Comparative risk of serious infections across biological drugs in patients with psoriatic arthritis or psoriasis: A target trial emulation using the Italian VALORE distributed database network
Risk of serious infections with biological drugs for psoriasis (PsO) and psoriatic arthritis (PsA) remains uncertain, particularly with long-term exposure and in older adults. We aimed to assess the comparative risk of serious infections among biological agents used for PsO/PsA. Using the Italian VALORE distributed database (2015-2021), we conducted a retrospective cohort study replicating the EXCEED trial (adalimumab vs. secukinumab), followed by a second-stage cohort extending follow-up, restricting analyses to older patients, and comparing other biological drugs. For replication, new users of adalimumab or secukinumab with PsO/PsA meeting observational analogues of EXCEED eligibility criteria were included. Additional new-user cohorts of etanercept, infliximab, ixekizumab, and ustekinumab were selected in second-stage analyses. Hazard ratio (HR) of hospitalization for serious infections was evaluated using Cox models. In second-stage cohort, the risk was evaluated over a long-term follow-up (3years) and in older patients. Risk of serious infection was similar for secukinumab (n = 2256) compared to adalimumab (n = 6441) at 1 year (HR:0.74 [CI:0.36-1.48]), consistent with EXCEED estimates (p = 0.54). No significant differences were observed at 3 years (HR:0.70 [CI:0.42-1.18]) or in older adults (HR:1.25 [CI:0.40-3.95]). Compared with adalimumab, infliximab showed higher risk (HR:2.66 [CI:1.04-6.78]), whereas ixekizumab showed a lower risk in older adults (HR:0.12 [CI:0.01-0.92]). Overall, incidence rates were higher among older users, with similar estimates across short- and long-term follow-up periods. Infliximab was the only biological drug associated with a higher risk of serious infections compared with adalimumab. Older adults had higher incidence rates, with comparable risks across short- and long-term treatment.
Authors
- Flávia Mayer (ORCID: https://orcid.org/0000-0003-0176-4208)
- Ester Sapigni
- Valeria Belleudi (ORCID: https://orcid.org/0000-0002-8286-443X)
- Luca L’Abbate (ORCID: https://orcid.org/0000-0003-0232-6402)
- Aurora Puccini
- Martina Zanforlini
- Giampaolo Bucaneve (ORCID: https://orcid.org/0009-0002-2695-9845)
- Domenica Ancona
- Paolo Carta
- Sebastiano Addario Pollina
- Massimo Carollo (ORCID: https://orcid.org/0000-0002-6523-6036)
- Ilenia Senesi
- Anna Cavazzana
- Stefania Spila Alegiani (ORCID: https://orcid.org/0000-0003-0656-1346)
- Elisabetta Patorno (ORCID: https://orcid.org/0000-0002-8809-9898)
- Chiara Bellitto (ORCID: https://orcid.org/0009-0000-5552-1506)
- Marco Tuccori (ORCID: https://orcid.org/0000-0002-7979-8486)
- Stefano Ledda
- Gianluca Trifirò (ORCID: https://orcid.org/0000-0003-1147-7296)
- Ugo Trama (ORCID: https://orcid.org/0000-0001-9473-8943)
- Andrea Fontana
- Carla Sorrentino
- Olivia Leoni (ORCID: https://orcid.org/0000-0002-6906-2424)
- Paolo Stella
- Alessandra Allotta (ORCID: https://orcid.org/0009-0006-2397-4977)
- Giovambattista De Sarro (ORCID: https://orcid.org/0000-0002-7629-6579)
- Rosa Gini (ORCID: https://orcid.org/0000-0002-6250-877X)
- Andrea Spini (ORCID: https://orcid.org/0000-0001-7496-5575)
- Lucian Ejlli
- Angela Scapin
- Francesca Futura Bernardi
- Roberto Da (ORCID: https://orcid.org/0000-0003-3416-6714)
- Antea Maria Pia Mangano
- Rita Francesca Scarpelli
- Francesco Balducci
- Paola Rossi
- Claudio Guarneri
- Paolo Gisondi
- Marco Massari
- Sara Lopes
- Ylenia Ingrasciotta
Institutions
- University of Messina (IT)
- University of Verona (IT)
- University of Teramo (IT)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Casa Sollievo della Sofferenza (IT)
- Magna Graecia University (IT)
- Agenzia Sanitaria e Sociale Regionale (IT)
- Regione Siciliana (IT)
- Regione Puglia (IT)
- National Observatory (BR)
- University of Campania "Luigi Vanvitelli" (IT)
- Accademia di Belle Arti di Catanzaro (IT)
- Regione del Veneto (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Agenzia Regionale di Sanità della Toscana (IT)
- Agenzia Sanitaria Regionale Abruzzo (IT)
- Regione Emilia-Romagna
- Regione Autonoma della Sardegna
- Regione Autonoma Friuli Venezia Giulia (IT)
- Regione Umbria
Publication Details
- Journal
- Pharmacological Research
- Published
- 2026-04-20
- DOI
- https://doi.org/10.1016/j.phrs.2026.108198
- Primary Topic
- Spondyloarthritis Studies and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Agenzia Italiana del Farmaco, Ministero della Salute