Assessing disease activity of rheumatoid arthritis patients and drug-utilization patterns of biologic disease-modifying antirheumatic drugs in the Tuscany region, Italy

Introduction: The disease activity associated with the drug-utilization patterns of biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs) is poorly investigated in real-world studies on rheumatoid arthritis (RA) patients. To investigate the relationship between biologic DMARD initiation/discontinuations in RA patients identified in the healthcare administrative databases of Tuscany and the Disease Activity Score 28 (DAS28) reported in the medical charts.Methods: This retrospective population-based study included RA’s first-ever biologic DMARD users of the Pisa University Hospital from 2014 to 2016. Patients were followed up until 31 December 2019. We evaluated the DAS28 recorded before (T0) and after (T1) the biologic DMARD initiation and before (TD0) and after (TD1) discontinuations. Patients were classified as “off-target” (DAS28 > 3.2) or “in-target” (DAS28 ≤ 3.2). We described the disease activity trends at initiation and discontinuation.Results: Ninety-five users were included (73 women, mean age 59.6). Among 70 patients (74%) with at least three DAS28 measures, 28 (40.0%) were off-target at T0 and 38 (54.3%) in-target at T1. Thirty-three (47%) patients had at least one discontinuation, among those with at least three DAS28 assessments. In the disease activity trend, disease stability or improvement was observed in 28 out of 37 (75.7%) patients at initiation and in 24 out of 37 (64.9%) at discontinuation.Discussion: Biologic DMARD discontinuations identified in the healthcare administrative databasese of Tuscany are frequently observed in situations of controlled RA disease. Further studies are warranted to confirm that these events can be used in studies using healthcare administrative databases as proxies of treatment effectiveness

Covid-19 vaccines-induced thrombosis with thrombocytopenia syndrome: a case series study of the openly accessible data of the Italian Pharmacovigilance national network

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has spread around the world with over 200 million confirmed cases and over 4 million deaths as at 26 August 2021. The extraordinary effort of the COVID-19 vaccination campaign is changing the course of this pandemic, drastically reducing the number of serious cases and deaths worldwide. As part of the enhanced surveillance of vaccines used against COVID-19, a continuous pharmacovigilance activity is ongoing to closely monitor the safety profile of available vaccines. This monitoring is based on reports made by healthcare professionals, vaccinated person or their families, with the aim of identify signals of potential adverse events that can allow regulatory agencies to issue appropriate risk minimization measures. In the first weeks of March 2021, several reports of unusual thrombotic events, in combination with thrombocytopenia after vaccination with the adenoviral vaccine Vaxzevria, caused concerns in the scientific community. Subsequent reports of similar cases also associated with the COVID-19 Janssen adenoviral vaccine reinforced the hypothesis that this new adverse event could have been triggered by adenovirus-based SARS-CoV-2 vaccines. This event is rare and characterized by cerebral and / or splanchnic venous thrombosis that can occurs even in healthy individuals. This clinical picture is often associated with thrombocytopenia and bleeding, and sometimes disseminated intravascular coagulation (DIC). Such new clinical entity has been termed vaccine-induced thrombotic immune thrombocytopenia (VITT) or thrombosis with thrombocytopenia syndrome (TTS). VITT was mainly observed in women under < 55 years-old within two weeks from vaccine administration, and it has a high mortality rate. The identification of this potential adverse event has prompted drug regulatory agencies to strengthen pharmacovigilance programs and provide some advice to limit the use of adenovirus-based vaccines to possibly sensible subjects. The present thesis is aimed at analyzing the reports collected in the Italian Pharmacovigilance database (National Pharmacovigilance Network [RNF]), concerning thrombotic events associated with thrombocytopenia following COVID-19 vaccination and providing a comprehensive review of the epidemiological problems, pathogenetic hypotheses and treatment strategies of this rare syndrome VITT

Investigating a Signal of Acquired Hemophilia Associated with COVID-19 Vaccination: A Systematic Case Review

