Anti-IL-5 and anti-IL-5R biologics for severe asthma. Are there any differences in their effects?

OBJECTIVE: The aim of this retrospective multicentre study is to describe the clinical characteristics of patients diagnosed with severe eosinophilic asthma receiving anti-IL-5/anti-IL-5Rα therapies and to compare their effectiveness. METHODS: We collected and analysed results separately for anti-IL-5 and anti-IL-5Rα therapies from January 2016 until December 2021 in multidisciplinary severe asthma units. We collected demographic and clinical data, treatment with previous anti-IgE and/or anti-IL-5 agents, and comorbidities. We compared the number of exacerbations and admissions to the hospital, daily oral corticosteroid intake, pulmonary function tests, and Asthma Control Test scores before and after 12 months of therapy. 261 patients were included: 176 patients in the anti-IL-5 group and 85 in the anti-IL-5Rα group. RESULTS: Both groups led to statistically significant reductions in asthma exacerbations, hospital admissions, and visits to the Emergency Room. Although both groups showed a significant reduction in blood eosinophiliccount, we found a difference, although not significant, in the magnitude of reduction as benralizumab was able to decrease eosinophil counts to zero. Patients in the anti-IL-5 group achieved higher ACT scores after treatment, although this improvement was seen in both treatment groups. CONCLUSION: The anti-IL-5 and anti-IL-5Rα biologics have shown similar effectiveness despite having different mechanisms of action. The anti-IL-5 group appeared to be better than benralizumab at improving ACT scores and FEV1/FVC and at reducing the number of inhalers. Although these differences were not statistically significant, it is not clear whether they may have clinical relevance and they might highlight the need for further head-to-head studies comparing these treatments.

Safety of biological therapy in elderly patients with severe asthma.

OBJECTIVE: To assess the safety of biological therapy for severe T2 asthma (omalizumab, mepolizumab, benralizumab and reslizumab) under real-life conditions in elderly patients older than 70 years. METHODS: Retrospective data collection including clinical characteristics, comorbidities, treatment, disease control and adverse events (AE) of all patients with severe asthma on biological therapy older than 70 years seen in the Severe Asthma Unit of our hospital. RESULTS: Of 147 patients with severe asthma being treated with biologics, 21 patients older than 70 years were included. The median age of these patients was 76.3 years (range 71-86) and the majority were women (n = 18, 85.7%). There were 9 patients (42.9%) who experienced an AE related to biological treatment. Four (44.4%) were in treatment with omalizumab, two (22.2%) with mepolizumab, two patients (22.2%) with reslizumab and one (11.1%) with benralizumab. The median FEV1 (%) was 66%. These patients had a considerably higher body mass index (BMI). No significant differences were found for any other variable. Most of the AE reported were considered mild with the exception of one case of systemic AE (anaphylaxis) associated with omalizumab. CONCLUSION: This study indicates that the prescription of biological therapy in elderly patients with severe asthma seems to be safe. More evidence is needed in this particular population.

Inhaled bronchodilators use and clinical course of adult inpatients with Covid-19 pneumonia in Spain: A retrospective cohort study.

BACKGROUND: In the current coronavirus health crisis, inhaled bronchodilators(IB) have been suggested as a possible treatment for patients hospitalized. Patients with evidence of Covid-19 pneumonia worldwide have been prescribed these medications as part of therapy for the disease, an indication for which this medications could be ineffective taken on account the pathophysiology and mechanisms of disease progression. OBJECTIVE: The main objective was to evaluate whether there is an association between IB use and length of stay. Primary end points were the number of days that a patient stayed in the hospital and death as a final event in a time to event analysis. Pneumonia severity, oxygen requirement, involved drugs, comorbidity, historical or current respiratory diagnoses and other drugs prescribed to treat coronavirus pneumonia were also evaluated. METHODS: A descriptive, observational, cross-sectional study was performed in this tertiary hospital in Madrid (Spain). Data were obtained regarding patients hospitalized with Covid-19, excluding those who were intubated. The primary and secondary outcomes such as duration of hospitalization and death were compared in patients who received IB with those in patients who did not. RESULTS: 327 patients were evaluated, mean age was 64.4 ± 15.8 years. Median length of hospitalization stay was 10 days. Of them 292 (89.3%) overcame the disease, the remaining 35 died. Patients who had received IB did not have less mortality rate (odds ratio 0.839; 95% CI: 0.401 to 1.752) and less hospitalization period when compared with patients who did not received IB (odds ratio 1.280; 95% CI: 0.813 to 2.027). There was no significant association between IB use and recovery or death. Hypertension and diabetes were the most common comorbidities. The prevalence of chronic respiratory disease in our cohort was low (21.1%). Anticholinergics were the IB more frequently prescribed for Covid-19 pneumonia. Better response in patients treated with inhaled corticosteroids was not observed. CONCLUSION: Off-label indication of inhaled-bronchodilators for Covid-19 patients are common in admitted patients. Taken on account our results, the use of IB for coronavirus pneumonia apparently is not associated with a significantly patient's improvement. Our study confirms the hypothesis that inhaled bronchodilators do not improve clinical outcomes or reduce the risk of Covid-19 mortality. This could be due to the fact that the virus mainly affects the lung parenchyma and the pulmonary vasculature and probably not the airway. More researches are necessary in order to fill the gap in evidence for this new indication.

