Table 3.

Population-pharmacokinetic parameter estimates

Parameter	Estimate	RSE (%)	Shrinkage (%)
Fixed effects
Vm (mg/day)	8.06	1.96	N/A
Km (mg/L)	0.939	4.38	N/A
Vc/F (L)	2.08	3.20	N/A
CLO/F (L/day)	0.260	5.36	N/A
Ka (day)	0.136	2.53	N/A
Q/F (L/day)	0.156	3.87	N/A
Vp/F (L)	5.23	5.98	N/A
WT effect on CLO/F	0.885	12.0	N/A
WT effect on Vm	0.516	9.45	N/A
ALBR effect on Vm	− 0.844	5.49	N/A
CrCl effect on Vm	0.212	9.59	N/A
DP2 effect on Ka	0.663	4.38	N/A
ADA effect on CLO/F	1.43	3.05	N/A
DP2 effect on CLO/F	1.30	4.48	N/A
Sex effect on CLO/F	0.846	4.74	N/A
BLCRP effect on Vm	0.0299	23.0	N/A
Inter-individual variability (CV%)
Vma	32.4	6.07	29.8
CLO/Fa	55.3	6.21	42.8
Vc/Fa	37.3	16.7	64.2
Kaa	32.1	9.52	49.6
Block Vm-CLO/Fb	− 0.566	10.8	N/A
Residual variability (CV%)
σ2c	0.395	0.811	N/A

ADA anti-drug antibody, ALBR albumin normalized to upper limit of normal, BLCRP baseline C-reactive protein, CLO/F apparent linear clearance from central compartment, CrCl body-surface-area-normalized creatinine clearance, DP2 sarilumab drug product, K_a absorption rate constant, K_m Michaelis–Menten constant, N/A not applicable, Q/F apparent inter-compartmental clearance, RSE (%) percentage of relative standard error (100 × standard error/estimate), V_c/F apparent volume of central compartment, V_m maximum elimination rate, V_p/F apparent peripheral volume of distribution, WT body weight

^aInter-individual variability is expressed as % coefficient of variation (CV%)

^bEstimate of covariance between two variances is expressed as a correlation coefficient

^cVariance of residual error is based on the log-transformed dependent variable (i.e., sarilumab concentration)