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.