Exposure–Response Relationship of Certolizumab Pegol and Achievement of Low Disease Activity and Remission in Patients With Rheumatoid Arthritis

• Published in: Clinical and translational science 2020-07, Vol.13 (4), p.743-751
• Main Authors: Paul, Stéphane, Marotte, Hubert, Kavanaugh, Arthur, Goupille, Philippe, Kvien, Tore K., Longueville, Marc, Mulleman, Denis, Sandborn, William J., Vande Casteele, Niels
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antirheumatic Agents - administration & dosage; Antirheumatic Agents - pharmacokinetics; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - drug therapy; Binding sites; Certolizumab Pegol - administration & dosage; Certolizumab Pegol - pharmacokinetics; Clinical medicine; Clinical trials; Disease control; Dose-Response Relationship, Drug; Drug dosages; Drug Monitoring - methods; FDA approval; Feasibility Studies; Female; Humans; Immunosuppressive agents; Immunotherapy; Inflammatory diseases; Joint diseases; Life Sciences; Male; Middle Aged; Monoclonal antibodies; Patients; Plasma; Polyethylene glycol; Randomized Controlled Trials as Topic; Remission; Remission (Medicine); Rheumatoid arthritis; Rheumatology; ROC Curve; Severity of Illness Index; Studies; TNF inhibitors; Treatment Outcome; Trends; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1752-8054; 1752-8062
• DOI: 10.1111/cts.12760

Anti‐tumor necrosis factor (anti‐TNF) drugs are often prescribed for the treatment of rheumatoid arthritis (RA) and other immune‐mediated inflammatory diseases. Although this treatment has been shown to be effective in many patients, up to 40% of patients do not achieve disease control. Drug concentration in plasma may be a factor affecting the observed variability in therapeutic response. In this study, we aimed to identify the plasma concentrations of the anti‐TNF certolizumab pegol (CZP), associated with improvement in disease activity in patients with RA. Data were pooled from three randomized, controlled clinical trials with a combined total of 1,935 patients analyzed. Clinical outcomes of low disease activity (LDA) and remission were defined as Disease Activity Score in 28 joints with C‐reactive protein (DAS28(CRP)) ≤ 2.7 and < 2.3, respectively. Quartile analysis results indicated that there may be an exposure‒response relationship between CZP concentration and LDA/remission outcomes at weeks 12 and 24; the association was strongest for LDA (P