Head-to-Head Study Shows CT-P13 Is Noninferior to Reference Infliximab in CD

Approval of biosimilars in indications for which they were not studied directly in phase 3 clinical trials relies on the extrapolation of indications, a concept that is scientifically justified but, nevertheless, has generated some concerns among clinicians. In the case of biosimilar infliximab CT-P13 (Inflectra, Remsima), some gastroenterologists have voiced a lack of confidence in the biosimilar for the treatment of inflammatory bowel disease, including Crohn disease (CD) and ulcerative colitis. Now, head-to-head study, published in The Lancet, has produced data that may help allay those worries.

Between 2014 and 2017, the randomized, multicenter, double-blind, phase 3 noninferiority PLANETCD study enrolled 220 patients with active CD who were naïve to biologic therapy. The patients were randomized to receive CT-P13 only (n = 56), CT-P13 followed by reference infliximab (n = 55), reference infliximab only (n = 54), or reference infliximab followed by CT-P13 (n = 55), with a switch taking place at week 30.

Patients received 5 mg/kg of their assigned infliximab treatment at weeks 0, 2, 6, followed by every 8 weeks up to week 54. The study’s primary end point was the proportion of patients with a decrease of 70 points or more in the Crohn’s Disease Activity Index (CADI-70) from baseline to week 6. The prespecified noninferiority margin was set at −20%.

The CDAI-70 response rates at week 6 were similar for the patients who began their treatment with CT-P13. Among those who either took CT-P13 only or began with CT-P13 and switched to reference infliximab, 69.4% achieved CDAI-70 (95% CI, 59.9%-77.8%). Among those who took reference infliximab only or began treatment with reference infliximab and then switched to CT-P13, 74.3% achieved CDAI-70 (95% CI, 65.1%-82.2%), for a difference of −4.9% (95% CI, −16.9% to 7.3%), which fell within the prespecified noninferiority margin.

Overall, 67% of patients of patients experienced at least 1 treatment-emergent adverse event (TEAE), with 64% of patients in the CT-P13-only group, 62% in the CT-P13 to infliximab switch group, 69% in the infliximab only group, and 73% in the infliximab to CT-P13 switch group experiencing a TEAE.

“This is the first head-to-head study demonstrating the equal efficacy of an anti-TNF [anti−tumor necrosis factor] biosimilar in inflammatory bowel disease,” said Stefan Schreiber, MD, director of the Clinic for Internal Medicine at Kiel Campus of the University Hospital Schleswig-Holstein in Germany, in a statement on the PLANETCD study. “This robust evidence makes a compelling case for the use of biosimilars and will inform decision-making by gastroenterologists when choosing anti-TNF therapy for their patients,” he added.

Hyoung-Ki Kim, vice chairman at Celltrion Healthcare, added, “The PLANETCD study is the first investigation of the therapeutic efficacy of an infliximab biosimilar powered to show noninferiority to reference infliximab in inflammatory bowel disease…[PLANETCD] together with the evidence from the influential NOR-SWITCH study, which was performed across multiple indications, support the equivalence between CT-P13 and reference infliximab.”

Reference

Ye BD, Pesegova M, Alexeeva O, Osipenko M, Lahat A, Dorofeyev A. Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn’s disease: an international, randomised, double-blind, phase 3 non-inferiority study [published online, March 28, 2019]. Lancet. doi: 10.1016/S0140-6736(18)32196-2.