Table 2.
Final covariate MT model with PD effect on margination and demargination rates: population PD parameters and bootstrap CIs
| Parameter value (SE) | Bootstrap median (95% CI) | |
|---|---|---|
| Parameters | ||
| ANC0, ×109/L | 4.57 (0.0572) | 4.56 (4.49–4.63) |
| k, 1/day | 1.31 (0.0771) | 1.32 (0.954–1.69) |
| Emax, unitless | 1.75 (0.131) | 1.74 (1.51–2.07) |
| EC50, mg/L: sarilumab | 0.137 (0.0187) | 0.131 (0.0612–0.440) |
| EC50, mg/L: tocilizumab | 1.78 | – |
| k tol, 1/day | 0.281 (0.00948) | 0.277 (0.255–0.328) |
| k out, 1/day | 0.887 Fixed | 0.877 Fixed |
| Covariates | ||
| β, ANCB on ANC0 | 0.887 (0.0263) | 0.889 (0.855–0.930) |
| β, ANCB on Emax | 0.549 (0.147) | 0.587 (0.247–0.847) |
| β, drug on EC50 | 2.56 (0.168) | 2.65 (1.11–3.77) |
| Omegas | ||
| ω, ANC0 | 0.102 (0.00737) | 0.101 (0.0804–0.119) |
| ω, Emax | 0.803 (0.0440) | 0.800 (0.713–0.887) |
| SD of residual error | ||
| σexponential | 0.249 (0.00156) | 0.249 (0.240–0.257) |
| Log‐likelihood estimation | ||
| −2 log‐likelihood | 11,963.699 | – |
| BIC | 12,064.88 | – |
ANC, absolute neutrophil count; ANC0, estimated baseline ANC; ANCB, ANC values observed before the first dose; β, covariate coefficient; BIC, Bayesian information criteria; CI, confidence interval; EC50, concentration of drug causing half‐maximal effect; Emax, maximum drug‐induced effect; k, intercompartmental rate; k out, neutrophil elimination rate; k tol, tolerance rate; MT, margination–tolerance; ω, between‐subject SD in parameters; PD, pharmacodynamic; SE, standard error; σ, SD.