VISIBLE 2CD · Biosimilars and dosing
Efficacy and Safety of Subcutaneous Vedolizumab in Patients With Moderately to Severely Active Crohn's Disease: Results From the VISIBLE 2 Randomised Trial
Vermeire S, et al.
J Crohns Colitis 2022 · PMID 34402887 (PubMed, opens in a new tab) · doi 10.1093/ecco-jcc/jjab133 (full paper, opens in a new tab)
| Endpoint | Vedolizumab SC | Placebo | Difference |
|---|---|---|---|
| Clinical remission, CDAI ≤150 (primary endpoint) | 48.0% (132/275) | 34.3% (46/134) | +13.7 points (95% CI 3.8–23.7); P=0.008 |
| Enhanced clinical response, CDAI down ≥100 · first secondary | 52.0% (143/275) | 44.8% (60/134) | P=0.167; endpoints below not formally tested |
| Corticosteroid-free remission, On steroids at baseline | 45.3% (43/95) | 18.2% (8/44) | Nominal P=0.002 |
| Remission, anti-TNF-naive | 48.6% (52/107) | 42.9% (27/63) | Nominal P=0.591 |
| Remission, prior anti-TNF failure, Exploratory subgroup | 46.4% (70/151) | 28.8% (17/59) | Nominal P=0.019 |
Placebo remission was high at 34.3%; the gap was widest for steroid-free remission and after anti-TNF failure.
Source: Vermeire 2022, full text (PMC8797168), Results 3.2.1 (full analysis set; 134 of 135 placebo patients were treated). The anti-TNF-failure subgroup was exploratory.
Structured abstract
BackgroundAfter VISIBLE 1 showed that subcutaneous vedolizumab maintains remission in UC, VISIBLE 2 tested the same 108 mg every-2-weeks regimen as maintenance in Crohn's disease.
MethodsPhase 3, randomised (2:1), double-blind, placebo-controlled maintenance trial after open-label IV induction (169 sites, 30 countries). 410 patients. Primary endpoint: Clinical remission (CDAI ≤150) at week 52.
ResultsPrimary result. 48.0% (132/275) vs 34.3% (46/134); difference 13.7% (95% CI 3.8–23.7); P=0.008
Take-homeAfter two IV doses, vedolizumab 108 mg SC every 2 weeks maintains remission in Crohn's disease better than placebo, so patients can switch to home injections.
| Patients | 410 |
|---|---|
| Population | Adults aged 18–80 with moderately to severely active Crohn's disease and inadequate response or intolerance to corticosteroids, immunomodulators and/or anti-TNF therapy. 644 received open-label vedolizumab 300 mg IV at weeks 0 and 2; week-6 responders (CDAI decrease ≥70) were randomised. |
| Comparison | Vedolizumab 108 mg SC every 2 weeks vs placebo, from week 6 to week 50 |
| Drugs | vedolizumab |
| Classes | Anti-integrin |
| Published | Vermeire S, et al. J Crohns Colitis 2022;16:27–38. |
Key points
- The first ranked secondary endpoint, enhanced clinical response (CDAI decrease ≥100), was not significantly different: 52.0% vs 44.8% (P=0.167). Later endpoints were therefore not formally tested.
- Corticosteroid-free remission (patients on steroids at baseline): 45.3% (43/95) vs 18.2% (8/44); nominal P=0.002.
- Remission in anti-TNF-failure patients: 46.4% (70/151) vs 28.8% (17/59); in anti-TNF-naive patients: 48.6% vs 42.9% (nominal P=0.591).
- Injection-site reactions occurred in 2.9% with SC vedolizumab; serious infections 1.5% vs 4.5% with placebo.
Limitations
- No IV vedolizumab reference arm, unlike VISIBLE 1.
- Endoscopy was optional and done in only a subset.
- The placebo remission rate was high; the authors point to open-label induction, steroid use and more ileum-only disease in the vedolizumab anti-TNF-naive group.
- Maintenance only, in responders to IV induction.
Commentary
Context. VISIBLE 2 is the Crohn’s disease companion to VISIBLE 1 in UC. The remission benefit was similar in size to IV vedolizumab every 8 weeks in GEMINI 2 (difference 13.7 points here vs 17.4 points in GEMINI 2, a cross-trial comparison), but the trial missed its first secondary endpoint.
Canada. The Canadian product monograph (Takeda Canada, revised November 2023) allows subcutaneous vedolizumab 108 mg every 2 weeks as maintenance for Crohn’s disease after at least two IV infusions, with the first injection given in place of the next scheduled IV dose. Check provincial or private coverage, which can differ from the IV form.
Journal club
Design
Phase 3, randomised (2:1), double-blind, placebo-controlled maintenance trial after open-label IV induction (169 sites, 30 countries). 410 patients.
Primary result. 48.0% (132/275) vs 34.3% (46/134); difference 13.7% (95% CI 3.8–23.7); P=0.008
Validity and applicability
- No IV vedolizumab reference arm, unlike VISIBLE 1.
- Endoscopy was optional and done in only a subset.
- The placebo remission rate was high; the authors point to open-label induction, steroid use and more ileum-only disease in the vedolizumab anti-TNF-naive group.
- Maintenance only, in responders to IV induction.
Where it sits now
After two IV doses, vedolizumab 108 mg SC every 2 weeks maintains remission in Crohn's disease better than placebo, so patients can switch to home injections.
- VISIBLE 1 (2020): After two IV induction doses, vedolizumab can be maintained with 108 mg subcutaneous injections every 2 weeks, with remission rates numerically similar to IV.
- GEMINI 2 (2013): Vedolizumab works in Crohn's disease but slowly: modest at week 6, clearer by week 10 and in maintenance, so it suits patients who can wait for the effect.
- REScUE (2026): After secondary loss of response to ustekinumab, IV reinduction plus every-4-week dosing is no better than reinduction plus every-8-week dosing, and few patients regain remission either way.
- LIBERTY-CD (2024): After IV infliximab induction, subcutaneous infliximab 120 mg every 2 weeks maintains remission and endoscopic response in Crohn's disease, an option for patients who prefer injections to infusions.
Questions for discussion
- The first ranked secondary endpoint failed, so later endpoints were not formally tested. How much weight should the steroid-free remission result carry?
- Placebo remission was 34.3%. Which design features may have raised it, and how does that bias the comparison?
- The benefit was larger after anti-TNF failure than in anti-TNF-naive patients. Is that plausible, or likely chance?