Pharmacokinetic Similarity and Comparative Pharmacodynamics, Safety, Efficacy, and Immunogenicity of DRL_RI Versus Reference Rituximab in Biologics-Naïve Patients with Moderate-to-Severe Rheumatoid Arthritis: A Double-Blind, Randomized, Three-Arm Study

• DOI: 10.1007/s40259-020-00406-1
• Publication Date: 2020-02-12T11:03:04Z
• Authors: Vikram Muralidhar...; Rahul Katta; Ajit Nalawade; Sandeep Kharkar; Vyacheslav Zhdan; Olena Garmish; Luis Lopez-Lazaro; Sonica Sachdeva B...; Suresh Kankanwadi
• Keywords: Bioequivalence; Pharmacodynamics; Clinical endpoint; Biosimilar

The aims were to demonstrate pharmacokinetic (PK) similarity between DRL_RI, a proposed rituximab biosimilar, and two reference innovator products (Rituxan® [RTX-US] MabThera® [RTX-EU]) compare their pharmacodynamics (PD), efficacy, safety, immunogenicity in rheumatoid arthritis (RA) patients with inadequate response methotrexate (MTX)-based therapy no prior biologic administration. In this randomized, double-blind, parallel-group study, 276 moderate-to-severe active RA randomized receive RTX-US, or RTX-EU on days 1 15. primary PK end points included area under the concentration–time curve from time 0 336 h after first infusion (AUC0–14 days, infusion), AUC day through week 16 (AUC0–∞, entire course), of last quantifiable concentration second dose (AUC0–t, infusion). Secondary other parameters, such as maximum (Cmax), Cmax each infusion, terminal half-life, systemic clearance, volume distribution infusion; PD parameters efficacy until 24; safety at 24 52; B cell recovery 52. over course course) was analyzed an exploratory point. 91% confidence intervals (CIs) geometric mean ratios (GMRs) for point AUC0–∞, within bioequivalence limits 80–125% all comparisons: DRL_RI versus RTX-US 100.37% (92.30–109.14), 93.58% (85.98–101.85), 93.24% (85.62–101.54). outcomes (peripheral blood B-cell depletion change Disease Activity Score [28 joints]–C-reactive protein), also comparable products. demonstrated three-way products, PD, immunogenicity. ClinicalTrials.gov identifier: NCT02296775.