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Title: Biologic therapies and the need for hip and knee replacement amongst patients with rheumatoid arthritis : a population-based epidemiology study using electronic medical records and registry data
Author: Hawley, Samuel
ISNI:       0000 0004 7960 0366
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2018
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Registry reports indicate over 200,000 hip or knee replacements are performed annually in England, Wales and Northern Ireland, with approximately 1-2% carried out for inflammatory conditions such as rheumatoid arthritis (RA). The aim of this DPhil was to estimate the impact of biologic therapies on the need for major joint replacement amongst RA patients using observational health data. An interrupted time-series analysis was used to estimate the impact of NICE approval of biologics on population-level temporal trends of total hip replacement (THR) and total knee replacement (TKR) amongst RA patients in England and Wales. Similar analyses were repeated for Denmark and Ontario. Overall, these studies indicated a decrease in TKR but not THR for RA patients following the introduction of biologics. When the rates in non-RA patients were taken into account (in Denmark and Ontario only), there was an inferred reduction in both THR and TKR for RA patients within the biologic era. There was a lack of guidance on sample size planning for such analyses, so a simulation study was also conducted to estimate power in various time-series scenarios. A patient-level analysis was then conducted using UK registry data, applying various novel methodologies to account for the inherent problem of confounding by indication. The results suggested no significant impact of biologics on rates of joint replacement, although in age-stratified analyses biologics was associated with a 40% reduction in THR rates amongst patients ≥60 years old. To conclude, a reduction is observed in population-level rates of THR and TKR amongst RA patients (compared to non-RA patients) following the introduction of biologics. Patient-level analyses confirmed a favourable impact on THR rates amongst older patients, but otherwise no significant associations. More patient-level analyses are required to confirm and/or further elucidate the impact of biologic therapies on the need for joint replacement in RA.
Supervisor: Prieto-Alhambra, Daniel ; Judge, Andrew ; Ali, M. Sanni Sponsor: NIHR Clinician Scientist Award
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Statistical Methods ; Epidemiology ; Musculoskeletal Sciences