Evaluation of the pharmacokinetic equivalence and 54-week efficacy and safety of CT-P13 and innovator infliximab in Japanese patients with rheumatoid arthritis

Abstract

Objectives. To demonstrate the pharmacokinetic equivalence of CT-P13 and its innovator infliximab (IFX) in Japanese patients with rheumatoid arthritis (RA), and to compare the efficacy and safety of these drugs, administered for 54 weeks. Methods. In a randomized, double-blind, parallel-group, multicenter study, 3 mg/kg of CT-P13 or IFX, in combination with methotrexate (MTX) (6–16 mg/week), was administered for 54 weeks to Japanese active RA patients with an inadequate response to MTX, to demonstrate the pharmacokinetic equivalence, based on the area under the curve (AUCτ) (weeks 6–14) and Cmax (week 6) of these drugs, and to compare their efficacy and safety. Results. The CT-P13-to-IFX ratios (90% confidence intervals) of the geometric mean AUCτ and Cmax values in patients negative for antibodies to infliximab at week 14 were 111.62% (100.24–124.29%) and 104.09% (92.12–117.61%), respectively, demonstrating the pharmacokinetic equivalence of these drugs. In the full analysis set, CT-P13 and IFX showed comparable therapeutic effectiveness, as measured by the American College of Rheumatology, Disease Activity Score in 28 joints, the European League Against Rheumatism, and other efficacy criteria, at weeks 14 and 30. The incidence of adverse events was similar for these drugs. Conclusion. CT-P13 and IFX, administered at a dose of 3 mg/kg in combination with MTX to active RA patients, were pharmacokinetically equivalent and comparable in efficacy and safety.

Safety and efficacy of CT-P13 in Japanese patients with rheumatoid arthritis in an extension phase or after switching from infliximab

“…The observed AEs in this extension study were all known, and the types and frequencies were similar to the results obtained in either the CT-P13 or IFX group in the phase I/II study [1]. AEs leading to study discontinuation, anaphylactic shock, pneumonia, infusion-related reaction, RA, and interstitial lung disease in the phase I/II study were already reported.…”

“…In the phase I/ II study in Japanese rheumatoid arthritis (RA) patients, pharmacokinetic (PK) equivalence between CT-P13 and IFX was confirmed as we reported previously [1]. The data in the study showed that the safety and efficacy of CT-P13 throughout the 54-week dosing were similar to those in the PLANETRA study conducted in Europe, Latin America, Middle East, and Asia (not including Japan) [2].…”

“…The average dose of CT-P13 at Week 134 (72x) in the maintenance group was 5.72 ± 3.00 mg, which was higher than that of 4.88 ± 2.87 mg in the switch group. The positive ratio of ADA was higher in the switch group (48.5%) than in the maintenance group (31.6%), but we believe this difference occurred by chance because the ratios in the previous studies were 25.5% in the CT-P13 group and 32.1% in the IFX group at Week 54 of the PI/II study [1], and 49.1% in the CT-P13 group and 49.3% in the IFX group at Week 54 of the PLANETRA study [4]. Given that (i) this extension study was not designed to compare the maintenance group and the switch group, (ii) the disease condition, one of the patient characteristics, was slightly different between the maintenance group and the switch group, and (iii) the dose of CT-P13 used differed, ranging from 3 to 10 mg/kg, among patients, it is difficult to compare the results between the two groups in the extension study.…”

The scientific and regulatory rationale for indication extrapolation: a case study based on the infliximab biosimilar CT-P13

“…PK equivalence was shown when the 90% confidence intervals (CIs) for the ratios of both AUC and Cmax (CT-P13/RMP) fell within a predefined margin of 80-125% (AUC: 104.5% [90% CI: 94-116%]; Cmax: 101.5% [90% CI: 95-109%]). Very close similarity between the PK of CT-P13 and RMP has also been shown in patients with RA and healthy volunteers [11,38,39].…”

Anti-TNFs: Originators and Biosimilars

“…EMA experts argued that since differences in glycosylation are not known to have a relevant impact on the PK behavior of mAbs, it is unlikely that micro-heterogeneity will affect PK behavior of the CT-P13 [41] . An independent study has confirmed the PK equivalence of Remsima ® and Remicade ® in RA [43] . A recent IBD study indicated that Remsima ® and Remicade ® share dominant immune epitopes and have exactly the same immunogenicity [44] .…”