Reasons for initiation of proton pump inhibitor therapy for hospitalised patients and its impact on outpatient prescription in primary care.

BACKGROUND: Proton-pump-inhibitors are often prescribed unnecessarily in hospitals, which in turn induces their prescriptions after discharge. OBJECTIVE: To evaluate patients starting treatment with proton-pump-inhibitors during hospitalisation and proportion of inappropriate prescriptions. Patient risk factors and whether initiation in hospital induced their continuation in ambulatory care were also analyzed. METHODS: An observational, cross-sectional study in a tertiary hospital (1350 beds) was carried out on the first Tuesday in February 2015. Pharmacists screened admitted patients treated with proton-pump-inhibitors using an electronic prescription program (FarmaTools®-5.0). They also checked patients' home medications before admission by accessing a primary care program (Horus®). Authorized indications according to Spanish-Medicines-Agency and those recommended in Spanish-Clinical-Practice-Guidelines were considered appropriate. Hospital-medical-records were checked to know whether proton-pump-inhibitors were prescribed at discharge. RESULTS: Three hundred seventy nine patients were analysed. Two hundred ninety four of them were prescribed proton-pump-inhibitors (77.6%). Treatment was initiated during admission for 143 patients (48.6%, 95% CI: 42.8-54.5). Of them, 91 (63.6%, 95% CI: 55.2-71.5) were inappropriate, mainly due to its inclusion unnecessarily in protocols associated with surgeries or diseases (56 cases of 91, 61.5%). Additional inappropriate indications were surgical stress ulcer prophylaxis for surgeries without bleeding risks (19.8%) and polypharmacy without drugs that increase the risk of bleeding (18.7%). Of 232 discharge reports assessed, in 153 (65.9%, 95% CI: 59.5-72), proton-pump-inhibitor continuation was recommended, of them, 51 (33.3%) were initiated at admission. CONCLUSION: In hospitalized patients there is a high prevalence of prescription of proton-pump-inhibitors unnecessarily. The superfluous use is often associated with the prescription of treatment protocols. Those treatments started in the hospital generally did not contribute to over-use existing primary care, most of them were removed at discharge.

Cardiovascular Events in Patients with Severe Asthma-A Retrospective Study of Two Cohorts: Asthma Type T2 Treated with Biologics and Non-Type T2.

Background: The prevalence of cardiovascular events (CVEs) in patients with asthma varies amongst studies, with little evidence as to their prevalence in patients treated with monoclonal antibodies (mAbs). In this retrospective, observational study, we aimed to evaluate the prevalence of CVEs in patients with T2 and non-T2 asthma and to identify risk factors associated with CVEs. Methods: A total of 206 patients with severe asthma were included. Demographic variables, respiratory comorbidities and cardiovascular risk factors were collected, along with respiratory function, laboratory parameters and respiratory pharmacotherapy, including treatment with mAbs. Results: A total of 10.7% of the patients had any CVE from the date of asthma diagnosis, with a higher risk in those patients with chronic obstructive pulmonary disease (odds ratio [OR] = 5.36, 95% CI 1.76-16.31; p = 0.003), arterial hypertension (OR = 2.71, 95% CI 1.13-6.55; p = 0.026) and dyslipidaemia (OR = 9.34, 95% CI 3.57-24.44; p < 0.001). No association between mAb treatment and a CVE or between time of mAb treatment and the event was found. No significant differences were observed between the T2 and non-T2 cohort. After a multivariate analysis, dyslipidaemia was identified as an independent risk factor (OR = 13.33, 95% CI 4.49-39.58; p < 0.001), whereas regular use of inhaled corticosteroids was associated with a reduced risk of a CVE (OR = 0.103, 95% CI 0.021-0.499; p = 0.005). Further research is needed to fully understand the relationship between severe asthma and CVEs. Conclusions: This study suggests that patients with severe asthma experience a higher percentage of CVEs compared with the general population.

[Telemedicine and severe asthma in our environment: Views on the experience of professionals and suggestions to make it a reality]. / Telemedicina y asma grave en nuestro entorno: reflexiones sobre la experiencia de los profesionales y propuestas para hacerla realidad.

