By Will Boggs MD
NEW YORK (Reuters Health) - 9/4/2019
The infliximab biosimilar CT-P13 is noninferior to infliximab for treating patients with active Crohn's disease, according to a randomized controlled trial.
"There is no need to consider the efficacy and safety when choosing originator infliximab or biosimilar infliximab," Dr. Young-Ho Kim from Samsung Medical Center, Sungkyunkwan University School of Medicine, in Seoul, South Korea, told Reuters Health by email. "We need to consider other aspects, such as cost-effectiveness."
CT-P13 was approved by the U.S. Food and Drug Administration and the European Medicines Agency for all indications of infliximab based on proof of biosimilarity in randomized controlled trials of patients with ankylosing spondylitis or rheumatoid arthritis. The approval in inflammatory bowel disease (IBD) and other non-rheumatological indications was based on extrapolation, and there have been no randomized controlled trials comparing the efficacy and safety of a biosimilar with infliximab in patients with IBD.
Dr. Kim and colleagues investigated the safety and efficacy of CT-P13 versus infliximab in a noninferiority trial of 220 patients with active Crohn's disease who were naive to biological therapy. Patients were randomly assigned to one of four groups: CT-P13 throughout the study; infliximab throughout the study; switching from CT-P13 to infliximab at week 30; or switching from infliximab to CT-P13 at week 30.
At week 6, 69.4% of patients assigned to receive CT-P13 and 74.3% of patients assigned to receive infliximab achieved a Crohn's Disease Activity Index-70 (CDAI-70) response, the primary efficacy endpoint. This 4.9-percentage-point difference was within the prespecified noninferiority criteria.
CDAI-70 response rates were also similar at weeks 14, 30 and 54, and the CDAI-100 response rates and clinical remission rates were similar in the CT-P13 and infliximab groups at weeks 6, 14, 30, and 54, the researchers reported in The Lancet, online March 28.
The two-item patient-reported outcome scores were less than 8 (i.e., equivalent to CDAI-defined remission) at week 54 in all four groups, and there was no notable difference in the scores between groups at any time point during the study.
About half of the patients achieved steroid-free remission at week 30, and sustained steroid-free remission rates were lower but similar between the groups after week 30.
Quality of life scores improved to a similar extent in patients treated with CT-P13 and infliximab before and after week 30.
Adverse event rates and the proportion of patients who developed antidrug antibodies were similar between the groups.
"This study demonstrated noninferiority of CT-P13 to originator infliximab in Crohn's disease, and this study provides evidence on the validity of the indication extrapolation process for the future development of biosimilars," Dr. Kim said.
"The sample size calculation was based on response rates during induction (with a liberal 20% non-inferiority margin)," write Dr. Krisztina B. Gecse and Dr. Geert R D'Haens from Amsterdam University Medical Center in a linked editorial. "Similar to NOR-SWITCH, which lacked power to separately evaluate the non-inferiority of switching in the IBD subpopulation, this study was not powered to assess the non-inferiority of switching beyond week 30. Additionally, the noninferiority margin was based on expert opinion rather than regulatory guidance, and whether a margin of 20% is clinically acceptable could be questioned."
"Since the approval of CT-P13, several biosimilar monoclonal antibodies have received marketing authorization and several in the pipeline are to follow," they conclude. "Setting up switching studies like (this one) for all new biosimilars seems unfeasible and unnecessary. The optimal approach to generate sufficient safety and efficacy data could be to set up nationwide or continent-wide registries, ideally governed by scientific organizations and using patient reporting."
Celltrion and Pfizer funded the study, employed four of the study authors and had various relationships with several others and with both authors of the accompanying editorial.