OA16 Therapeutic certolizumab pegol drug levels to achieve good EULAR response in patients with rheumatoid arthritis: results from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS) cohort

Abstract

Background/Aims Rheumatoid arthritis (RA) is a systemic inflammatory disease which is often treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) like tumour-necrosis factor inhibitors (TNFi) including certolizumab pegol (CTZ). A proportion of patients (approximately 30%) do not respond to treatment, and previous studies have shown that low drug levels and poor adherence are associated with poor response; however, an optimal drug level has not been defined or applied in clinical practice. The aim of this analysis is to determine an optimal CTZ drug level associated with a ''good'' European Alliance of Associations for Rheumatology (EULAR) response in fully adherent and non-adherent patients with RA. Methods In a prospective observational cohort study, patients with RA were treated with CTZ. At baseline, and at 6 months, 4-component DAS28 scores, as well as self-reported treatment adherence data were collected. Drug levels were measured using ELISA during follow-up at 6 months from treatment initiation. Patients were considered fully adherent if they self-reported never having altered, forgotten or omitted any dose of their biologic drug at follow-up. Patients without drug levels were excluded. In fully adherent patients, the relationship between random CTZ levels and clinical efficacy after 6 months was determined using a concentration-effect curve, and a receiver-operator characteristics (ROC) curve established a therapeutic cut-off concentration using the EULAR response classification. Median drug levels in ''good'' EULAR responders were compared between adherent and non-adherent patients to provide an estimated therapeutic range. Results Of 347 RA patients taking CTZ recruited, 111 (32.0%) had drug levels and EULAR response measured at 6 months, of which 42 (37.8%) also provided self-reported treatment adherence data. Of those, 37 (88.1%) reported being fully adherent. In 37 fully adherent RA patients taking CTZ, clinical efficacy was positively correlated with increasing CTZ concentration reaching a maximum median DAS28CRP improvement of 2.99 (IQR 2.67-3.40) with levels above 30mg/L. Levels exceeding 30mg/L showed no significant additional benefit. The ROC curve showed an area under the curve (AUC) of 0.714 (95% CI 0.526-0.901) for random CTZ levels with EULAR good response versus non/moderate responders. A cutoff of 30mg/L had a sensitivity and specificity of 86.4% and 60.0%, respectively, to classify good responders in fully adherent patients. Fully adherent good responders (n=37) had a median drug level of 34.5mg/L (IQR 31-38), whereas good responders in the remaining cohort (n=76) had a median drug level of 23.5 (IQR 15-30). Conclusion In RA patients taking CTZ, random drug levels were higher in EULAR good responders, and in fully adherent patients. A target lower threshold drug level cut-off of 30mg/L or a target range from 23.5mg/L to 34.5mg/L may be useful in clinical practice.