High frequency of antidrug antibodies and association of random drug levels with efficacy in certolizumab pegol-treated patients with rheumatoid arthritis: results from the BRAGGSS cohort.



Jani, Meghna ORCID: 0000-0002-1487-277X, Isaacs, John D ORCID: 0000-0002-6103-7056, Morgan, Ann W, Wilson, Anthony G, Plant, Darren ORCID: 0000-0003-1395-9344, Hyrich, Kimme L ORCID: 0000-0001-8242-9262, Chinoy, Hector ORCID: 0000-0001-6492-1288, Barton, Anne ORCID: 0000-0003-3316-2527 and BRAGGSS,
(2017) High frequency of antidrug antibodies and association of random drug levels with efficacy in certolizumab pegol-treated patients with rheumatoid arthritis: results from the BRAGGSS cohort. Annals of the rheumatic diseases, 76 (1). 208 - 213.

[img] Text
Braggs.pdf - Published Version

Download (514kB)
[img] Text
High frequency of antidrug antibodies and association of random drug levels with efficacy in certolizumab pegol-treated patients with rheumatoid arthritis: results from the BRAGGSS cohort.pdf - Published Version

Download (501kB)

Abstract

<h4>Objectives</h4>To evaluate (i) the association between random certolizumab drug levels, antidrug antibodies (ADAbs) and treatment response in patients with rheumatoid arthritis (RA); (ii) longitudinal factors associated with ADAbs and certolizumab drug levels.<h4>Methods</h4>This prospective cohort included 115 patients with RA treated with certolizumab. Serum samples were collected at 3, 6 and 12 months following treatment initiation. Drug levels and ADAbs were measured using ELISA and radioimmunoassay, respectively, at 3, 6 and 12 months. Disease Activity Score in 28 joints (DAS28) were measured at each visit and 12 months European League Against Rheumatism (EULAR) response was calculated. Patient self-reported adherence was collected longitudinally. Ordinal logistic regression and generalised estimating equation were used to test the association: (i) between drug levels, from serum sampled and treatment response; (ii) between ADAbs and drug levels; (iii) patient-centred factors and drug levels.<h4>Results</h4>ADAbs were detected in 37% (42/112 patients by 12 months). The presence of ADAbs were significantly associated with lower drug levels over 12 months (β=-0.037, 95% CI -0.055 to 0.018, p<0.0001) but not independently with 12 months EULAR response (β=0.0013 (95% CI -0.0032 to 0.00061), p=0.18). Drug level was associated with 12 months EULAR response (β=0.032 (95% CI 0.0011 to 0.063), p=0.042). In the multivariate model, ADAb level and adherence were significantly associated with drug concentrations.<h4>Conclusions</h4>This is the first study to demonstrate that higher certolizumab drug levels are associated with better 12 months EULAR response. ADAbs in certolizumab-treated patients with RA were detected at higher levels than previous studies and help determine the aetiology of a low drug level.

Item Type: Article
Uncontrolled Keywords: BRAGGSS, Humans, Arthritis, Rheumatoid, Antirheumatic Agents, Antibodies, Treatment Outcome, Severity of Illness Index, Cohort Studies, Prospective Studies, Dose-Response Relationship, Drug, Adult, Aged, Middle Aged, Female, Male, Certolizumab Pegol
Depositing User: Symplectic Admin
Date Deposited: 11 Apr 2018 14:12
Last Modified: 18 Jan 2021 21:33
DOI: 10.1136/annrheumdis-2015-208849
URI: https://livrepository.liverpool.ac.uk/id/eprint/3020048