Effectiveness of sequential biologic and targeted disease modifying anti-rheumatic drugs for rheumatoid arthritis

Introduction. Whether patients with rheumatoid arthritis (RA) benefit from repeated trials of biologic or targeted synthetic DMARDs (b/tsDMARDs) after three or more attempts is unknown. We aimed to describe treatment outcomes in each line of b/tsDMARD therapy.

Methods. Using data from the British Society for Rheumatology Biologics Register for RA from 2001 to 2020, change to a new b/tsDMARD (except biosimilar switches) was defined as a new line of therapy. Treatment outcomes were compared across lines of therapy, including DAS28 remission (≤2.6), low disease activity (LDA, ≤3.2) at 6 months, and median time to drug discontinuation. Multiple imputation was used for missing data.

Results. 22,934 individuals starting a first b/tsDMARD were included (mean age 56 years, 76% female), among whom 10,823 commenced a second-line drug, 5,056 third, 2,128 fourth, 767 fifth and 292 sixth. Most (71%) had sufficient data for DAS28-derived outcome analyses. TNF inhibitors were the commonest first-line drug, but choice of subsequent-line drugs changed over time. Seventeen percent achieved DAS28 remission following first-line, 13% second and 8 to 13% with third through sixth. LDA was achieved in 29% of first-line, 23% second, 17-22% through to the sixth. Patients stayed on first-line therapy for a median of 2.6 years, ranging from 1.0-1.4 years for lines two to six.

Conclusion. Many patients will eventually benefit after repeated trials of b/tsDMARD. Further research to improve treatment selection are needed to prevent prolonged trial and error approaches in some patients.

Keywords: rheumatoid arthritis, difficult to treat, switching, effectiveness, biologics, DMARDs