Infliximab Did Not Result in Lower Rate of Hospitalizations, Surgeries in Canadian Study

The introduction of infliximab for the treatment of inflammatory bowel diseases (IBD) did not result in lower population rates of hospitalizations or intestinal surgeries among patients living with IBD in Ontario, Canada, according to a study published Thursday.

The results are somewhat surprising, as biologics have represented a major step forward in the treatment of both Crohn disease (CD) and ulcerative colitis (UC), which together make up IBD. However, name-brand biologics are high-cost therapies, and their expense is often cited as a challenge for healthcare systems worldwide.

Infliximab, first marketed as Janssen’s originator product, Remicade, became available in Ontario for CD in 2001 and for UC in 2006. There are also 2 approved infliximab biosimilars: Samsung Bioepis and Merck’s Renflexis and Pfizer’s Inflectra.

Writing in the journal Gut, authors from several Canadian hospitals and the Institute for Clinical Evaluative Sciences (ICES), an independent, non-profit health evaluation research institute, said misguided use of infliximab in patients with CD and underuse of infliximab in patients with UC may explain the findings.

Researchers studied trends in hospitalizations, surgeries, and drug costs in CD and UC between 1995 and 2012. They compared trends following the introduction of infliximab in Ontario in 2001 to trends that would have been expected had the drug not been introduced.

For patients with CD, there were no reductions in hospitalization or intestinal resection rates.

People with UC who received infliximab also did not experience lower surgery rates; they did see some improvement in hospitalization rates.

“These findings are disappointing for a class of therapy that has demonstrated benefit in reducing IBD-related hospitalizations and surgeries in clinical trials," said Sanjay Murthy, MD, lead author on the study and an IBD specialist and associate scientist at The Ottawa Hospital, in a statement.

"We had expected to see larger declines in these adverse health events because they are more common in IBD patients with severe disease, and these are the same patients that we should be targeting with this therapy early in their disease to prevent hospitalizations and surgeries."

The study did not include the impact of this therapy on other health outcomes, such as quality of life or workplace attendance and productivity.

Compared with what would have been expected without the entry of infliximab, there were no reductions in the rates of CD-related hospitalizations (odds ratio [OR] at the last observation quarter, 1.06; 95% CI, 0.811-1.39) or intestinal resections (OR, 1.10; 95% CI, 0.810-1.50). There were also no declines in the rates of UC-related hospitalizations (OR, 1.22; 95% CI, 1.07-1.39) or colectomies (OR, 0.933; 95% CI, 0.54-1.61).

The findings were similar among all patients on infliximab, except that hospitalization rates declined substantially among patients with UC following marketplace introduction of infliximab (OR, 0.515; 95% CI, 0.342-0.777).

In addition, there was a 3-fold rise over expected trends in public payer drug costs among patients with CD following infliximab introduction (OR, 2.98; 95% CI, 2.29-3.86), although there was no significant change among patients with UC (OR, 1.06; 95% CI, 0.955-1.18).

Compared with all persons with IBD in the population, patients obtaining infliximab through public funds were generally younger, made up of a higher proportion of males, were slightly more likely to be living in a rural location, and were more likely to have lower incomes.

"Clinicians have seen how anti-[tumor necrosis factor] therapy can dramatically improve their patients' symptoms, and in many cases even lead to complete bowel healing," said Murthy, an assistant professor at the University of Ottawa. "But even though the drug clearly helps some individuals, we are not seeing some of the important benefits we would expect at a broader population level. This suggests that we may need to improve how we are using this drug in clinical practice to realize greater benefits."

Across Canada, 41.8% of prescribed drug spending is paid for by provincial healthcare plans. As of the last observation quarter, 10.2% of persons with CD and 3.3% of persons with UC had received infliximab through public assistance.

The study also showed that the average per patient drug costs for IBD have risen dramatically since the introduction of infliximab, particularly among people with CD, where average annual publicly-funded drug costs rose from approximately $1000 before infliximab introduction in 2001 to more than $14,000 by 2012. For patients with UC, the mean drug costs rose from approximately $2500 before infliximab introduction in 2006 to more than $10,000 by 2012.

The researchers hypothesize that selecting the wrong patients, delaying the start of treatment by not recognizing disease severity or through poor access to treatment, and incorrectly optimizing drug dosage could all be factors that make the real-world experience of these therapies different at a population level.

Criteria for reimbursement through public or private health insurance may also limit timely access to the therapy.

Reference

Murthy SK, Begum J, Benchimol EI, et al. Introduction of anti-TNF therapy has not yielded expected declines in hospitalisation and intestinal resection rates in inflammatory bowel diseases: a population-based interrupted time series study [published online June 13, 2019]. Gut. doi:10.1136/gutjnl-2019-318440