One year of treatment with Entyvio (vedolizumab) was found to be superior to Humira (adalimumab) in achieving disease remission in people with ulcerative colitis (UC), a common form of inflammatory bowel disease (IBD), Takeda announced.
A head-to-head comparison of these anti-inflammatory therapies was made in the VARSITY trial (NCT02497469), a Phase 3b, randomized, double-blind, multi-center study sponsored by the company.
Trial results were published in The New England Journal of Medicine in the study, “Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis”.
AbbVie’s Humira is an anti-inflammatory medication used to treat UC. Adalimumab is an anti-TNF therapy that works by blocking the inflammatory signaling molecule TNF (tumor necrosis factor). However, some patients either do not respond well to or cannot tolerate this therapy, or other standard corticosteroid therapies.
Entyvio, by Takeda, is an alternative anti-inflammatory medicine that works by a different mechanism — it prevents inflammatory cells from getting into the intestines.
This study directly compared the efficacy and safety of Entyvio to Humira in 769 people with moderately or severely active UC, all of whom failed to adequately respond to a previous treatment.
Patients were divided into two groups. The Entyvio group, which had 383 people, were given 300 mg of the therapy intravenously (IV) on day one, and again at weeks two and six, followed by infusions every eight weeks until week 46.
Humira was given to 386 patients by subcutaneous (SC) injection at 160 mg on day one and 80 mg at week two, followed by 40 mg every two weeks until week 50.
As these medicines were administered differently (IV versus SC), patients in the Entyvio group also received an SC injection of a placebo while the Humira group was given a placebo by IV. In this way, both patients and researchers were blind to who received which treatment.
The patients were assessed for clinical remission 52 weeks after the treatment began. Clinical remission was defined as a Mayo score — an assessment of disease severity — of two points or less, and a Mayo subscore — assessing the endoscopic component alone — of less than one point.
Analysis found that clinical remission rates in Entyvio treatment (31.3%) group were significantly better than in those being treated with Humira (22.5%) after 52 weeks.
Entyvio treatment was better at achieving remission after 14 weeks (26.6%) compared to Humira (21.2%). Sustained remission was also higher in the Entyvio-treated group (18.3%) than in the Humira-treated group (11.9%).
A comparison of these two treatments between UC patients previously treated with anti-TNF therapies and those who had not been was also made. Among previously treated patients, remission was achieved in 20.3% of those given Entyvio compared to 16.0% of patients treated with Humira. In patients without a previous anti-TNF treatment, 34.2% of those given Entyvio achieved remission compared to 24.3% in the Humira-treated group.
In contrast, clinical remission without a previous corticoisteroid therapy occurred in 12.6% of patients in the Entyvio group and in 21.8% in the Humira group.
Further analysis showed that Entyvio treatment was associated with improvements in quality of life, as assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ) score — a measure of IBD related to primary bowel disturbance, systemic symptoms, and emotional and social function. In the Entyvio-treated group, 52.0% of patients reported an IBDQ score of 16 or greater, while 42.2% of Humira-treated patients reported the same score.
In terms of safety, adverse events were reported in 62.7% of Entyvio-treated patients over 52 weeks, and in 69.2% of Humira-treated patients. The number of patients who stopped treatment due to adverse events was similar in both groups.
“In this trial involving patients with moderately to severely active ulcerative colitis, vedolizumab [Entyvio] was superior to adalimumab [Humira] with respect to achievement of clinical remission and endoscopic improvement, but not corticosteroid-free clinical remission,” the researchers concluded.
“The VARSITY study, a first-of-its-kind comparison of two biologics in ulcerative colitis, shows the benefits vedolizumab treatment provides to patients versus adalimumab across efficacy outcomes, in addition to improvements in overall quality of life,” Jeff Bornstein, MD, executive medical director of Takeda, said in a press release. “These data further support the use of vedolizumab as a first-line biologic therapy in ulcerative colitis.”