Biologic Therapies Show Favorable Cancer Safety Profile in Psoriatic Disease Patients
Key Insights
TNF inhibitors demonstrated a statistically significant 20% reduction in primary malignancy risk among psoriasis (search) patients compared to biologic-naïve controls in a large retrospective study.
Long-term ixekizumab treatment showed cancer incidence rates consistent with general U.S. population rates across psoriatic diseases and axial spondyloarthritis (search) patients.
Both studies support the oncologic safety of biologic therapies, with TNF inhibitors showing particular benefit in reducing nonmelanoma skin cancer (search) risk.
Two major studies provide compelling evidence that biologic therapies for psoriatic diseases carry favorable cancer safety profiles, with TNF inhibitors showing particular protective effects against malignancy development.
TNF Inhibitors Demonstrate Protective Effect Against Cancer
A large retrospective cohort study involving 32,230 patients with psoriasis (search) revealed that those initiating biologic therapy, particularly TNF inhibitors, experienced reduced long-term risk of developing primary malignancies compared with biologic-naïve individuals. Using a propensity score-matched design, researchers grouped participants by drug class: TNF inhibitors (n=16,011), IL-23 inhibitors (search) (n=5,604), IL-12/23 inhibitors (search) (n=3,856), and IL-17 inhibitors (search) (n=5,467).
TNF (search) inhibitor recipients demonstrated a statistically significant reduction in the incidence of any primary malignancy with a hazard ratio of 0.80 (95% CI=0.73-0.87). While similar risk reductions were observed among IL-23 inhibitors (search) (HR=0.83; 95% CI=0.68-1.02), IL-12/23 inhibitors (search) (HR=0.85; 95% CI=0.71-1.03), and IL-17 inhibitors (search) (HR=0.87; 95% CI=0.73-1.04), these findings did not reach statistical significance.
Analysis by cancer subtype revealed that TNF (search) inhibitor users were less likely to develop nonmelanoma skin cancer (search) than biologic-naïve controls (HR=0.82; 95% CI=0.71-0.96). No significant differences in nonmelanoma skin cancer risk were observed for IL-23 (search), IL-12 (search)/23, or IL-17 (search) inhibitor cohorts.
Ixekizumab Shows Consistent Safety Profile
A pooled analysis of 25 randomized clinical trials examining ixekizumab treatment provided additional reassurance regarding biologic safety. The study included participants with psoriasis (search) (n=6,892; mean age 45.7 years; 68.1% men), psoriatic arthritis (search) (n=1,401; mean age 49.1 years; 48.5% men), and axial spondyloarthritis (search) (n=932; mean age 42.8 years; 69.7% men) who received at least one dose of ixekizumab for 3 or 5 years.
Malignant neoplasm incidence rates were notably low across all patient groups: 0.8 per 100 patient-years (95% CI, 0.7-0.9) for psoriasis (search) patients, 0.7 per 100 patient-years (95% CI, 0.4-1.1) for psoriatic arthritis (search) patients, and 0.4 per 100 patient-years (95% CI, 0.2-0.8) for axial spondyloarthritis (search) patients.
Standardized incidence ratios were below or near 1 across all three groups, indicating no excess malignant neoplasms (search) were observed among people treated with ixekizumab compared with reported rates in the U.S. general population.
Clinical Implications and Expert Perspectives
Mark G. Lebwohl, MD, dean of clinical therapeutics and chair emeritus of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai, emphasized the clinical significance of these findings. "Because biologics have an impact on the immune system, it was not far reaching to assume they might be associated with malignancies. Indeed, [tumor necrosis factor (search) (TNF (search))]-blocking antibodies were," Lebwohl told Healio.
He noted the practical impact on clinical practice: "To this day, I get multiple calls, every week, from my colleagues across the country or from patients, asking, 'Which biologic is safe to use for my patient with a malignancy?' I am still cautious with patients who have lymphomas (search), although I have had a small but growing number of patients with lymphomas treated with IL-17 (search) blockers. Thus far, not one has had progression of their disease."
Regarding skin cancer specifically, Lebwohl observed: "In dermatology practice, especially for patients who have had treatments like [psoralen plus ultraviolet A] therapy that contributed to skin cancers, we have many patients with skin cancers. When we put them on TNF (search) blockers, we saw an explosion of skin cancers. When we put them on IL-17 (search) blockers, nothing. We do not see any increase."
Safety Across Cancer Types
Both studies found no increased incidence of melanoma (search) or lymphoid/hematopoietic malignancies (search) associated with biologic exposure. The incidence rates of malignant neoplasms (search) at 1-year intervals remained consistently low at fewer than 1.2 per 100 patient-years and were constant over time in the ixekizumab analysis.
These findings support the long-term oncologic safety of biologic therapies in psoriasis (search) management and may help inform long-term treatment decisions for clinicians managing patients with moderate-to-severe psoriatic diseases. The researchers noted that more research is needed comparing incidence rates among people with and without a history of malignant neoplasms (search), as well as examining potential risk factors that may influence the association between biologic treatment and malignant neoplasm development.