Comparing IBD Originator Therapy Efficacy to a Biosimilar

Ana Martínez Feito, MD

More patients achieved clinical remission for inflammatory bowel disease (IBD) taking the originator drug compared to the biosimilar, regardless of immunomodulator (IM) use, according to a paper published in Scientific Reports.

Investigators from Spain conducted a study of 86 IBD patients in order to compare the differences between infliximab and its biosimilar CT-P13 in terms of their effectiveness, safety and pharmacokinetics.

The study authors also noted that beginning at their hospital in 2015, when biosimilars were introduced, patients who have started a biological treatment with infliximab have received the biosimilar compound. They wanted to compare the concentrations and immunogenicity development at treatment induction between the drug and its biosimilar.

The patients were followed from the start of infliximab treatment through 22 weeks later, with check-ins at weeks 0, 2, 6, 14, and 22, the study authors said, with remission outcomes measured at weeks 14 and 22.

All patients were administered intravenous infusions of 5 mg/kg of infliximab at weeks 0, 2, and 6, and every 8 weeks after that. Overall, 44 patients received the originator drug Remicade and 42 patients received CT-P13 (either Remsima or Inflectra). About two-thirds of the patients had Crohn’s disease and a third had ulcerative colitis.

The study authors found that the originator trough levels were higher than the biosimilar trough levels:

• 35 vs. 21 μg/mL at week 2
• 20.1 vs. 11 μg/mL at week 6
• 6.6 vs. 2.9 μg/mL at week 14
• 4.3 vs. 1.7 μg/mL at week 22

There were changes in mean serum levels over time and based on the drug employed, the study authors also noted, but not with diagnosis, sex, smoking status, or previous biological therapy.

About 4 in 5 patients were administered an IM concomitantly with the infliximab therapy (95% azathioprine and 5% methotrexate). The study authors said that it is acknowledged that IM has a well-known effect on serum drug concentrations, leading to them needing to determine the possible interactions between IM and infliximab concentrations.

At each week measured, the investigators determined that serum infliximab levels were higher in the patients with an IM compared to those without, regardless of treatment. But, they also found, that the only significant effect on serum infliximab levels was on the type of infliximab, and that concomitant IM use had no significant effect, they wrote.

By week 14, only 16 patients had achieved clinical remission (11 from Remicade therapy, 5 from CT-P13 therapy), the study authors learned. At week 22, 13 of the 16 patients who had reached remission were treated with the originator and 3 were treated with the biosimilar.

The investigators estimated that the risk of achieving clinical remission was 4.9-fold higher in patients treated with the originator compared to those treated with the biosimilar.

And for patients treated with concomitant IM, a third treated with the originator compared to 10% treated with CT-P13 achieved remission. For patients not using IM, a quarter of the originator patients and none of the biosimilar patients achieved remission. In general, more patients treated with the originator achieved clinical remission, the study authors said, regardless of their IM use.

No patients withdrew from the originator cohort, though 7 patients in the biosimilar group withdrew at week 22 due to secondary failure, primary failure, and 1 surgery.

“Our findings show significant differences in serum trough infliximab levels between the originator Remicade and the biosimilar CT-P13 during the treatment induction phase in the patients with IBD,” the study authors concluded. “The type of administered compound also affects clinical outcomes such as disease remission and drug survival.”