Table 2.
Pharmacodynamic parameter estimates from the final population exposure‐response model for hemoglobin in patients with rheumatoid arthritis on baricitinib
| Model parameter | Unit |
Population mean (%SEE)a |
BSVb (%SEE)a |
|---|---|---|---|
| Baseline RETc, d | 109 cells/L | 16.3 (2.12) | 28.3 (10.4) |
| Transit rate constant from proliferation pool to RET (ktr1) | Hour | 0.0418 (7.51) | — |
| Feedback factor for RET | — | 0.352 (14.4) | — |
| Transit rate constant from RET to RBC (ktr2) | Hour | 0.0975 (1.82) | — |
| Drug effect on proliferation pool | — | 0.00534 (21.9) | — |
| Sigmoidal function for drug effect on proliferation pool | — | 0.586 (7.27) | — |
| Transit rate constant for RBC (kcir) | Hour | 0.00139 FIX | 27.4 (10.6) |
| Proportionality scaling factor (SHb) | pg/cell | 30.2 (0.0748) | — |
| Feedback factor for RBC | — | 0.925 (12.5) | — |
| Age effect on baseline RETd | — | −0.00164 (92.7) | — |
| Age effect on transit rate constant on RBCe | — | −0.00131 (115) | — |
| Gender effect on baseline RETd | — | −0.110 (9.27) | — |
| Covariance for baseline RET and kcir f | — | 0.0722 (10.7) | — |
| Proportional residual error for RETg | — | 0.219 (4.18) | — |
| Additive residual error for RETg | — | 11.2 (5.04) | — |
| Proportional residual error for RBCg | — | 0.0655 (4.55) | — |
| Additive residual error for RETg | — | 78.3 (60.8) | — |
| Additive residual error for Hgbg | — | 7.82 (1.99) | — |
BSV, between‐subject variability; FIX, fixed; Hgb, hemoglobin; RBC, red blood cell; RET, reticulocyte; SEE, standard error of estimate; SQRT, square root.
The standard errors were obtained by selecting the S matrix feature.
% coefficient of variation = (square root(SQRT)(exponential (EXP)(OMEGA(N)))−1) * 100%.
Estimate for each RET‐related compartment.
Baseline RET*EXP((Age‐48)*Age effect on baseline RET) * (1 + IND*Gender effect on baseline RET); where IND = 1 for women and 0 for men; age is age at study entry; 48 is the median age in years from the phase I/IIa analysis.
Transit rate constant for RBC*EXP((Age‐48)*Age effect on transit rate constant on RBC); where age is age at study entry; 48 is the median age in years from the phase I/IIa analysis.
Covariance between ω2.
Standard deviation.