The CNIC-polypill (acetylsalicylic acid, atorvastatin, and ramipril), an effective and cost-saving secondary prevention strategy compared with other therapeutic options in patients with ischaemic heart disease.

Aims: The retrospective NEPTUNO study evaluated the effectiveness of the Centro Nacional de Investigaciones Cardiovasculares (CNIC)-polypill (including acetylsalicylic acid, ramipril, and atorvastatin) vs. other therapeutic approaches in secondary prevention for cardiovascular (CV) disease. In this substudy, the focus was on the subgroup of patients with ischaemic heart disease (IHD). Methods and results: Patients on four strategies: CNIC-polypill, its monocomponents as loose medications, equipotent medications, and other therapies. The primary endpoint was the incidence of recurrent major adverse CV events (MACEs) after 2 years. After matching, 1080 patients were included in each cohort. The CNIC-polypill cohort had a significantly lower incidence of recurrent MACE compared with monocomponents, equipotent drugs, and other therapies cohorts (16.1 vs. 24, 24.4, and 24.3%, respectively; P < 0.001). The hazard ratios (HRs) for recurrent MACE were higher in monocomponents (HR = 1.12; P = 0.042), equipotent drugs (HR = 1.14; P = 0.031), and other therapies cohorts (HR = 1.17; P = 0.016) compared with the CNIC-polypill, with a number needed to treat of 12 patients to prevent a MACE. The CNIC-polypill demonstrated a greater reduction in LDL cholesterol (LDL-c; -56.1 vs. -43.6, -33.3, and -33.2% in the monocomponents, equipotent drugs, and other therapies, respectively; P < 0.001) and systolic blood pressure (-13.7 vs. -11.5, -10.6, and -9.1% in the CNIC-polypill, monocomponents, equipotent drugs, and other therapies, respectively; P < 0.001) compared with other cohorts. The CNIC-polypill intervention was less costly and more effective than any other therapeutic option, with €2317-€2407 cost savings per event prevented. Conclusion: In IHD, the CNIC-polypill exemplifies a guideline-recommended secondary prevention treatment linked to better outcomes and cost saving compared with other therapeutic options.

Healthcare resource use and costs reduction with aripiprazole once-monthly in schizophrenia: AMBITION, a real-world study.

Objective: This study aims to compare the hospitalization rate in individuals with schizophrenia who started their treatment with aripiprazole once monthly (AOM400) or atypical oral antipsychotics (OA) in Spain. Methods: This is an observational and retrospective study based on the electronic medical records from the BIG-PAC database. The study population consisted of individuals diagnosed with schizophrenia who initiated their treatment with AOM400 (AOM cohort) or atypical OA (OA cohort) from 01/01/2017 to 31/12/2019. A 1:1 propensity score matching (PSM) procedure was conducted to match individuals of both cohorts. The number and duration of hospitalizations, persistence to treatment, healthcare resources use, and costs were analyzed after 12 months. Results: After the PSM, 1,017 individuals were included in each cohort [age: 41.4 years (SD: 10.6); males: 54.6%]. During the follow-up period, the AOM cohort had a 40% lower risk of hospitalization than the OA group [HR: 0.60 (95% confidence interval, CI: 0.49-0.74)]. The median time to the first hospitalization was longer in individuals with AOM400 compared to those with OA (197 days compared to 174 days; p < 0.004), whereas hospital admissions were shorter (AOM400: 6 compared to OA: 11 days; p < 0.001). After 12 months, individuals receiving AOM400 were more persistent than those with OA (64.9% compared to 53.7%; p < 0.001). The OA cohort required more healthcare resources, mainly visits to primary care physicians, specialists, and emergency rooms than those receiving AOM400 (p ≤ 0.005 in all comparisons). AOM400 reduced the costs of hospitalizations, and emergency room, specialist and primary care visits by 50.4, 36.7, 16.1, and 10.9%, respectively, in comparison to the treatment with atypical OA. AOM400 led to annual cost savings of €1,717.9 per individual, from the societal perspective. Conclusion: Aripiprazole once monthly reduces the number and duration of hospitalizations, together with the treatment costs of schizophrenia, as it reduces the use of healthcare resources and productivity losses in these individuals.

Economic Burden Associated with the Treatment with a Cardiovascular Polypill in Secondary Prevention in Spain: Cost-Effectiveness Results of the NEPTUNO Study.