This paper aims to examine the recent experience in telemedicine (TM) management of patients with severe asthma (SA). A committee of health professionals involved in asthma management (pulmonology, allergology, respiratory nursing, and hospital pharmacy) held discussion meetings on the practical experience of TM for the management of SA and the means available complemented with a bibliographic search to know the current status of TM in SA. The main barriers detected for the implementation of TM in SA have been the lack of technological training, the lack of registration of TM in the clinical history, the care overload, or the connectivity problems at the administration level. The practical solutions are provided such as the selection of the patient suitable for TM, the registration of TM in the medical record, its inclusion in the care objectives or the increase of funding for systems. Moreover, the main App and Webapp for use by patients are provided, and the portable equipment for remote functional respiratory tests. In conclusion, it is necessary that the teleconsultation has the same entity as the face-to-face visit with a schedule in the appointment's agenda and a structure of both the medical interview and the tests to be performed in each consultation. Additionally, should be promoted the implementation of a video call system, tools that allow the monitoring of both therapeutic adherence and inhalation technique, as well as the patient's lung function.

Impact of systemic corticosteroids on hospital length of stay among patients with COVID-19.

BACKGROUND AND OBJECTIVE: The COVID-19 pandemic has posed a threat to hospital capacity due to the high number of admissions, which has led to the development of various strategies to release and create new hospital beds. Due to the importance of systemic corticosteroids in this disease, we assessed their efficacy in reducing the length of stay (LOS) in hospitals and compared the effect of 3 different corticosteroids on this outcome. METHODS: We conducted a real-world, controlled, retrospective cohort study that analysed data from a hospital database that included 3934 hospitalised patients diagnosed with COVID-19 in a tertiary hospital from April to May 2020. Hospitalised patients who received systemic corticosteroids (CG) were compared with a propensity score control group matched by age, sex and severity of disease who did not receive systemic corticosteroids (NCG). The decision to prescribe CG was at the discretion of the primary medical team. RESULTS: A total of 199 hospitalized patients in the CG were compared with 199 in the NCG. The LOS was shorter for the CG than for the NCG (median = 3 [interquartile range = 0-10] vs. 5 [2-8.5]; p = 0.005, respectively), showing a 43% greater probability of being hospitalised ≤ 4 days than > 4 days when corticosteroids were used. Moreover, this difference was only noticed in those treated with dexamethasone (76.3% hospitalised ≤ 4 days vs. 23.7% hospitalised > 4 days [p < 0.001]). Serum ferritin levels, white blood cells and platelet counts were higher in the CG. No differences in mortality or intensive care unit admission were observed. CONCLUSIONS: Treatment with systemic corticosteroids is associated with reduced LOS in hospitalised patients diagnosed with COVID-19. This association is significant in those treated with dexamethasone, but no for methylprednisolone and prednisone.

Impact of systemic corticosteroids on length of hospitalization among patients with COVID-19. / [Artículo traducido] Impacto de los corticoides sistémicos en el tiempo de hospitalización en pacientes con COVID-19.

OBJECTIVE: The COVID-19 pandemic has posed a threat to hospital capacity due to the high number of admissions, which has led to the development of various strategies to release and create new hospital beds. Due to the importance of systemic corticosteroids in this disease, we assessed their efficacy in reducing the length of stay (LOS) in hospitals and compared the effect of 3 different corticosteroids on this outcome. MéTHOD: We conducted a real-world, controlled, retrospective cohort study that analysed data from a hospital database that included 3934 hospitalised patients diagnosed with COVID-19 in a tertiary hospital from April to May 2020. Hospitalised patients who received systemic corticosteroids (CG) were compared with a propensity score control group matched by age, sex and severity of disease who did not receive systemic corticosteroids (NCG). The decision to prescribe CG was at the discretion of the primary medical team. RESULTS: A total of 199 hospitalized patients in the CG were compared with 199 in the NCG. The LOS was shorter for the CG than for the NCG (median=3 [interquartile range=0-10] vs. 5 [2-8.5]; p=0.005, respectively), showing a 43% greater probability of being hospitalised ≤4 days than >4 days when corticosteroids were used. Moreover, this difference was only noticed in those treated with dexamethasone (76.3% hospitalised ≤4 days vs. 23.7% hospitalised >4 days [p<0.001]). Serum ferritin levels, white blood cells and platelet counts were higher in the CG. No differences in mortality or intensive care unit admission were observed. CONCLUSIONS: Treatment with systemic corticosteroids is associated with reduced LOS in hospitalised patients diagnosed with COVID-19. This association is significant in those treated with dexamethasone, but no for methylprednisolone and prednisone.

Relationship between air pollution exposure and the progression of idiopathic pulmonary fibrosis in Madrid: Chronic respiratory failure, hospitalizations, and mortality. A retrospective study.

