Approximately 6% of patients with rheumatoid arthritis (RA) who are initiated on first-line TNF inhibitor (TNFi) will eventually prove to be refractory to biologic DMARDs (bDMARDs), according to the first national study of its kind.
The finding is based on data from the British Society for Rheumatology Biologics Register for RA from 2001 to 2014. Patients who had been exposed to at least 3 different classes of bDMARDs were classified as bDMARD refractory, irrespective of the reason for failure to prior bDMARD.
Of 13,502 patients, 867 were found to be treatment refractory. The median time to initiation of a third bDMARD class was 7.9 years (95% CI, 5.7-10.0). Overall, patients with refractory disease remained on their first TNFi for a median of 3.9 years.
20% of refractory patients have used more than 3 classes of bDMARDs, with 38% having used 4 different bDMARDs, 20% having used 5 and 8% having used at least 6. The most common reasons for discontinuation of the first TNFi were ineffectiveness (52%) and adverse events (24%).
In multivariable analysis, the risk for refractory disease was higher in women (HR, 1.3; 95% CI, 1.1-1.5), higher patient global assessment (HR, 1.1/cm; 95% CI, 1.0-1.1), higher Health Assessment Questionnaire score (HR, 1.3/unit; 95% CI, 1.1-1.5), current smoking (HR vs never 1.5; 95% CI, 1.2-1.7) and obesity (HR, 1.2 for BMI ≥30; 95% CI, 1.0-1.4) at the start of first TNFi, and was lower in patients with shorter disease duration (HR, 0.8 for disease duration >10 years; 95% CI, 0.7-0.95).
Of note, the risk for bDMARD refractory disease was 15 times higher among patients recruited from 2011 onwards compared with 2001-2008.
The findings are published in the Annals of the Rheumatic Diseases.