番茄社区

A novel real-world study of mandatory reverse switching from biosimilar to originator infliximab (Remicade) in inflammatory bowel disease (IBD) patients found no significant changes in clinical remission rates, drug trough levels, or anti-drug antibody status after reverse switching during a 24-week follow-up.

Short-term drug sustainability was good, and no new safety signals emerged, Hungarian researchers reported in .

"As the number of biosimilar agents on the market increases, data on reverse and/or multiple switches are needed to guide decision making and provide information on their interchangeability," wrote Peter L. Lakatos, MD, DSc, of Semmelweis University in Budapest and McGill University in Montreal, and colleagues.

They noted that while there is evidence for the safety and efficacy of switching IBD patients from maintenance therapy with an original infliximab drug to a biosimilar, little is known about the outcomes of a reverse switch and/or multiple switches. No biosimilars in the U.S. have received FDA approval to be used interchangeably with the originator products.

Lakatos and colleagues prospectively studied 174 Hungarian unselected and consecutive patients with IBD, 136 with Crohn's disease (CD) and 38 with ulcerative colitis (UC). All had been on maintenance therapy with the biosimilar CT-P13 (Inflectra, Remsima). The CD group was 50.7% female and the UC group 55.3% female. Age of disease onset in the two groups was at 27.5 years and 25 years, respectively, and disease duration was 8 and 7 years.

These patients' switch from biosimilar to originator infliximab resulted from a tug of war between the products' manufacturers. When CT-P13 first became available in Hungary in 2014, the country's healthcare payment authority gave it preference over Remicade. In 2017, however, "the national tender for [infliximab] therapy reimbursement [was] won by Remicade, and as a consequence the originator became the only fully reimbursed" infliximab product in Hungary. For financial reasons, therefore, some patients on CT-P13 were compelled to switch to Remicade.

Complications and perianal manifestations were present in 39.7% and 48.5% of CD patients, respectively, and 54.1% of UC patients had extensive colitis. Previous exposure to infliximab was noted in 8% (n=14) of patients.

Clinical and biochemical information was collected in patients at time of switch and at 16 and 24 weeks thereafter. Clinical remission was defined as a CD activity index <150 points or no fistula drainage, or a partial Mayo score <3 points for patients with UC. Serum drug trough levels and anti-drug antibodies were measured at baseline and week 16.

For all patients, mean serum trough levels of infliximab were 5.33±4.70 μg/mL at baseline and 5.69±4.94 μg/mL at week 16 (P=0.71). No significant differences emerged in prevalence of anti-drug antibodies at baseline (16.2%) versus week 16 (16.9%).

Adverse events were few, with four infusion reactions at week 24 in patients who had detectable antidrug antibodies at baseline but no previous exposure to the originator drug. No anaphylaxis occurred.

Clinical remission rates also did not change significantly for either CD or UC patients following the switch.

Last year, 番茄社区 reported on French research confirming the comparable safety and efficacy of infliximab and CT-P13 in CD patients.

Asked for his perspective on the findings, Benjamin H. Click, MD, of the Cleveland Clinic, said the study was a timely and important contribution to the area of biosimilars in IBD, as many American healthcare systems implement biosimilars in clinical practice.

"The authors should be commended for recognizing and diligently evaluating a unique clinical opportunity," said Click, who was not involved with the research. "While several studies have addressed switching from originator to a biosimilar product, this novel study examines the unique situations of reverse biosimilar to originator switching and multiple switching in an IBD population."

This study provides reassuring real-world data that reverse and multiple switching may be safe and clinically well tolerated, Click added. "Patients may be faced with different formularies or coverage plans, and switching to and from biosimilars will likely become a practical reality in the near future. Understanding the implications of switching is critical to providing high-quality care for IBD patients while reducing healthcare costs in America."

Click cautioned, however, that the study was limited by a small sample size, relatively short 24-week follow-up, and lack of a control population. "Larger, prospective, controlled studies with reverse, multiple, and cross-switches with long-term follow-up are needed to confirm these findings and further inform this important topic in IBD."

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