VISIBLE 1UC · Biosimilars and dosing
Efficacy and Safety of Vedolizumab Subcutaneous Formulation in a Randomized Trial of Patients With Ulcerative Colitis
Sandborn WJ, et al.
Gastroenterology 2020 · PMID 31470005 (PubMed, opens in a new tab) · doi 10.1053/j.gastro.2019.08.027 (full paper, opens in a new tab)
| Endpoint | SC vedolizumab | IV vedolizumab | Placebo | Difference |
|---|---|---|---|---|
| Clinical remission, Week 52 (primary endpoint) | 46.2% | 42.6% | 14.3% | SC vs placebo +32.3 points (95% CI 19.7–45.0); P<0.001 |
SC and IV vedolizumab gave similar remission, but the trial was not designed to prove they are equivalent.
Source: Sandborn 2020, abstract. IV vedolizumab was a reference arm, not formally compared with SC.
Structured abstract
BackgroundVedolizumab maintenance was given only by IV infusion. Some patients prefer injections at home, so a subcutaneous formulation was tested as maintenance after IV induction.
MethodsPhase 3, double-blind, double-dummy randomised maintenance trial after open-label IV induction (141 sites, 29 countries). 216 patients. Primary endpoint: Clinical remission at week 52 (total Mayo score ≤2, no subscore >1).
ResultsPrimary result. 46.2% (SC) vs 42.6% (IV) vs 14.3% (placebo); SC vs placebo difference 32.3% (95% CI 19.7–45.0); P<0.001
Take-homeAfter two IV induction doses, vedolizumab can be maintained with 108 mg subcutaneous injections every 2 weeks, with remission rates numerically similar to IV.
| Patients | 216 |
|---|---|
| Population | Moderately to severely active UC with clinical response at week 6 to open-label IV vedolizumab 300 mg at weeks 0 and 2 |
| Comparison | Vedolizumab SC 108 mg every 2 weeks vs IV 300 mg every 8 weeks vs placebo |
| Drugs | vedolizumab |
| Classes | Anti-integrin |
| Published | Sandborn WJ, et al. Gastroenterology 2020;158:562–72. |
Key points
- Endoscopic improvement and durable clinical response at week 52 were also better with SC vedolizumab than placebo (both P<0.001).
- Injection-site reactions: 10.4% with SC vs 1.9% with IV and 0% with placebo; mostly mild, none led to stopping treatment.
- Remission was numerically similar with SC and IV vedolizumab (46.2% vs 42.6%); the IV arm served as a reference, not a formal comparison.
- Safety was otherwise similar for SC and IV vedolizumab.
Limitations
- Small trial (216 randomised).
- Maintenance only, in responders to IV induction; SC induction was not tested.
- Not designed to prove SC is equivalent to IV.
Commentary
In practice. VISIBLE 1 lets patients who respond to IV induction switch to home injections. The parent trial for vedolizumab in UC is GEMINI 1 (PMID 23964932).
Crohn’s disease. The companion trial, VISIBLE 2, found week-52 remission of 48.0% with SC vedolizumab vs 34.3% with placebo (P=0.008).
Canada. Subcutaneous vedolizumab is marketed in Canada; check provincial or private coverage, which can differ from the IV form.
Journal club
Design
Phase 3, double-blind, double-dummy randomised maintenance trial after open-label IV induction (141 sites, 29 countries). 216 patients.
Primary result. 46.2% (SC) vs 42.6% (IV) vs 14.3% (placebo); SC vs placebo difference 32.3% (95% CI 19.7–45.0); P<0.001
Validity and applicability
- Small trial (216 randomised).
- Maintenance only, in responders to IV induction; SC induction was not tested.
- Not designed to prove SC is equivalent to IV.
Where it sits now
After two IV induction doses, vedolizumab can be maintained with 108 mg subcutaneous injections every 2 weeks, with remission rates numerically similar to IV.
- VISIBLE 2 (2022): 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.
Questions for discussion
- The IV arm was a reference, not a formal comparator. What would a trial need to show that SC and IV are equivalent?
- How would you switch a patient in stable remission on IV vedolizumab to SC, and what would you monitor?
- Injection-site reactions occurred in 10.4% on SC. How would you counsel a patient choosing between routes?