Biologic Refractory Disease in Rheumatoid Arthritis: Results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Objectives: Biologic disease modifying anti-rheumatic drugs (bDMARD) 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 (TNFi) in the BSRBR-RA from 2001-2014 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-Nov-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 13502 (6%) patients were bDMARD refractory; median time to third bDMARD class of eight years. In the multivariable analysis, baseline factors associated with bDMARD refractory disease included: patients registered more recently, females, younger age, shorter disease duration, higher patient global assessment, higher HAQ, 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. Focussing resources, such as nursing support, on these patients may help them achieve more stable, controlled disease.