Table 2.

Model parameters

Parameter	Final value [Ref.]
Infliximab
Molecular weight	149,100 kDa
Hydrodynamic radius	5.34 nm [Ref. 13]
Rate of uptake into endosomal space ($k_{\mathrm{up}}$)	0.35 min −1
Dissociation constant for FcRn binding $(K_D^{\mathrm{FcRn}})$	727 nM [Ref. 45]
Dissociation constant for TNF binding $(K_D^{\mathrm{TNF}})$	30 pM [Ref. 46]
Dissociation constant for ADA binding $(K_D^{\mathrm{ADA}})$	500 pM [Ref. 47]
TNF
TNF maximum plasma concentrationa $({\text{TNF}}_{\mathrm{organ}})$	0.5 pM [Ref. 25, 26, 37]
TNF factor for autoimmune disease	2 [Ref. 25, 26, 27, 28]
TNF degradation rate $\left(k_{\mathrm{deg}}^{\mathrm{TNF}}\right)$	0.0231 min−1 [Ref. 48, 49]
mAb‐TNF complex degradation rate $\left(k_{\mathrm{deg}}^{\mathrm{mAb}-\mathrm{TNF}}\right)$	0.0231 min−1
ADA
Duration of IgM production $\left(T_{\mathrm{prod}}^{\mathrm{IgM}}\right)$	30.7 days [Ref. 36]
Lag time prior to IgG production $\left(T_{\mathrm{lag}}^{\mathrm{IgG}}\right)$	38.8 days [Ref. 36]
IgM maximum plasma concentrationa $\left({\mathrm{E}}_{\max }^{\mathrm{IgM}}\right)$	$\frac{k_{\mathrm{deg}}^{\mathrm{IgG}}\times {\mathrm{E}}_{\max }^{\mathrm{IgG}}}{k_{\mathrm{deg}}^{\mathrm{IgM}}}$
IgG maximum plasma concentration a $\left({\mathrm{E}}_{\max }^{\mathrm{IgG}}\right)$	136 nM
ADA (IgM) degradation rate $\left(k_{\mathrm{deg}}^{\mathrm{IgM}}\right)$	0.1 day−1 [Ref. 36]
ADA (IgG) degradation rate in healthy $\left(k_{\mathrm{deg}}^{\mathit{IgG}}\right)$	0.014 day−1 [Ref. 36]
ADA (IgG) degradation rate in autoimmune $\left(k_{\mathrm{deg}}^{\mathrm{IgG}}\right)$	0.008 day−1 [Ref. 36]
mAb‐ADA complex degradation rate $\left(k_{\mathrm{deg}}^{\mathrm{mAb}-\mathrm{ADA}}\right)$	0.48 day−1 [Ref. 50]
Inflamed organ
Inflammation factor for inflamed pores $({\text{IF}}^{\mathrm{\sigma }})$	1.5 [Ref. 31, 32, 33]
TNF factor for inflamed organ	3 [Ref. 29, 30]

Italicized values were mathematically optimized to their final value in the model building process.

ADA, antidrug antibody; FcRn, neonatal Fc receptor; mAb, monoclonal antibody; TNF, tumor necrosis factor.

Zero order synthesis rates were calculated by multiplying the degradation rate by the maximum concentration of the molecule.