medwireNews: A population-based cohort study evaluating a range of systemic therapies for psoriatic disease suggests that biologics targeting interleukin (IL)-12, 23, and 17 reduce the risk for serious infections among adults aged 66 years and older versus no therapy.
“For older adults with psoriatic disease, among whom the baseline risk of infection is higher than younger populations, biologics targeting IL-12, IL-23, and IL-17 may offer important safety benefits over other treatment options, which should be considered when making clinical and policy decisions,” write the researchers in JAMA Dermatology.
Aaron Drucker, from the Women’s College Hospital in Toronto, Ontario, Canada, and colleagues examined the risk for serious infections, defined as hospitalization for infection as the primary reason for admission, in 11,641 adults (mean age 73 years, 53% women) with psoriasis (73%), psoriasis and psoriatic arthritis (24%), or psoriatic arthritis alone (4%).
The study participants initiated systemic therapy between 2002 and 2020, primarily methotrexate in 49.1% of patients, while the remaining patients started on older systemic agents such as cyclosporine, acitretin, sulfasalazine, and leflunomide, tumor necrosis factor (TNF) inhibitors, IL-12/23 or IL-17 inhibitors, or tofacitinib.
During a median follow-up of 4.8 years, the number of people exposed to each therapy was 6751 for methotrexate, 6176 for older systemic agents, 1300 for TNF inhibitors, 1434 for IL-targeting biologics, and 110 for tofacitinib.
Over the same time period, 12% of the patients were hospitalized with a total of 1967 serious infections.
This equated to 2.7 serious infections per 100 person–years during methotrexate use, 2.5 per 100 person–years during the use of other older systemic agents, 2.2 per 100 person–years with TNF inhibitor use, 1.4 per 100 person–years with IL-12/23 or IL-17 biologic use, and 8.9 per 100 person–years with tofacitinib use.
“The most common infections were pneumonia (n=581), urinary tract infections (n=502), sepsis (n= 433), and cellulitis (n=250),” state the authors. There were also 36 hospitalizations for COVID-19.
In multivariable analyses comparing the risk for serious infection in people when using each medication compared with when they were not, the use of biologics targeting IL-12, 23, or 27 was associated with a 35% lower risk for serious infection (relative risk [RR]=0.65), the researchers report.
When analyzed separately, both IL-12/23 inhibitors and IL-17 inhibitors were significantly associated with lower infection rates, with RRs of 0.68 and 0.59, respectively.
By comparison, the risk for serious infection was nearly threefold higher during tofacitinib use (RR=2.89), and unaffected during the use of methotrexate (RR=0.95), older systemic agents (RR=0.92), or TNF inhibitors (RR=0.87) compared with periods of no therapy.
The results were consistent when deaths due to infection outside of the hospital were included in a secondary analysis, and across multiple sensitivity analyses that excluded cellulitis cases and prior infection history or were restricted to patients without a rheumatoid arthritis diagnosis.
Similar patterns were also seen in subgroup analyses by sex and psoriatic disease phenotype. The only exceptions being that the protective effect of the IL-targeting biologics appeared attenuated in women, while the use of methotrexate, older systemic agents, and TNF inhibitors in individuals with both psoriasis and psoriatic arthritis was associated with “lower rates of infection than in the main analysis,” observes the team.
Drucker et al point out that some payers in Ontario follow mandated step therapy (MST), where older therapies are used first “for potential cost savings,” including in older adults, despite “a lack of comparative safety data in this vulnerable population.”
In an accompanying editor’s note, Andrea Maderal, from the University of Miami Miller School of Medicine in Florida, USA, explains that MST requires patients in Canada to try and fail “2 of 3 initial systemic therapies before initiating therapy with biologics.”
She adds that the study by Drucker and colleagues “provides evidence in support of direct initiation of newer biologic therapies in older adult patients with psoriasis who require systemic treatment,” and that the findings “highlight the need for more nuanced considerations when selecting ideal therapies for patients and the potential harms of blanket MST programs.”
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JAMA Dermatol 2025; doi:10.1001/jamadermatol.2025.0144
JAMA Dermatol 2025; doi:10.1001/jamadermatol.2025.0141
