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
Authors: Hum Ryan M , Ho Pauline , Nair Nisha , Plant Darren , Morgan Ann W , Isaacs John D , Wilson Anthony G , Hyrich Kimme L , Barton Anne ,   Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate
Published: April 2022

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 cut-off 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.

Disclosure
R.M. Hum: None. P. Ho: None. N. Nair: None. D. Plant: None. A.W. Morgan: None. J.D. Isaacs: None. A.G. Wilson: None. K.L. Hyrich: None. A. Barton: None.