Fracture risk after deprescription of bisphosphonates: Application of real-world data in primary care / Riesgo de fractura después de la desprescripción de bifosfonatos: aplicación de real-world data en atención primaria

Purpose: To compare the effect of discontinuing bisphosphonate treatment on fracture risk in postmenopausal women at high versus low risk of fracture. Design: Retrospective, longitudinal and population-based cohort study. Setting: Barcelona City Primary Care. Catalan Health Institute. Participants: All women attended by primary care teams who in January 2014 had received bisphosphonate treatment for at least five years were included and followed for another five years. Intervention: Patients were classified according to their risk of new fractures, defined as those who had a history of osteoporotic fracture and/or who received treatment with an aromatase inhibitor, and the continuity or deprescription of the bisphosphonate treatment was analyzed over fiver year follow-up. Main measurements: The cumulative incidence of fractures and the incidence density were calculated and analyzed using logistic regression and Cox models. Results: We included 3680 women. There were no significant differences in fracture risk in high-risk women who discontinued versus continued bisphosphonate treatment (hazard ratio [HR] 1.17, 95% confidence interval [CI] 0.87–1.58 for total osteoporotic fractures). However, discontinuers at low risk had a lower incidence of fracture than continuers. This difference was significant for vertebral fractures (HR 0.64, 95% CI 0.47–0.88) and total fractures (HR 0.77, 95% CI 0.64–0.92). Conclusion: Our results suggest that deprescribing bisphosphonates in women who have already received five years of treatment does not increase fracture risk. In low-risk women, continuing this treatment might could even favor the appearance of new osteoporotic fractures.(AU)

Objetivo: Comparar el efecto de la desprescripción de bifosfonatos sobre el riesgo de fractura en mujeres posmenopáusicas con alto y bajo riesgo de fractura. Diseño: Estudio de cohortes retrospectivo, longitudinal y de base poblacional. Emplazamiento: Atención primaria Barcelona. Institut Català de la Salut. Participantes: Se incluyeron todas las mujeres atendidas por los equipos de atención primaria que a enero de 2014 habían recibido tratamiento con bifosfonatos durante al menos cinco años. Intervención: Se clasificó a las pacientes según su riesgo de nuevas fracturas, definido como presencia de antecedentes de fractura osteoporótica y/o tratamiento con un inhibidor de la aromatasa, y se analizó la continuidad o desprescripción del tratamiento con bifosfonatos a lo largo de cinco años de seguimiento. Mediciones principales: La incidencia acumulada de fracturas y la densidad de incidencia se calcularon y analizaron mediante regresión logística y modelos de Cox. Resultados: Se incluyeron 3.680 mujeres. No hubo diferencias significativas en el riesgo de fractura en mujeres de alto riesgo que desprescribieron el bisfosfonato comparado con aquellas que continuaron (hazard ratio [HR] 1,17, intervalo de confianza [IC] de 95% 0,87-1,58 para fracturas osteoporóticas totales). Sin embargo, los que discontinuaron con bajo riesgo tuvieron una menor incidencia de fractura que los que continuaron. Esta diferencia fue significativa para fracturas vertebrales (HR 0,64, IC 95% 0,47-0,88) y fracturas totales (HR 0,77, IC 95% 0,64-0,92). Conclusiones: Nuestros resultados sugieren que la desprescripción de bifosfonatos en mujeres que ya han recibido cinco años de tratamiento no aumenta el riesgo de fractura. En mujeres de bajo riesgo, la continuación de este tratamiento podría incluso favorecer la aparición de nuevas fracturas osteoporóticas.(AU)

Fracture risk after deprescription of bisphosphonates: Application of real-world data in primary care.

PURPOSE: To compare the effect of discontinuing bisphosphonate treatment on fracture risk in postmenopausal women at high versus low risk of fracture. DESIGN: Retrospective, longitudinal and population-based cohort study. SETTING: Barcelona City Primary Care. Catalan Health Institute. PARTICIPANTS: All women attended by primary care teams who in January 2014 had received bisphosphonate treatment for at least five years were included and followed for another five years. INTERVENTION: Patients were classified according to their risk of new fractures, defined as those who had a history of osteoporotic fracture and/or who received treatment with an aromatase inhibitor, and the continuity or deprescription of the bisphosphonate treatment was analyzed over fiver year follow-up. MAIN MEASUREMENTS: The cumulative incidence of fractures and the incidence density were calculated and analyzed using logistic regression and Cox models. RESULTS: We included 3680 women. There were no significant differences in fracture risk in high-risk women who discontinued versus continued bisphosphonate treatment (hazard ratio [HR] 1.17, 95% confidence interval [CI] 0.87-1.58 for total osteoporotic fractures). However, discontinuers at low risk had a lower incidence of fracture than continuers. This difference was significant for vertebral fractures (HR 0.64, 95% CI 0.47-0.88) and total fractures (HR 0.77, 95% CI 0.64-0.92). CONCLUSION: Our results suggest that deprescribing bisphosphonates in women who have already received five years of treatment does not increase fracture risk. In low-risk women, continuing this treatment might could even favor the appearance of new osteoporotic fractures.

