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

Sizheng Steven Zhao, Lianne Kearsley-Fleet, Ailsa Bosworth, Kath Watson, BSRBR-RA Contributors Group, Kimme L. Hyrich

Research output: Contribution to journalArticlepeer-review


Objectives: Whether patients with 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: A total of 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, 5056 third, 2128 fourth, 767 fifth and 292 sixth. Most (71%) had sufficient data for DAS28-derived outcome analyses. TNF inhibitors were the most common first-line drug, but choice of subsequent-line drugs changed over time. Seventeen percent achieved DAS28 remission following first-line, 13% second and 8-13% 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.

Original languageEnglish
Article numberkeac190
Pages (from-to)4678-4686
Number of pages9
JournalRheumatology (Print)
Issue number12
Early online date31 Mar 2022
Publication statusPublished - 1 Dec 2022


  • effectiveness
  • switching
  • difficult to treat
  • biologics
  • DMARDs
  • RA
  • Humans
  • Middle Aged
  • Rheumatology
  • Arthritis, Rheumatoid/drug therapy
  • Male
  • Treatment Outcome
  • Biological Products/therapeutic use
  • Female
  • Antirheumatic Agents/therapeutic use


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  • Apothecaries Prize

    Zhao, Sizheng (Recipient), 21 Nov 2022

    Prize: Prize (including medals and awards)

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