The gut-selective alpha₄beta₇ integrin antibody vedolizumab is safe and effective for long-term use in patients with inflammatory bowel disease (IBD), according to data from more than 2,200 patients in the GEMINI LTS trial.

With a median cumulative exposure of approximately 3 years and some patients taking vedolizumab for more than 9 years, the study revealed no new safety concerns and showed that responses were stable over time, reported lead author Edward V. Loftus Jr., MD, of the Mayo Clinic in Rochester, Minn., and colleagues.

“Interim analyses (based on 4 years of follow-up) demonstrated that long-term vedolizumab therapy was well-tolerated and also provided clinical and health-related quality of life (HRQOL) benefits,” the investigators wrote in Alimentary Pharmacology & Therapeutics. “In this final analysis ... we report the final safety outcomes, along with exploratory clinical and HRQOL outcomes.”

The phase 3 trial involved 1,822 patients with IBD from previous phase 2 and 3 trials, plus 421 vedolizumab-naive patients. Out of 2,243 participants in the final analysis, 894 had ulcerative colitis, and 1,349 had Crohn’s disease.

All patients received vedolizumab 300 mg IV every 4 weeks, which the investigators noted is more frequent than the dosing interval of 8 weeks that was approved after the trial was designed.

Median cumulative exposure times among patients with ulcerative colitis and Crohn’s disease were 42.4 months and 31.5 months, respectively. Adverse events of any grade occurred in 93% of patients with ulcerative colitis and 96% of patients with Crohn’s disease, approximately one-third of which were exacerbations of IBD. Serious adverse events occurred in 31% and 41% of patients with ulcerative colitis and Crohn’s disease, respectively. Adverse events led to discontinuation in 15% of ulcerative colitis patients and 17% of those with Crohn’s disease. Of the 10 deaths that occurred during the study period, the investigators categorized 2 of them as drug related (hepatocellular carcinoma and West Nile virus infection–related encephalitis). No increase in the rate of overall malignancies was observed.

Dr. Loftus and colleagues noted that rates of serious infection with vedolizumab treatment were superior to historical long-term data for adalimumab, at 18.0 (ulcerative colitis) and 33.6 (Crohn’s disease) per 1,000 person-years for vedolizumab, compared with 35 (ulcerative colitis) and 67 (Crohn’s disease) per 1,000 person-years for adalimumab, as reported by Colombel and colleagues.

“While these data suggest a decreased risk of systemic infections with vedolizumab, an increased risk of gastrointestinal infections is plausible given the gut-selective mechanism of action and evidence for reduced immune response in the gastrointestinal tract,” the investigators wrote, reporting rates of 34.9 and 39.6 per 1,000 person-years for ulcerative colitis and Crohn’s disease, respectively. Comparative, historical rates for adalimumab were not provided.

In the present trial, clinical response rates, clinical remission rates, and HRQOL estimates remained stable over time. At 400 treatment weeks, clinical remission was maintained in 33% and 28% of patients with ulcerative colitis and Crohn’s disease, respectively.

“[T]he final analysis of GEMINI LTS comprehensively demonstrates that vedolizumab therapy has a safety and tolerability profile suitable for long-term treatment of patients with moderately to severely active ulcerative colitis or Crohn’s disease,” the investigators concluded.

According to Randy Longman, MD, director of the Jill Roberts Center for Inflammatory Bowel Disease at Weill Cornell Medicine and New York-Presbyterian, “The results from the GEMINI LTS trial help to solidify the favorable safety profile of vedolizumab for the treatment of IBD. With large patient numbers and cumulative duration of vedolizumab exposure, these pivotal data convincingly reveal low rates of serious infections, identified no cases of progressive multifocal leukoencephalopathy, and showed no increased risk of malignancy. Arthralgias, or joint pain, was the most common treatment-emergent adverse event, but occurred largely in patients with a history of IBD-associated arthralgia and suggest that these symptoms should be monitored during treatment. Overall, these results provide meaningful reassurance to patients and providers using vedolizumab for the treatment of IBD.”

GEMINI LTS was funded by Takeda. The investigators reported additional relationships with AbbVie, Janssen, Amgen, and others. Dr. Longman reported no conflicts of interest.

SOURCE: Loftus Jr EV et al. AP&T. 2020 Sep 2. doi: 10.1111/apt.16060.

Vedolizumab shows long-term safety, efficacy