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Biologics / Biosimilars

5F-06 - Randomized clinical trial replication and second-stage study to evaluate the risk of serious infections in biological drug users with psoriatic arthritis/psoriasis using the Italian VALORE distributed database network

Tuesday, August 26, 2025
9:45 AM - 10:00 AM ET
Location: 207AB

    Presenting Author(s)

  • Andrea Spini

    Department of Diagnostics and Public Health, University of Verona, Verona, Italy, Italy

    • Co-Author(s)

  • LL

    Luca L'Abbate

    Department of Diagnostics and Public Health, University of Verona, Verona, Italy, Italy

  • MC

    Massimo Carollo

    University of Verona, Verona, Italy

  • Ylenia Ingrasciotta

    Department of Diagnostics and Public Health, University of Verona, Verona, Italy, Italy

  • FS

    Federica Soardo

    Department of Diagnostics and Public Health, University of Verona, Verona, Italy, Italy

  • CB

    Chiara Bellitto

    Department of Diagnostics and Public Health, University of Verona, Verona, Italy, Italy

  • GP

    Giorgia Pellegrini

    Department of Diagnostics and Public Health, University of Verona, Verona, Italy, Italy

  • OL

    Olivia Leoni

    Lombardy Regional Epidemiologic Observatory, Milan, Italy, Italy

  • MZ

    Martina Zanforlini

    Lombardy Region, Italy

  • DA

    Domenica Ancona

    Apulian Regional Health Department, Bari, Italy, Italy

  • PS

    Paolo Stella

    Apulian Regional Health Department, Bari, Italy, Italy

  • AC

    Anna Cavazzana

    Azienda Zero, Regione Veneto, Italy, Italy

  • AS

    Angela Scapin

    Azienda Zero, Regione Veneto, Italy, Italy

  • SL

    Sara Lopes

    Department of Epidemiology, Lazio Regional Health Service, Rome, Italy, Italy

  • VB

    Valeria Belleudi

    Department of Epidemiology ASL Roma 1, Italy

  • SL

    Stefano Ledda

    Regione Autonoma della Sardegna, Cagliari, Italy, Italy

  • PC

    Paolo Carta

    Regione Autonoma della Sardegna, Cagliari, Italy, Italy

  • PR

    Paola Rossi

    Friuli-Venezia Giulia Regional Center of Pharmacovigilance, Trieste, Italy, Italy

  • LE

    Lucian Ejlli

    Friuli-Venezia Giulia Regional Center of Pharmacovigilance, Trieste, Italy, Italy

  • ES

    Ester Sapigni

    Emilia-Romagna Regional Center of Pharmacovigilance, Bologna, Italy, Italy

  • AP

    Aurora Puccini

    Emilia-Romagna Regional Center of Pharmacovigilance, Bologna, Italy, Italy

  • RS

    Rita Francesca Scarpelli

    Dipartimento Salute e Welfare, Calabria region, Catanzaro, Italy, Italy

  • GD

    Giovambattista De Sarro

    University “Magna Graciae” of Catanzaro, Catanzaro, Italy, Italy

  • AA

    Alessandra Allotta

    Epidemiologic Observatory of the Sicily Regional Health Service, Palermo, Italy, Italy

  • SA

    Sebastiano Addario Pollina

    Epidemiologic Observatory of the Sicily Regional Health Service, Palermo, Italy, Italy