Introduction: Air pollution has a significant impact on the morbidity and mortality of various respiratory diseases. However, this has not been widely studied in diffuse interstitial lung diseases, specifically in idiopathic pulmonary fibrosis. Objective: In this study we aimed to assess the relationship between four major air pollutants individually [carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and nitrogen oxides (NOx)] and the development of chronic respiratory failure, hospitalization due to respiratory causes and mortality in patients with idiopathic pulmonary fibrosis. Methods: We conducted an exploratory retrospective panel study from 2011 to 2020 in 69 patients with idiopathic pulmonary fibrosis from the pulmonary medicine department of a tertiary hospital. Based on their geocoded residential address, levels of each pollutant were estimated 1, 3, 6, 12, and 36 months prior to each event (chronic respiratory failure, hospital admission and mortality). Data was collected from the air quality monitoring stations of the Community of Madrid located <3.5 km (2.2 miles) from each patient's home. Results: The increase in average values of CO [OR 1.62 (1.11-2.36) and OR 1.84 (1.1-3.06)], NO2 [OR 1.64 (1.01-2.66)], and NOx [OR 1.11 (1-1.23) and OR 1.19 (1.03-1.38)] were significantly associated with the probability of developing chronic respiratory failure in different periods. In addition, the averages of NO2, O3, and NOx were significantly associated with the probability of hospital admissions due to respiratory causes and mortality in these patients. Conclusion: Air pollution is associated with an increase in the probability of developing chronic respiratory failure, hospitalization due to respiratory causes and mortality in patients with idiopathic pulmonary fibrosis.

Air pollution exposure and its effects on idiopathic pulmonary fibrosis: clinical worsening, lung function decline, and radiological deterioration.

Introduction: Major urban pollutants have a considerable influence on the natural history of lung disease. However, this effect is not well known in idiopathic pulmonary fibrosis (IPF). Aim: This study aimed to investigate the effects of air pollution on clinical worsening, lung function, and radiological deterioration in patients with IPF. Methods: This exploratory retrospective cohort study included 69 patients with IPF, monitored from 2011 to 2020. Data on air pollution levels, including carbon monoxide (CO), nitrogen dioxide (NO2), particulate matter ≤ 2.5 µM (PM2.5), ozone (O3), and nitrogen oxides (NOx), were collected from the nearest air quality monitoring stations (<3.5 km from the patients' homes). Patient outcomes such as clinical worsening, lung function decline, and radiological deterioration were assessed over various exposure periods (1, 3, 6, 12, and 36 months). The statistical analyses were adjusted for various factors, including age, sex, smoking status, and treatment. Results: There was an association between higher O3 levels and an increased likelihood of clinical worsening over 6 and 36 months of exposure (odds ratio [OR] and 95% confidence interval [CI] = 1.16 [1.01-1.33] and OR and 95% CI = 1.80 [1.07-3.01], respectively). Increased CO levels were linked to lung function decline over 12-month exposure periods (OR and 95% CI 1.63 = [1.01-2.63]). Lastly, radiological deterioration was significantly associated with higher CO, NO2, and NOx levels over 6-month exposure periods (OR and 95% CI = 2.14 [1.33-3.44], OR and 95% CI = 1.76 [1.15-2.66] and OR and 95% CI = 1.16 [1.03-1.3], respectively). Conclusion: This study suggests that air pollution, specifically O3, CO, NO2, and NOx, could affect clinical worsening, lung function, and radiological outcomes in patients with IPF. These findings highlight the potential role of air pollution in the progression of IPF, emphasizing the need for further research and air quality control measures to mitigate its effects on respiratory health.

Adherence to inhalers in patients with severe asthma treated with anti-interleukin-5 biologics.

OBJECTIVE: Given poor medication adherence in severe asthma is difficult to  evaluate in daily practice, using at least two methods concurrently is recommended. We aimed to determine the prevalence of nonadherence  to  inhalers using the Test of Adherence to Inhalers questionnaire and the medication possession ratio obtained from the pharmacy refill data in patients with severe asthma treated with anti-interleukin-5 biologics and to evaluate their concordance. METHOD: This was a cross-sectional retrospective observational study of 53  patients with severe asthma recruited from the severe asthma unit of a tertiary  hospital in Madrid from June to December 2020. We registered demographic data, comorbidities and concomitant therapy for  sthma. Nonadherence was defined as pharmacy refill data < 80% and/or Test of Adherence to Inhalers questionnaire results < 50. Concordance was assessed by determining the Cohen's kappa statistic. Results: The median age was 61 years (interquartile range 51.8-67.0), and 33  (61%) were women. According to the pharmacy refill data lack of  adherence to the primary inhaler was 58.5%. However, when using the Test of  Adherence to Inhalers questionnaire, it was 22.6%. Combining both methods,  17% of patients were considered to have nonadherence to inhalers. Likewise,  when identifying nonadherence by either of these methods, it reached a  prevalence of 64.2%. The pharmacy refill data and Test of Adherence to  Inhalers questionnaire agreed in 53.1% and disagreed in 46.9% of patients (k  = 0.137; 95% confidence interval -0.057 to 0.331; p = 0.318). CONCLUSIONS: We observed a higher prevalence of non-adherence to inhalers  in patients with severe asthma treated with anti-interleukin-5 biologics. The  agreement between the Test of Adherence to Inhalers questionnaire and the  pharmacy refill data is lower when evaluating nonadherence in patients with  severe asthma treated with anti-interleukin-5 biologics. The pharmacy refill  data detect a higher proportion of nonadherence compared with the Test of  Adherence to Inhalers questionnaire.

