Population Pharmacokinetics of Risankizumab in Healthy Volunteers and Subjects with Moderate to Severe Plaque Psoriasis: Integrated Analyses of Phase I-III Clinical Trials

Clin Pharmacokinet. 2019 Oct;58(10):1309-1321. doi: 10.1007/s40262-019-00759-z.


Background and objective: Risankizumab is an anti-interleukin (IL)-23 monoclonal antibody being developed for treatment of moderate to severe plaque psoriasis. This study provided a comprehensive analysis of risankizumab pharmacokinetics in healthy subjects and patients with plaque psoriasis using data across phase I-III clinical trials.

Methods: Plasma pharmacokinetic data from 1899 subjects, including 13,123 observations, who received single or multiple intravenous or subcutaneous doses of risankizumab (0.01-5 mg/kg intravenous [IV], 200-1200 mg IV, 0.25-1 mg/kg subcutaneous [SC], and 18-300 mg SC) across the phase I-III clinical program were analyzed using a non-linear mixed-effects modeling approach. The developed model was qualified and the clinical relevance of covariates statistically correlated with risankizumab clearance (CL) was evaluated using simulation analyses.

Results: Risankizumab pharmacokinetics were best described using a two-compartment model with first-order absorption and elimination. Risankizumab CL, volume of distribution at steady state (Vss), and terminal-phase elimination half-life (t½) were estimated to be approximately 0.31 L/day, 11.2 L, and 28 days, respectively, for a typical 90 kg psoriatic subject, approaching steady-state plasma exposures by week 16 of dosing. Absolute SC bioavailability (F) was 89%. Bodyweight, anti-drug antibody (ADA) titers ≥ 128 (detected in only 1% of ADA-evaluable subjects in phase III studies), baseline serum albumin, high-sensitivity C-reactive protein (hs-CRP), and serum creatinine were statistically correlated with risankizumab CL; however, they had no clinically relevant impact on exposure.

Conclusion: Risankizumab is characterized by dose-proportional, bi-exponential disposition with no difference in exposure between healthy subjects and patients with psoriasis. None of the covariates identified as being statistically correlated with risankizumab CL has a clinically meaningful impact on its exposure with the proposed psoriasis clinical regimen of 150 mg administered SC at weeks 0 and 4, and every 12 weeks thereafter. CLINICALTRIALS.

Gov identifiers: NCT01577550, NCT02054481, NCT02596217, NCT02684370, NCT02672852, NCT02684357, NCT02694523.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / pharmacokinetics*
  • C-Reactive Protein / analysis
  • Creatinine / blood
  • Female
  • Healthy Volunteers
  • Humans
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Models, Biological*
  • Psoriasis / blood
  • Psoriasis / metabolism*
  • Serum Albumin, Human / analysis
  • Young Adult


  • Antibodies, Monoclonal
  • C-Reactive Protein
  • risankizumab
  • Creatinine
  • Serum Albumin, Human

Associated data

  • ClinicalTrials.gov/NCT01577550
  • ClinicalTrials.gov/NCT02054481
  • ClinicalTrials.gov/NCT02596217
  • ClinicalTrials.gov/NCT02684370
  • ClinicalTrials.gov/NCT02672852
  • ClinicalTrials.gov/NCT02684357
  • ClinicalTrials.gov/NCT02694523