Early dual therapy with infliximab and an immunomodulator significantly decreased the 1-year risk of hospitalization and surgery in patients with inflammatory bowel disease, in a cohort study of almost 20,500 patients.
The improvements in hospitalization and surgery rates became apparent as quickly as 5 months after therapy initiation. By 9 months after dual therapy began, there was an 86% decrease in hospitalization and a 92% decrease in surgery compared with the rates in those who had not taken these medications.
The study shows that aggressive treatment of inflammatory bowel disease can reap robust results, Dr. Neena S. Abraham and colleagues reported in the Aug. 29 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.04.051).
The results probably underestimate the potential benefits of dual therapy, wrote Dr. Abraham of the Mayo Clinic, Scottsdale, Ariz., and associates. Only 11% of patients in the database took one of the studied treatment regimens, and of those, most (85%) got an immunomodulator only.
"Given the paucity prescribed dual therapy (8.5%), the dose-response data are even more impressive and suggest that if dual therapy had been initiated earlier, greater benefit may have been observed," the investigators wrote.
The study examined 1-year hospitalization and surgical rates in 20,474 patients with either ulcerative colitis or Crohn’s disease. The patients were all included in a database that covered 176 U.S. Department of Veteran Affairs facilities.
Three treatment protocols were examined: immunomodulator monotherapy, anti–tumor necrosis factor (TNF)-alpha monotherapy with infliximab, and dual therapy with an immunomodulator and infliximab.
Most of the patients (12,432) had ulcerative colitis (UC); the remainder had Crohn’s disease (CD). Most (94%) were male; the mean age was 72 years.
The most common strategy was the anti–TNF-alpha alone (8%). Among patients receiving infliximab, 63% had evidence of induction therapy preceding a maintenance regimen.
"Despite their clear therapeutic benefit, less than 15% of patients with inflammatory bowel disease receive anti-TNF monotherapy, and 40% of patients with active CD receive anti-TNF agents in combination with immunomodulator agents (thiopurines or methotrexate)," they commented.
Most patients (66%) were taking other drugs, including steroids (14%), nonsteroidal anti-inflammatory agents (39%), aspirin (21%), cyclosporine (0.21%), antimetabolites (0.67%), and antibiotics (29%).
A 50% relative reduction in hospitalization occurred at 7.7 months with dual therapy compared with 9 months with immunomodulator monotherapy and 8 months with anti–TNF-alpha therapy. All of these differences were statistically significant after the model was adjusted for diagnosis (UC or CD), smoking status, race/ethnicity, and other medications that could modify the treatment effect.
By 1 year, there was a 45% relative reduction in hospitalization for immunomodulator therapy and a 78% relative reduction with anti–TNF-alpha monotherapy. But patients taking dual therapy reached a similar reduction of 73% by 9 months.
"Results suggested that, if dual therapy had been initiated earlier, perhaps a greater response in the outcome may have been observed," the investigators wrote.
There was a similar beneficial effect on surgeries related to the disorders. In the first year of treatment, there were 276 procedures. By 9 months, there was a 28% risk reduction associated with immunomodulator monotherapy, a 90% reduction associated with anti–TNF-alpha monotherapy, and a 92% reduction associated with dual therapy.
This also suggests that a "greater response may have been observed with earlier initiation of dual therapy," the authors said.
Safety concerns may be one reason for the dearth of these treatment protocols, the authors noted. However, recent long-term safety data suggest that there is a very low risk of mortality associated with them.
"[Five-year] outcome data on infliximab use has failed to demonstrate increased risk of mortality, and, although increased risk of infection was observed, the presence of severe disease and use of prednisone or narcotics carried higher risks," they said, referring to a 2012 study (Am. J. Gastroenterol. 2012;107:1409-22).
A 2011 study also suggested that the benefits of dual therapy outweigh the risks of developing a serious infection or cancer (Clin. J. Gastroenterol. Hepatol. 2012;10:46-51).
Janssen Biotech funded the study. None of the authors reported having any relevant financial disclosures.