OBJETIVO: Dado que la mala adherencia a la medicación en el asma grave es  difícil de evaluar en la práctica diaria, se recomienda utilizar al menos dos métodos simultáneamente. El objetivo es determinar la prevalencia de la  falta de adherencia a los inhaladores mediante el cuestionario Test de  Adherencia a los Inhaladores y la ratio de posesión de la medicación obtenida a  partir de los datos de dispensación de la farmacia en pacientes con asma  grave tratados con biológicos anti interleucina 5 y evaluar su concordancia.Método: Estudio observacional retrospectivo transversal de 53 pacientes con  asma grave reclutados en la unidad de asma grave de un hospital terciario de  Madrid de junio a diciembre de 2020. Se registraron datos demográficos, comorbilidades y el tratamiento concomitante para el asma. La  falta de adherencia se definió como una ratio de posesión de la medicación <  80% y/o un valor en los resultados del cuestionario Test de Adherencia a los  Inhaladores < 50. La concordancia se evaluó con el coeficiente kappa de  Cohen. RESULTADOS: La mediana de edad fue de 61 años (rango intercuartílico 51,8- 67,0), y 33 (61%) eran mujeres. Según la ratio de posesión de la medicación,  la falta de adherencia al inhalador primario fue del 58,5%. Sin embargo, al  utilizar el cuestionario Test de Adherencia a los Inhaladores, ésta fue del  22,6%. Combinando ambos métodos, se consideró que el 17% de los  pacientes presentaban no adherencia a los inhaladores. Asimismo, al identificar  la no adherencia por cualquiera de estos métodos, se alcanzó una  prevalencia del 64,2%. El cuestionario Test de Adherencia a los Inhaladores y  la ratio de posesión de la medicación coincidieron en el 53,1% y discreparon en  el 46,9% de los pacientes (k = 0,137; intervalo de confianza del 95% ­0,057 a 0,331; p = 0,318). CONCLUSIONES: Se observó una alta prevalencia de no adherencia a los inhaladores en los pacientes con asma grave tratados con biológicos anti interleucina 5. La concordancia entre el cuestionario Test de Adherencia a los Inhaladores y la ratio de posesión de la medicación es menor cuando se  evalúa la no adherencia en pacientes con asma grave tratados con biológicos  anti interleucina 5. La ratio de posesión de la medicación detecta una mayor  proporción de no adherencia en comparación con el cuestionario Test de  Adherencia a los Inhaladores.

Cost evolution of biological drugs in rheumatoid arthritis patients in a tertiary hospital: Influential factors on price.

OBJECTIVE: To assess the evolution of cost per patient/year and the cost per patient/year/drug in patients with rheumatoid arthritis (RA) receiving biological treatments. To analyze and quantify the factors influencing this evolution, such as the optimization of the biological drugs, the use of biosimilars, and official discounts and discounts obtained after negotiated procedures. In addition, to assess specific clinical parameters of disease activity in these patients. METHODS: Retrospective, observational study conducted in a Spanish tertiary hospital. Adult patients diagnosed with RA under treatment from 2009 to 2017 were included. RESULTS: 320, 270 and 389 patients were included in 2009, 2013 and 2017, respectively. The patient/year cost decreased from 10,789€ in 2009, 7491€ in 2013 to 7116€ in 2017. In 2017, due to the established competition, discounts of 14% and 29.5% were achieved on etanercept and its biosimilar; 11.5%, 17.8%, 17.9%, 17.3% on adalimumab, certolizumab, golimumab and tocilizumab IV respectively, and 24.6% and 43.1% on infliximab and its biosimilar. The percentage of patients optimized in 2017 was 35.2%. The annual saving in 2017 was 1,288,535€ (830,000€ due to dose optimization and/or administration regimens, 249,666€ corresponding to 7.5% of the official discount and 208,868€ after negotiated procedures). CONCLUSION: The annual cost per patient in RA decreased considerably due to different factors, such as discounts on the purchase of drugs due to official discounts and negotiated procedures, together with the optimization of therapies, the latter being the factor that contributed most to this decrease.