Purpose: The aim of this study was to estimate health-care resources utilization, costs and cost-effectiveness associated with the treatment with CNIC-Polypill as secondary prevention of atherosclerotic cardiovascular disease (ASCVD) compared to other treatments, in clinical practice in Spain. Patients and Methods: An observational, retrospective study was performed using medical records (economic results [healthcare perspective], NEPTUNO-study; BIG-PAC-database) of patients who initiated secondary prevention between 2015 and 2018. Patients were followed up to 2 years (maximum). Four cohorts were balanced with a propensity-score-matching (PSM): 1) CNIC-Polypill (aspirin+atorvastatin+ramipril), 2) Monocomponents (same separate drugs), 3) Equipotent (equipotent drugs) and 4) Other therapies ([OT], other cardiovascular drugs). Incidence of cardiovascular events, health-care resources utilization and healthcare and non-healthcare costs (2020 Euros) were compared. Incremental cost-effectiveness ratios per cardiovascular event avoided were estimated. Results: After PSM, 1614 patients were recruited in each study cohort. The accumulated incidence of cardiovascular events during the 24-month follow-up was lower in the CNIC-Polypill cohort vs the other cohorts (19.8% vs Monocomponents: 23.3%, Equipotent: 25.5% and OT: 26.8%; p<0.01). During the follow-up period, the CNIC-Polypill cohort also reduced the health-care resources utilization per patient compared to the other cohorts, particularly primary care visits (16.6 vs Monocomponents: 18.7, Equipotent: 18.9 and OT: 21.0; p<0.001) and hospitalization days (2.3 vs Monocomponents: 3.4, Equipotent: 3.7 and OT: 4.0; p<0.001). The treatment cost in the CNIC-Polypill cohort was lower than that in the other cohorts (€4668 vs Monocomponents: €5587; Equipotent: €5682 and OT: €6016; p<0.001) (Difference: -€919, -€1014 and -€1348, respectively). Due to the reduction of cardiovascular events and costs, the CNIC-Polypill is a dominant alternative compared to the other treatments. Conclusion: CNIC-Polypill reduces recurrent major cardiovascular events and costs, being a cost-saving strategy as secondary prevention of ASCVD.

Impact of COPD Exacerbations and Burden of Disease in Spain: AVOIDEX Study.

Purpose: Chronic obstructive pulmonary disease (COPD) is characterized by high morbidity and mortality, with a considerable consumption of healthcare resources (HRU). This study aims to obtain real world evidence regarding the consequences of COPD exacerbations and to provide updated data on the burden of this disease and its treatment. Patients and Methods: A retrospective study in seven Spanish regions was conducted among COPD patients diagnosed between 1/01/2010 and 31/12/2017. The index date was the diagnosis of COPD and patients were followed until lost to follow-up, death or end of the study, whichever occurred first. Patients were classified by patient pattern (incident or prevalent), type and severity of exacerbations, and treatments prescribed. Demographic and clinical characteristics were evaluated, together with the incidence of exacerbations, comorbidities, and the use of HRU, during the baseline (12 months before the index date) and the follow-up periods by incident/prevalent and treatment prescribed. Mortality rate was also measured. Results: The study included 34,557 patients with a mean age of 70 years (standard deviation: 12). The most frequent comorbidities were diabetes, osteoporosis, and anxiety. Most patients received inhaled corticosteroids (ICS) with long-acting beta agonists (LABA), or long-acting muscarinic agonists (LAMA), followed by LABA with LAMA. Incident patients (N=8229; 23.8%) had fewer exacerbations than prevalent patients (N=26328; 76.2%), 0.3 vs 1.2 exacerbations per 100 patient-years. All treatment patterns present a substantial disease burden, which seems to increase with the evolution of the disease (ie moving from initial treatments to combination therapies). The overall mortality rate was 40.2 deaths/1000 patient-years. General practitioner visits and tests were the HRU most frequently required. The frequency and severity of exacerbations positively correlated with the use of HRU. Conclusion: Despite receiving treatment, patients with COPD suffer a considerable burden mainly due to exacerbations and comorbidities, which require a substantial use of HRU.

Disease burden and costs for patients with hip and knee osteoarthritis and chronic moderate-to-severe refractory pain on treatment with strong opioids in Spain.

INTRODUCTION AND OBJECTIVES: To determine the disease burden and costs in patients with hip or knee OA and chronic moderate-to-severe refractory pain, receiving strong opioids in Spain. MATERIALS AND METHODS: This was a 36-month longitudinal secondary analysis of the real-word OPIOIDS study. Patients aged ≥18 years with hip or knee OA and chronic moderate-to-severe refractory pain receiving strong opioids were considered. The disease burden included analgesia assessments (NRS scale), cognitive functioning (MMSE scale), basic activities of daily living (Barthel index), and comorbidities (severity and frequency). Costs due to the use of healthcare resources and productivity loss were estimated. RESULTS: 2832 patients were analyzed; age was 72.0 years (SD=14.3), 76.8% were women. Patients had mainly been treated with fentanyl (n=979; 37.6%), tapentadol (n=625; 24.0%), oxycodone (n=572; 22.0%), and buprenorphine (n=425; 16.3%). Pain intensity decreased by 1 point (13.7%), with a 2.6-point decline in the cognitive scale (14.3%, with a 5.3%-increase in patients with cognitive deficit) over a mean treatment period of 384.6 days (SD: 378.8). Barthel scores decreased significantly yielding to a slightly increase in proportion of patients with severe-to-total dependency; 1.2%-2.9%. In the first year of treatment, average healthcare costs were €2013/patient, whereas the average productivity loss cost was €12,227/working-active patient. DISCUSSION AND CONCLUSIONS: Strong opioids resulted in high healthcare costs with a limited reduction in pain, an increase in cognitive deficit, and a slight increase of patients with severe to total dependency over 36 months of treatment.

