Background. Response to anti-tumour necrosis factor (anti-TNF) therapy in patients with rheumatoid arthritis (RA) varies between patients. Incidence of sustained remission in the UK is not known, and factors contributing to its achievement are poorly understood. Prior knowledge of response would enable better targeting of anti-TNF therapy, leading to better outcomes and reduced morbidity.Aims. This thesis aims to identify incidence of sustained remission and low disease activity (LDA) in patients with rheumatoid arthritis (RA) taking anti-TNF therapy. Clinical and demographic factors associated with sustained remission and LDA were identified.Methods. I undertook a systematic literature review of the incidence of, and factors associated with, sustained remission in patients with RA taking anti-TNF therapy. Results informed a subsequent analysis of data extracted from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA). I used two approaches to examine sustained remission and LDA. Firstly, pre-defined DAS28 thresholds were used to identify individuals in sustained remission and LDA. Secondly, a data-driven approach used latent class mixed modelling (LCMM) to identify independent trajectories of response within the data. Results. Sustained remission and LDA occurred infrequently in the literature review (range 4.2 – 38.1% sustained remission) and was uncommon in the BSRBR-RA (14.9% and 26.3% respectively), but had improved significantly over time. Significant associations were identified between the candidate variables and sustained remission and LDA, both using pre-defined thresholds and LCMM analyses. LCMM analyses identified response at six months to be a good indicator of long-term outcomes. Conclusions. Sustained remission and LDA remains uncommon, although outcomes are improving. Clinical and demographic features are associated with achieving these outcomes, suggesting it may be possible to use phenotypic features to guide therapy. Additionally, the clear response trajectories identified at six months, suggest it may be possible to identify non-responders to anti-TNF therapy earlier than six months.
|Date of Award||4 Feb 2018|
|Sponsors||British Society for Rheumatology|
|Supervisor||Neil McHugh (Supervisor), John Pauling (Supervisor), Gavin Shaddick (Supervisor) & Kimme Hyrich (Supervisor)|