Is it safe to use Rinvoq (upadacitinib) in a patient with a history of breast cancer?

Rinvoq Should Not Be Used in Patients with a History of Breast Cancer

Rinvoq (upadacitinib) is contraindicated in patients with a history of breast cancer due to the FDA's Boxed Warning regarding increased risk of malignancies, including breast cancer, with JAK inhibitors. 1

Critical Safety Concerns with JAK Inhibitors

The FDA issued a drug safety communication on September 9,2021, requiring revisions to the Boxed Warning for all JAK inhibitors, including Rinvoq, to include information about the risk of serious heart-related events, cancer, blood clots, and death. 1

Cancer Risk Profile

• Rinvoq and other JAK inhibitors carry a significant cancer risk, which is particularly concerning in patients with pre-existing malignancy or history of cancer. 1
• Analysis of FDA Adverse Event Reporting System data revealed that baricitinib (another JAK inhibitor in the same class) had the highest proportion of cancer-related events at 4.1%, while upadacitinib (Rinvoq) demonstrated higher proportions of serious adverse events overall compared to other JAK inhibitors. 1
• The Boxed Warning was based on a large safety randomized clinical trial, though neither baricitinib nor upadacitinib has been studied in similar large safety trials specifically for cancer outcomes. 1

Clinical Decision Algorithm

For patients with a history of breast cancer requiring treatment for inflammatory conditions:

1. Avoid JAK inhibitors entirely - The cancer risk outweighs potential benefits in this population 1
2. Consider alternative immunomodulatory therapies that do not carry the same malignancy risk profile
3. If inflammatory disease is severe and refractory, consultation with both oncology and rheumatology is mandatory before considering any immunosuppressive therapy

Important Caveats

• The differential adverse event profile between JAK inhibitors suggests that findings from one agent may not be directly applicable to others, but the FDA has applied the cancer warning across the entire class. 1
• There is no established "safe" time interval after breast cancer treatment completion that would make Rinvoq acceptable, as the mechanism of action (JAK inhibition affecting immune surveillance) poses ongoing risk. 1
• Patients with hormone receptor-positive breast cancer face additional theoretical concerns, as immune modulation may affect cancer surveillance mechanisms that prevent recurrence. 2

Monitoring Considerations if Alternative Therapies Fail

If absolutely no alternative exists (an extremely rare scenario):

• Baseline and serial oncologic surveillance including mammography and clinical breast examination at shortened intervals
• Multidisciplinary tumor board discussion involving medical oncology, rheumatology, and the patient
• Documented informed consent specifically addressing the increased cancer risk
• Consideration of the patient's breast cancer subtype, stage, time since treatment, and recurrence risk - though none of these factors eliminate the contraindication 2

In practice, the presence of breast cancer history should be considered an absolute contraindication to Rinvoq use, and alternative therapeutic strategies should be pursued. 1