Population PK/PD Modeling and Simulation to Predict the Comparative Long-Term Efficacy of Olokizumab in Rheumatoid Arthritis Patients.
6 affiliations
- 1M&S Decisions FZ-LLC, Dubai 1318, United Arab Emirates.
- 2Research Center of Model-Informed Drug Development, I.M. Sechenov First Moscow State Medical University, Moscow 119991, Russia.
- 3Marchuk Institute of Numerical Mathematics of the Russian Academy of Sciences, Moscow 119333, Russia.
- 4Medical Department, R-Pharm JSC, Moscow 119421, Russia.
- 5Experimental Rheumatology, OvG University Magdeburg, 39120 Magdeburg, Germany.
- 6Rheumatology and Clinical Immunology, HELIOS Fachklinik Vogelsang/Gommern, 39245 Gommern, Germany.
Abstract
Background/Objectives: Olokizumab (OKZ) is a humanized monoclonal antibody targeting interleukin-6 (IL-6). OKZ demonstrated efficacy in subjects with active rheumatoid arthritis (RA) in randomized controlled trials versus adalimumab (ADLM) and placebo over 24 weeks, with sustained efficacy confirmed through 106 weeks in an open-label single-arm extension study (OLE). This analysis aimed to predict 1-year efficacy of OKZ 64 mg administered every two weeks (q2w) and every four weeks (q4w) compared with ADLM and placebo through virtual clinical trial simulations based on population pharmacokinetic/pharmacodynamic (PK/PD) models. Methods: Nonlinear mixed-effects models were developed using pooled data from phase III studies. Turnover models with a maximum inhibition Imax-type relationship between OKZ concentrations and clinical scores were applied. Simulated clinical trials were performed to estimate 52-week response rates, defined as proportions of patients achieving low disease activity (DAS28-CRP ≤ 3.2) and remission (CDAI ≤ 2.8). The reliability of the simulated extrapolations was validated against published data. Results: Log-transformed C-reactive protein (CRP) baseline levels and region were identified as significant covariates, influencing the dynamics of RA activity scores. OKZ and ADLM showed comparable predicted efficacy profiles, with overlapping 95% prediction intervals, and both were superior to placebo. Model predictions showed strong agreement with published long-term data for ADLM and placebo and closely reproduced the actual 1-year response profiles from the OKZ OLE. Conclusions: The developed PK/PD models showed good agreement with observed long-term efficacy outcomes for OKZ, ADLM, and placebo in MTX-IR RA patients. Both OKZ dosing regimens sustained low disease activity and remission rates comparable with those for ADLM over 52 weeks, supporting their use as effective treatment options.
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BibTeX
@article{kosinsky2026population,
title = {{Population PK/PD Modeling and Simulation to Predict the Comparative Long-Term Efficacy of Olokizumab in Rheumatoid Arthritis Patients.}},
author = {Yuri Kosinsky and Ivan Azarov and Kirill Zhudenkov and Kirill Peskov and Sergey Grishin and Alina Egorova and Yuliya Berezovskaya and Maria Lemak and Mikhail Samsonov and Eugen Feist},
journal = {Journal of clinical medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15197660},
url = {https://europepmc.org/article/MED/42882121},
note = {CC BY},
}
RIS
TY - JOUR
TI - Population PK/PD Modeling and Simulation to Predict the Comparative Long-Term Efficacy of Olokizumab in Rheumatoid Arthritis Patients.
AU - Yuri Kosinsky
AU - Ivan Azarov
AU - Kirill Zhudenkov
AU - Kirill Peskov
AU - Sergey Grishin
AU - Alina Egorova
AU - Yuliya Berezovskaya
AU - Maria Lemak
AU - Mikhail Samsonov
AU - Eugen Feist
PY - 2026
DA - 2026/10/02
JO - Journal of clinical medicine
DO - 10.3390/jcm15197660
UR - https://europepmc.org/article/MED/42882121
AB - Background/Objectives: Olokizumab (OKZ) is a humanized monoclonal antibody targeting interleukin-6 (IL-6). OKZ demonstrated efficacy in subjects with active rheumatoid arthritis (RA) in randomized controlled trials versus adalimumab (ADLM) and placebo over 24 weeks, with sustained efficacy confirmed through 106 weeks in an open-label single-arm extension study (OLE). This analysis aimed to predict 1-year efficacy of OKZ 64 mg administered every two weeks (q2w) and every four weeks (q4w) compared with ADLM and placebo through virtual clinical trial simulations based on population pharmacokinetic/pharmacodynamic (PK/PD) models. Methods: Nonlinear mixed-effects models were developed using pooled data from phase III studies. Turnover models with a maximum inhibition Imax-type relationship between OKZ concentrations and clinical scores were applied. Simulated clinical trials were performed to estimate 52-week response rates, defined as proportions of patients achieving low disease activity (DAS28-CRP ≤ 3.2) and remission (CDAI ≤ 2.8). The reliability of the simulated extrapolations was validated against published data. Results: Log-transformed C-reactive protein (CRP) baseline levels and region were identified as significant covariates, influencing the dynamics of RA activity scores. OKZ and ADLM showed comparable predicted efficacy profiles, with overlapping 95% prediction intervals, and both were superior to placebo. Model predictions showed strong agreement with published long-term data for ADLM and placebo and closely reproduced the actual 1-year response profiles from the OKZ OLE. Conclusions: The developed PK/PD models showed good agreement with observed long-term efficacy outcomes for OKZ, ADLM, and placebo in MTX-IR RA patients. Both OKZ dosing regimens sustained low disease activity and remission rates comparable with those for ADLM over 52 weeks, supporting their use as effective treatment options.
SN - 2077-0383
ER -