Acquired hemophilia A (AHA), a rare but life-threatening disorder, most commonly occurs in older people and during pregnancy. During the coronavirus disease 2019 (COVID-19) vaccination campaign, an unexpected number of newly diagnosed AHA patients have been identified in clinical practice that were temporally related to COVID-19 vaccination. We present the result of a signal detection analysis aimed at exploring a possible association between COVID-19 immunization and occurrence of AHA. A disproportionality analysis on the World Health Organization (WHO) database was performed to investigate the presence of a signal of risk for AHA associated with COVID-19 vaccines. Reports of AHA associated with any COVID-19 vaccine included in the WHO database were then integrated with those available on the Food and Drug Administration Vaccine Adverse Events Reporting System and those published in the medical literature. The WHO database included 146 reports of AHA. The information component (IC) was significant for the association of AHA with all COVID-19 vaccines (IC025: 1.1) and with the vaccine product BNT162b2 (IC025: 1.6). After duplicate exclusion, 96 unique cases of AHA following COVID-19 vaccines have been reviewed. Median time to diagnosis was 18 days and 40% of cases documented the occurrence after the second dose. Overall, in 57% of the investigated cases, a preexisting condition predisposing to AHA was excluded. About 22% of cases occurred in subjects with age ≤65 years and there was no case associated with pregnancy. Mortality was 11%. Although we cannot exclude that the unexpected frequency of AHA diagnosis can be explained by a detection bias, the signal for COVID-19 vaccine-related AHA is robust and deserves further investigations

Drug-Utilization, Healthcare Facilities Accesses and Costs of the First Generation of JAK Inhibitors in Rheumatoid Arthritis

: This study is aimed at describing tofacitinib and baricitinib users by characterizing their prescription and healthcare histories, drug and healthcare utilization patterns, and direct costs from a healthcare system perspective. This retrospective cohort study was performed using Tuscan administrative healthcare databases, which selected two groups of Janus kinase inhibitors (JAKi) incident users (index date) from 1st January 2018 to 31 December 2019 and from 1 January 2018 to 30 June 2019. We included patients ≥18 years old, at least 10 years of data, and six months of follow-up. In the first analysis, we describe mean time, standard deviation (SD), from the first-ever disease-modifying antirheumatic drug (DMARD) to the JAKi, and costs of healthcare facilities and drugs in the 5 years preceding the index date. In the second analysis, we assessed Emergency Department (ED) accesses and hospitalizations for any causes, visits, and costs in the follow-up. In the first analysis, 363 incident JAKi users were included (mean age 61.5, SD 13.6; females 80.7%, baricitinib 78.5%, tofacitinib 21.5%). The time to the first JAKi was 7.2 years (SD 3.3). The mean costs from the fifth to the second year before JAKi increased from 4325 € (0; 24,265) to 5259 € (0; 41,630) per patient/year, driven by hospitalizations. We included 221 incident JAKi users in the second analysis. We observed 109 ED accesses, 39 hospitalizations, and 64 visits. Injury and poisoning (18.3%) and skin (13.8%) caused ED accesses, and cardiovascular (69.2%) and musculoskeletal (64.1%) caused hospitalizations. The mean costs were 4819 € (607.5; 50,493) per patient, mostly due to JAKi. In conclusion, the JAKi introduction in therapy occurred in compliance with RA guidelines and the increase in costs observed could be due to a possible selective prescription

Biosimilars approvals by thirteen regulatory authorities: A cross-national comparison

Biosimilars are biological medicines highly similar to a previously licensed reference product and their licensing is expected to improve access to biological therapies. This study aims to present an overview of biosimilars approval by thirteen regulatory authorities (RA). The study is a cross-national comparison of regulatory decisions involving biosimilars in Argentina, Australia, Brazil, Chile, Canada, Colombia, Europe, Hungary, Guatemala, Italy, Mexico, Peru and United States. We examined publicly available documents containing information regarding the approval of biosimilars and investigated the publication of public assessment reports for registration applications, guidelines for biosimilars licensing, and products approved. Data extraction was conducted by a network of researchers and regulatory experts. All the RA had issued guidance documents establishing the requirements for the licensing of biosimilars. However, only three RA had published public assessment reports for registration applications. In total, the investigated jurisdictions had from 19 to 78 biosimilars approved, most of them licensed from 2018 to 2020. In spite of the advance in the number of products in recent years, some challenges still persist. Limited access to information regarding the assessment of biosimilars by RA can affect confidence, which may ultimately impact adoption of these products in practice.Fil: Machado, Fernanda Lacerda da Silva. Universidade Federal do Rio de Janeiro; BrasilFil: Cañás, Martín. Universidad Nacional Arturo Jauretche; ArgentinaFil: Doubova, Svetlana V.. Mexican Institute Of Social Security; MéxicoFil: Urtasun, Martín Alejandro. Universidad Nacional Arturo Jauretche; ArgentinaFil: Marin, Gustavo Horacio. Universidad Nacional de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Osorio de Castro, Claudia Garcia Serpa. Instituto Oswaldo Cruz; BrasilFil: Albuquerque, Flavia Caixeta. Sorocaba University; BrasilFil: Ribeiro, Tatiane Bonfim. Universidade de Sao Paulo; BrasilFil: Pont, Lisa. University of Technology Sydney; AustraliaFil: Crisóstomo Landeros, José. Instituto de Salud Pública de Chile; ChileFil: Roldán Saelzer, Juan. Instituto de Salud Pública de Chile; ChileFil: Sepúlveda Viveros, Dino. Universidad del Desarrollo; Chile. Universidad Autónoma de Chile; ChileFil: Acosta, Angela. Universidad Icesi; ColombiaFil: Machado Beltrán, Manuel A.. Universidad Nacional de Colombia; ColombiaFil: Gordillo Alas, Lily Iracema. Ministry of Public Health and Social Assistance; GuatemalaFil: Orellana Tablas, Lourdes Abigail. Ministry of Public Health and Social Assistance; GuatemalaFil: Benko, Ria. University of Szeged; HungríaFil: Convertino, Irma. University of Pisa; ItaliaFil: Bonaso, Marco. University of Pisa; ItaliaFil: Tuccori, Marco. University of Pisa; ItaliaFil: Kirchmayer, Ursula. Lazio Regional Health Service; ItaliaFil: Contreras Sánchez, Saúl E.. Mexican Institute of Social Security; MéxicoFil: Rodríguez Tanta, L. Yesenia. Universidad Cientifica del Sur;Fil: Gutierrez Aures, Ysabel. Ministry of Health of Peru; PerúFil: Lin, Boya. University of Florida; Estados UnidosFil: Alipour Haris, Golnoosh. University of Florida; Estados UnidosFil: Eworuke, Efe. Real World Solutions; Estados UnidosFil: Lopes, Luciane Cruz. Sorocaba University; Brasi

