Title: A randomised, double-blind trial to demonstrate bioequivalence of GP2013 and reference rituximab combined with methotrexate in patients with active rheumatoid arthritis
Smolen, JS et al.
What You Need to Know:
In patients with active rheumatoid arthritis (RA), GP2013, a rituximab biosimilar, not only demonstrated pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence to rituximab (RTX), but also exhibited a similar efficacy, safety, and immunogenicity profile as well.
- Double-blind, parallel-group, multinational study compared the safety, efficacy, immunogenicity, and PK/PD equivalence of GP2013 with RTX in patients with active RA despite previous tumor necrosis factor inhibitor treatment
- 312 patients were randomized to receive GP2013 or either EU or US reference product (RTX-EU or RTX-US), in addition to methotrexate and folic acid
- Primary PK endpoint: “area under the serum concentration–time curve from study drug infusion to infinity (AUC0-inf)”
- “To claim bioequivalence, the 90% CI of the ratio of the geometric mean AUCs had to be within the predefined range of 80%–125%”
- Primary PD parameter: “peripheral CD19 positive B-cell count relative to baseline, up to the second infusion (AUEC0-14d)”
- Additional analyses assessed (up to week 24): PK/PD parameters, efficacy, immunogenicity, safety
- Ratio of geometric mean AUCs for GP2013 vs RTX-EU: 1.106 (90% CI: 1.010, 1.210)
- Ratio of geometric mean AUCs for GP2013 vs RTX-US: 1.012 (90% CI: 0.925, 1.108)
- Ratio of geometric mean AUCs for RTX-EU vs RTX-US: 1.093 (90% CI: 0.989, 1.208)
- PD equivalence: three-way equivalence was demonstrated
- GP2013 exhibited a similar efficacy, safety, and immunogenicity profile to RTX