Real-world use of advanced therapy in rheumatoid arthritis

Student thesis: Phd

Abstract

The aim of this thesis was to evaluate and compare effectiveness and safety of recent advanced therapies (e.g. abatacept, IL-6 inhibitors and JAK inhibitors) for rheumatoid arthritis (RA) in the real world, using large national registers, to complement results from randomised controlled trials and help guide treatment choice, considering the vast array of therapeutic options available. This thesis used data from several national RA drug registers worldwide. The effectiveness of advanced therapies was evaluated and compared using treatment retention, change of disease activity scores, disease activity score response (remission or low-disease activity) and glucocorticoid-sparing effect. Safety was evaluated by comparing risk of serious infections and active tuberculosis disease (TB). Analyses were adjusted for baseline patient, disease and treatment characteristics. The association between line of therapy and the risk of serious infections or TB was also investigated. Analyses of several thousands of participants across treatment categories indicated similar effectiveness of TNF inhibitors (TNFi), abatacept, IL-6 inhibitors and JAK inhibitors (JAKi). The tocilizumab (TCZ) cohort, both as monotherapy and in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), showed superior effectiveness when compared with the TNFi and csDMARDs combination. Overall, the incidence of serious infection in patients with biologic disease-modifying antirheumatic drugs (bDMARDs) was 4.4/100 patient-years. When comparing treatments, results varied when adjusting or not for some confounding factors, suggesting that any differences are likely small and not clinically significant. After stratification by line of therapy, no clear pattern by line of therapy emerged. The incidence of TB was rare (8.5/10,000) and limited to first lines of therapy. In conclusion, overall, JAKi, IL-6i, TNFi, and abatacept all display comparable effectiveness in real-world settings. Additionally, the risk for serious infections is similar across various bDMARDs. Consequently, other factors should be evaluated to guide treatment choice. When combination therapy is not possible, TCZ should be favoured over TNFi. TB is infrequent with bDMARDs and primarily arise with the first lines of treatment.
Date of Award1 Aug 2024
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorMark Lunt (Supervisor) & Kimme Hyrich (Supervisor)

Keywords

  • real-world
  • safety
  • effectiveness
  • epidemiology
  • JAK
  • observational
  • rheumatoid arthritis
  • bDMARDs
  • register

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