Clinical and Economic Impact of Long-Term Inhaled Corticosteroid Withdrawal in Patients with Chronic Obstructive Pulmonary Disease Treated with Triple Therapy in Spain.

Purpose: To determine the clinical and economic impact of inhaled corticosteroid (ICS) withdrawal in Spanish patients with COPD receiving triple therapy (TT) with ICS, long-acting ß2-agonist (LABA), and long-acting muscarinic antagonist (LAMA). Patients and Methods: This was an observational, retrospective study of BIG-PAC database medical records. Patients aged ≥40 years receiving TT from 2016 to 2018 were followed for 1 year. Two cohorts were identified: patients continuing TT (ICS+LABA+LAMA), and patients receiving TT with ICS withdrawn (LABA+LAMA). Variables included medication, exacerbations (moderate and severe), pneumonia, mortality, health resource use (HRU), and cost per patient/year. Cohorts were compared using propensity score matching (PSM). Multivariate statistical analysis using analysis of covariance and Cox proportional risks was conducted. Results: Of 6541 patients included, 5740 (87.8%) continued TT and 801 (12.2%) had ICS withdrawn. Patients with ICS withdrawal were younger, had lower disease burden, higher ICS doses, and more exacerbations compared with those continuing ICS. PSM matched 795 patients in each cohort. Mean age was 68.5 years (SD: 11.2), 69.9% were male, and mean Charlson index was 2.0. Patients with ICS withdrawal had more total exacerbations in the 12 months following withdrawal compared with patients continuing TT (36.6% vs 31.4%; p=0.030). No significant differences were found for pneumonia (3.3% vs 3.6%; p=0.583) and mortality (9.9% vs 7.5%; p=0.092). Median time to first exacerbation was shorter in patients with ICS withdrawal compared with those continuing ICS (HR: 0.69, 95% CI: 0.57-0.83; p<0.001). Mean health cost per patient/year among patients with ICS withdrawal was higher than those continuing TT (€2993 vs €2130; p<0.001). Conclusion: ICS withdrawal in patients with COPD receiving TT was associated with increased exacerbations, HRU, and costs compared with continuing TT, with health and economic impacts on patients and the Spanish National Healthcare System, respectively. Pneumonia and mortality rates were similar between groups.

Persistence, use of resources and costs in patients under migraine preventive treatment: the PERSEC study.

BACKGROUND: Migraine represents a serious burden for national health systems. However, preventive treatment is not optimally applied to reduce the severity and frequency of headache attacks and the related expenses. Our aim was to assess the persistence to traditional migraine prophylaxis available in Spain and its relationship with the healthcare resource use (HRU) and costs. METHODS: Retrospective observational study with retrospective cohort design of individuals with migraine treated with oral preventive medication for the first time from 01/01/2016 to 30/06/2018. One-year follow-up information was retrieved from the Big-Pac™ database. According to their one-year persistence to oral prophylaxis, two study groups were created and describe regarding HRU and healthcare direct and indirect costs using 95% confidence intervals (CI). The analysis of covariance (ANCOVA) was performed as a sensitivity analysis. Patients were considered persistent if they continued on preventive treatment until the end of the study or switched medications within 60 days or less since the last prescription. Non-persistent were those who permanently discontinued or re-initiated a treatment after 60 days. RESULTS: Seven thousand eight hundred sixty-six patients started preventive treatment (mean age (SD) 48.2 (14.8) and 80.4% women), of whom 2,545 (32.4%) were persistent for 6 months and 2,390 (30.4%) for 12 months. Most used first-line preventive treatments were antidepressants (3,642; 46.3%) followed by antiepileptics (1,738; 22.1%) and beta-blockers (1,399; 17.8%). The acute treatments prescribed concomitantly with preventives were NSAIDs (4,530; 57.6%), followed by triptans (2,217; 28.2%). First-time preventive treatment prescribers were mostly primary care physicians (6,044; 76.8%) followed by neurologists (1,221; 15.5%). Non-persistent patients required a higher number of primary care visits (mean difference (95%CI): 3.0 (2.6;3.4)) and days of sick leave (2.7 (0.8;4.5)) than the persistent ones. The mean annual expenditure was €622 (415; 829) higher in patients who not persisted on migraine prophylactic treatment. CONCLUSIONS: In this study, we observed a high discontinuation rate for migraine prophylaxis which is related to an increase in HRU and costs for non-persistent patients. These results suggest that the treatment adherence implies not only a clinical benefit but also a reduction in HRU and costs.

Achieving Lower LDL-C Levels After a Recent Myocardial Infarction Might Be Associated with Lower Healthcare Resource Use and Costs in Spain.