Sars-Cov-2 Infection in Patients on Long-Term Treatment with Macrolides in Spain: A National Cross-Sectional Study.

The aim of this study was to know the prevalence and severity of COVID-19 in patients treated with long-term macrolides and to describe the factors associated with worse outcomes. A cross-sectional study was conducted in Primary Care setting. Patients with macrolides dispensed continuously from 1 October 2019 to 31 March 2020, were considered. Main outcome: diagnosis of coronavirus disease-19 (COVID-19). Secondary outcomes: symptoms, severity, characteristics of patients, comorbidities, concomitant treatments. A total of 3057 patients met the inclusion criteria. Median age: 73 (64-81) years; 55% were men; 62% smokers/ex-smokers; 56% obese/overweight. Overall, 95% of patients had chronic respiratory diseases and four comorbidities as a median. Prevalence of COVID-19: 4.8%. This was in accordance with official data during the first wave of the pandemic. The most common symptoms were respiratory: shortness of breath, cough, and pneumonia. Additionally, 53% percent of patients had mild/moderate symptoms, 28% required hospital admission, and 19% died with COVID-19. The percentage of patients hospitalized and deaths were 2.6 and 5.8 times higher, respectively, in the COVID-19 group (p < 0.001). There was no evidence of a beneficial effect of long-term courses of macrolides in preventing SARS-CoV-2 infection or the progression to worse outcomes in old patients with underlying chronic respiratory diseases and a high burden of comorbidity.

Risk of Venous Thromboembolism Associated With Tofacitinib and Baricitinib: A Systematic Review and Indirect Meta-Analysis.

To conduct a systematic review and meta-analysis investigating the effect of tofacitinib and baricitinib on venous thromboembolism (VTE) risk. Search of PubMed, EMBASE, Web of Science, Scopus, ClinicalTrials.gov, LILACS, and Google Scholar databases to identify controlled observational and clinical trials reporting on adverse effects in patients treated with oral tofacitinib or baricitinib up to July 2020. The outcome measure was occurrence of VTE events. We analyzed 59 studies involving 14,335 patients treated with tofacitinib or baricitinib and 11,612 patients who received another active drug or placebo. The meta-analysis showed an odds ratio (OR) for VTE events of 0.29 (95% confidence interval [CI] = 0.10-0.84) overall for tofacitinib based on data from 10 clinical trials with 15 treatment arms; similar ORs were observed for the 10 mg/d dose (OR = 0.18; 95% CI = 0.02-1.60) and the 20 mg/d dose (OR = 0.19; 95% CI = 0.04-0.91). The ORs for VTE events for baricitinib were 3.39 (95% CI = 0.82-14.04) overall, 3.05 (95% CI = 0.12-75.43) for 2 mg, 3.64 (95% CI = 0.59-22.46) for 4 mg, and 3.0 (95% CI = 0.12-76.49) for 7 mg. The indirect meta-analysis comparing tofacitinib with baricitinib (10 clinical trials with 15 treatment arms) showed an OR for VTE events of 0.086 (95% CI = 0.02-0.51) for tofacitinib and a superior safety profile for VTE events. In the meta-regression analysis (19 clinical trials with 21 treatment arms), the effect was 0.02 (95% CI = -0.04 to 0.08) for tofacitinib and -0.01 (95% CI = -1.29 to 1.26 for baricitinib. Plotting of the data for tofacitinib showed that VTE risk increased with high doses. The effect, however, was less than 1 for the 10-mg and 20-mg doses, indicating a protective effect. This effect was not observed for baricitinib. Tofacitinib is not associated with an increased risk of VTE and has a superior safety profile to baricitinib in this respect. Tofacitinib may exert a protective effect against VTE.