Analysis Finds Opzelura Not Associated with Cancer or Cardiovascular Events | AAD 2025

A new analysis finds a lack of causal relationship between Opzelura (ruxolitinib) cream and the rate of serious adverse events such as major adverse cardiac events (MACE), thromboembolic events, malignancies, serious infections, and mortality, according to a poster presented at the American Academy of Dermatology (AAD) Association annual meeting in Orlando, March 7, 2025, to March 11, 2025.

In this analysis, serious adverse events were low, unrelated to cream strength, and generally reflective of background rates in the broader population with atopic dermatitis.

Developed by Incyte Corp., Opzelura was approved in September 2021 to treat mild to moderate atopic dermatitis (AD) in patients 12 and older who are not immunocompromised. It is also approved to treat nonsegmental vitiligo in patients 12 and older.

Atopic dermatitis is a chronic skin condition that causes inflammation, itching and dryness, as well as significantly impacting a person’s quality of life.

Opzelura is a topical treatment that targets JAK1 and JAK2 proteins. JAK inhibitors work by targeting a central pathway in inflammation. But regulators have found that JAK inhibitors may cause adverse events, including major adverse cardiac events (MACE), thromboembolic events, malignancies, serious infections, and mortality

The FDA has even issued warnings about the potential for these serious side effects associated with JAK inhibitors. In the United States and Canada, the labels for JAK inhibitors have warnings about the risk of serious infections, malignancies, thromboembolic events, MACE and mortality. This warning originated from an FDA review of the systemic JAK inhibitor Xeljanz (tofacitinib), which is used to treat patients with rheumatoid arthritis.

Related: Study: JAK Inhibitors May Have Different Side Effects

Other studies have looked at the risk of adverse events from JAK inhibitors for various indications. One study, which was presented as an abstract at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in October, found no increased risk of cardiovascular events in patients with inflammatory bowel disease who were taking JAK inhibitors.

Eric L. Simpson, M.D.

Specific to Opzelura, serious adverse events associated with the FDA’s warning are uncommon in individual clinical trials in patients aged as young as 2 years. Researchers — led by Eric L. Simpson, M.D., professor of Dermatology, School of Medicine at Oregon Health & Science University — wanted to further assess the risk of MACE, thromboembolic events, malignancies, serious infections, and mortality associated with Opzelura.

In the study presented at AAD, data from TRuE-AD1 and TRuE-AD2 phase 3 studies — which demonstrated Opzelura’s efficacy in atopic dermatitis — were analyzed at 52 weeks specifically for the serious adverse events associated with the FDA’s warnings with a focus on exposure-adjusted incidence rates (EAIRs) of adverse events. The EAIR measure takes into account variations in the duration of exposure and provides a look at the risk of an adverse event over a specific time period.

In this analysis, the incidence of adverse events was compared with literature-reported values for patients 12 years of age and older with mild-to-moderate atopic dermatitis. Among the 598 patients who applied 1.5% Opzelura cream or who used 0.75% Opzelura, the serious adverse events that were being studied were infrequent and generally similar to the patients with atopic dermatitis in general.

Researchers found that serious infections, nonmelanoma skin cancer, other malignancies, MACE and thromboembolic events were generally consistent between strengths. These events, researchers said, were among patients who often had other risk factors and were not considered related to treatment with Opzelura. None of these events occurred in adolescents.

Additionally, no lymphomas or fatalities occurred among patients in the TRuE-AD1/TRuE-AD2 clinical trials.