INTRODUCTION: There is little evidence on the relationship between achieved low-density lipoprotein cholesterol (LDL-C) levels and costs in patients on lipid-lowering therapy (LLT). We described healthcare resource use and costs (direct and indirect) by achieved LDL-C in patients receiving LLT after a recent myocardial infarction (MI) in Spain. METHODS: This was a retrospective observational study of anonymized electronic medical records from seven regions in Spain (BIG-PAC® database; n = 1.9 million). Eligible patients were adults (≥ 18 years) hospitalized for an MI between January 2015 and December 2017, treated with a statin and/or ezetimibe, and having recorded LDL-C values at baseline and during follow-up. Healthcare resource use and direct and indirect costs (in 2018, €) were described by achieved LDL-C levels during a follow-up of 18 months. RESULTS: Of 6025 patients (mean age, 69.7 years; 77% male), only 11% achieved LDL-C goals as defined in the 2016 ESC/EAS guidelines (< 70 mg/dL), and just 1% reached the lower target (< 55 mg/dL) in the current 2019 guidelines. Achieving lower LDL-C levels translated to lower healthcare resource use and costs. Mean total (direct and indirect) costs ranged from €5044 for patients with LDL-C < 55 mg/dL to €7567 for patients with LDL-C ≥ 130 mg/dL. CONCLUSION: Very few patients achieved recommended LDL-C goals despite using LLT. Achieving lower LDL-C levels after an MI might be associated with lower healthcare resource use and costs. Use of more intensive LLT, leading to greater reductions in LDL-C, could therefore be beneficial both from a clinical and an economic perspective.

Sick Leave and Costs in Active Workers with Chronic Osteoarthritis Pain in Spain: Outcomes of the OPIOIDS Real World Study.

Purpose: To estimate the number of sick leave days and productivity costs in active workers with osteoarthritis (OA) who initiated opioid treatment for moderate/severe chronic pain in clinical practice in Spain. Patients and Methods: This is a secondary analysis of the longitudinal, retrospective OPIOIDS study, using electronic medical records (EMR) of patients aged ≥18 years, who started an opioid treatment for moderate/severe chronic OA pain between 2010 and 2015 after treatment failure with ≥1 first-line drugs (acetaminophen, metamizole and/or nonsteroidal anti-inflammatory drugs [NSAIDs]). The number of days of sick leave and productivity costs were analyzed during a follow-up period of 36 months. Results: A total of 5089 patients with moderate/severe chronic OA pain, aged 56.8 years (standard deviation [SD]: 4.6) (56.6% were female), were analyzed: 73.3% of them started a treatment with weak opioids and 26.7% of them were treated with strong opioids. At 36 months, adherence was 21.0% (strong opioids: 15.4%; weak opioids: 23.0%; p<0.001), and 77% of patients had at least one sick leave related with chronic OA pain, with an average of 93 days off work in all working patients (120.5 days in patients with sick leaves). Besides, 16.9% of the study population had sick leave periods that lasted at least 6 months. Pain reduction was modest (-1.2 points; -4.0%, p<0.001). The cost of sick leave was €2594 patient/year, and factors such as older age (ß=0.043), female sex (ß=0.036), comorbidities (ß=0.035) and strong opioid use (ß=0.031) were associated with higher productivity costs (p<0.05 in all associations). Conclusion: Active workers who started opioid treatment for moderate/severe chronic OA pain showed an increased frequency of sick leave and productivity cost, with a modest effect on pain relief. Older age, female sex, comorbidities, and strong opioids were associated with higher costs for society.

All-cause community acquired pneumonia cost by age and risk in real-world conditions of care in Spain.

BACKGROUND: Economic burden of community-acquired pneumonia (CAP) is recognized. Few studies have documented such burden in adults stratified by age, risk status, and by care setting. Spanish data available is scarce. METHOD: A retrospective, multicenter study in seven regions of Spain (2017-2019) was conducted. Patients ≥18 years with a primary all-cause CAP episode diagnosis were identified. Episode-level variables included risk-stratum based on presence of an immunocompromising/chronic condition, age, number and length of hospitalized and outpatient episodes, and CAP-related healthcare costs/sick leaves were included. RESULTS: 7,108 episodes [mean age (SD): 59.2 (19.6), 50.42% male, 31.0% hospitalized] were analyzed. Low-risk group accounted for 47.7% of all CAP episodes, 31.5% moderate-risk and 20.8% high-risk. Pneumococcus was identified in 42.2% of cases. Mean CAP episode length was 22.9 days for hospitalized and 13.7 days for outpatient episode. Total healthcare cost for episode was higher in inpatient vs. outpatient: €3,955 vs. €511, p < 0.001, with higher sick leave cost (€3,281 vs. €2,632, p < 0.001), respectively. CONCLUSION: CAP required hospitalization cost is high regardless of age or comorbidities for the Spanish NHS. Given that almost half of the patients in this study did not have traditional risk factors for CAP, better preventative strategies should seriously be considered.

Clinical and economic consequences of ozenoxacin vs. other topical antibiotics for the treatment of impetigo: a real-life study in Spain.

