A Pharmacodynamic Markov Mixed-Effects Model for Determining the Effect of Exposure to Certolizumab Pegol on the ACR20 Score in Patients With Rheumatoid Arthritis

• The American College of Rheumatology 20% preliminary definition of improvement of rheumatoid arthritis (ACR20) is widely used in clinical trials to assess response to treatment. The objective of this analysis was to develop an exposure-response model of ACR20 in subjects treated with certolizumab pegol, and to predict clinical outcome following various treatment schedules. At each visit, subjects were classified as being ACR20 responders, ACR20 non-responders, or having dropped out. A Markov mixed-effect model was developed to investigate the drug effect on the transitions between the 3 defined states. Increasing certolizumab pegol exposure predicted an increasing probability of becoming a responder and remaining a responder, as well as a reduced probability of dropping out of treatment. Simulations of the ACR20 response rate support dosing regimens of 400 mg at weeks 0, 2 and 4 followed by 200 mg every 2 weeks, or alternative maintenance regimen of 400 mg every 4 weeks.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Keyword

Rheumatoid arthritis

ACR20

exposure-response modeling

Markov

certolizumab pegol

Clinical Pharmacology

Klinisk farmakologi

Pharmacokinetics and Drug Therapy

Farmakokinetik och läkemedelsterapi

PHARMACY

Publication and Content Type

ref (subject category)

art (subject category)