DataSheet1_Assessing disease activity of rheumatoid arthritis patients and drug-utilization patterns of biologic disease-modifying antirheumatic drugs in the Tuscany region, Italy.pdf

Introduction: The disease activity associated with the drug-utilization patterns of biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs) is poorly investigated in real-world studies on rheumatoid arthritis (RA) patients. To investigate the relationship between biologic DMARD initiation/discontinuations in RA patients identified in the healthcare administrative databases of Tuscany and the Disease Activity Score 28 (DAS28) reported in the medical charts.Methods: This retrospective population-based study included RA’s first-ever biologic DMARD users of the Pisa University Hospital from 2014 to 2016. Patients were followed up until 31 December 2019. We evaluated the DAS28 recorded before (T0) and after (T1) the biologic DMARD initiation and before (TD0) and after (TD1) discontinuations. Patients were classified as “off-target” (DAS28 > 3.2) or “in-target” (DAS28 ≤ 3.2). We described the disease activity trends at initiation and discontinuation.Results: Ninety-five users were included (73 women, mean age 59.6). Among 70 patients (74%) with at least three DAS28 measures, 28 (40.0%) were off-target at T0 and 38 (54.3%) in-target at T1. Thirty-three (47%) patients had at least one discontinuation, among those with at least three DAS28 assessments. In the disease activity trend, disease stability or improvement was observed in 28 out of 37 (75.7%) patients at initiation and in 24 out of 37 (64.9%) at discontinuation.Discussion: Biologic DMARD discontinuations identified in the healthcare administrative databasese of Tuscany are frequently observed in situations of controlled RA disease. Further studies are warranted to confirm that these events can be used in studies using healthcare administrative databases as proxies of treatment effectiveness.</p

An overview of biosimilars approvals by thirteen regulatory authorities: A cross national comparison

Biosimilars are biological medicines highly similar to a previously licensed reference product and their licensing is expected to improve access to biological therapies. This study aims to present an overview of biosimilars approval by thirteen regulatory authorities (RA). The study is a cross-national comparison of regulatory decisions involving biosimilars in Argentina, Australia, Brazil, Chile, Canada, Colombia, Europe, Hungary, Guatemala, Italy, Mexico, Peru and United States. We examined publicly available documents containing information regarding the approval of biosimilars and investigated the publication of public assessment reports for registration applications, guidelines for biosimilars licensing, and products approved. Data extraction was conducted by a network of researchers and regulatory experts. All the RA had issued guidance documents establishing the requirements for the licensing of biosimilars. However, only three RA had published public assessment reports for registration applications. In total, the investigated jurisdictions had from 19 to 78 biosimilars approved, most of them licensed from 2018 to 2020. In spite of the advance in the number of products in recent years, some challenges still persist. Limited access to information regarding the assessment of biosimilars by RA can affect confidence, which may ultimately impact adoption of these products in practice.Facultad de Ciencias Médica