Background: Impetigo is a common dermatological paediatric infection that can be treated with topical antibiotics: the common are mupirocin (MUP), fusidic acid (FA) and, most recently, ozenoxacin (OZ). Aim: This study assesses the clinical and economic consequences of the use of OZ vs. MUP and vs. FA for the treatment of impetigo in routine clinical practice in Spain. Methods: This is a retrospective observational study using real-life data from electronic medical records of patients with impetigo who started treatment with OZ, MUP or FA (maximum follow-up: 3 months; n = 10,974). We compared treatment duration, comorbidities, use of systemic medication, complications, utilization of resources and associated costs across treatments (p<0.05). Cost-effectiveness of OZ was assessed from a social perspective. Complication rates and treatment duration were the effectiveness measures. Results: Mean age was 12.6 (standard deviation [SD]: 16.6) years; 48.6% were male; treatment: 9.3% (OZ), 56.4% (MUP), 34.5% (FA). The percentage of patients ending treatment after 2 weeks was 87.6% (OZ) vs. 83.2% (MUP) vs. 82.4% (FA); p<0.001; complication rates were 1.8% (OZ), 3.3% (MUP) and 3.2% (FA), p<0.001; mean costs were €158 (OZ), €265 (MUP) and €287 (FA), p<0.001. Conclusions: OZ is a cost-effective and dominant alternative for the treatment of impetigo.

Economic impact of treatment-resistant depression: A retrospective observational study.

BACKGROUND: To determine the incidence of Treatment-Resistant Depression (TRD) in Spain and to estimate its economic burden, using real world data. METHODS: A retrospective, observational-study was carried out using data from the BIG-PAC database®. Patients aged ≥18 years with a diagnosis of major depressive-disorder (MDD) who initiated a new antidepressant treatment in 2015-2017 were included. The patients were classified as TRD and non-TRD. Patients were classified as TRD if they had, during the first year of antidepressant treatment: a) failure with ≥2 antidepressants including the prescription of ≥3 antidepressants (N06A) or ≥2 antidepressant and ≥1 antipsychotic (N05A; including lithium) b) antidepressants administered for ≥ 4 weeks each, and c) the time between the end of one treatment and the initiation of the next was ≤ 90 days. Inherent limitations of data collection from databases should also be considered in this analysis (e.g., lack of information about adherence to treatment). Follow-up period: 18 months. The incidence rate was calculated as the number of TRD patients per 1,000 persons-year divided by the population attended. OUTCOMES: direct healthcare and indirect costs. Two sensitivity analyses were performed varying the index date and the period used to define TRD patients (6 vs.12 months). RESULTS: 21,630 patients with MDD aged ≥ 18 years (mean age: 53.2 years; female: 67.2%) were analyzed, of whom 3,559 met TRD criteria, yielding a 3-year cumulative incidence of 16.5% (95%CI: 16%-17%) among MDD patients. The annual population incidence rate of TRD in 2015-2017, was 0.59, 1.02 and 1.18/1,000 person-years, respectively (mean: 0.93/1,000 person-year). Overall, mean total costs per MDD patient were €4,147.9, being higher for TRD than for non-TRD patients (€6,096 vs. €3,846; p<0.001): a) direct costs (€1,341 vs. €624; p<0.001), b) lost productivity (€1,274 vs. €821; p<0.001) and c) permanent disability (€3,481 vs. €2,401; p<0.001, adjusted). Sensitivity analyses showed no differences with the reported results. CONCLUSIONS: The population based TRD incidence in Spain was similar to recent data from other European countries. TRD is associated with greater resource use and higher costs compared with non-TRD patients.

Future projections of opioid use and cost in patients with chronic osteoarthritis pain in Spain.

BACKGROUND: Opioids are widely used in moderate-to-severe chronic pain which is non-responsive to standard analgesics. Prescriptions have increased in Europe in the last decade, although remain lower than in USA. This work projected the future utilization and costs of opioids in chronic osteoarthritis (OA) pain in the Spanish National Health System (NHS). METHODS: An epidemiological model was populated with the opioid dispensing trends from 2010 to 2019 using Spanish Medicinal Agency rates of opioid utilization in subjects over 18 years of age and the real-world OPIOIDS study to estimate chronic-OA-pain patients receiving opioids. A best-fitted trend analysis model was applied estimating the likely number of DHD (defined daily dose/1000 inhabitants per day) to calculate projected opioid utilization and costs for the period 2020-2029. RESULTS: In 2010, an estimated 5.67 DHD were dispensed for the equivalent of 217,076 chronic OA pain patients per day [1.99 DHD, 76,084 refractory to non-steroidal anti-inflammatory drugs (NSAIDs)]. From these trends and OA prevalence, the projected number of DHDs is expected to increase more than threefold to 17.98 DHDs by the year 2029 for the equivalent of 727,356 chronic OA pain patients per day (8.18 DHD, 330,720 refractory to NSAIDs); 41.8% on strong opioids. The estimated cost was €116.9m (€45.0m in NSAID-refractory OA) in 2010 rising by 222% to €376.1m (€199.7m refractory to NSAIDs) by 2029. CONCLUSION: Chronic-OA-pain-related opioid dispensing and costs to the NHS are set to increase more than threefold from 2010 to 2029 in Spain. Using opioids for OA pain is concerning given disease chronicity and other related costs not computed in these projections. PLAIN LANGUAGE SUMMARY: • Opioids are widely used in chronic pain which is non-responsive to standard analgesics. Prescriptions have increased in Europe, although remain lower than in USA. Osteoarthritis (OA) is a degenerative joint disease usually accompanied by pain. Despite not recommended, opioids use in OA have been expanded because this health condition is increasing with ageing and, also, because physicians both primary and specialist boosted their use.• This study aimed to quantify the current burden of opioids used for chronic moderate-to-severe OA pain by estimating the number of defined daily doses per 1000 inhabitants per day (DHD) and associated costs, and to forecast the likely burden on the National Health System (NHS) in Spain for the years 2020-2029.• In 2010, an estimated 5.67 DHDs were dispensed for the equivalent of 217,076 chronic OA pain patients per day. From these trends, the projected number of DHDs is expected to increase more than threefold to 17.98 DHDs by the year 2029 for the equivalent of 727,356 chronic OA pain patients per day; 41.8% on strong opioids. The estimated cost was €116.9m in 2010 rising by 222% to €376.1m by 2029.• Chronic OA-pain-related opioid dispensing and costs to the NHS are set to increase substantially (threefold to more than fourfold) from 2010 to 2029 in Spain. Thus, using opioids for OA pain is concerning given disease chronicity, aging population and other related costs not computed in these projections. Our findings can inform payors and clinicians about ongoing discussions on appropriate analgesic management for longer-term OA pain, including resource requirements at a national level. Clinicians who prescribe opioids for OA pain should consider the potential implications of side effects such as sedation, cognitive deterioration, incremental need of caregivers, particularly in older people, and carefully consider the risk-benefit balance.

