Are all JAK inhibitors for the treatment of rheumatoid arthritis equivalent? An adjusted indirect comparison of the efficacy of tofacitinib, baricitinib, upadacitinib, and filgotinib.

INTRODUCTION: Comparisons of Janus kinase inhibitors (JAKi) for treatment of rheumatoid arthritis in patients with inadequate response to biologic disease-modifying anti-rheumatic drugs are lacking. We assessed the relative efficacy and safety of four JAKi (tofacitinib, baricitinib, upadacitinib, and filgotinib) in this context. METHOD: We performed an adjusted indirect comparison (IC) of randomized clinical trials using Bucher's method with an IC and mixed calculator. Endpoints were Disease Activity Score C-reactive protein (DAS28-CRP) and American College of Rheumatology-20 (ACR20). Equivalence was assessed using the equivalent therapeutic alternatives (ETA) guidelines. RESULTS: We included four of 133 potentially relevant studies. IC showed no statistically significant differences between the four JAKi regarding DAS28-CRP < 3.2. Results were similar in terms of ACR20 except for tofacitinib showing lower efficacy than upadacitinib (RAR -18.4% [IC95% -33.4 to -3.5], p=0.0157). Statistically significant differences were related to the relevant difference for tofacitinib in both endpoints. Despite no statistical differences for baricitinib, we observed a probably clinically relevant difference regarding DAS28-CRP. Probably clinically relevant differences were found for tofacitinib vs. upadacitinib in both endpoints, and for baricitinib vs. upadacitinib in DAS28-CRP. Safety, drug-drug interactions, and convenience considerations did not modify the result of therapeutic equivalence assessment based on efficacy data. CONCLUSIONS: In conclusion, our results show that filgotinib and upadacitinib are ETA. Baricitinib and upadacitinib are also ETA due to a lack of clear differences and for showing superiority over placebo. The results for tofacitinib and upadacitinib show some inconsistency and more data are needed. Key Points • To date, neither a head-to-head comparison nor an indirect comparison between the Janus kinase inhibitors has been performed in patients with rheumatoid arthritis and an inadequate response to biologic disease-modifying anti-rheumatic drugs. • We performed an adjusted indirect comparison that included randomized clinical trials of tofacitinib, baricitinib, upadacitinib, and filgotinib to assess their equivalence in this scenario. • Our results show that baricitinib and filgotinib are equivalent therapeutic alternatives compared to upadacitinib. However, there is some inconsistency in the results of tofacitinib in front of upadacitinib.

Drug-Related Problems in Elderly Patients Attended to by Emergency Services.

The progressive aging and comorbidities of the population have led to an increase in the number of patients with polypharmacy attended to in the emergency department. Drug-related problems (DRPs) have become a major cause of admission to these units, as well as a high rate of short-term readmissions. Anticoagulants, antibiotics, antidiabetics, and opioids have been shown to be the most common drugs involved in this issue. Inappropriate polypharmacy has been pointed out as one of the major causes of these emergency visits. Different ways of conducting chronic medication reviews at discharge, primary care coordination, and phone contact with patients at discharge have been shown to reduce new hospitalizations and new emergency room visits due to DRPs, and they are key elements for improving the quality of care provided by emergency services.

Anticholinergic burden in patients treated for constipation in an emergency department. / Carga anticolinérgica en pacientes atendidos por estreñimiento en un servicio de ugencias.

OBJECTIVES: To evaluate the anticholinergic burden on discharge of patients treated for constipation in an emergency department (ED) and to assess the effect on emergency revisiting within 30 days. MATERIAL AND METHODS: Observational retrospective cohort study. We collected cases with a discharge diagnosis of constipation after ED treatment between September 2018 and June 2019 and recorded information on all drugs taken and the anticholinergic burden of treatment. A revisit to the ED within 30 days was the primary outcome. RESULTS: We included 104 patients. A high anticholinergic burden of treatment was identified in 47 (56.6%), an intermediate burden in 30 (36.1%), and a low burden in 6 (7.2%). Twenty-nine (27.9%) patients revisited the ED within 30 days of discharge. An intermediate anticholinergic burden (23 patients [31.1%] vs 4 [13.3%]; P = .061) and high burden (19 [40.4%] vs 8 [14.1%]; P = .002] was associated with revisiting within 30 days in the univariate analysis. On multivariate analysis, a high anticholinergic burden was independently associated with a higher rate of revisiting than a low burden: adjusted odds ratio (aOR), 4.21; 95% CI, 1.07-16.5; P = .039. An intermediate load was not associated with more revisits, however: aOR, 1.27; 95% CI, 0.25-6.41; P = .776. Prescription of long-term treatment with laxatives on discharge did not reduce revisiting withing 30-days in the group with a high anticholinergic load (OR, 0.86; 95% CI, 0.48-3.27; P = .526), but it did have an effect in patients an intermediate burden (OR, 0.13; 95% CI, 0.02-0.99; P = .049). CONCLUSION: The prescription of drugs leading to a high anticholinergic burden was a factor associated with ED revisits within 30 days in patients treated for constipation.

