Subcutaneous vedolizumab also effective for ulcerative colitis treatment: VISIBLE 1 trial

A subcutaneous (SC) formulation of vedolizumab could be beneficial for patients with moderate to severe ulcerative colitis (UC), a recent study presented at the American College of Gastroenterology's Annual Scientific Meeting (ACG 2019).

In the trial—dubbed VISIBLE 1—the new treatment demonstrated a statistically significant efficacy superior to placebo as maintenance treatment in patients with ulcerative colitis who had achieved a response to vedolizumab IV induction.

Mayo Clinic defines ulcerative colitis as an inflammatory bowel disease (IBD) that causes long-lasting inflammation and ulcers (sores) in the digestive tract. It affects the innermost lining of your large intestine (colon) and rectum. While it has no known cure, treatment can greatly reduce signs and symptoms of the disease and even bring about long-term remission.

Vedolizumab (VDZ) is a monoclonal antibody targeting α₄β₇ integrin approved as an intravenous (IV) formulation to treat ulcerative colitis.

Douglas Wolf, Atlanta Gastroenterology Associates, and colleagues tested a new type of vedolizumab therapy for varying durations to treat moderate-to-severe ulcerative colitis.

The new data comes from the first-ever completed study with a new vedolizumab subcutaneous (SC) formulation, a randomized, double-blind, double-dummy, placebo-controlled, phase 3 trial assessing vedolizumab subcutaneous as a maintenance treatment in adults with moderately to severely active ulcerative colitis.

Efficacy of VDZ SC treatment after initial VDZ IV (300 mg) infusion was evaluated in 3 groups according to the duration of VDZ IV treatment before transitioning to VDZ SC (108 mg): (A) After 2 VDZ IV infusions (Week [W] 0 and 2) in patients who achieved clinical response at W6 and were randomized to VDZ SC maintenance treatment in VISIBLE 1; (B) After 3 VDZ IV infusions in patients who did not achieve clinical response at W6 who received a third VDZ IV infusion at W6 and had clinical response at W14 in VISIBLE 1 before enrolling in the OLE and transitioning to VDZ SC; (C) After 8 VDZ IV infusions (W0, W2, W6, and every 8 weeks thereafter until W52) in patients randomized to VDZ IV maintenance treatment in VISIBLE 1, completed 52 weeks of VDZ IV treatment, and transitioned to VDZ SC in the OLE.

Key findings include:

• Patients who transitioned to VDZ SC after 2 infusions of VDZ IV (N=106) had a clinical remission rate of 46.2% and a clinical response rate of 65.1% at W52.


• Among patients who received 3 VDZ IV infusions before transitioning to VDZ SC (N= 107), 39.2% achieved clinical remission and 48.0% achieved clinical response at W54 (14 weeks of IV; 40 weeks of SC).


• For patients who transitioned to VDZ SC after receiving 8 VDZ IV infusions over 52 weeks in VISIBLE 1 (N=35), clinical remission and clinical response rates (both 76.9%) were maintained during the OLE on SC through W24.

The vedolizumab subcutaneous clinical program also includes an open-label extension and analysis across both studies allow the team to evaluate the efficacy of patients transitioning from vedolizumab IV to vedolizumab subcutaneous in patients who achieved clinical benefit with vedolizumab IV treatment for varying durations.

"Transitioning from initial VDZ IV treatment to VDZ SC maintenance treatment retains the therapeutic benefit, independent of initial vedolizumab IV treatment duration," the authors wrote.

The investigators evaluated the efficacy of the subcutaneous treatment after 300 mg of initial vedolizumab IV infusions in 3 groups according to the duration of the vedolizumab IV treatment before transitioning to vedolizumab subcutaneous.

The first group was evaluated after 2 vedolizumab IV infusions (week [w] 0 and 2) in patients who achieved clinical response at week 6 were randomized to subcutaneous maintenance treatment in VISIBLE 1.

The second group included patients who received 3 infusions who did not achieve a clinical response at week 6 who received a third vedolizumab IV infusion at week 6 and had a clinical response at week 14 in VISIBLE 1 before enrolling in the open-label extension and transitioning to vedolizumab subcutaneous.

The third and final group evaluated patients after 8 vedolizumab IV infusions (weeks 0, 2, 6, and every 8 weeks after until week 52) who were randomized to vedolizumab IV maintenance therapy in VISIBLE 1, completed 52 weeks of vedolizumab treatment, and transitioned to the subcutaneous version in the open-label extension.

"Patients who transitioned to VDZ SC after 2 infusions of VDZ IV (N=106) had a clinical remission rate of 46.2% and a clinical response rate of 65.1% at W52," the authors wrote. "Among patients who received 3 VDZ IV infusions before transitioning to VDZ SC (N= 107), 39.2% achieved clinical remission and 48.0% achieved clinical response at W54 (14 weeks of IV; 40 weeks of SC).

"For patients who transitioned to VDZ SC after receiving 8 VDZ IV infusions over 52 weeks in VISIBLE 1 (N=35), clinical remission and clinical response rates (both 76.9%) were maintained during the OLE on SC through W24."

The symposium, "Transitioning From Vedolizumab IV to Vedolizumab SC in Patients With Ulcerative Colitis: Results From the VISIBLE Program," was presented Monday, October 28, 2019, at the American College of Gastroenterology Annual Scientific Meeting (ACG 2019) in San Antonio, Texas.