Efficacy and Safety Equivalence of Proposed High-Concentration Adalimumab Biosimilar to Reference Adalimumab in Moderate-to-Severe, Active RA

A randomized, double-blind phase 3 study demonstrated the efficacy and safety equivalence of the adalimumab biosimilar candidate CT-P17 to reference adalimumab in patients with moderate-to-severe active rheumatoid arthritis (RA).

CT-P17 is a proposed biosimilar of the high-concentration (100 mg/mL) and citrate-free formulation of reference adalimumab. A randomized, double-blind phase 3 study was initiated to compare the efficacy and safety of CT-P17 with reference adalimumab in patients with active, moderate-to-severe rheumatoid arthritis (RA) up to week 52; study results were reported at the American College of Rheumatology (ACR) Convergence 2020 meeting.

Inclusion criteria were adult patients with active, moderate-to-severe RA despite methotrexate treatment. Eligible patients were randomized 1:1 to receive CT-P17 40 mg or reference adalimumab every 2 weeks up to week 24. Prior to dosing at week 26, patients in the reference adalimumab group were re-randomized to either continue reference adalimumab or switch to CT-P17 until the end of the study; all patients initially randomized to CT-P17 continued receiving CT-P17. The primary end point was ACR20 (a composite measure defined as improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in 3 of the following 5 criteria: patient global assessment, physician global assessment, functional ability measure, visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein) response rate at week 24; secondary end points were efficacy, pharmacokinetics, safety, and immunogenicity.

A total of 648 eligible patients received CT-P17 (n = 324) or reference adalimumab (n = 324). Baseline characteristics were similar between groups. The ACR20 response rate at week 24 was the same between the CT-P17 and reference adalimumab groups (82.7% for both), with confidence intervals of the treatment difference within the prespecified equivalence margins (European Medicines Agency, ±15%; US Food and Drug Administration, –12% to +15%). Secondary efficacy end points were also similar between groups.

Overall, safety profiles of the 2 groups were similar; 52.2% of patients in the biosimilar group and 56.8% of patients in the reference adalimumab group experienced ≥1 treatment-emergent adverse events (TEAEs); the majority of TEAEs were grade 1/2. The most common TEAEs were injection-site reactions, occurring in 4.9% of patients in the CT-P17 group versus 6.8% in the reference adalimumab group. A total of 26 patients experienced ≥1 treatment-emergent serious adverse events. TEAEs leading to study discontinuation were reported in 5 patients in the CT-P17 group versus 8 patients in the reference adalimumab group.

A lower proportion of patients developed antidrug antibodies (ADAs) at week 24 in the CT-P17 group versus the reference adalimumab (28.7% vs 35.8%; P = .0643). Of these, neutralizing ADAs were developed by 83 (25.6%) CT-P17–treated patients and 103 (31.8%) patients who received reference adalimumab.

This study demonstrated efficacy equivalence between the biosimilar CT-P17 and reference adalimumab over 24 weeks in patients with active, moderate-to-severe RA in terms of ACR20 response rates and other efficacy end points assessed.

Reference
Kay J, et al. ACR 2020. Abstract 800.