Osteoarthritis is a condition that causes joints to become painful and stiff, it is a common cause of pain and disability. Management of osteoarthritis involves reducing pain and maintaining function. Simple treatments include activity modification, staying active to maintain muscle strength and taking pain medication. Complex treatments include joint replacement (replacing the painful joint with an artificial joint), which may be required for those with pain that cannot be well controlled by other means.
Before a joint replacement is considered, it is possible to use other techniques, such as injections, into the affected joint to try to reduce pain. These injections are most commonly used for knee osteoarthritis. The injection usually contains both an anaesthetic to help with the pain and a steroid to reduce the inflammation (swelling, redness, heat and pain) within the joint. It is known that these injections can help with pain if used infrequently and that their use is recommended by a variety of organisations, including NICE and the NHS. However, little is known about the effect of using repeated injections.
We wish to use data that has already been collected on patients treated for osteoarthritis in primary care (by their GP, physiotherapist or other practitioner) who have or have not received an injection. Using this data, we will look at current use of injections, the safety of their use, how good they are, and whether they affect other treatments and the timing of these.
Objective
To establish current practice of the use of intra-articular corticosteroid injection (IACI) for the treatment of joint pain due to osteoarthritis (OA). Then to establish the long-term safety and outcomes of the use of IACI.
Method
We will use data from three large prospective routinely collected datasets: Clinical Practice Research Datalink
(CPRD) GOLD with linkage to Hospital Episode Statistics (HES) and National Patient Reported Outcomes
Measures (PROMs) data. Feasibility estimates from CPRD indicate approximately 25000 patients with knee, 9000 with hip, 5000 with hand, 3000 with shoulder, 2000 with ankle/foot and 1000 with wrist/elbow OA have received IACI with >100000 control cases available.
Data analysis
Current practice will be described by analysis of population (incidence, prevalence) and patient level utilisation (number of injections, persistence/adherence) including secular trends. Safety (pain, bleeding, infection, diabetes, cardiovascular) and association of IACI with outcomes (drug utilisation, timing to surgical intervention, subsequent outcome of arthroplasty, PROMs).
As intra-articular injections of corticosteroids (IACI) have not been randomly allocated due to the observational study design, we will use instrumental variables (IV), if fulfilling certain key assumptions, to address the issue of
unmeasured confounding. The instrument will be based upon clinician preference for IACI. We will perform further secondary analyses using alternative statistical methodological approaches, in order to assess the robustness of our findings. These will include: a) Propensity score (PS) matching, where this matches each patient not receiving IACI to a comparable IACI user in an attempt to minimise confounding by indication; b) Inverse probability weights (IPW), where the analysis is weighted according to the inverse of a patients probability of receiving IACI. PS matching focuses on the treated population, whereas IPW estimates the average effect of treatment in the entire study population (e.g. the outcome if everyone got the intervention, compared to the outcome if no one got the intervention).
Current practice study:
joint site injected (knee, hip, hand, shoulder, ankle/foot, wrist and elbow) (CPRD)
Utilisation study:
Population-level use:
incidence and prevalence of use of injections (CPRD)
secular trends of use of injections over the GOLD overall population (CPRD)
Patient-level utilisation:
number of repeat injections over time (CPRD)
cumulative use (number of daily defined doses of steroid/s injected in total), and medication possession ratio (number of daily defined doses of steroid injected over number of days from first to last injection) (CPRD)
Safety:
use of analgesia post-intra-articular injection (up to 1-year): paracetamol (acetaminophen), topical & parenteral NSAIDs, opioids and/or use of gabapentinoids. Number of medication prescriptions. Daily defined doses (DDD) of different types of analgesia (NSAID, opioids) received following the Index Prescription. (CPRD)
Bleeding post-intra-articular injection and post-operative (joint replacement surgery) (up to 6-months). (CPRD)
Infection post-intra-articular injection and post-operative (joint replacement surgery) (up to 6-months). (CPRD)
Diabetes decompensation post-intra-articular injection and post-operative (joint replacement surgery) (up to 6-months). (CPRD and HES)
Cardiovascular events post-intra-articular injection and post-operative (joint replacement surgery) (up to 6-months). (CPRD and HES)
Mortality (up to 6-months). (CPRD and ONS)
Association with outcomes:
use of analgesia post-operative (joint replacement surgery) (up to 1-year): paracetamol (acetaminophen), topical & parenteral NSAIDs, opioid analgesia and/or use of gabapentinoids and anti-epileptic drugs. Number of medication prescriptions. Daily defined doses (DDD) of different types of analgesia (NSAID, opioids) received following the Index Prescription. (CPRD)
use of steroid injections post-intra-articular injection and post-operative (joint replacement surgery) (up to 1-year). (CPRD)
use of oral corticosteroids post-intra-articular injection and post-operative (joint replacement surgery) (up to 1-year). (CPRD)
time to intermediate surgical interventions post-intra-articular injection including: joint injections (up to 10-years), joint arthroscopy (up to 10-years), joint debridement (meniscal and labral) (up to 10-years), subacromial decompression, rotator cuff repair acromioclavicular joint or distal clavicle resection/excision in the shoulder (up to 10-years), joint washout (lavage) (up to 10-years), ACL reconstruction (up to 10-years), joint arthroplasty (up to 10-years). (CPRD and HES)
For those that receive hip and knee arthroplasty outcomes will include:
joint infection (Wound infection, Wound dehiscence) (up to 6-months) (CPRD and HES)
Pneumonia, Urinary tract infection (up to 6-months) (CPRD and HES)
further surgery to the same joint (e.g. debridement, manipulation under anaesthetic, revision, reduction of hip dislocation) (up to 10-years) (CPRD and HES)
readmission due to thrombosis, myocardial infarction and stroke (up to 6-months) (HES)
patient reported outcomes (PROMs) including Oxford Hip Score, Oxford Knee Score and EQ5D (up to 6-months) (HES-PROMS).
Feasibility study:
Measures of effect sizes for association with outcomes between patients that did, compared to those that did not, receive intra-articular injection of corticosteroid
proportion of primary care practitioners performing intra-articular injection of corticosteroid and practices in which intra-articular injection of corticosteroid are performed.
Daniel Prieto-Alhambra - Chief Investigator - University of Oxford
Andrew Judge - Corresponding Applicant - University of Oxford
Albert Prats Uribe - Collaborator - University of Oxford
Amanda Burston - Collaborator - University of Bristol
Andrew Moore - Collaborator - University of Bristol
Antonella Delmestri - Collaborator - University of Oxford
Ashley Blom - Collaborator - University of Bristol
Michael Whitehouse - Collaborator - University of Bristol
Nick Snelling - Collaborator - NHS England
Rachael Gooberman-Hill - Collaborator - University of Bristol
Samuel Hawley - Collaborator - University of Bristol
Vikki Wylde - Collaborator - University of Bristol
HES Admitted Patient Care;HES PROMS (Patient Reported Outcomes Measure);ONS Death Registration Data;Patient Level Index of Multiple Deprivation