, results from a phase 3, double-blind trial demonstrated.
Dr. William J. Sandborn
“The route of drug administration can be an important determinant of a patient’s treatment experience, particularly for chronic diseases such as UC [ulcerative colitis],” investigators led by William J. Sandborn, MD, of the division of gastroenterology and hepatology at the University of California, San Diego, wrote in a study published online in Gastroenterology (doi: 10/1053/j.gastro.2019.08.027). “Intravenous administration of a biologic treatment requires the patient to set time aside and travel to a treatment center for an infusion. In addition, the greater use of a health care facility increases the direct costs of care. Some studies show that even with the option of self-injection some patients may still prefer an IV route of administration for the reassurance provided by the opportunity for interacting with a health care professional or because they are averse to self-injection. The availability of both an SC and IV injection of vedolizumab will enable patients to choose the route of administration for maintenance treatment.”
Between Dec. 18, 2015, and Aug. 21, 2018, Dr. Sandborn and colleagues at 141 sites in 29 countries enrolled 353 patients with moderate to severely active UC to receive IV vedolizumab 300 mg at weeks 0 and 2. At week 6, 216 patients who demonstrated clinical response were randomly assigned to maintenance treatment: 106 to SC vedolizumab 108 mg every 2 weeks, 54 to IV vedolizumab 300 mg every 8 weeks, and 56 to placebo. The study’s primary endpoint was clinical remission at week 52, which was defined as a total Mayo score of 2 or lower and no subscore greater than 1.
The mean age of patients was 40 years and 60% were male, and they had UC for a mean of 8 years. At week 52, the researchers found that clinical remission was achieved by 46.2% of patients in the SC vedolizumab group, compared with 42.6% of patients in the IV vedolizumab group and 14.3% of patients in the placebo group. In addition, patients in the SC vedolizumab group experienced significantly greater rates of endoscopic improvement and durable clinical response compared with those in the placebo group (P less than .001).
In terms of safety, injection-site reactions were noted by 10.4% of patients in the SC vedolizumab group (mostly rash, swelling, erythema, and pruritus), compared with 1.9% of patients in the IV vedolizumab group and in no patients in the placebo group. “No serious cases were reported for the AEs of special interest: hypersensitivity (including injection site reactions or infusion-related AEs), malignancies, and liver injury,” the researchers wrote. “There were no cases of PML [progressive multifocal leukoencephalopathy] and no deaths.” They acknowledged that the study’s sample size was smaller than the previous GEMINI pivotal trial for vedolizumab IV in ulcerative colitis (N Engl J Med 2013;369:699-710). “This limitation may have contributed to the findings of numerically greater but not statistically significant differences between treatment arms for some secondary endpoints such as durable clinical remission and corticosteroid-free clinical remission,” they wrote.
Takeda sponsored the study. Dr. Sandborn and coauthors reported having numerous financial ties to industry.
SOURCE: Sandborn WJ et al. Gastroenterol 2019 Aug. 27. doi: 10/1053/j.gastro.2019.08.027.