What is the comparison between Anifrolumab (Saphnelo) and Belimumab (Benlysta)?

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Last updated: April 27, 2025View editorial policy

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From the Guidelines

Saphnelo (anifrolumab) is preferred over Benlysta (belimumab) for the treatment of systemic lupus erythematosus (SLE) due to its potential for better efficacy in patients with high interferon signatures and its ability to target type I interferon receptors, blocking the activity of multiple interferons that drive inflammation in lupus. When considering the treatment of SLE, it is essential to evaluate the efficacy and safety of different biologic medications. Saphnelo and Benlysta are two such medications that have shown effectiveness in reducing disease activity and flares in lupus patients.

  • Saphnelo targets type I interferon receptors, blocking the activity of multiple interferons that drive inflammation in lupus.
  • Benlysta targets B-lymphocyte stimulator (BLyS), reducing abnormal B cell activity and autoantibody production. According to the study by Kostopoulou et al. 1, Saphnelo has been shown to be effective in reducing disease activity and flares in lupus patients, with a significant reduction in the number of swollen and tender joints.
  • The TULIP trials found that anifrolumab was associated with a greater percentage of patients achieving ≥50% reduction in active swollen and tender joints (treatment Δ: 12.6% (95% CI 2.4% to 22.9%)) 1. In contrast, Benlysta has been shown to be effective in reducing disease activity and flares in lupus patients, but with a less significant reduction in the number of swollen and tender joints.
  • The post hoc analysis of the BLISS trials found a reduction in the number of swollen and tender joints, but with no significant difference compared to placebo 1. It is also important to consider the safety profiles of both medications.
  • Saphnelo has been associated with higher rates of herpes zoster reactivation, while Benlysta has been associated with upper respiratory infections 1. Ultimately, the choice between Saphnelo and Benlysta depends on individual patient factors, including disease characteristics, comorbidities, administration preference, and insurance coverage.
  • Neither medication is recommended during pregnancy, and patients should be screened for infections before starting either therapy 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Saphnelo (Anifrolumab) vs Benlysta (Belimumab)

  • Both Saphnelo (anifrolumab) and Benlysta (belimumab) are biologic agents used in the treatment of systemic lupus erythematosus (SLE) 2, 3, 4, 5, 6.
  • Anifrolumab targets the interferon alpha receptor, while belimumab targets B-cell-activating factor (BAFF) 3, 6.
  • A comparative risk-benefit assessment of both drugs suggests that anifrolumab may elicit organ-specific effects, while belimumab modulates SLE activity and prevents flares without interfering with local innate host defense mechanisms 3.
  • Indirect treatment comparison of anifrolumab and belimumab efficacy in adults with SLE shows that anifrolumab-treated patients are more likely to achieve a reduction in disease activity than belimumab-treated patients 5.
  • Expert opinion suggests that patient profiling on a clinical and endotypical basis can help identify better candidates for targeted drugs, with anifrolumab potentially being more effective for patients with inflammatory organ involvement and belimumab being more suitable for patients with B-mediated manifestations 6.

Key Differences

  • Mechanism of action: anifrolumab targets interferon alpha receptor, while belimumab targets BAFF 3, 6.
  • Efficacy: anifrolumab may be more effective in reducing disease activity in patients with SLE 5.
  • Safety: both drugs have different safety profiles, with anifrolumab potentially increasing the risk of viral infections and belimumab having a more favorable safety profile 3, 4.

Treatment Considerations

  • Patient profiling and identification of clinical and endotypical characteristics can help guide treatment decisions 6.
  • Anifrolumab may be more suitable for patients with inflammatory organ involvement, while belimumab may be more effective for patients with B-mediated manifestations 6.
  • Careful management is required when using both drugs, especially in patients with longer disease history and mixed manifestations 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Novel therapies in SLE treatment: A literature review.

Advances in clinical and experimental medicine : official organ Wroclaw Medical University, 2025

Research

Belimumab for systemic lupus erythematosus.

The Cochrane database of systematic reviews, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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