OBJETIVO: Evaluar la frecuencia e impacto de la carga anticolinérgica del tratamiento en la reconsulta a los 30 días en los pacientes atendidos por estreñimiento en un servicio de urgencias (SU). METODO: Estudio observacional de cohortes retrospectivo. Se incluyeron por oportunidad pacientes que fueron dados de alta con diagnóstico de estreñimiento desde un SU entre septiembre 2018 y junio 2019. Se recogieron los fármacos y su carga anticolinérgica. La variable de resultado fue la reconsulta por cualquier causa a los 30 días. RESULTADOS: Se incluyeron 104 pacientes, 47 (56,6%) se clasificaron como tratamiento con alta carga colinérgica, 30 (36,1%) intermedia y 6 (7,2%) baja. Veintinueve (27,9%) pacientes sufrieron una reconsulta a urgencias en los primeros 30 días tras el alta. Los pacientes con fármacos con una carga anticolinérgica alta tuvieron una mayor frecuencia de reconsultas a 30 días [19/47 (40,4%) vs 8/57 (14,1%); p = 0,002]. Tras el análisis multivarible, en comparación con aquellos con tratamiento con baja carga anticolinérgica, el tener una alta carga (ORa = 4,21; IC 95% 1,07-16,5; p = 0,039), pero no intermedia (ORa = 1,27; IC 95% 0,25-6,41; p = 0,776), se asoció de forma independiente con una mayor reconsulta a los 30 días. La prescripción de laxantes crónicos al alta no redujo la reconsulta a 30 días en el grupo con alta carga anticolinérgica (OR = 0,86; IC 95% 0,48-3,27; p = 0,526), pero sí en aquellos con carga intermedia (OR = 0,13; IC 95% 0,02-0,99; p = 0,049). CONCLUSIONES: La prescripción de fármacos con alta carga anticolinérgica fue un factor asociado con reconsulta a los 30 días en los pacientes atendidos por estreñimiento en urgencias.

Carga anticolinérgica en pacientes atendidos por estreñimiento en un servicio de ugencias / Anticholinergic burden in patients treated for constipation in an emergency department

OBJETIVO: Evaluar la frecuencia e impacto de la carga anticolinérgica del tratamiento en la reconsulta a los 30 días en los pacientes atendidos por estreñimiento en un servicio de urgencias (SU). MÉTODO: Estudio observacional de cohortes retrospectivo. Se incluyeron por oportunidad pacientes que fueron dados de alta con diagnóstico de estreñimiento desde un SU entre septiembre 2018 y junio 2019. Se recogieron los fármacos y su carga anticolinérgica. La variable de resultado fue la reconsulta por cualquier causa a los 30 días. RESULTADOS: Se incluyeron 104 pacientes, 47 (56,6%) se clasificaron como tratamiento con alta carga colinérgica, 30 (36,1%) intermedia y 6 (7,2%) baja. Veintinueve (27,9%) pacientes sufrieron una reconsulta a urgencias en los primeros 30 días tras el alta. Los pacientes con fármacos con una carga anticolinérgica alta tuvieron una mayor frecuencia de reconsultas a 30 días [19/47 (40,4%) vs 8/57 (14,1%); p = 0,002]. Tras el análisis multivarible, en comparación con aquellos con tratamiento con baja carga anticolinérgica, el tener una alta carga (ORa = 4,21; IC 95% 1,07-16,5; p = 0,039), pero no intermedia (ORa = 1,27; IC 95% 0,25-6,41; p = 0,776), se asoció de forma independiente con una mayor reconsulta a los 30 días. La prescripción de laxantes crónicos al alta no redujo la reconsulta a 30 días en el grupo con alta carga anticolinérgica (OR = 0,86; IC 95% 0,48-3,27; p = 0,526), pero sí en aquellos con carga intermedia (OR = 0,13; IC 95% 0,02-0,99; p = 0,049). CONCLUSIONES: La prescripción de fármacos con alta carga anticolinérgica fue un factor asociado con reconsulta a los 30 días en los pacientes atendidos por estreñimiento en urgencias

OBJECTIVES: To evaluate the anticholinergic burden on discharge of patients treated for constipation in an emergency department (ED) and to assess the effect on emergency revisiting within 30 days. METHODS: Observational retrospective cohort study. We collected cases with a discharge diagnosis of constipation after ED treatment between September 2018 and June 2019 and recorded information on all drugs taken and the anticholinergic burden of treatment. A revisit to the ED within 30 days was the primary outcome. RESULTS: We included 104 patients. A high anticholinergic burden of treatment was identified in 47 (56.6%), an intermediate burden in 30 (36.1%), and a low burden in 6 (7.2%). Twenty-nine (27.9%) patients revisited the ED within 30 days of discharge. An intermediate anticholinergic burden (23 patients [31.1%] vs 4 [13.3%]; P = .061) and high burden (19 [40.4%] vs 8 [14.1%]; P = .002] was associated with revisiting within 30 days in the univariate analysis. On multivariate analysis, a high anticholinergic burden was independently associated with a higher rate of revisiting than a low burden: adjusted odds ratio (aOR), 4.21; 95% CI, 1.07-16.5; P = .039. An intermediate load was not associated with more revisits, however: aOR, 1.27; 95% CI, 0.25-6.41; P = .776. Prescription of long-term treatment with laxatives on discharge did not reduce revisiting withing 30-days in the group with a high anticholinergic load (OR, 0.86; 95% CI, 0.48-3.27; P = .526), but it did have an effect in patients an intermediate burden (OR, 0.13; 95% CI, 0.02-0.99; P = .049). CONCLUSION: The prescription of drugs leading to a high anticholinergic burden was a factor associated with ED revisits within 30 days in patients treated for constipation