From the Guidelines
Rinvoq (upadacitinib) may have a slightly better cardiovascular safety profile compared to Xeljanz (tofacitinib), while Xeljanz carries higher risks for major adverse cardiovascular events and malignancies. Both medications have similar safety profiles as JAK inhibitors, but the differences in their selectivity for JAK enzymes may explain some variations in their safety profiles 1. Rinvoq is more selective for JAK1, whereas Xeljanz inhibits JAK1, JAK2, and JAK3.
Key Considerations
- Both medications can cause serious infections, including tuberculosis reactivation, and require monitoring for neutropenia, lymphopenia, anemia, and elevated liver enzymes 1.
- They both carry black box warnings for increased risk of serious infections, malignancy, thrombosis, and major adverse cardiovascular events 1.
- Laboratory monitoring is required for both medications, including complete blood counts, lipid panels, and liver function tests before starting therapy and periodically thereafter 1.
- Neither medication should be used with other immunosuppressants like biologics or potent immunosuppressants, and both should be temporarily discontinued during serious infections 1.
- Patients should be screened for tuberculosis before starting either medication and monitored for signs of infection during treatment 1.
Safety Profiles
- The safety profiles of Rinvoq and Xeljanz are similar, but Rinvoq may have a slightly better cardiovascular safety profile 1.
- Xeljanz carries higher risks for major adverse cardiovascular events and malignancies, particularly in older adults with cardiovascular risk factors 1.
- Both medications require careful consideration of the benefits and risks, particularly in patients with a history of cardiovascular disease or malignancy 1.
Monitoring and Precautions
- Regular monitoring of complete blood counts, liver function tests, and lipid panels is necessary to minimize the risks associated with both medications 1.
- Patients should be educated on the signs and symptoms of serious infections and the importance of seeking medical attention promptly if they occur 1.
- The use of Rinvoq and Xeljanz should be avoided in patients with active or chronic infections, including tuberculosis, and in those with a history of malignancy 1.
From the Research
Safety Profile Comparison
- Rinvoq (upadacitinib) and Xeljanz (tofacitinib) are both Janus kinase inhibitors used to treat various inflammatory conditions, including rheumatoid arthritis and psoriasis.
- A study published in 2022 2 analyzed adverse event reports for Xeljanz, Olumiant, and Rinvoq to the US Food and Drug Administration, finding that higher proportions of Xeljanz adverse events were related to cardiovascular and blood clot events, while Olumiant had higher proportions of death and cancer-related events.
- Another study from 2025 3 compared the efficacy and safety of IL-17 and JAK inhibitors in ankylosing spondylitis, finding no statistical significance in adverse events among the treatments, including upadacitinib and tofacitinib.
- A 2020 systematic review and meta-analysis 4 assessed the efficacy and safety of tofacitinib, baricitinib, and upadacitinib for rheumatoid arthritis, finding that upadacitinib had a higher risk of adverse events, while tofacitinib had a higher risk of infection.
Key Differences
- The safety profiles of Rinvoq and Xeljanz differ, with Xeljanz having a higher risk of cardiovascular and blood clot events, and Rinvoq having a higher risk of adverse events overall.
- The choice between Rinvoq and Xeljanz may depend on individual patient factors, such as medical history and comorbidities, as well as the specific condition being treated.
- Further research is needed to fully understand the safety profiles of these medications and to inform treatment decisions 2, 3, 4.