Ustekinumab Linked to Lower 5-Year Cancer Risk vs Adalimumab in Psoriasis

A new study observed no substantial differences in overall cancer risk between the biologics of adalimumab, secukinumab, or ustekinumab. However, ustekinumab was associated with a numerically lower 5-year standardized risk of any first cancer compared with adalimumab.1

“Risk estimates for ustekinumab were numerically lowest; although precision was limited for secukinumab and should be interpreted with caution, the low incidence suggests a clinically reassuring signal given the growing use of IL-17 inhibitors,” wrote investigators, led by Christopher Willy Schwarz, MD, from the department of dermatology and allergy at Copenhagen University Hospital, Herlev and Gentofte Hospital.1

Biologic therapies for moderate to severe psoriasis may affect the body’s ability to detect and control cancer development. In a nationwide Danish cohort study, investigators investigated the risk of developing any first cancer, excluding nonmelanoma skin cancer, in patients with psoriasis treated with these biologics. They used an active comparator, a new-user design to emulate a head-to-head randomized trial.

The sample included 2876 patients with psoriasis who were new to biologics and had no history of cancer. In total, 62.8% were males, and the mean age was 44.6 years. Participants were either on adalimumab (n = 2001; mean age, 45.1; 62.3% males), secukinumab (n = 286; mean age, 43.5 years; 64.3% males), or ustekinumab (n = 591; mean age, 43.5 years; 63.8% males).1

Previous treatments included methotrexate (adalimumab = 92.6%; secukinumab = 95.55%, ustekinumab = 90.2%), cyclosporine (adalimumab = 10.8%, secukinumab = 5.6% ustekinumab = 8.3%), and acitretin (adalimumab = 30.8%; secukinumab = 31.5%, ustekinumab = 36.9%). Comorbidities included psoriatic arthritis (PsA) (26.9%, 36%, 15.6%, respectively), type 2 diabetes (8.6%, 8.4%, 7.1%), alcohol-associated conditions (9.4%, 11.2%, 10.2%), dyslipidemia (19.4%, 18.5%, 17.1%), ischemic heart disease (5.3%, 4.2%, 4.1%), and COPD (2.5%, 2.1%, 3.2%).1

Investigators implemented a 12-month lag period following treatment initiation and another 12-month lag after discontinuation to account for cancer induction and latency periods. A secondary analysis extended these lag periods to 24 months. They estimated the 5-year standardized risks of any first cancer using the g-formula with Cox proportional hazards regression models adjusted for age, sex, and PsA.

With 12-month lag periods applied, investigators identified 36 first cancers over 4120 person-years in the adalimumab group, 5 over 706 person-years in the secukinumab group, and 10 over 2242 person-years in the ustekinumab group. Using 12-month lag times again, the 5-year standardized cancer absolute risks were 0.040 (95% confidence interval [CI], 0.024-0.056) for adalimumab, 0.036 (95% CI, 0.005-0.066) for secukinumab, and 0.024 (95% CI, 0.009-0.040) for ustekinumab.1

The analysis estimated that a 5-year cancer risk is 41% (95% CI, −1% to 82%) lower with ustekinumab than adalimumab (P =.06) and 12% (95% CI, −69% to 93%) lower with secukinumab than adalimumab (P =.77). When 24-month lag periods were applied, the findings strengthened, with the analysis estimating a 56% lower 5-year cancer risk for ustekinumab compared with adalimumab (95% CI, 24%-88%; P < .001).1

For clinicians, these results are reassuring regarding the long-term malignancy risk of IL-12/23 (ustekinumab) and IL-17 (secukinumab) inhibitors compared with TNF inhibitors (adalimumab), supporting their continued use in psoriasis management. Investigators wrote that the results aligned with another study that found tumor necrosis factor inhibitors were associated with a greater risk of certain cancers, including non-Hodgkin lymphoma, colorectal cancer, hepatobiliary cancer, ovarian cancer, melanoma, and basal cell carcinoma, compared with IL-17 and IL-23.2 The previous study had not included lag times to account for the time it takes for cancer to develop, unlike this recent study.

“Study limitations include inability to investigate risks for specific cancers,” Schwarz and colleagues wrote.1 “Larger studies on specific cancers are needed to confirm the results.”

References

1. Schwarz CW, Rasmussen MK, Bertelsen T, Iversen L, Skov L, Loft N. Comparative Cancer Risk in Patients With Psoriasis Treated With Adalimumab, Secukinumab, or Ustekinumab. JAMA Dermatol. Published online October 22, 2025. doi:10.1001/jamadermatol.2025.3928

2. Kridin K, Abdelghaffar M, Mruwat N, Ludwig RJ, Thaçi D. Are interleukin 17 and interleukin 23 inhibitors associated with malignancies?-Insights from an international population-based study. J Eur Acad Dermatol Venereol. 2024;38(2):315-324. doi:10.1111/jdv.19520