Off-label use of inhaled bronchodilators in hospitalised patients in Spain: a multicentre observational study.

BACKGROUND: Off-label prescription of inhaled bronchodilators (IB) is frequent, despite the fact that they can be ineffective and increase avoidable healthcare costs. OBJECTIVE: To analyse the frequency of off-label prescription of IB in hospitalised patients. Indications and level of evidence, involved drugs, medical specialties prescribing off-label IB and patients' adherence to IBs were also evaluated. METHOD: A descriptive, observational, cross-sectional study was performed in four tertiary hospitals in Spain. The main outcome measure was the number of patients prescribed off-label IBs. Prescriptions were checked against the European Medicines Agency-approved indications. The level of evidence supporting off-label prescription of IBs (according to MICROMEDEX 2.0) was also analysed. Patients were interviewed to test differences (off-label vs on-label) in adherence and knowledge about their inhaled therapy. RESULTS: 217 patients were prescribed IBs, 92 of whom were givend off-label IBs (54.7% men, mean age 73.9±12.9 years). The most common off-label prescriptions for IBs were: unspecified dyspnoea (not related to COPD or asthma) (27.2%), respiratory infections (23.9%) and heart failure (22.8%). 76.8% of patients did not have evidence supporting them. Beta2-agonist+corticosteroids and anticholinergics were most commonly prescribed off-label. Internal Medicine was the main medical specialty involved. There were no differences between off-label and on-label users in terms of patients' knowledge about treatment and adherence. CONCLUSION: Off-label indications for IBs are common in hospitalised patients and are generally indicated without scientific support. Dyspnoea not related to COPD or asthma, respiratory infections and heart failure were the main off-label indications, most frequently treated with anticholinergics and beta2-agonists+corticosteroids, for which their efficacy and safety has not been proved. Our results show that prescribing needs to be improved to follow the evidence that exists. Moreover, further research focused on off-label indications is needed to clarify whether they are effective, safe and cost-effective.

Persistence of biological agents over an eight-year period in rheumatoid arthritis and spondyloarthritis patients.

OBJECTIVE: To calculate the persistence, over a period of eight years, the retention rate of first and second-line of treatment with biological agents in  patients with rheumatoid arthritis, spondyloarthritis and psoriatic arthritis and to compare retention rates of the various drugs for each pathology. METHOD: Retrospective observational study that included patients affected by  rheumatoid arthritis, spondyloarthritis and psoriatic arthritis, who started  treatment with biological agents between January 2009 and December 2012 and followed until December 2016. RESULTS: 132, 87 and 33 patients were included in rheumatoid arthritis, spondyloarthritis and psoriatic arthritis, respectively. The median  retention duration of all biological agents for the first and second-line, was 30.9 months and 14.0 months, respectively for rheumatoid arthritis; 63.06  months and 25.6 months, respectively in spondyloarthritis. Psoriatic arthritis did  not reach the median (> 70 months in first-line) (first line p = 0.002). Individual drug survival in first line: the median retention duration of tocilizumab was 58.3 months, followed by etanercept (p = 0.79) in rheumatoid arthritis. For spondyloarthritis, golimumab and etanercept had greater retention than the other drugs (they did not reach the median): adalimumab was 63.0 months and for infliximab was 50.1 months. In psoriatic arthritis, golimumab,  infliximab and etanercept not reach the median and they had greater retention than adalimumab (59.4 months). Individual drug survival in second  line: tocilizumab was the most persistent drug (median 22.1 months) in  rheumatoid arthritis, and golimumab for spondyloarthritis and psoriatic arthritis. CONCLUSIONS: Tocilizumab and etanercept in rheumatoid arthritis, and golimumab in spondyloarthritis and psoriatic arthritis also, were the most persistent drugs in first-line and second-line treatment.