Epidemiology and costs of depressive disorder in Spain: the EPICO study.

Depressive Disorders are the most common psychiatric diagnoses in the general population. To estimate the frequency, costs associated with Depressive Disorders in usual clinical practice, and in the whole Spanish population, a longitudinal, retrospective, observational study was carried out using data from the BIG-PAC database®. Study population: all patients aged ≥ 18 years with a diagnosis of a Depressive Disorder in 2015-2017. Prevalence was computed as the proportion of Depressive Disorder cases in the adult general population, and the incidence rate, as the number of new Depressive Disorder cases diagnosed per 1,000 person-years in the population using health services, during 2015-2017. We collected demographic variables, comorbidity, direct health costs, and indirect costs (temporary and permanent disability). Health costs related to Depressive Disorders were estimated according to the annual resource use rate (resource/patient/year). Indirect costs were calculated according to the human capital method. Using the study data and information from the Spanish National Institute of Statistics, we estimated the cost of Depressive Disorders corresponding to the Spanish adult population, including premature mortality. 69,217 Depressive Disorder patients aged ≥ 18 years who met the inclusion/exclusion criteria were studied (mean age: 56.8 years; female: 71.4%). Prevalence of Depressive Disorders in the general population was 4.73% (95% CI: 4.70-4.76%). Annual incidence rates (2015-2017) were 7.12, 7.35 and 8.02 per 1,000 person-years, respectively. Total costs observed in our Depressive Disorder patients were € 223.9 million (corresponding to a mean of € 3,235.3; mean/patient/year), of which, 18.4% were direct health care costs and 81.6%, non-health indirect costs (18% temporary occupational disability, 63.6% permanent disability). Considering also the cost of premature death, the mean cost per patient/year was € 3,402 and the estimated societal costs of Depressive Disorders in Spain were € 6,145 million. The prevalence and incidence of Depressive Disorders are consistent with other series reviewed. Resource use and total costs (especially non-health costs) were high.

Disease Burden and Costs in Moderate-to-Severe Chronic Osteoarthritis Pain Refractory to Standard of Care: Ancillary Analysis of the OPIOIDS Real-World Study.

INTRODUCTION: To determine the disease burden and costs in moderate-to-severe chronic osteoarthritis (OA) pain refractory to standard-of-care treatment in the Spanish National Health System (NHS). METHODS: Ancillary analysis of the OPIOIDS real-world, non-interventional, retrospective, 4-year longitudinal study including patients aged at least 18 years with moderate-to-severe chronic OA pain refractory to standard-of-care with sequential NSAIDs plus opioids. Burden assessment included measurement of analgesia, cognitive functioning, basic activities of daily living, severity and frequency of comorbidities, and all-cause mortality. Costs accounted for healthcare resource utilization and related costs (year 2018). RESULTS: Records of 13,317 patients were analyzed; 68.9 (14.7) years old, 71.3% (70.5-72.1%) women, 58.1% refractory to NSAID plus weak opioid and 41.9% to NSAID plus strong opioid, accounting for 10.7% (10.5-10.8%) of patients with chronic OA pain. Mean number of comorbidities was 2.9 (1.8) and its severity was 1.8 (1.7). Pain decreased by 0.9 points (12.2%) and cognitive declined by 2.3 points (9.1%, with 4.3% more patients with cognitive deficit) and dependency worsened by 0.4 points (0.5%, with 2.3% more patients with severe-to-total dependence) over a mean treatment period of 188.6 (185.4-191.8) days on NSAIDs followed by 400.6 (393.7-407.5) days on opioids. The adjusted mortality rate was higher in patients with OA taking NSAID plus strong opioids; hazard ratio 1.44 (1.26-1.65; p < 0.001). The 4-year healthcare cost was €7350/patient (€7193-7507 or €1838/year) and was higher in those taking strong versus weak opioids; €9886 (€9608-10,164, €2472/year) vs. €5519 (€5349-5689, €1380/year), p < 0.001. Analgesia cost (16.0% of total cost, 70.2% opioids) was higher with strong versus weak opioids, 19.6% vs. 11.3%, p < 0.001. CONCLUSIONS: In routine clinical practice in Spain, patients with moderate-to-severe chronic OA pain refractory to standard analgesic treatment with NSAIDs plus opioids reported modest reductions in pain, while presenting a considerable burden of comorbidities, cognitive impairment, and dependency. Healthcare costs significantly increased for the NHS particularly with NSAIDs plus strong opioids.

