Drug utilisation in patients with knee osteoarthritis and the associated risk of falls: a population based study

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

“Application of five different strategies to define a cohort of patients with knee osteoarthritis in a large primary care database”

BackgroundElectronic health records (EHR) are frequently used for epidemiological research including drug utilisation studies in a defined population such as the population with knee osteoarthritis (KOA). We sought to describe the process of defining a cohort of patients with KOA from a large UK primary care database and estimate the annual incidence of diagnosed KOA between 2000 and 2015.MethodThis was a retrospective study using data from the clinical practice research datalink (CPRD). CPRD is a large primary care longitudinal electronic medical records’ database that contains anonymous records of patients from general practices across United Kingdom. Five different cohort definition strategies were applied including symptoms-based or diagnosis-based strategies or a combination of both. To validate results, the annual incidence of KOA was estimated and compared to published data.ResultsThe study defined 898,690 patients when symptoms-based strategy was applied, 137,541 patients when diagnosis based and 83,294 when a combination of both strategies were applied. The final cohort was defined using a diagnosis-based strategy that avoided overestimation (with symptoms-based definition) or underestimation (with a combination of symptoms and diagnosis). The incidence of KOA ranged from 1.33 per 1000 CPRD registrants in 2000, 1.76 in 2008 and 1.45 patients in 2015.ConclusionThis study logically/sensibly defined a cohort of patients with diagnosed KOA through the application of several strategies. This was an essential step to avoid subsequent over or underestimation of the prevalence of drug utilisation and the associated adverse clinical outcomes within primary care patients with KAO

Analgesic Utilisation in People with Knee Osteoarthritis: A Population‐ Based Study Using Primary Care Data

PurposeOsteoarthritis (OA) is a chronic painful condition that often affects large joints such as the knee. Treatment guidelines recommend paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) and opioids. Antidepressants and Anti-epileptic drugs (AEDs) are commonly prescribed for chronic non-cancer pain conditions including OA, as an off-label use. This study describes analgesic utilisation in patients with knee OA at population-level using standard pharmaco-epidemiological methods.MethodThis was a cross-sectional study between 2000 and 2014 using data from the UK Clinical Practice Research Datalink (CPRD). The use of antidepressants, AEDs, opioids, NSAIDs and paracetamol was studied in adults with knee OA using the following measures: annual number of prescriptions, Defined Daily Doses (DDD), oral morphine equivalent dose (OMEQ) and days’ supply.ResultsIn total, there were 8,944,381 prescriptions prescribed for 117,637 patients with knee OA during the 15-year period. There was a steady increase in the prescribing of all drug classes, except for NSAIDs, over the study period. Opioids were the most prevalent class prescribed in every study year. Tramadol was the most commonly prescribed opioid, with the number of DDD increasing from 0.11 to 0.71 DDDs per 1000 registrants in 2000 and 2014, respectively. The largest increase in prescribing was for AEDs, where the number of prescriptions increased from 2 to 11 per 1000 CPRD registrants.ConclusionThere was an overall increase in the prescribing of analgesics apart from NSAIDs. Opioids were the most frequently prescribed class however, the greatest increase in prescribing between 2000 and 2014, was observed in AEDs

Current Use of Analgesics and the Risk of Falls in people with Knee Osteoarthritis: A Population-based Cohort Study Using Primary Care and Hospital Records

ObjectiveTo examine the association between the current use of analgesics and the risk of falls in people with knee osteoarthritis (KOA).MethodsA retrospective cohort study using data from the UK Clinical Practice Research Datalink, with linkage to Hospital Episode Statistics data. People diagnosed with KOA in England between 2000 and 2014 were included. The studied analgesic classes were antidepressants, antiepileptic drugs (AEDs), opioids, non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol. Cox Proportional Hazards model was used to estimate the risk of fall with current use of analgesics within one year of KOA diagnosis, reported as Hazard Ratio (HR) with 95% Confidence Intervals (CI).ResultsThis study included 57,383 patients (mean age [SD] 67.0 [12.8] years, 59.3% were female); 44,010 (76.7%) were prescribed analgesics at least once within one year of KOA diagnosis. Within the first six months of KOA diagnosis, the reported HR (95%CI) were 1.46 (1.20, 1.78), 1.40 (0.91, 2.16), 2.40 (2.01, 2.85), 1.72 (1.43, 2.07), 1.98 (1.68, 2.33), while between 6 and 12 months after KOA diagnosis, the 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 and adjusted for important potential confounders.ConclusionThe current use of analgesics was associated with an increased risk of falls within one year of KOA diagnosis. These findings identify people with KOA who use analgesics as a priority for fall prevention programs/interventions, in an effort to optimise safety of analgesics in this population

Drug utilisation in patients with knee osteoarthritis and the associated risk of falls: a population based study

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