Taqi, Aqila Mohammed Hassan
(2020)
Drug utilisation in patients with knee osteoarthritis and the associated risk of falls: a population based study.
PhD thesis, University of Nottingham.
Abstract
Background
Osteoarthritis is a chronic musculoskeletal condition that affects around 8 million people in the UK. It results in pain and disability that compromise quality of life and has substantial societal and economic burdens. Osteoarthritis can affect any joint, however, knees are most commonly affected, and the prevalence increases with age. Management involves non-pharmacological approaches such as exercise and weight control, and pharmacological approaches including prescribing analgesics. Recently a role of antidepressants and antiepileptic drugs (AEDs) was suggested in osteoarthritis related pain based on findings confirming the involvement of central sensitisation and neuropathic pain mechanisms. Patients with osteoarthritis use various analgesics and for varying periods, which may subject them to adverse drug events such as falls. Falls are a major public health concern in the UK and worldwide. Patients with osteoarthritis might be at an increased risk of falls due to joint pathology and chronic pain, coupled with age related physiological changes. However, in the UK, data on drug utilisation and the associated outcomes in patients with osteoarthritis are limited.
This research aimed to describe the utilisation of several analgesic drug classes including antidepressants, antiepileptic drugs (AEDs), opioids, NSAIDs and paracetamol in patients with knee osteoarthritis (KOA), and examine the association between analgesic use and the risk of falls.
Methods
Data were obtained from the Clinical Practice Research Datalink (CPRD), and the Hospital Episode Statistics. The study selected patients with a diagnosis of KOA from CPRD and measured the incidence of diagnosed KOA in primary care between 2000 and 2015. Subsequently, a cross-sectional analysis described the temporal changes in the utilisation of analgesic drug classes in patients with KOA between 2000 and 2015. This was followed by a cohort study on the patterns of analgesic use at an individual patient level. The association between analgesic use and the risk of fall within one year of KOA diagnosis was examined using two cohort studies. Analgesic use was treated as a time fixed exposure in the first analysis and as a time varying variable in the second analysis.
Results
A cohort of 137,051 patients with KOA was selected from CPRD. The annual incidence of KOA diagnosis in the years 2000 and 2015 was 1.33 and 1.47 patients per 1000 CPRD registrants, respectively.
The cross-sectional analysis showed a steady increase in the prescribing of all analgesic drugs classes, except for NSAIDs. In particular, the use of opioids was most prevalent in every study year. Tramadol was the most commonly prescribed opioid, with the number of defined daily doses (DDD) increasing from 0.11 to 0.64 DDDs per 1000 registrants per day between 2000 and 2015. Similarly, there was an increase in the oral morphine equivalent dose from 32.6 to 71.7 mg per day between 2000 and 2015. AEDs showed a marked increase in the number of new users doubled from 0.1 to 0.2 per 1000 registrants from 2000 to 2015. Variable proportions of patients used respective analgesic classes persistently during the first year after prescribing, between 36% (antidepressants) and 15% (opioids).
A significant association between any analgesic use and the risk of fall was found with HR (95% CI) 1.89 (1.66, 2.16) adjusted for age, gender and use of fall risk increasing drugs (FRIDs). Additionally, the study found that compared to those not using any analgesic, patients using three analgesic groups (neuropathic pain medications, opioids and non opioid analgesics) were at more than three times the risk of falling HR (95%CI) 3.24 (2.77, 3.78) adjusted for age, gender and use of FRIDs. The time varying analysis showed that current use of analgesics was associated with a greater risk of fall compared to periods of no analgesic use. The reported HR (95%CI) were 2.68 (2.14, 3.36), 2.22 (1.70, 2.91), 1.96 (1.70, 2.26), 1.47 (1.21, 1.78), 1.92 (1.63, 2.26) for antidepressants, AEDs, opioids, NSAIDs and paracetamol, respectively, adjusted for age, gender and use of FRIDs.
Conclusion
The study showed an overall increase in the prescribing of analgesic medicines in patients with KOA, with opioids being the most prevalent during the period between 2000 and 2015. The greatest increase in prescribing over time was observed in AEDs. The use of analgesics was associated with a significant risk of fall within a year after diagnosis of KOA. These findings inform policy and practice on the safety of analgesics in patients with KOA and identify this group of patients as a priority for administration of fall prevention programs/interventions.
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