Title: Using NHS data for musculoskeletal epidemiology: the risk/benefit of total knee and hip arthroplasty in patients with rheumatoid arthritis, and the potential effects of biologics on reducing the need for surgery.
Funder: Department of Health and Social Care

Abstract: BACKGROUND. About 1/4 patients with rheumatoid arthritis (RA) require a knee or hip replacement. However, there is controversy around the risks and benefits of total knee (TKA)/hip(THA) arthroplasty for RA patients. New biologic therapies are effective modulators of inflammation and immunity in RA. Biologics have been shown to reduce clinical measures of joint damage (erosion and joint space narrowing), but have not yet been proven to reduce TKA/THA rates. This has potentially significant implications for cost-effectiveness modeling, as the current models used by NICE guidelines assume no effect of biologics on the need for TKA/THA. OBJECTIVES. We aim to: 1.study the risks of TKA/THA in RA compared to osteoarthritis patients, and to identify predictors of complications in RA patients [work-package WP1]; 2.compare patient-reported outcomes (PROMs) following TKA/THA in RA versus osteoarthritis patients [WP2]; 3.estimate incidence rates of TKA/THA in RA patients before and after the introduction of biologic therapies [WP3]; 4.study the association between the use of biologics and TKA/THA risk at a patient level [WP4]; and 5.calculate the cost-utility of biologics to reduce TKA/THA in RA patients [WP5]. METHODS. WP1. We will obtain data on all patients registered in the Clinical Practice Research Datalink (CPRD) linked to Hospital Episodes Statistics (HES) with an RA diagnosis undergoing TKA/THA in 1995-2012. To each of these, we will match up to 5 patients undergoing TKA/THA for osteoarthritis by age, gender, primary care practice, and year of surgery. Poisson models will be fitted to estimate the rates of complications, first-year revision, and mortality in RA and osteoarthritis patients, and to estimate rate ratios for each outcome according to RA status. Logistic regression will be used to identify key predictors of, and to produce predictive tools for post-operative complications in RA patients. WP2. From the national PROMs (Patient Reported Outcome Measures) Database linked to the National Joint Registry, we will identify all patients undergoing TKA/THA for RA, matched 1:5 to TKA/THAs for osteoarthritis of similar age, gender, hospital where surgery was performed, and index year. We will compare adjusted improvement in Oxford Knee/Hip Score (OKHS) (6-month post-surgery minus pre-operative OKHS) for RA and OA patients using linear regression. WP3. We will identify all patients in CPRD-HES with a diagnosis of RA. Primary TKA/THA procedures will be identified in HES using OPCS codes. Annual incidence rates of TKA/THA will be estimated using Poisson methods. Interrupted time series analyses will be carried out to assess whether secular trends of TKA/THA changed significantly after the introduction of biologics in 2002. WP4. We will obtain data from the BSR/Biologics Register on RA patients on biologics and on non-biologic therapies. Propensity score techniques will be used to adjust for confounding by indication, and survival analysis will be used to estimate the relative risk of TKA/THA amongst patients on biologics compared to controls. WP5. We will assess the cost-effectiveness of using biologics (compared to non-biologic therapies) to prevent TKA/THA in RA patients by populating and running the current model (Birmingham RA model) with estimates of costs (WP1), health-related quality of life (WP 2), and rates of TKA/THA for patients taking and not taking biologics (WP 4) from the perspective of the NHS. POTENTIAL BENEFITS This study will provide extensive information on the risks and benefits (PROMs) of TKA/THA for RA compared to osteoarthritis patients in NHS settings. In addition, we will report the potential effects of biologics on reducing the need for TKA/THA in this population. All these data will help informed decision on the use of TKA/THA in RA patients, and will feed current cost-effectiveness models, which assume no effect of biologics on the prevention of TKA/THA.

Lay abstract: Over 2,000 patients with rheumatoid arthritis (RA) undergo a knee/hip replacement in the UK every year. However, the related risks, benefits, and costs of these procedures for RA patients within the NHS are unknown. Moreover, new biologic therapies could potentially reduce the need for surgery in patients with severe RA, but research in this area is lacking. We aim to study: 1.The risks, benefits, and NHS costs of knee/hip replacement in RA patients; 2.The potential impact of biologic therapies on the need for surgery; and 3.The cost and effectiveness of these drugs in minimising the need for knee/hip replacement.

Research activity codes: 6.1 PHARMACEUTICALS;6.4 SURGERY
Health categories: INFLAMMATORY AND IMMUNE SYSTEM