Saphnelo and Benlysta Differ in Lupus Side-Effect Reports

Key Takeaway: A new analysis of the FDA’s Adverse Event Reporting System (FAERS) compared the lupus medications Saphnelo (anifrolumab) and Benlysta (belimumab), revealing distinct side-effect patterns for each.

Researchers reviewed more than 21,000 reports submitted to FAERS between 2011 and 2024.

For Saphnelo, the most common safety signals were shingles (herpes zoster), headache, rash, and pericarditis, a type of heart inflammation. Saphnelo blocks the type I interferon pathway, a key part of the body’s antiviral defense, which may increase vulnerability to viral infections such as shingles.

For Benlysta, side effects were more often linked to injection or administration issues, such as pain or bleeding at the injection site, dosing mistakes, or problems using the delivery device. Benlysta, by contrast, targets B-cell activity and antibody production, which affects how the immune system responds over time but does not typically heighten viral risk.

Differences likely stem from how each medication affects the immune system and how it is administered, with Saphnelo by infusion and Benlysta often by self-injection, which may also influence the types of reported side effects.

Both drugs occasionally showed reports of urinary tract infections, but these tended to appear sooner with Saphnelo (about 18 days after starting treatment) than with Benlysta (around 29 days).

The authors caution that FAERS data come from voluntary reports, so they do not show how often these events actually occur—only that they have been reported more than expected.

Understanding these differences can help personalize care and guide clinicians in monitoring for early warning signs and managing risk, for example, by discussing shingles vaccination before starting Saphnelo.

Citation

Ren, N., Tian, X., & Chen, L. (2025). Comparing adverse events of Saphnelo and Benlysta: A real-world observational study based on the FDA adverse event reporting system (FAERS) following STROBE guidelines. Medicine, 104(41), e44960. https://doi.org/10.1097/MD.0000000000044960