  • RD

    Roberto Da cas

    Italian National Institute of Health, Rome, Italy, Italy

  • GB

    Giampaolo Bucaneve

    Umbria Regional Centre of Pharmacovigilance, Perugia, Italy, Italy

  • AM

    Antea Maria Pia Mangano

    Agenzia regionale sanitaria della regione Marche, Ancona, Italy, Italy

  • FB

    Francesco Balducci

    Agenzia regionale sanitaria della regione Marche, Ancona, Italy, Italy

  • CS

    Carla Sorrentino

    Regional Pharmaceutical Unit, Abruzzo Region, Italy, Italy

  • IS

    Ilenia Senesi

    Abruzzo Regional Centre of Pharmacovigilance, Teramo, Italy, Italy

  • MT

    Marco Tuccori

    University of Verona, Verona, Italy

  • Rosa Gini, PhD

    Agenzia Regionale di Sanità della Toscana (ARS Toscana), Florence, Italy, Italy

  • UT

    Ugo Trama

    Regional Pharmaceutical Unit, Campania Region, Naples, Italy., Italy

  • FB

    Francesca Futura Bernardi

    Department of Pharmacology, University of Campania “Luigi Vanvitelli”, Naples, Italy., Italy

  • FM

    Flavia Mayer

    Italian National Institute of Health, Rome, Italy, Italy

  • SS

    Stefania Spila Alegiani

    Italian National Institute of Health, Rome, Italy, Italy

  • MM

    Marco Massari

    Italian National Institute of Health, Rome, Italy, Italy

  • CG

    Claudio Guarneri

    Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy, Italy

  • PG

    Paolo Gisondi

    Department of Medicine, University of Verona, Verona, Italy, Italy

  • aF

    andrea Fontana

    Unit of Biostatistics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy, Italy

  • Elisabetta Patorno, MD, DrPH

    Brigham and Women's Hospital
    Boston, Massachusetts, United States

  • GT

    Gianluca Trifirò

    Department of Diagnostics and Public Health, University of Verona, Verona, Italy, Italy

Background: The evidence on the risk of serious infections with different biological drugs in patients with psoriasis (PsO) or psoriatic arthritis (PsA) remains scarce, particularly in the long term and in older patients. The information from head-to-head comparisons among biological drugs is also limited.

Objectives: To assess the risk of serious infections associated with different biological drugs in PsO or PsA patients in a study replicating an index trial and, to conduct a “second-stage” study to explore the risk of infections in the setting of long-term follow-up, older age, and head-to-head comparisons among individual biological drugs.

Methods: Using the Italian VALORE distributed database network, we replicated the EXCEED randomized clinical trial (index trial) using a cohort study. After applying observational analogues of the inclusion/exclusion criteria of the index trial, first-ever users of adalimumab and secukinumab were selected from 01/2015 to 12/2021. We used a propensity score fine stratification to balance baseline characteristics. The agreement between the replication study and the index trial was statistically assessed by comparing risk ratios of serious infections using a log-binomial model and looking at the significance of the drug-by-study interaction term. Finally, in a “second stage study” based on the same study design, we assessed the risk of serious infections at 3 years of follow-up and in older patients (≥ 65 years old), comparing secukinumab vs other biologics approved for PsO/PsA (etanercept, infliximab, ixekizumab, and ustekinumab). We estimated hazard ratios (HR) and 95% CI in Cox proportional hazard models.

Results: Overall, we included 6,495 and 2,258 adalimumab and secukinumab initiators and identified agreement of serious infection estimates between index trial and replication (p=0.54). Compared to adalimumab, new users of secukinumab had a similar risk of infections at one year of follow-up (HR: 0.74; 95%CI: 0.36-1.48), at 3 years of follow-up (HR: 0.70; 95%CI: 0.42-1.18), and among older patients (HR: 1.25; 95%CI: 0.4-3.96). When adalimumab was compared to other biologics, only infliximab was associated with an increased risk of serious infection (HR: 2.66; 95%CI: 1.04-6.78), while we observed a trend towards a lower risk of infections for ixekizumab (HR: 0.41; 95%CI: 0.12-1.43)

Conclusions: In this study, new users of secukinumab and adalimumab had a similar risk of serious infections in the long-term and among older people. As expected, we observed a higher risk of infections among infliximab users compared with adalimumab users. Replication of an index trial and conduction of a second-stage study can provide reliable evidence with respect to questions on the safety of biological drugs that remain unanswered in RCTs.