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Data from 'BISCUITS', a large Nordic cohort study linking several registries, were used to estimate differences in average direct and indirect costs between patients with osteoarthritis and controls (matched 1:1 based on birth year and sex) from the general population in Sweden, Norway, Finland and Denmark for 2017. Patients ≥18 years with ≥1 diagnosis of osteoarthritis (ICD-10: M15–M19) recorded in specialty or primary care (the latter available for a subset of patients in Sweden and for all patients in Finland) during 2011–2017 were included. Patients with a cancer diagnosis (ICD-10: C00–C43/C45–C97) were excluded. Productivity loss (sick leave and disability pension) and associated indirect costs were estimated among working-age adults (18–66 years). In 2017, average annual incremental direct costs among adults with osteoarthritis (n=1,157,236) in specialty care relative to controls ranged between €1,259 and €1,693 (p<0.001) per patient across all countries. Total average annual incremental costs were €3,224–€4,969 (p<0.001) per patient. Healthcare cost differences were mainly explained by osteoarthritis patients having more surgeries. However, among patients with both primary and secondary care data, primary care costs exceeded the costs of surgery. Primary care constituted 41 and 29 % of the difference in direct costs in Sweden and Finland, respectively. From a societal perspective, the total economic burden of osteoarthritis is substantial, and the incremental cost was estimated to €1.1–€1.3 billion yearly for patients in specialty care across the Nordic countries. When including patients in primary care, incremental costs rose to €3 billion in Sweden and €1.8 billion in Finland. Given the large economic impact, finding cost-effective and safe therapeutic strategies for these patients will be important. [ABSTRACT FROM AUTHOR]

Objectives: Osteoarthritis can have a profound effect on patients' quality of life. The Burden of Disease and Management of Osteoarthritis and Chronic Low Back Pain: Health Care Utilization and Sick Leave in Sweden, Norway, Finland and Denmark (BISCUITS) study aimed to describe the impact of osteoarthritis on quality of life and determine the association with factors such as pain severity and pharmacological treatment. Methods: An observational study was performed with a cross-sectional design including patients with a confirmed osteoarthritis diagnosis enrolled in the National Quality Register for Better management of patients with Osteoarthritis (BOA) between 2016 and 2017 in Sweden. Patient-reported information from BOA was linked to administrative data from three national health registers. The impact of osteoarthritis on quality of life was estimated using the EQ-5D-5L and the first developed experienced-based time-trade-off value set for Sweden to calculate the EQ-5D-5L index scores. EQ-5D-3L index scores were also estimated based on a UK hypothetical value set via a crosswalk method. Ordinary least squares regression models were used to analyse the association between quality of life and potential influencing factors. Results: For the 34,254 patients evaluated, mean EQ-5D-5L index score was 0.792 (SD 0.126). Stratifications showed that the index score varied across different levels of pain severity. Increased pain severity and use of pain-relieving medications remained significantly associated with a lower quality of life index score when controlled for potential confounders. The mean EQ-5D-3L index score was 0.605 (SD 0.192). Conclusions: This large population-based study from Sweden highlights the substantial impact of osteoarthritis on quality of life amongst different patient groups and that currently available treatment options for osteoarthritis pain do not appropriately address the needs for many osteoarthritis patients. [ABSTRACT FROM AUTHOR]

Objectives: Osteoarthritis (OA) is one of the leading causes of disability worldwide. Pain is the most important symptom in OA, driving medical care, disability, reduced functionality, and decreased quality of life. The objective of this study was to describe prescription patterns of difficult-to-treat OA and explore possible predictors of unmet pain relief in Nordic patients. Methods: This observational cohort study included patients with a confirmed diagnosis of OA (index date) in specialty care in Sweden, Norway, Finland and Denmark between 1 January 2011 and 31 December 2012 who were followed for up to 5 years. Four subgroups were pre-defined to characterize difficult-to-treat OA: (1) ≥2 chronic comorbidities in the 3-year pre-index period; (2) top 10% of healthcare resource users, 1-year post-index; (3) ≥3 types of prescription pain medications during pre-index period to first year post-index, with ≥30 days between types; (4) having a contraindication to a nonsteroidal anti-inflammatory drug (NSAID). Patient characteristics, prescription patterns and predictors of unmet pain relief (defined as persistent opioid use, using several types of opioids or long-term NSAID use) were analyzed. Results: We identified 288,174 OA patients and the average age was 63.5 years at time of diagnosis and 58% of them were female. After 5 years, 35-50% of the patients defined as 'difficult-to-treat' had ≥1 prescription of opioids, compared to 20-25% of all OA patients (p-value <0.05). Comorbidities and disability pension were strong predictors of unmet pain relief (p-value <0.001). Conclusions: This study shows a substantial use of pain medications (NSAID and opioids) in difficult-to-treat OA patients. These findings suggest that pain may be inadequately managed in a considerable number of patients with OA, particularly those with contraindications to an NSAID. A high comorbid and socioeconomic burden are relevant risk factors among patients who continue to use opioids for a long period of time. [ABSTRACT FROM AUTHOR]

