By Gene Emery
NEW YORK (Reuters Health) - 25/9/2019
In a head-to-head comparison, vedolizumab scored better than widely used adalimumab in treating moderately to severely active ulcerative colitis (UC) in two out of three measures, according to a report online September 25 in The New England Journal of Medicine.
Meanwhile, a second study, published along with the first, found that ustekinumab not only induces but maintains remission in people with moderate to severe UC.
None of the drugs produced clinical remission in an overwhelming majority of the patients, however.
"The treatment options for people with ulcerative colitis are so limited, knowing how to best use the drugs we have and in what sequence is very important, and having additional options such as ustekinumab is equally important," Dr. Bruce Sands, chief author of both studies, told Reuters Health by phone.
Ulcerative colitis affects an estimated 700,000 people in the U.S. and as many as a million people in Europe.
In the two-drug comparison, involving 769 randomized patients, the clinical remission rate at week 52 was 31.3% with vedolizumab versus 22.5% with adalimumab (P=0.006), and endoscopic improvement rates were 39.7% compared to 27.7%, respectively (P<0.001).
When the research team looked at corticosteroid-free clinical remission, the anti-tumor necrosis factor (TNF) biologic adalimumab came out on top, with remission in 21.8% of the 386 patients in that arm versus 12.6% of the 383 volunteers who received vedolizumab, but the difference fell just short of statistical significance.
Vedolizumab produced a lower rate of infections.
"This was a somewhat surprising result because all of us in the field believed anti-TNFs were the most powerful agent that could be used in ulcerative colitis," said Dr. Sands, chief of the division of gastroenterology at Mount Sinai School of Medicine in New York. "This suggests otherwise, particularly for patients who were biologically naive."
The study, known as VARSITY, was done at 245 centers in 34 countries. Doctors gave 300 mg of vedolizumab on a staggered schedule that, by the end of the trial, was very eight weeks. Adalimumab was given roughly every two weeks after two weeks of loading doses.
"Any clinical superiority of vedolizumab should be balanced against the significant cost advantages of a subcutaneous regimen of adalimumab," Dr. Richard Farrell of Connolly Hospital and Royal College of Surgeons in Dublin, Ireland, writes in a linked editorial.
Takeda Pharmaceuticals International in Zurich, which sells vedolizumab under the brand name Entyvio, designed and funded the comparison. Each infusion costs more than $6,400, according to the website GoodRX.com.
Adalimumab, available as a generic but best known by the brand name Humira, is the world's best-selling prescription medicine and is also used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, chronic psoriasis, hidradenitis suppurativa, and juvenile idiopathic arthritis. It sells for more than $5,100 for a week's treatment.
In the ustekinumab study of 961 patients who had failed to respond or couldn't tolerate other treatments, the induction arm found rates of clinical remission of 15.6% at eight weeks in the group that received a one-time 130 mg intravenous dose, 15.5% in the group whose dose was 6 mg per kilogram of body weight and 5.3% with placebo (P<0.001 versus placebo).
Among the 348 volunteers who responded to induction therapy, maintenance therapy of 90 mg was given subcutaneously on two schedules.
The rate of clinical remission at week 44 was 43.8% for those who received the drug every eight weeks, 38.4% among patients who got it every 12 weeks and 24.0% for the volunteers given placebo injections (P=0.001 or lower versus placebo).
Each 90 mg dose of ustekinumab costs more than $22,000.
There were no deaths and one case of testicular cancer in the placebo group, but two deaths and seven cases of cancer in the ustekinumab patients, three of which were non-melanoma skin cancer.
Johnson & Johnson, which sells the drug under the brand name Stelara, paid for that study, known as UNIFI.
Previous treatment with interleukins 12 or 23 was prohibited. Volunteers in the induction trial were kept on oral corticosteroids, which were tapered for the maintenance portion of the trial. Patients were treated at 244 sites worldwide.
Corticosteroids were discontinued at a median of seven weeks in the two ustekinumab maintenance groups compared with a median of 16 weeks in the placebo group. The side effect profiles were similar for the three groups but four patients developed what may have been opportunistic infections.
"We would love to see that the majority of patients are well at the end of the year, but there's not a single agent we've ever studied for which that is true," said Dr. Sands.
"We're seeing a plateauing of efficacy for single-agent therapy. We can't predict who will respond to which mechanism, so it's good to have additional options," he said.
Dr. Sands said others "are studying combinations of drugs to try to understand if we can get even better efficacy, but those are harder studies to do and typically are not going to be done in period of registrational drug studies."
N Engl J Med 2019.
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