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Biologic refractory disease in rheumatoid arthritis: Results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Lookup NU author(s): Professor John IsaacsORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ. Objectives: Biologic disease-modifying antirheumatic drugs (bDMARDs) have revolutionised treatment and outcomes for rheumatoid arthritis (RA). The expanding repertoire allows the option of switching bDMARD if current treatment is not effective. For some patients, even after switching, disease control remains elusive. This analysis aims to quantify the frequency of, and identify factors associated with, bDMARD refractory disease. Methods: Patients with RA starting first-line tumour necrosis factor inhibitor in the British Society for Rheumatology Biologics Register for RA from 2001 to 2014 were included. We defined patients as bDMARD refractory on the date they started their third class of bDMARD. Follow-up was censored at last follow-up date, 30 November 2016, or death, whichever came first. Switching patterns and stop reasons of bDMARDs were investigated. Cox regression identified baseline clinical factors associated with refractory disease. Multiple imputation of missing baseline data was used. Results: 867 of 13 502 (6%) patients were bDMARD refractory; median time to third bDMARD class of 8 years. In the multivariable analysis, baseline factors associated with bDMARD refractory disease included patients registered more recently, women, younger age, shorter disease duration, higher patient global assessment, higher Health Assessment Questionnaire score, current smokers, obesity and greater social deprivation. Conclusions: This first national study has identified the frequency of bDMARD refractory disease to be at least 6% of patients who have ever received bDMARDs. As the choice of bDMARDs increases, patients are cycling through bDMARDs quicker. The aetiopathogenesis of bDMARD refractory disease requires further investigation. Focusing resources, such as nursing support, on these patients may help them achieve more stable, controlled disease.

Publication metadata

Author(s): Kearsley-Fleet L, Davies R, De Cock D, Watson KD, Lunt M, Buch MH, Isaacs JD, Hyrich KL

Publication type: Article

Publication status: Published

Journal: Annals of the Rheumatic Diseases

Year: 2018

Volume: 77

Issue: 10

Pages: 1405-1412

Print publication date: 01/10/2018

Online publication date: 06/07/2018

Acceptance date: 18/06/2018

Date deposited: 23/07/2018

ISSN (print): 0003-4967

ISSN (electronic): 1468-2060

Publisher: BMJ Publishing Group


DOI: 10.1136/annrheumdis-2018-213378


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Funder referenceFunder name
MREC 00/8/53