Studies Unveils News Drugs Vedolizumab, Adalimumab And Ustekinumab For Treating Previously Untreatable Ulcerative Colitis
Source: Thailand Medical News Sep 29, 2019 5 years, 2 months, 4 days, 15 hours, 43 minutes ago
Thailand Gastroenterology
Ulcerative colitis(UC) is one of many immune-mediated diseases with a rising prevalence globally. Previously there were no treatments available to cure the condition but recently a number of drugs were introduced. However researchers from Mount Sinai conducted two separate clinical trials to evaluate three specific biologic agents: adalimumab, vedolizumab, and ustekinumab. All three drugs evaluated in these studies work through different mechanisms to modify the immune responses that causes bowel inflammation in ulcerative colitis.
In the first clinical trial to evaluate two biologic therapies for moderate to severe ulcerative colitis head to head, the researchers found vedolizumab to be superior to adalimumab in a variety of measures. In a separate study, the investigators reported that ustekinumab is more effective than placebo as an induction and maintenance therapy for UC.
Professor of Gastroenterology, Dr Bruce E. Sands from Icahn School of Medicine at Mount Sinai and Chief of Gastroenterology for the Mount Sinai
Health System commented in an interview with
Thailand Medical News "Every patient responds differently to these agents, and the treatments we have today are not effective for everyone, adding to the urgency to identify treatments that are both safe and effective".
Although newer classes of pharma drugs have been approved to treat ulcerative colitis over the last 10 years, no study has yet directly evaluated and compared two biologic agents for inflammatory bowel disease. in a blinded, randomized controlled trial.
Vedolizumab Versus Adalimumab
In the clinical studies of vedolizumab versus adalimumab, the VARSITY trial found vedolizumab to be superior to adalimumab in achieving clinical remission and endoscopic improvement at 52 weeks. No significant difference was found between the two agents in achieving corticosteroid-free remission. Both agents showed good safety over the year of treatment.
The VARSITY trial enrolled 769 patients with moderately to severely active UC across 244 centers in 34 countries in a phase 3b, randomized, double-blind, double-dummy, active controlled study. Vedolizumab, versus a
dalimumab, achieved significantly higher week-52 rates of remission, 31.3 percent versus 22.5 percent, respectively, and endoscopic improvement of 39.7 percent versus 27.7 percent. Corticosteroid-free clinical remission rates were 12.6 percent for vedolizumab versus 21.8 percent for adalimumab, a difference that is not statistically significant. The authors note that adjusted adverse event rates were lower with vedolizumab, at 23.4 percent versus 34.6 percent per 100 patient years for infections, and for serious infections, the comparison is 1.6 versus 2.2.
The VARSITY study provides the highest level of evidence to date to guide the initial choice of biologic therapy in patients with moderately to severely active ulcerative colitis. Further head-to-head studies like VARSITY are however needed to advance the field.
Ustekinumab For Ulcerative Colitis
Another clinical study involving a study of ustekinumab as an induction and maintenance therapy, researchers concluded that this agent is more effective than placebo for inducing and maintaining remission in patients with moderate to severe UC. Ustekinumab, already approved for the treatment of Crohn's disease, psoriatic arthritis, and psoriasis, blocks interleukin-12 and interleukin-23, immune proteins known to be involved in immune responses in inflammatory bowel disease and other immune-mediated conditions.
In the study, 961 patients were randomized to intravenous induction doses of ustekinumab or placebo. Clinical remission rates at week eight among patients receiving intravenous ustekinumab were significantly higher than placebo-treated patients. Rates of clinical remission among patients who received intravenous ustekinumab, either 130 mg or approximately 6 mg/kg, were significantly higher than among those who received placebo, at 15.6 and 15.5 percent 151.5% vs. 5.3%; statistically significant for both comparisons.
Among ustekinumab-treated induction responders, the rate of clinical remission at week 44 was significantly higher for patients re-randomized to subcutaneous ustekinumab than for patients re-randomized to placebo: 38.4 percent for patients dosed every 8 weeks and 43.8 percent for patients dosed every 12 weeks, versus 24 percent for those patients taking placebo injections. The authors note that serious adverse event rates were similar in ustekinumab- and placebo-treated patients.
Considering the excellent efficacy and safety of ustekinumab, this should be a valuable addition to the drugs use to treat ulcerative colitis.”
The studies were published in the The
New England Journal of Medicine
The team are have other ongoing clinical studies and also initiating other newer clinical trials with regards to ulcerative colitis and also other inflammatory bowel diseases.
Reference:
Bruce E. Sands et al. Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis, New England Journal of Medicine (2019). DOI: 10.1056/NEJMoa1905725
Bruce E. Sands et al. Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis, New England Journal of Medicine (2019). DOI: 10.1056/NEJMoa1900750
