Vedolizumab (Entyvio) was much more effective than placebo as a treatment for ulcerative colitis (UC) in a range of patients, researchers found in a follow-up analysis of trial data.
Patients who’d previously failed TNF-antagonist therapy with infliximab, however, fared worse at 6 and 52 weeks than those who hadn’t tried the treatment. Still, Brian G. Feagan, MD, of Western University, London, Ont., and fellow researchers report that vedolizumab had a “consistent benefit” in patients with moderate to severe active UC, regardless of whether their experience with TNF-antagonist therapy was poor or nonexistent. Remission rates at 52 weeks reached as high as 46.9%.
At issue is how do different groups of UC patients benefit from vedolizumab, which was approved by the Food and Drug Administration in 2014 as a treatment for adult patients with moderate to severe ulcerative colitis or Crohn’s disease?
According to background information in the study, tumor necrosis factor–alpha (TNF) antagonist therapy has significantly improved treatment for ulcerative colitis, but many patients fail to respond. There is also a risk of infection.
The new study, published online Sept. 14 in Clinical Gastroenterology and Hepatology (2016. doi: 10.1016/j.cgh.2016.08.044 ), offers prespecified exploratory and post hoc analyses of vedolizumab vs. placebo in sets of UC patients from a phase III trial.
In a blinded group, 374 patients were randomly assigned to receive intravenous vedolizumab or placebo on days 1 and 15; 521 other patients in an open-label group received intravenous vedolizumab in the same fashion.
Patients in both groups who responded to vedolizumab at 6 weeks were randomly assigned to one of three groups: They continued vedolizumab every 8 weeks or every 4 weeks, or they received a placebo at week 6 for as many as 46 weeks. Patients who initially received the placebo either continued taking it over the maintenance period or stopped; those who didn’t respond to vedolizumab continued to get it every 4 weeks through week 52.
The new study focuses on 464 patients had not taken a TNF antagonist previously and 367 who’d failed TNF-antagonist therapy.
At week 6, 53.1% of the vedolizumab patients who hadn’t tried a TNF antagonist saw a clinical response, compared with 26.3% of counterparts who took a placebo (absolute difference, 26.4%; 95% confidence interval, 12.4-40.4; relative risk, 2.0; 95% CI, 1.3-3.0).
Among patients who had failed TNF antagonists, 39.0% saw a clinical response on vedolizumab at 6 weeks, and 20.6% saw one on placebo (absolute difference, 18.1%; 95% CI, 2.8-33.5; RR, 1.9; 95% CI, 1.1-3.2.). All those who’d failed TNF antagonists had taken infliximab because it was the only drug of its type available at the time of enrollment.
At week 52, the percentage of TNF antagonist–naive patients who were in remission was 46.9% in those on vedolizumab and 19.0% in those on placebo (absolute difference: 28.0%; 95% CI, 14.9-41.1; RR, 2.5; 95% CI, 1.5-4.0.) Among those who’d failed TNF-antagonist therapy, 36.1% of those on vedolizumab reached remission, and just 5.3% of those on placebo did (absolute difference, 29.5%; 95% CI, 12.8-46.1; RR, 6.6; 95% CI, 1.7-26.5.)
“These analyses show that vedolizumab had a consistent benefit for inducing and maintaining clinical response and remission in both TNF-naive and TNF-failure patients with moderately to severely active UC,” the authors write. “Further, no increased rates of serious infections were observed with vedolizumab treatment relative to placebo in either subgroup.”
The study authors caution against comparing the efficacy statistics in this study to the results of trials of TNF antagonists. While it’s “alluring” to make the comparison, they write, “We would caution against using such an approach to determine relative efficacy, given the confounding effects of differences in patient populations, outcome definitions, and, notably, trial design.”
They note that a study comparing the safety and efficacy of vedolizumab to adalimumab (Humira) in ulcerative colitis is underway ( NCT02497469 ) – it’s now recruiting patients – and “the results of such studies will be critical in informing payers regarding the relative value of these agents.”
What’s next? The researchers note that TNF-antagonist alternatives to infliximab now exist. “Randomized trials should be performed comparing vedolizumab to the use of a second TNF antagonist in TNF -antagonist failure patients with adequate serum drug concentrations,” they write.
Millennium Pharmaceuticals (Takeda Pharmaceuticals) funded the clinical studies. Some of the study authors are employees of Takeda. Other study authors have received support from Takeda, Millennium, or both.
