab alone but did not clearly separate from guselkumab alone; this phase 2 signal needs phase 3 confirmation.
| Patients | 214 |
|---|---|
| Population | Adults aged 18–65 with moderately to severely active UC (Mayo 6–12, centrally read endoscopic subscore ≥2) |
| Comparison | Combination (golimumab SC plus guselkumab IV for 12 weeks, then guselkumab SC 100 mg every 8 weeks) vs golimumab alone vs guselkumab alone |
| Drugs | guselkumab, golimumab |
| Classes | Anti-IL-23 (p19), Anti-TNF |
| Published | Feagan BG, et al. Lancet Gastroenterol Hepatol 2023;8:307–20. |
Key points
- Combination beat golimumab alone, but not guselkumab alone, on the primary endpoint.
- Results use 80% confidence intervals and nominal P values: this was a hypothesis-generating trial.
- Adverse events to week 50: 63% (combination), 76% (golimumab), 65% (guselkumab). One case of tuberculosis occurred in the combination group after week 12.
- After 12 weeks, the combination group continued on guselkumab alone, so this tests combination induction, not long-term dual therapy.
Limitations
- Proof-of-concept phase 2 trial with 80% confidence intervals.
- Small arms (about 70 patients each); efficacy analysed only to week 38.
- Combination biologic therapy is off-label.
Commentary
Why it matters. Remission rates with any single advanced therapy remain low, the so-called therapeutic ceiling. VEGA tested whether combining two biologics with different mechanisms for induction could raise it.
Related. A small open-label randomised trial from China (120 patients; PMID 42173298) tested another combination: 8 weeks of upadacitinib added to vedolizumab induction. Phase 3 confirmation of either approach was not published as of October 2026.
Journal club
Design
Phase 2 (2a), randomised (1:1:1), double-blind, controlled proof-of-concept trial (54 sites, 9 countries). 214 patients.
Primary result. 83% (59/71) with combination vs 61% (44/72) with golimumab (adjusted difference 22.1%, 80% CI 12.9–31.3; nominal P=0.0032) and 75% (53/71) with guselkumab (8.5%, 80% CI −0.2 to 17.1; nominal P=0.2155)
Validity and applicability
- Proof-of-concept phase 2 trial with 80% confidence intervals.
- Small arms (about 70 patients each); efficacy analysed only to week 38.
- Combination biologic therapy is off-label.
Where it sits now
Combining an anti-TNF with an IL-23 antibody for induction outperformed golimumab alone but did not clearly separate from guselkumab alone; this phase 2 signal needs phase 3 confirmation.
- Upadacitinib plus vedolizumab induction (2026): Adding 8 weeks of upadacitinib to vedolizumab induction improved early endoscopic remission over vedolizumab alone, but this small open-label trial is hypothesis-generating.
- UC-SUCCESS (2014): When starting infliximab in anti-TNF-naive UC, adding azathioprine improves steroid-free remission at 16 weeks (40% vs 22%).
Questions for discussion
- VEGA used 80% confidence intervals and nominal P values. What can a proof-of-concept trial justify, and what can it not?
- The combination beat golimumab but not clearly guselkumab. Is the benefit additive, or mostly the IL-23 component?
- Combination induction was followed by guselkumab alone. What safety and cost questions would a phase 3 trial need to answer?