Certolizumab pegol 200mg/1ml solution for injection pre-filled disposable devices

ObjectivesTo determine how certolizumab pegol (CZP) dose and dose adjustments influence CZP plasma trough levels to facilitate therapeutic drug monitoring of CZP.MethodsThe effect of CZP dose and dose adjustments on CZP plasma trough levels was evaluated post hoc using longitudinal data from a 52-week randomized phase III trial (RAPID 1) and its open-label extension trial. Patients with active rheumatoid arthritis treated with methotrexate for ≥6 months were randomized to CZP 200 mg, 400 mg, or placebo every other week (EOW). Patients in the extension trial were initially treated with CZP 400 mg EOW, then reduced to 200 mg EOW after ≥6 months.ResultsOf 982 randomized patients, 846 patients entered the open-label extension trial. Median (interquartile range) plasma CZP concentrations after 12 weeks of treatment were 21.3 mg/L (14.7, 27.7) in the 200-mg group and 38.3 mg/L (29.2, 63.8) in the 400-mg group and increased from 18.3 (12.4, 26.5) to 43.4 (26.8, 63.3) mg/L after dose escalation from 200 to 400 mg EOW. Following CZP dose reduction from 400 mg to 200 mg, median CZP levels decreased from 36.1 (24.9, 49.0) to 17.2 (11.5, 23.1) mg/L.ConclusionsCZP plasma concentrations were influenced by both dose and dose adjustment in a predictable manner, with median plasma levels twice as high in the 400-mg group than in the 200-mg group, with a 2-fold increase after the dose increase from 200 to 400 mg. This facilitates the development of algorithms for therapeutic drug monitoring of CZP.

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