Overall clinical and economic impact of non-alcoholic fatty liver disease.

OBJECTIVES: to establish the clinical and economic consequences (resource utilization and healthcare costs) of non-alcoholic fatty liver in the setting of the usual clinical practice in Spain. PATIENTS AND METHODS: an observational, retrospective study was performed based on a review of the medical records of adult patients ≥ 18 years of age who sought medical care from 2017 to 2018. Patients were categorized into two groups according to fibrosis stage (estimation method: FIB-4): a) F0-F2; and b) F3-F4 (advanced fibrosis). Follow-up lasted one year. Primary endpoints included comorbidity, concomitant medication, resource utilization and costs. Results were analyzed using a multivariate approach with p < 0.05. RESULTS: a total of 8,151 patients were recruited with a mean age of 61.1 years and 51.5 % were male. By group: a) mild fibrosis n = 7,127, 87.4 %; and b) advanced fibrosis n = 1,024, 12.6 % (6.8 % with liver cirrhosis). The most common comorbidities included 63 % dyslipidemia, 52 % obesity, 52 % hypertension and 35 % diabetes. The average number of drugs used was 2.1 per patient. Patients with advanced fibrosis (F3-F4) had a higher average number of concomitant medications (2.5 vs 2.1; p < 0.001) and a higher AST/ALT ratio (1.1 vs 0.8; p < 0.001). The average cost (patient-year) for subjects with advanced fibrosis, corrected for covariates, was higher (€1,812 vs €1,128, p < 0.001). Age, morbidity, concomitant medication, fibrosis stage and total costs were higher in patients with diabetes. CONCLUSIONS: patients with advanced fibrosis were associated with more comorbidity and concomitant medications, which resulted in higher healthcare costs for the National Health System.

Clinical and Economic Consequences of Inhaled Corticosteroid Doses and Particle Size in Triple Inhalation Therapy for COPD: Real-Life Study.

Objective: To determine the clinical and economic consequences of inhaled corticosteroid doses and particle size in patients on triple-inhalation therapy for COPD. Methods: Patients aged ≥40 years who initiated treatment with multi-inhaler triple-inhaled therapy between 1 January 2015 and 31 March were included and followed for 1 year. Patients were grouped according to inhaled corticosteroid (ICS) dose (low/medium/high) and particle size device (extrafine/non-extrafine particles). Outcome variables were moderate and severe exacerbations, pneumonia and healthcare resource use (HCRU) costs. A multivariate analysis was performed for model correction (p<0.05). Results: A total of 2185 patients (mean age 72.3 years, 82.9% male) were analysed. Of these, 849 (38.9%) patients received low-dose ICS, 612 medium-dose ICS (28.0%) and 724 (33.1%) high-dose ICS. Exacerbations occurred more frequently with increasing IC dose (low: 26.4%, medium: 28.7% and high: 30.4%; p=0.047), as did the proportion of pneumonia (3.4%, 4.2% and 6.9%, respectively (p=0.041)). The annual mean cost/unit was € 2383 for low dose, € 2401 for medium dose and € 2625 for high dose (p=0.024). Four hundred and sixty-two (31.6%) patients used an extrafine particle device and 999 (68.4%) a non-extrafine particle device: the proportion of exacerbations was 24.0% vs 30.4% (p=0.012), and the annual mean cost/unit was € 2090 vs € 2513, respectively (p<0.001). The number of exacerbations was directly correlated with FEV1 (ß= -0.157), age (ß=0.071), Charlson index (ß=0.050) and device type (extrafine: ß=0.049) (p<0.02). Conclusion: In patients with COPD receiving multi-inhaler triple therapy, higher ICS doses were not associated with a further reduction in exacerbations, whereas we found an increased risk of pneumonia. The use of inhaler devices delivering extrafine ICS particle was associated with a lower rate of exacerbations, resulting in lower overall HCRU costs.

Health outcomes and costs in patients with osteoarthritis and chronic pain treated with opioids in Spain: the OPIOIDS real-world study.