Objetivo: Calcular y analizar la persistencia global y por medicamento, en  primera y segunda línea de tratamiento, en pacientes con artritis reumatoide, espondiloartritis axial radiográfica y no radiográfica y artritis  psoriásica durante un periodo de ocho años.Método: Estudio retrospectivo observacional de persistencia en pacientes que  iniciaron su terapia con medicamentos biológicos entre enero de 2009 y  diciembre de 2012 en seguimiento hasta diciembre de 2016. Resultados: Se analizaron 132, 87 y 33 pacientes con artritis reumatoide, espondiloartritis y artritis psoriásica, respectivamente. La  persistencia mediana global para los biológicos en primera y segunda línea  fueron: 30,9 meses y 14 meses, respectivamente, en artritis reumatoide; 63,06 meses y 25,6 meses en espondiloartritis. No se alcanzó la persistencia mediana en los ocho años de seguimiento en artritis psoriásica (>  70 meses) (p = 0,002 para la función de supervivencia entre patologías en primera línea). Persistencia mediana alcanzada en primera línea por  medicamento: tocilizumab (58,3 meses), seguido de etanercept (44 meses) en  artritis reumatoide (p = 0,79); en espondiloartritis golimumab y etanercept fueron los más persistentes (no alcanzaron la mediana), seguidos deadalimumab (44 meses) e infliximab (50,1 meses). En artritis psoriásica, golimumab seguido de infliximab y etanercept fueron los más persistentes (no alcanzaron la mediana), y adalimumab (59,4 meses).  Persistencia mediana alcanzada en segunda línea por medicamento: tocilizumab (22,1 meses) en artritis reumatoide. Golimumab fue el más persistente en espondiloartritis y artritis psoriásica (sin alcanzar la mediana).Conclusiones: Tocilizumab y etanercept fueron los medicamentos más persistentes en artritis reumatoide, y golimumab en espondiloartritis y  artritis psoriásica en primera y segunda línea de tratamiento.

Impacto de los corticoides sistémicos en el tiempo de hospitalización en pacientes con COVID-19 / Impact of systemic corticosteroids on length of hospitalization among patients with COVID-19

Objetivo: la COVID-19 supuso una amenaza para la capacidad hospitalaria por el elevado número de ingresos, lo que llevó al desarrollo de diversas estrategias para liberar y crear nuevas camas hospitalarias. Dada la importancia de los corticoides sistémicos en esta enfermedad, se evaluó la eficacia de estos en la reducción de la duración de la estancia hospitalaria (EH) y se comparó el efecto de 3 corticosteroides diferentes sobre este resultado.Métodose realizó un estudio de vida real de diseño tipo cohorte retrospectiva y controlado. Se analizó una base de datos hospitalaria de 3.934 pacientes hospitalizados con diagnóstico de COVID-19 en un hospital terciario entre abril y mayo de 2020. Se comparó un grupo de enfermos que recibieron corticosteroides sistémicos (grupo con corticoides [GC]) frente a un grupo control que no recibió corticosteroides sistémicos (grupo sin corticoides [GSC]) emparejado por edad, sexo y gravedad de la enfermedad mediante una puntuación de propensión. La decisión de prescribir glucocorticoides dependía principalmente del criterio del médico responsable.Resultadosse compararon un total de 199 pacientes hospitalizados en el GC con 199 en el GSC. La EH fue más corta para el GC que para el GSC (mediana=3 [rango intercuartílico=0-10] vs. 5 [2-8,5]; p=0,005, respectivamente), mostrando un 43% más de probabilidad de ser hospitalizado ≤4 días que >4 días cuando se usaron corticosteroides. Además, esta diferencia solo la mostraron aquellos tratados con dexametasona (76,3% hospitalizados ≤4 días vs. 23,7% hospitalizados >4 días [p<0,001]). Los niveles de ferritina sérica, glóbulos blancos y plaquetas fueron más elevados en el GC. No se observaron diferencias en la mortalidad ni en el ingreso a la unidad de cuidados intensivos. (AU)

Objective: The COVID-19 pandemic has posed a threat to hospital capacity due to the high number of admissions, which has led to the development of various strategies to release and create new hospital beds. Due to the importance of systemic corticosteroids in this disease, we assessed their efficacy in reducing the length of stay (LOS) in hospitals and compared the effect of 3 different corticosteroids on this outcome.MéthodWe conducted a real-world, controlled, retrospective cohort study that analysed data from a hospital database that included 3934 hospitalised patients diagnosed with COVID-19 in a tertiary hospital from April to May 2020. Hospitalised patients who received systemic corticosteroids (CG) were compared with a propensity score control group matched by age, sex and severity of disease who did not receive systemic corticosteroids (NCG). The decision to prescribe CG was at the discretion of the primary medical team.ResultsA total of 199 hospitalized patients in the CG were compared with 199 in the NCG. The LOS was shorter for the CG than for the NCG (median=3 [interquartile range=0–10] vs. 5 [2–8.5]; p=0.005, respectively), showing a 43% greater probability of being hospitalised ≤4 days than >4 days when corticosteroids were used. Moreover, this difference was only noticed in those treated with dexamethasone (76.3% hospitalised ≤4 days vs. 23.7% hospitalised >4 days [p<0.001]). Serum ferritin levels, white blood cells and platelet counts were higher in the CG. No differences in mortality or intensive care unit admission were observed.ConclusionsTreatment with systemic corticosteroids is associated with reduced LOS in hospitalised patients diagnosed with COVID-19. This association is significant in those treated with dexamethasone, but no for methylprednisolone and prednisone. (AU)

Cost evolution of biological agents for the treatment of spondyloarthritis in a tertiary hospital: influential factors in price.