Abstract Background The Transient Receptor Potential (TRP) ion channel TRPA1 is a key player in pain pathways. Irritant chemicals activate ion channel TRPA1 via covalent modification of N-terminal cysteines. We and others have shown that 15-Deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2) similarly activates TRPA1 and causes channel-dependent nociception. Paradoxically, 15d-PGJ2 can also be anti-nociceptive in several pain models. Here we hypothesized that activation and subsequent desensitization of TRPA1 in dorsal root ganglion (DRG) neurons underlies the anti-nociceptive property of 15d-PGJ2. To investigate this, we utilized a battery of behavioral assays and intracellular Ca2+ imaging in DRG neurons to test if pre-treatment with 15d-PGJ2 inhibited TRPA1 to subsequent stimulation. Results Intraplantar pre-injection of 15d-PGJ2, in contrast to mustard oil (AITC), attenuated acute nocifensive responses to subsequent injections of 15d-PGJ2 and AITC, but not capsaicin (CAP). Intraplantar 15d-PGJ2—administered after the induction of inflammation—reduced mechanical hypersensitivity in the Complete Freund’s Adjuvant (CFA) model for up to 2 h post-injection. The 15d-PGJ2-mediated reduction in mechanical hypersensitivity is dependent on TRPA1, as this effect was absent in TRPA1 knockout mice. Ca2+ imaging studies of DRG neurons demonstrated that 15d-PGJ2 pre-exposure reduced the magnitude and number of neuronal responses to AITC, but not CAP. AITC responses were not reduced when neurons were pre-exposed to 15d-PGJ2 combined with HC-030031 (TRPA1 antagonist), demonstrating that inhibitory effects of 15d-PGJ2 depend on TRPA1 activation. Single daily doses of 15d-PGJ2, administered during the course of 4 days in the CFA model, effectively reversed mechanical hypersensitivity without apparent tolerance or toxicity. Conclusions Taken together, our data support the hypothesis that 15d-PGJ2 induces activation followed by persistent inhibition of TRPA1 channels in DRG sensory neurons in vitro and in vivo. Moreover, we demonstrate novel evidence that 15d-PGJ2 is analgesic in mouse models of pain via a TRPA1-dependent mechanism. Collectively, our studies support that TRPA1 agonists may be useful as pain therapeutics.

Objective: To describe utilization patterns, negative clinical outcomes and economic burden of patients diagnosed with osteoarthritis (OA) of the hip and/or knee who received a prescription for tramadol or non-tramadol opioids vs. non-opioid drugs., Methods: Optum Healthcare Solutions, Inc. commercial claims data were used (1/2012--3/2017). Adults with ≥2 diagnoses of OA of the hip and/or knee, and ≥30 days supply of pain medications were identified during the three-year period from the date of first prescription (index date) after the first OA diagnosis. Drug utilization statistics in the follow-up period were summarized by initial treatment (i.e. tramadol, non-tramadol opioids, non-opioid drugs). Opioid initiators were matched to those initiated on non-opioid treatments using a propensity score model accounting for baseline characteristics. Matched pairs analysis compared outcomes for these cohorts., Results: Of 62,715 total patients, 15,270 (24.3%) initiated treatment with opioids, including 3,513 (5.6%) on tramadol and 11,757 (18.7%) on non-tramadol opioids. Opioid initiators had more comorbidities, higher baseline healthcare costs, and were more likely to have OA of the hip. Among non-opioid initiators, 27.5% switched to tramadol and 63% switched to non-tramadol opioids. Among tramadol initiators, 71% switched to non-tramadol opioids. Patients initiated on opioids had 20.4% ( p  < .01) higher all-cause healthcare costs and higher percentages experiencing multiple negative clinical outcomes (all p  < .01) compared to matched controls., Conclusions: Most patients with OA of the hip and/or knee either initiate on or switch to opioids for long-term management of OA-related pain despite known risks. This highlights the need for new treatments that delay or prevent use of opioids.