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.
- rheumatoid arthritis
- dmards (biologic)
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Handling editor Francis Berenbaum
Contributors All authors were involved in the design and statistical analysis of the study as well as manuscript drafting and gave approval to the final version. See bsrbr.org for a full list of contributors .
Funding This work was supported by the British Society for Rheumatology (BSR).
Competing interests MHB has received grants from Pfizer Ltd and Roche Pharmaceuticals, as well as expert advice and honoraria from Abbvie, Astra-Zeneca, BMS, Lilly, Roche, Sandoz and UCB. JDI has received research grants from Pfizer Ltd and Roche Pharmaceuticals, as well as honoraria/fees from Abbvie, Roche, Pfizer, Janssen and BMS.
Patient consent Obtained.
Ethics approval UK North West Multicentre Research Ethics Committee (MREC 00/8/53).
Provenance and peer review Not commissioned; externally peer reviewed.
Author note The BSR commissioned the BSR Biologics Register in Rheumatoid Arthritis (BSRBR-RA) as a UK-wide national project to investigate the safety of biologic and other targeted therapies in routine medical practice. KH is the principal investigator. The BSR currently receives restricted income from UK pharmaceutical companies, including Abbvie, Celltrion, Eli Lilly, Pfizer, Roche, Samsung Bioepis, Sandoz, Sanofi, UCB and in the past Hospira, MSD and Swedish Orphan Biovitrum (SOBI). This income finances a wholly separate contract between the BSR and The University of Manchester to host the BSRBR-RA. The principal investigator and the BSRBR-RA team at the University of Manchester have full academic freedom and are able to work independently of pharmaceutical industry influence. All decisions concerning analyses, interpretation and publication are made autonomously of any industrial contribution. Members of the BSRBR-RA University of Manchester team, BSR trustees, committee members and staff complete an annual declaration in relation to conflicts of interest. All relevant information regarding serious adverse events outlined in the manuscript have been reported to the appropriate pharmaceutical company as per the contractual agreements/standard operating procedures.
Presented at This manuscript has been previously presented at ACR 2017 (Kearsley-Fleet L, et al. Refractory disease in rheumatoid arthritis: results from the British Society of Rheumatology Biologics Register for rheumatoid arthritis (abstract). Arthritis Rheumatol . 2017; 69 (suppl 10). http://acrabstracts.org/abstract/refractory-disease-in-rheumatoid-arthritis-results-from-the-british-society-of-rheumatology-biologics-register-for-rheumatoid-arthritis) and BSR 2018 (Kearsley-Fleet L, et al. Refractory disease in rheumatoid arthritis: results from the British Society of Rheumatology Biologics Register for rheumatoid arthritis (abstract). Rheumatology . 2018; 57 (suppl 3). https://doi.org/10.1093/rheumatology/key075.311).
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