IBD patients in remission can safely switch to infliximab biosimilar

Last Updated: 2018-04-12

By Marilynn Larkin

NEW YORK (Reuters Health) - Switching to CT-P13, an infliximab biosimilar, is safe and well tolerated in patients with IBD whose disease is in remission, researchers say.

"Biological treatment of chronic inflammatory diseases has improved patient outcomes but increased health care costs," Dr. Anne Strik of Academic Medical Center in Amsterdam and colleagues noted in their report online March 29 in The Lancet Gastroenterology and Hepatology. "Switching patients from originator infliximab to a biosimilar can reduce costs, but prospective data about pharmacokinetics and potential immunogenicity are scarce."

To investigate, Strik's team conducted a noninferiority trial at 13 sites in Belgium and the Netherlands in 46 patients with ulcerative colitis (UC) and 42 with Crohn's disease (CD).

In the UC group, the mean age was 48.3 years; 46% were male; and median disease duration was 9 years. In the CD group, the mean age was 41.5; 52% were male, and the median disease duration was 10 years.

Patients were switched from originator infliximab to CT-P13 at a dose and infusion duration identical to those of the originator (i.e., approximately 5 mg/kg every 7 to 9 weeks). After switching, patients were followed up for 16 weeks.

Serum concentrations of infliximab were measured at baseline (before the first dose of CT-P13), 8 weeks, and 16 weeks.

The geometric mean ratio of serum infliximab concentrations at week 16 (CT-P13) compared with those at baseline (originator) was 110.1% (90% CI 96.0-126.3) in patients with UC and 107.6% (97.4-118.8) in those with CD.

In both groups of patients, the lower bound of the 90% CI was higher than the prespecified non-inferiority margin of 85%, meaning that serum concentrations of infliximab after switching to CT-P13 were non-inferior to concentrations of the originator infliximab in this patient population.

Six serious adverse events were reported in six patients. Only one of these adverse events, a perianal abscess, was judged to be related to study treatment.

"This trial was performed in patients in clinical remission, which is important to keep in mind while discussing extrapolation of results or making a . . . statement concerning switching the entire IBD population," Dr. Strik told Reuters Health by email.

"Currently, we are working on a Cochrane review about switching IBD patients from the originator to CT-P13," she added. "After gathering all available literature and looking at all the results, more definitive advice about switching IBD patients can be given."

Dr. Richard Bloomfeld, director of IBD Services at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina, told Reuters Health, "Although the U.S. Food and Drug Administration tells us that 'a biosimilar is a biologic product that is highly similar to and has no clinically meaningful differences from an existing FDA-approved reference product,' physicians and patients may still have some concerns about using biosimilars."

"This study provides further reassurance to physicians and patients that biosimilars are an acceptable option in the treatment of IBD and may allow us to realize the potential cost savings."

Dr. Lisa Malter, a gastroenterologist at NYU Langone Health in New York City, told Reuters Health by email, "The study methods were strong and the results are promising in this diverse group of patients in clinical remission."

But, she added, "A few limitations of this work limit their generalizability."

"First," she said, "patients were in clinical remission only as assessed by the Simple Clinical Colitis Activity Index and the Harvey Bradshaw Index; (the authors) did not evaluate patients in deep remission - endoscopic or histologic remission known as mucosal healing."

"Deep remission is a therapeutic endpoint," she noted. "It is possibly riskier to study a group only in clinical remission, despite the results of the study being positive."

"Second, the included patients may not have aggressive disease, as all participants were receiving infliximab at standard doses of 5 mg/kg every 7-9 weeks," she said. "In more severe disease, patients may take up 10 mg/kg at intervals as frequently as every four weeks."

"Third, the study period was short - 16 weeks - and immunogenicity may not appear during this window; it may take longer," she explained.

"In addition, the assay used to measure serum concentrations does not allow for detection of antibodies in the presence of drug," she said. "It is possible that some participants did develop immunogenicity in the form of antibody production that was not detected with these study methods."

"Long-term observational studies are needed with biosimilars, especially as more come to market, to assess for continued efficacy, safety and immunogenicity," Dr. Malter concluded.

Dr. Rudolph Bedford, a gastroenterologist at Providence Saint John's Health Center in Santa Monica, California, added in an email that as costs decrease, therapy "will become available to a larger number of patients."

The study was funded by Mundipharma, which produces CT-P13. Dr. Strik and two coauthors have received fees from Mundipharma and two coauthors are employees of the company.

SOURCE: http://bit.ly/2GSvkuU and http://bit.ly/2GYxqcQ

Lancet Gastroenterol Hepatol 2018.