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Rituximab, ANCA and gammaglobulin turnover

Coupled two-compartment rituximab PK, gammaglobulin turnover and two-coordinate ANCA feedback.

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How do the fixed MPO maintenance schedules change ANCA and gammaglobulin?

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induction 375mgm2 q1w 6mo — MPO

Conditional reference-covariate trajectory with one-hour infusions and a30day month convention.

0–180 day

Scenario details

induction 375mgm2 q1w 6mo — MPO

Conditional reference-covariate trajectory with one-hour infusions and a30day month convention.

Readouts

Central concentration · mg/L
Conditional model quantity; exposure and elimination integrals are added nonfeedback accounting readouts.
Gg g · g/L
Gg g over the selected simulation window.
Anca blood u · count/mL
Anca blood u over the selected simulation window.
Anca baseline fraction · dimensionless
Anca baseline fraction over the selected simulation window.

Study purpose

  • How do the model's key biological readouts change under induction 375mgm2 q1w 6mo — mpo?

Assumptions

  • Conditional fixed-effect joint PK/PD, with no individual random deviations or residual observation noise.
  • Reference covariates follow Supplement S5: age52years, weight68kg, CRP11mg/L; sex is male unless explicitly changed.
  • Both ANCA compartments start at the CRP-conditioned baseline, and gammaglobulins start at their baseline. These coupled initial values are frozen with their inputs.
  • A month is represented by30days, an authored calendar convention. One-hour infusions follow the cohort methods; nominal event arrays do not reconstruct individual records.
  • The 375mg/m2 amount is667.5mg at the frozen1.78m2 administration reference; another BSA requires dose recalculation.
  • ANCA U/mL is a source assay calibration coordinate. The typed count/mL unit retains its numerical scale and is not a molecular count or enzyme-activity unit.
  • ANCA production is a latent model coordinate, not a directly measured blood compartment.
  • Published population medians, percentiles and threshold probabilities do not become conditional trajectory targets.
  • Clinical utility, infection/relapse risk, statistical fitting and the original1000-person simulation are not reconstructed.

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Simulation time
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day
180 → 168

Time between reported samples.

day

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Biology

Compare exposure and antibody-turnover dynamics for six induction/maintenance designs and both ANCA subtypes.

Compare exposure and antibody-turnover dynamics for six induction/maintenance designs and both ANCA subtypes.

Model details

21 parameters · 7 states · 7 equations · 22 derived outputs

Classification & API access
Therapeutic
Rituximab
Modality
Monoclonal antibody
Target
CD20 / MS4A1
Disease / scope
ANCA-associated vasculitis
ParameterDefaultUnitDescription
Age clearance powerage_cl_power-0.33—Final Table2/SupplementS5 reference input; frozen within each conditional context.
Ageage_year52yearFinal Table2/SupplementS5 reference input; frozen within each conditional context.
Base anca reference ubase_anca_reference_u_ml75.6count/mLFinal Table2/SupplementS5 reference input; frozen within each conditional context.
Base gg gbase_gg_g_l9.35g/LFinal Table2/SupplementS5 reference input; frozen within each conditional context.
Clearance referencecl_reference_l_day0.15L/dayFinal Table2/SupplementS5 reference input; frozen within each conditional context.
Crp baseline powercrp_baseline_power0.21—Final Table2/SupplementS5 reference input; frozen within each conditional context.
Crpcrp_mg_l11mg/LFinal Table2/SupplementS5 reference input; frozen within each conditional context.
Female clearance log effectfemale_cl_log_effect-0.23—Final Table2/SupplementS5 reference input; frozen within each conditional context.
Female flagfemale_flag0—Final Table2/SupplementS5 reference input; frozen within each conditional context.
Gamma ancagamma_anca0.03—Final Table2/SupplementS5 reference input; frozen within each conditional context.
IC50 anca referenceic50_anca_reference_mg_l264mg/LFinal Table2/SupplementS5 reference input; frozen within each conditional context.
IC50 ggic50_gg_mg_l41.8mg/LFinal Table2/SupplementS5 reference input; frozen within each conditional context.
Turnover loss rate ggkout_gg_per_day0.00341/dayFinal Table2/SupplementS5 reference input; frozen within each conditional context.
Mtt ancamtt_anca_day31.9dayFinal Table2/SupplementS5 reference input; frozen within each conditional context.
PR3 flagpr3_flag0—Final Table2/SupplementS5 reference input; frozen within each conditional context.
PR3 IC50 log effectpr3_ic50_log_effect-0.96—Final Table2/SupplementS5 reference input; frozen within each conditional context.
Intercompartmental clearanceq_l_day0.52L/dayFinal Table2/SupplementS5 reference input; frozen within each conditional context.
Central distribution volume referencevc_reference_l2.61LFinal Table2/SupplementS5 reference input; frozen within each conditional context.
Peripheral distribution volumevp_l3.01LFinal Table2/SupplementS5 reference input; frozen within each conditional context.
Weightweight_kg68kgFinal Table2/SupplementS5 reference input; frozen within each conditional context.
Weight central distribution volume powerweight_vc_power0.71—Final Table2/SupplementS5 reference input; frozen within each conditional context.

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