EXPLORER, a recent phase 4 study led by the Feinstein IBD Center at the Icahn School of Medicine in New York City researching the effects of combining biologics with each other or other drugs, has shown positive results in the treatment of Chron’s disease.
The study is led by Dr. Jean-Frederic Colombel and used a combination of three drugs and two biologics.
“The alpha4beta7 integrin receptor antagonist vedolizumab (Entyvio, Takeda) and the tumor necrosis factor inhibitor adalimumab (Humira, AbbVie) were combined with methotrexate in biologic-naive patients considered to be at moderate to high risk for complications,” a September article from Gastroenterology & Endoscopy News states.
After 26 weeks 54.5-percent of participants saw clinical remission, while 34.5-percent were in endoscopic remission. Importantly, no patrician saw safety signals related to the triple-agent therapy according to Colombel.
Colombel and his team aimed to see how the combination of treatments would improve patient outcomes in comparison to single drug options.
“Although biologics have revolutionized treatment of Crohn’s disease, an efficacy plateau has been reached,” according to Dr. Colombel. “Combining biologic therapies, such as vedolizumab and adalimumab, may be effective in overcoming this plateau.”
According to Gastro & Endo News, 32 locations across the United States and Canada participated in the study, enrolling “biologic-naïve patients at a moderate or severe risk for complications based on the CDPATH prognostic tool,” according to the report.
The median age of participating patients was 32.4 years old, with over half (56-percent) being male. Patients had been dealing with Chron’s disease for a median of four months, and no patient had been diagnosed for longer than 2 years and, according to the report, 29-percent of participants were on a steroid at the time of entry into the study. The site of Chron’s disease did vary among participants. 20-percent of patients Chron’s disease was colonic, while 40-percent were ileal. The remaining 40-percent were ileocolonic.
Results showed a minor improvement in the usage of multiple drugs and biologics, which pleased researchers such as Dr. Stephen B. Hanauer, a professor of medicine at Northwestern University’s Feinberg School of Medicine.
“There does appear to be a therapeutic ceiling for individual drugs to treat IBD,” Dr. Hanauer said, agreeing with Dr. Colombel’s rationale for this direction of research. “The issue is that although these combinations have incremental benefits over monotherapy, the efficacy increase of 10% to 15% doesn’t raise the ceiling very much.”
Despite only a minor increase, Dr. Hanauer supports continued testing to identify improved combinations to boost results.
“Current trials are beginning to explore combining different mechanisms of action together, such as anti-adhesion molecules with a cytokine blocker or blocking two different cytokines at the same time,” he noted.
Future research will continue to test new combinations, and long-term trials will need to be performed to determine safety. Hanauer also adds that the costs of these experiments may cause problems in future research.
