Are there interactions between Saphnelo (anifrolumab) and Kesimpta (ofatumumab)?

Potential Drug Interactions Between Saphnelo (Anifrolumab) and Kesimpta (Ofatumumab)

There are no documented direct drug-drug interactions between Saphnelo (anifrolumab) and Kesimpta (ofatumumab), but combining these two immunosuppressive medications may increase the risk of serious infections and potentially compromise immune function.

Mechanism of Action and Immunosuppressive Effects

Saphnelo (Anifrolumab)

• Type I interferon receptor antagonist monoclonal antibody 1
• Blocks interferon signaling, which is central to SLE pathogenesis 2
• Administered intravenously every 4 weeks for moderate to severe SLE 3
• Associated with increased risk of viral infections, particularly herpes zoster (5.1-9.5% vs 2.0% with placebo) 4

Kesimpta (Ofatumumab)

• Fully human anti-CD20 monoclonal antibody that targets B cells 3
• Targets a different CD20 epitope than rituximab 3
• Causes B-cell depletion, which can persist for extended periods 3
• B-cell depleting agents are associated with high risk of hepatitis B reactivation 3

Potential Concerns with Combination Use

1. Additive Immunosuppression:

   • Both medications suppress different aspects of the immune system
   • Anifrolumab inhibits type I interferon signaling 3
   • Ofatumumab depletes B cells 3
   • Combined use may lead to profound immunosuppression

2. Increased Infection Risk:

   • B-cell depleting agents like ofatumumab have potent and durable immunosuppressive effects 3
   • Anifrolumab is associated with increased herpes zoster and influenza infections 4
   • Combined use may significantly increase risk of opportunistic infections

3. Viral Reactivation:

   • B-cell depleting agents are associated with highest risk of hepatitis B reactivation 3
   • Monitoring for viral reactivation would be essential if combination is necessary

4. Prolonged Immune Recovery:

   • B-cell depleting drugs can have effects lasting beyond 12 months after cessation 3
   • This could complicate management if adverse effects occur

Clinical Recommendations

If treatment with both medications is being considered:

• Perform baseline screening:

  • Hepatitis B serology (HBsAg, anti-HBc) 3
  • Tuberculosis screening
  • Varicella zoster virus immunity status

• Consider prophylactic measures:

  • Antiviral prophylaxis for herpes zoster
  • Hepatitis B prophylaxis if serologically indicated 3

• Implement enhanced monitoring:

  • Regular assessment for signs of infection
  • Vigilance for unusual or opportunistic infections
  • Extended monitoring period (up to 12 months after discontinuation) 3

Conclusion

While no formal contraindication exists for using Saphnelo and Kesimpta together, the combination presents theoretical concerns for additive immunosuppression and increased infection risk. Clinical decisions should be based on a careful assessment of benefit versus risk, with implementation of appropriate prophylactic measures and monitoring if both agents are deemed necessary.