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Large-Scale Postmarketing Surveillance of Biological Drugs for Immune-Mediated Inflammatory Diseases Through an Italian Distributed Multi-Database Healthcare Network: The VALORE Project

2021; Adis, Springer Healthcare; Volume: 35; Issue: 6 Linguagem: Inglês

10.1007/s40259-021-00498-3

1179-190X

Gianluca Trifirò, Valentina Isgrò, Ylenia Ingrasciotta, Valentina Ientile, Luca L’Abbate, Saveria Serena Foti, Valeria Belleudi, Francesca Romana Poggi, Andrea Fontana, Ugo Moretti, Riccardo Lora, Alberto Sabaini, Ilenia Senesi, Carla Sorrentino, Maria R. Puzo, Angela Padula, Mariano Fusco, Roberta Giordana, Valentina Solfrini, Aurora Puccini, Paola Rossi, Stefania Del Zotto, Olivia Leoni, Martina Zanforlini, Domenica Ancona, Vito Bavaro, Donatella Garau, Stefano Ledda, Salvatore Scondotto, Alessandra Allotta, Marco Tuccori, Rosa Gini, Giampaolo Bucaneve, David Franchini, Anna Cavazzana, Valeria Biasi, Stefania Spila Alegiani, Marco Massari, Gianluca Trifirò, Ugo Moretti, Riccardo Lora, Alberto Sabaini, Valentina Isgrò, Ylenia Ingrasciotta, Valentina Ientile, Luca L’Abbate, Saveria Serena Foti, Stefania Spila Alegiani, Valeria Belleudi, Francesca Romana Poggi, Andrea Fontana, Marco Massari, Ilaria Andretta, Matilde Tanaglia, Ilenia Senesi, Carla Sorrentino, Maria Rosalia Puzo, Angela Padula, Antonio Carriero, S. Sassano, Caterina De Sarro, Simona Mirarchi, Caterina Palleria, Caterina De Sarro, Mariano Fusco, Roberta Giordana, Marianna Balestrieri, Stefania Rostan, Annalisa Capuano, Francesca Futura Bernardi, Ugo Trama, Alessandro Russo, Maria Grazia Fumo, Valeria Belleudi, Francesca Romana Poggi, Antonio Addis, Felice Musicco, Valentina Solfrini, Ester Sapigni, Aurora Puccini, Ilaria Mazzetti, Debora Podetti, Anna Maria Potenza, Victoria Nikitina, Rita Ricciardelli, Nazanin Mogheiseh, Silvia Croce, Paola Rossi, A. Pettinelli, Stefania Del Zotto, Lucian Ejlli, Olivia Leoni, Ida Fortino, Michele Ercolanoni, Arianna Mazzone, Andrea Angelo Nisic, Simone Schiatti, Monica Ludergnani, Martina Zanforlini, Mauro Mancini, Luigi Patregnani, Paolo Fabbietti, Elisa Antonicelli, Antea Maria Pia Mangano, Annalisa Campomori, Silvana Anna Maria Urru, Giorgio Costa, Giovanni Maria Guarrera, Domenica Ancona, Vito Bavaro, Paolo Stella, Donatella Garau, Enrico Serra, Stefano Ledda, Paolo Carta, Salvatore Scondotto, Alessandra Allotta, Rosa Gini, Marco Tuccori, Alfredo Vannacci, Ersilia Lucenteforte, M Parrilli, Irma Convertino, Giampaolo Bucaneve, Marcello De Giorgi, David Franchini, R Rocchi, Mariangela Rossi, Giovanna Scroccaro, Anna Cavazzana, Valeria Biasi, Paola Deambrosis, Giampietro Grindelli, Eliana Ferroni,

Tuberculosis Research and Epidemiology

Biological drugs have improved the management of immune-mediated inflammatory diseases (IMIDs) despite being associated with important safety issues such as immunogenicity, infections, and malignancies in real-world settings.The aim of this study was to explore the potential of a large Italian multi-database distributed network for use in the postmarketing surveillance of biological drugs, including biosimilars, in patients with IMID.A retrospective cohort study was conducted using 13 Italian regional claims databases during 2010-2019. A tailor-made R-based tool developed for distributed analysis of claims data using a study-specific common data model was customized for this study. We measured the yearly prevalence of biological drug users and the frequency of switches between originator and biosimilars for infliximab, etanercept, and adalimumab separately and stratified them by calendar year and region. We then calculated the cumulative number of users and person-years (PYs) of exposure to individual biological drugs approved for IMIDs. For a number of safety outcomes (e.g., severe acute respiratory syndrome coronavirus 2 [SARS-COV-2] infection), we conducted a sample power calculation to estimate the PYs of exposure required to investigate their association with individual biological drugs approved for IMIDs, considering different strengths of association.From a total underlying population of almost 50 million inhabitants from 13 Italian regions, we identified 143,602 (0.3%) biological drug users, with a cumulative exposure of 507,745 PYs during the entire follow-up. The mean age ± standard deviation of biological drug users was 49.3 ± 16.3, with a female-to-male ratio of 1.2. The age-adjusted yearly prevalence of biological drug users increased threefold from 0.7 per 1000 in 2010 to 2.1 per 1000 in 2019. Overall, we identified 40,996 users of biosimilars of tumor necrosis factor (TNF)-α inhibitors (i.e., etanercept, adalimumab, and infliximab) in the years 2015-2019. Of these, 46% (N = 18,845) switched at any time between originator and biosimilars or vice versa. To investigate a moderate association (incidence rate ratio 2) between biological drugs approved for IMIDs and safety events of interest, such as optic neuritis (lowest background incidence rate 10.4/100,000 PYs) or severe infection (highest background incidence rate 4312/100,000 PYs), a total of 43,311 PYs and 104 PYs of exposure to individual biological drugs, respectively, would be required. As such, using this network, of 15 individual biological drugs approved for IMIDs, the association with those adverse events could be investigated for four (27%) and 14 (93%), respectively.The VALORE project multi-database network has access to data on more than 140,000 biological drug users (and > 0.5 million PYs) from 13 Italian regions during the years 2010-2019, which will be further expanded with the inclusion of data from other regions and more recent calendar years. Overall, the cumulated amount of person-time of exposure to biological drugs approved for IMIDs provides enough statistical power to investigate weak/moderate associations of almost all individual compounds and the most relevant safety outcomes. Moreover, this network may offer the opportunity to investigate the interchangeability of originator and biosimilars of several TNFα inhibitors in different therapeutic areas in real-world settings.