Summary: This article compares ustekinumab and adalimumab for chronic inflammatory conditions, focusing on malignancy risk. Ustekinumab has a favorable safety profile with no significant cancer associations, making it preferable for patients with a history of malignancy or higher risk. In contrast, adalimumab is linked to increased cancer risks, particularly lymphomas.

In the realm of biologic therapies for chronic inflammatory conditions such as psoriasis, psoriatic arthritis, and inflammatory bowel diseases (IBD), selecting the right medication is crucial. Both ustekinumab and adalimumab have proven efficacy, but concerns about malignancy risks can influence treatment decisions. This article delves into scenarios where ustekinumab may be preferable to adalimumab, focusing on malignancy risk and the underlying reasons for the differences in risk profiles.

Understanding the Medications

Ustekinumab

Ustekinumab is a fully human monoclonal antibody targeting the p40 subunit shared by interleukins 12 and 23 (IL-12/23). By inhibiting these cytokines, ustekinumab modulates the Th1 and Th17 inflammatory pathways, which are pivotal in autoimmune and inflammatory processes.

Adalimumab

Adalimumab is a fully human monoclonal antibody against tumor necrosis factor-alpha (TNF-α), a cytokine involved in systemic inflammation and immune regulation. By neutralizing TNF-α, adalimumab reduces inflammation but may also impact immune surveillance mechanisms against malignancies.

Malignancy Risks: A Comparative Analysis

Adalimumab and Increased Malignancy Risk

Several studies indicate an elevated risk of certain malignancies with TNF-α inhibitors like adalimumab. Notably, there is evidence of increased rates of lymphoma and non-melanoma skin cancers. A meta-analysis reported a statistically significant association between TNF-α inhibitors and malignancy, particularly lymphomas. This risk may stem from TNF-α’s role in apoptosis and tumor suppression; inhibiting TNF-α could impair these protective mechanisms.

Ustekinumab’s Favorable Safety Profile

Conversely, ustekinumab has not been significantly associated with an increased overall malignancy risk. Clinical trials and long-term studies have shown that malignancy rates in patients treated with ustekinumab are comparable to those in the general population. A pooled analysis demonstrated no significant difference in cancer incidence between ustekinumab and placebo groups.

Why Ustekinumab May Be Safer

Mechanistic Insights

TNF-α Inhibition and Cancer Risk

TNF-α plays a dual role in cancer—it promotes inflammation that can lead to tumor development but also mediates apoptosis of malignant cells. Inhibiting TNF-α may disrupt this balance, reducing immune-mediated tumor suppression and potentially increasing cancer risk.

IL-12/23 Inhibition and Cancer Risk

IL-12 and IL-23 are involved in immune responses but have less direct involvement in tumor surveillance compared to TNF-α. Inhibiting these cytokines with ustekinumab may have a less pronounced impact on the body’s ability to detect and eliminate malignant cells, possibly explaining the lower associated cancer risk.

Clinical Evidence Supporting Ustekinumab

Psoriasis Studies

In the PHOENIX 1 and 2 trials, ustekinumab showed sustained efficacy and a safety profile comparable to placebo over five years, with no significant increase in malignancy rates. Long-term results

Psoriatic Arthritis

The PSUMMIT trials reported that ustekinumab was effective and well-tolerated, with low malignancy incidence over two years. Efficacy and safety data

Crohn’s Disease

In the UNITI trials, ustekinumab demonstrated efficacy in inducing and maintaining remission with a safety profile similar to placebo. Study findings

Registry Data

Long-term registry data, such as the Psoriasis Longitudinal Assessment and Registry (PSOLAR), support the favorable safety profile of ustekinumab, indicating no increased malignancy risk compared to other biologics. PSOLAR results

When Ustekinumab is Preferable

Patients with a History of Malignancy

For patients with a prior history of cancer, minimizing additional malignancy risk is paramount. Ustekinumab’s lower association with malignancies makes it a preferable option over adalimumab in these cases. Guidelines of care

High-Risk Populations

Patients with risk factors such as a family history of cancer, chronic UV exposure, or immunodeficiency may benefit from therapies with lower malignancy risks. Ustekinumab may be favored for these individuals. Monitoring recommendations

Long-Term Therapy Requirements

Chronic conditions requiring lifelong treatment necessitate consideration of cumulative risks. Ustekinumab’s favorable long-term safety data support its use in patients needing extended therapy durations. Five-year results

Non-Responders to TNF-α Inhibitors

Patients who do not respond to or cannot tolerate TNF-α inhibitors like adalimumab may achieve better outcomes with ustekinumab. Additionally, switching to ustekinumab may reduce potential malignancy risks associated with prolonged TNF-α inhibition. Clinical insights, Switching efficacy

Conclusion

While both ustekinumab and adalimumab are effective for treating inflammatory diseases, ustekinumab may be the safer choice in situations where malignancy risk is a significant concern. Its mechanism of action appears to carry a lower risk of impairing tumor surveillance compared to TNF-α inhibitors. Clinicians should consider individual patient factors, including malignancy history and risk factors, when selecting appropriate biologic therapy.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always consult a healthcare professional for medical recommendations tailored to your condition.