Background Spending on biological agents has risen dramatically due to the high cost of the drugs and the increased prevalence of spondyloarthritis. Objective To evaluate the annual cost per patient and cost for each biological drug for treating patients with spondyloarthritis from 2009 to 2016, and to calculate factors that affect treatment cost, such as optimizing therapies by monitoring drug serum levels, the use of biosimilar-TNF inhibitors, and official discounts or negotiated rebates in biologicals acquired by the pharmacy department. Method Retrospective, observational study in a Spanish tertiary hospital. Main outcome Annual cost per patient and per drug. Factors that influenced the costs and socio-demographic parameters and disease activity. Results A total of 129, 215, and 224 patients were treated in 2009, 2013, and 2016, respectively. The annual cost per patient decreased: EUR11,604 in 2009, EUR8513 in 2013, and EUR7464 in 2016. The introduction of new drugs drives economic competition, leading to total savings per drug, with discounts reaching 5.8, 12.4, 16.7, 17.7, 13.7, and 24.8% for original infliximab, etanercept, adalimumab, ertolizumab, golimumab, and secukinumab, respectively, while rebates for biosimilar infliximab reached 31.90% in 2016. The number of patients with optimized therapies reached 47.5% in 2016, which led to cost savings of EUR798,614, in addition to savings from official discounts and rebates of EUR252,706 and savings from optimized therapies of EUR545,908 in 2016. Conclusion The cost of biological treatments declined after official discounts, negotiated rebates, and optimized therapies, leading to a significant decrease in the annual cost per patient. The greatest contribution to economic savings in biological therapy according to our study was biological therapy optimization.

Complications associated with the use of oral anticoagulation in patients with pulmonary arterial hypertension from two referral centers.

Anticoagulants are widely used in patients with pulmonary arterial hypertension (PAH) to prolong survival. However, there is a lack of robust evidence demonstrating the benefits of anticoagulants in PAH patients and very little is known about the complications of their use in this population. The objective of this study is to compare the safety of routine administration of oral anticoagulants between PAH patients who were and were not treated with oral anticoagulants. This observational, retrospective cohort study included consecutive patients with confirmed PAH from two centers: Brigham and Women's Hospital in Boston and Hospital Universitario La Paz in Madrid from January 2009 to August 2015. The study group comprised patients who received therapeutic anticoagulation; patients who had never received anticoagulants were placed in the control group. Of the 201 included patients, 60.2% were treated with oral anticoagulants and 39.8% were not treated. The hazard ratio for major bleeding was 2.7 (95% confidence interval [CI] = 1.1-6.8; P = 0.036). The incidence rate for the anticoagulation group was 4.7 per 100 patient-years (95% CI = 2.5-8.0). The most frequent major hemorrhage was gastrointestinal bleeding with 24 cases (72.7%). Prior bleeding, poor anticoagulation, HAS-BLED score ≥3, diabetes, and number of medications were factors that increased the risk of major bleeding in patients using anticoagulants. The harmful effects of anticoagulants could outweigh the benefits in PAH patients. Therefore, anticoagulants should be prescribed on a case-by-case basis and should not be systematically recommended.

Assessment of the quality of anticoagulation management in patients with pulmonary arterial hypertension.

BACKGROUND: Studies assessing the quality of anticoagulation therapy in patients with pulmonary arterial hypertension (PAH) have not been conducted. OBJECTIVE: To assess the quality of anticoagulation management, the rate of anticoagulation-related complications in patients with PAH, and to identify risk factors for poor anticoagulation. METHODS: This observational, retrospective cohort study included patients with confirmed PAH taking a regimen of oral anticoagulants from two centers: Brigham and Women's Hospital in Boston, and Hospital Universitario La Paz in Madrid from January 2009 to August 2015. Efficacy of anticoagulation management and time spent within therapeutic range of study participants were assessed. RESULTS: There were a total of 121 patients with PAH taking oral anticoagulants. Time spent within range (TTR) of those taking vitamin K antagonists (VKAs) was 57.0%. Forty-seven patients (38.8%) had a total of 105 anticoagulation-related events. The odds ratio of having an event in patients with a TTR<60% was 2.43 (CI 95%, 1.01-5.83; p=0.046). Possible factors that affected the quality of the anticoagulation were the age, sex, functional capacity, atrial fibrillation and certain pulmonary arterial hypertension specific medications. CONCLUSION: The quality of targeted anticoagulation in patients with PAH was low. Patients with low TTR were at a higher risk of experiencing anticoagulation-related complications. Specialized anticoagulation centers showed better management of oral anticoagulants.