A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study

Abstract

Objectives: To compare the efficacy and safety of innovator infliximab (INX) and CT-P13, an INX biosimilar, in active rheumatoid arthritis patients with inadequate response to methotrexate (MTX) treatment.

Methods: Phase III randomised, double-blind, multicentre, multinational, parallel-group study. Patients with active disease despite MTX (12.5-25 mg/week) were randomised to receive 3 mg/kg of CT-P13 (n=302) or INX (n=304) with MTX and folic acid. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was concluded if the 95% CI for the treatment difference was within ±15%. Secondary endpoints included ACR response criteria, European League Against Rheumatism (EULAR) response criteria, change in Disease Activity Score 28 (DAS28), Medical Outcomes Study Short-Form Health Survey (SF-36), Simplified Disease Activity Index, Clinical Disease Activity Index, as well as pharmacokinetic (PK) and pharmacodynamic (PD) parameters, safety and immunogenicity.

Results: At week 30, ACR20 responses were 60.9% for CT-P13 and 58.6% for INX (95% CI -6% to 10%) in the intention-to-treat population. The proportions in CT-P13 and INX groups achieving good or moderate EULAR responses (C reactive protein (CRP)) at week 30 were 85.8% and 87.1%, respectively. Low disease activity or remission according to DAS28-CRP, ACR-EULAR remission rates, ACR50/ACR70 responses and all other PK and PD endpoints were highly similar at week 30. Incidence of drug-related adverse events (35.2% vs 35.9%) and detection of antidrug antibodies (48.4% vs 48.2%) were highly similar for CT-P13 and INX, respectively.

Conclusions: CT-P13 demonstrated equivalent efficacy to INX at week 30, with a comparable PK profile and immunogenicity. CT-P13 was well tolerated, with a safety profile comparable with that of INX. CLINICALTRIALS.GOV IDENTIFIER: NCT01217086.

Figure 1

Flowchart of patient disposition. A total of 1077 patients were screened for the study, and 606 eligible patients were randomised into a CT-P13 group (N=302) or an innovator infliximab (INX) group (N=304) to receive 3 mg/kg of CT-P13 or INX, respectively, coadministered with methotrexate (MTX) and folic acid. All 606 randomly assigned patients were included in the intention-to-treat population. A total of 107 out of 606 randomised patients were excluded from the per-protocol population due to the various protocol violations. *Eleven patients from a potentially fraudulent study site were excluded from analyses.

Figure 2

American College of Rheumatology (ACR) response rates. (A) ACR20 improvement criteria at week 30 (primary efficacy endpoint) for the intention-to-treat (ITT) (N=302 and 304 in CT-P13 and innovator infliximab (INX) groups, respectively) and per-protocol (PP) populations (N=248 and 251 patients in CT-P13 and INX groups, respectively). (B) ACR20, ACR50 or ACR70 improvement criteria at week 14 for the PP population. (C) ACR50 or ACR70 improvement criteria at week 30 for the PP population. ACR20, ACR50 and ACR70 are the ACR 20%, 50% and 70% improvement criteria, respectively. 95% CI was calculated by the exact binomial method.

Figure 3

Changes over time in the Disease Activity Score in 28 joints (DAS28) and European League Against Rheumatism (EULAR) responses for CT-P13 (3 mg/kg) and innovator infliximab (INX) (3 mg/kg) treatment in the per-protocol population. (A) Adjusted mean DAS28 score based on erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) at baseline, weeks 14 and 30. Error bars represent SE. (B) EULAR response criteria based on DAS28 score at weeks 14 and 30 following treatment. (C) Disease activity based on DAS28 (ESR) and DAS28 (CRP) at baseline, weeks 14 and 30.