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

Abstract

Objectives 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% to13% 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.

Restrictions on the use of higher cost drugs for rheumatoid arthritis in England: Surveys of Clinical Commissioning Groups; prescribers

“…Similarly, a review of multiple use of HCDs from the BSR biologics registry (Zhao et al, 2022) showed maintenance of response rates from fourth to sixth choices. However, the survey of HCD prescribers revealed that they were more pessimistic about the likelihood of response which highlights the importance of collecting systematic follow-up data.…”

Patterns in the sequential treatment of rheumatoid arthritis patients starting a b/tsDMARD: 10-year experience from a US-based registry

“…The trend of decreasing therapy duration was observed also in recent work by Mease et al (23), although they used data of patients enrolled in the CorEvitas RA registry between 2004 and 2015 and studied a smaller set of therapies. There exist some studies that have tried to describe sequential therapies using Sankey diagrams (12,13). Our sequence visualizations contain more information in the sense that they show entire therapy trajectories and not only transitions between consecutive therapies.…”

“…Our sequence visualizations contain more information in the sense that they show entire therapy trajectories and not only transitions between consecutive therapies. Still, it is worth noting that Zhao et al (13) identi ed the transition between TNFi and rituximab as the second most common transition between the rst two lines of treatment. In contrast, there are no sequences starting in this way in Fig.…”

“…However, these studies are mostly limited to the choice of second-line b/tsDMARD and do not give a complete picture of current practice. Other studies have extended the duration of follow-up and examined sequential therapies using observational designs (12,13). Most often, these studies demonstrate transitions between therapies in a ow diagram-typically in the form of a Sankey diagram-and not the whole sequences of treatments.…”

Therapeutic advances in rheumatoid arthritis

“…Most patients will be offered subsequent b/tsDMARDs on inadequate response to their first but, for some, disease remission remains elusive. A 2022 UK study describing patients who had received up to 10 sequential b/tsDMARDs illustrates this point 106. Although the full definition of the EULAR difficult-to-treat definition is difficult to apply to existing research databases, a UK publication including 13 502 patients starting their first anti-TNF treatment found that 29% went on to receive two different classes of bDMARDs, and 6% received three different classes 107.…”