OBJECTIVE: The objective of this study was to analyze health outcomes, resource utilization, and costs in osteoarthritis patients with chronic nociceptive pain who began treatment with an opioid in real-world practice in Spain. METHODS: We designed a non-interventional, retrospective, longitudinal study with 36 months of follow-up using electronic medical records (EMRs) from primary care centers, of patients aged 18+ years who began a new treatment with an opioid drug in usual practice for chronic pain due to osteoarthritis. Health/non-health resource utilization and costs, treatment adherence, pain change, cognitive functioning, and dependence for basic activities of daily living (BADL) were assessed. RESULTS: A total of 38,539 EMRs [mean age (SD); 70.8 (14.3) years, 72.3% female; 53.3% hip/knee, 25.0% spine, and 21.7% other sites] were recruited. A total of 19.1% of patients remained on initial opioid at 36 months, without significant differences by osteoarthritis site (p = 0.125). Mean total adjusted cost was €17,915, with 27.7% corresponding to healthcare resources and 72.3% to lost productivity. Hospital admissions for osteoarthritis-related surgical interventions accounted for 15.8% of total healthcare cost. A slight mean pain reduction was observed: -1.3 points, -16.9%, p < 0.001, with increases in cognitive deficit (+3.3%, p < 0.001) and moderate to total dependence for BADL (+15.6%, p < 0.001) in a median duration of opioid use of 203 days (IQR: 89-696). CONCLUSIONS: In real-world practice in Spain, opioid use in osteoarthritis was high, but with low adherence. There were meaningful increases in resource use and costs for the National Health System. Pain reduction was modest, whereas cognitive impairment and dependence for BADL increased significantly.

Resource use and costs in patients with poorly controlled type 2 diabetes mellitus and obesity in routine clinical practice in Spain.

OBJECTIVE: To compare healthcare resource use (HRU) and annual costs in type 2 diabetes mellitus (T2DM) patients with poor glycaemic control and obesity versus good glycaemic control without obesity. METHODS: Observational retrospective study based on the analysis of electronic medical records from the BIG-PAC database, with one year of follow-up. T2DM patients aged ≥30 years who requested medical care during 2013 were included. Annual HRU and costs per patient were compared between a reference group (HbA1c ≥ 8%, BMI ≥30 kg/m2, receiving ≥2 oral antidiabetic drugs [OADs]) and a control group (HbA1c < 7% and BMI <30 kg/m2). Direct and indirect costs (lost productivity) were analysed. Cost comparisons across groups were made using the analysis of covariance (ANCOVA) for each cost component, with age, sex, time from diagnosis, Charlson comorbidity index, OAD number and sex by group interaction as covariates. RESULTS: During the follow-up, patients in the reference group (N = 2709) had a greater HRU than those in the control group (N = 5266), especially in the number of primary care (PC) visits (11.8 vs. 9.8; 95%CI: 11.5-12.1 vs. 9.6-10.0) and days of hospitalization (1.1 vs 0.6; 95%CI: 1.0-1.2 vs. 0.5-0.7). The main components of the total cost were hospital admissions (24.5%), productivity losses (16.3%), complementary tests (14.4%), PC visits (14.2%) and medication (13.6%) in the reference group and medication (19.6%), hospital admissions (18.7%) and PC visits (18.2%) in the control group. The corrected mean annual cost per patient was higher in the reference than in the control group: €1804 vs. €1309; p < .001. CONCLUSIONS: Poor glycaemic control and obesity in T2DM patients were associated with increased HRU and costs in routine clinical practice.

Real-life retrospective observational study to determine the prevalence and economic burden of severe asthma in Spain.

Objective: We determined the percentage of patients with severe asthma and exacerbations and evaluated the costs of the disease based on blood eosinophil counts.Methods: A retrospective observational study based on the review of medical records in Spain was carried out. Patients ≥18 years of age requiring care during the years 2014-2015; diagnosed with asthma with at least 2 years of continuous records (at least one year prior to the index date defined as the first asthma medication prescription and at least one year after the index date) were included. Study groups: eosinophil counts <300 cells/µl and ≥300 cells/µl. Main variables: comorbidity, clinical parameters, exacerbations and annual asthma total costs.Results: A total of 268 severe asthmatic patients in Spain were included, representing 6.3% of the asthma population, with 58.6% having eosinophil count ≥300 cells/µl and 41.4% eosinophil count <300 cells/µl. The mean age was 56.1 years (63.4% women). Patients with eosinophilic inflammation (≥300 cells/µl) had lower FEV1 values (54.3% vs. 60.7%; p < .001), poorer treatment adherence (65.6% vs. 77.3%; p < .001), and a greater mean number of exacerbations (3.3 vs. 1.9; p < .001). Exacerbations were correlated to FEV1 (ß=‒.606), eosinophils (ß = .255), immunoglobulin E (ß = .152), and age (ß = .128), p < .001. The mean total asthma annual cost (ANCOVA) was 6222 vs. 4152 euros, respectively (p = .016). Health costs were associated with age (ß = .323), FEV1 (ß = .239), eosinophils (ß = .177) and exacerbations (ß = .158), p < .01.Limitations: Those inherent to retrospective studies; the possible inaccuracy of diagnostic coding referring to severe asthma and other comorbidities and the external validity of the results.Conclusions: Health costs of patients with severe asthma were high. Total annual asthma costs and resource use were greater in patients with ≥300 cells/µl. Age, eosinophilia, exacerbations and FEV1 were associated with greater resource utilization and costs for the health system.