What are the latest updates on the malignancy risk associated with risankizumab (Skyrizi) therapy?

Risankizumab and Malignancy Risk: Latest Evidence

Based on the most current evidence, risankizumab does not appear to increase malignancy risk compared to placebo or the general population, with long-term safety data now extending up to 6 years showing consistently low and stable rates of both non-melanoma skin cancer (NMSC) and other malignancies.

Current Safety Profile

Malignancy Rates with Long-Term Use

The most robust long-term data comes from the LIMMitless extension trial, which provides the longest follow-up available:

• Through 6 years of continuous treatment: Malignancy rates remained low and stable, with NMSC occurring at 0.7 per 100 patient-years and malignant tumors excluding NMSC at 0.5 per 100 patient-years 1
• No increase with extended exposure: Exposure-adjusted adverse event rates did not increase with long-term treatment across 7,927 patient-years of exposure 2
• Consistent safety through 5 years: Interim analysis through 304 weeks demonstrated rates of treatment-emergent adverse events of safety interest remained low and stable 3

Guideline Perspective on IL-23 Inhibitors

The Joint AAD-NPF Guidelines provide important context for the entire IL-23 inhibitor class:

• IL-23 inhibitors (including risankizumab) do not appear to alter malignancy risk when used as monotherapy for moderate-to-severe psoriasis, though the guidelines acknowledge that larger and longer-term studies were needed at the time of publication in 2019 4
• The effect on solid tumor or lymphoreticular malignancy is unknown for the IL-23 inhibitor class, with large long-term follow-up studies necessary to more fully define cancer risk 5

Important Clinical Context

Baseline Psoriasis-Associated Cancer Risk

It is critical to understand that psoriasis itself carries inherent malignancy risk, independent of treatment:

• Patients with severe psoriasis have significantly elevated risk for melanoma (SIR 11.01), lymphoma (SIR 2.3), and NMSC (particularly squamous cell carcinoma with SIR 7.08) compared to those with mild disease 4
• The increased cancer risk in psoriasis patients is particularly notable for lymphohematopoietic cancers (especially cutaneous T-cell lymphoma), head and neck cancers, and digestive tract malignancies 4
• NMSC risk is especially elevated in patients who have received PUVA photochemotherapy or cyclosporine, not necessarily from biologics 4

Comparative Safety Among Biologics

• TNF inhibitors show some studies suggesting increased NMSC risk, whereas IL-23 inhibitors like risankizumab do not demonstrate this pattern 4
• Ustekinumab (IL-12/23 inhibitor) has shown no increased malignancy risk with standardized incidence ratios comparable to the general population across multiple cancer types 4

FDA-Approved Labeling Information

The FDA label for risankizumab (Skyrizi) does not include specific warnings about increased malignancy risk, which is notable given the extensive safety monitoring in clinical trials 6. The label reports adverse events comprehensively but does not highlight malignancy as a significant safety signal.

Recent Comparative Evidence

Favorable Safety Profile in Elderly and High-Risk Populations

• In elderly IBD patients, risankizumab (along with vedolizumab and ustekinumab) has a favorable side effect profile regarding infections and malignancy, and should be considered first-line treatment from a safety perspective 7
• Direct comparison with fumaric acid esters in treatment-naïve patients showed no malignancies, tuberculosis, or opportunistic infections in the risankizumab arm through 24 weeks 8

Most Recent Long-Term Data (2025)

The final LIMMitless results published in 2025 represent the most comprehensive long-term safety assessment:

• 661 of 897 patients completed the full 6-year study (4,921.2 patient-years of exposure) 1
• Rates of treatment-emergent adverse events leading to discontinuation remained low throughout the entire study period 1
• No important identified risks emerged with extended follow-up 2

Clinical Recommendations

Monitoring Approach

While risankizumab does not increase malignancy risk, appropriate cancer screening remains essential:

• Perform baseline skin examination and monitor for NMSC development, as this risk is elevated in psoriasis patients regardless of treatment choice 4
• Follow standard age-appropriate cancer screening guidelines as outlined in the AAD-NPF recommendations (mammography, cervical cancer screening, colorectal cancer screening, lung cancer screening in appropriate populations) 4
• Consider skin biopsy for atypical lesions or psoriasis that does not respond appropriately to therapy to rule out cutaneous T-cell lymphoma 4

Patient Counseling

• Reassure patients that current evidence through 6 years does not show increased cancer risk with risankizumab compared to placebo or general population rates 2, 1, 3
• Explain that psoriasis itself carries cancer risk, particularly for certain malignancies, independent of treatment 4
• Emphasize the importance of continued cancer screening based on individual risk factors and age-appropriate guidelines 4

Key Caveats

• The 2019 AAD-NPF guidelines appropriately noted that longer-term studies were necessary at that time; these studies have now been completed and continue to show favorable safety 4, 5
• Patients with pre-existing immunosuppression-related conditions should be approached with caution when using IL-23 inhibitors, though this is expert opinion rather than evidence-based 5
• Post-marketing surveillance continues, and the FDA label notes that adverse reactions are reported voluntarily from populations of uncertain size 6