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

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

There are no documented direct drug-drug interactions between Kesimpta (ofatumumab) and Saphnelo (anifrolumab), but concurrent use of these two immunosuppressive biologics may increase infection risk and potentially lead to excessive immunosuppression.

Mechanism of Action and Immunosuppressive Effects

Kesimpta (Ofatumumab)

• Fully human anti-CD20 monoclonal antibody that depletes B cells 1
• Administered subcutaneously at 20 mg monthly after initial loading doses 1
• B-cell depletion can persist for extended periods

Saphnelo (Anifrolumab)

• Human IgG1κ monoclonal antibody that binds to type I interferon receptor subunit 1 2
• Blocks type I interferon signaling, which is central to SLE pathogenesis 2
• Administered intravenously at 300 mg every 4 weeks 2

Potential Concerns with Concurrent Use

1. Increased Infection Risk

• Both medications independently increase infection risk:
  • Ofatumumab is associated with upper respiratory tract infections, urinary tract infections, and nasopharyngitis 3
  • Anifrolumab has been associated with increased herpes zoster infections (11% vs. placebo) 4
  • Combined use may amplify this risk through different immunosuppressive mechanisms

2. Risk of Hepatitis B Reactivation

• Ofatumumab is classified as high-risk (≥10%) for hepatitis B reactivation in HBsAg-positive patients 5
• B-cell depleting agents like ofatumumab are in the highest risk category for HBV reactivation 5
• Screening for hepatitis B is essential before initiating either therapy

3. Vaccination Considerations

• Live vaccines should be avoided while patients are being treated with immunosuppressive biologics 5
• Vaccination responses may be impaired due to B-cell depletion from ofatumumab

4. Additive Immunosuppression

• The combination of B-cell depletion (ofatumumab) and type I interferon blockade (anifrolumab) affects multiple immune pathways simultaneously
• This could potentially lead to excessive immunosuppression beyond what is seen with either agent alone

Monitoring Recommendations

If concurrent therapy is necessary, consider:

1. Enhanced infection surveillance:

   • Regular temperature monitoring
   • Prompt reporting of infection signs (fever, cough, skin lesions)
   • Low threshold for antimicrobial therapy

2. Laboratory monitoring:

   • Complete blood counts with differential
   • Immunoglobulin levels (IgG, IgM)
   • Hepatitis B viral load monitoring in patients with history of HBV

3. Vaccination planning:

   • Complete all necessary vaccinations before initiating therapy when possible
   • Avoid live vaccines during treatment

4. Herpes zoster prophylaxis:

   • Consider antiviral prophylaxis due to increased risk with anifrolumab 4

Clinical Considerations

While there are no specific contraindications to using these medications together, clinicians should:

• Carefully weigh the potential benefits against the increased immunosuppression risks
• Consider sequential rather than concurrent therapy if disease control allows
• Monitor closely for signs of infection, particularly during the initial treatment period
• Be vigilant for unusual or opportunistic infections that may result from combined immunosuppression

The decision to use both agents concurrently should be based on the severity of the underlying disease and the patient's response to individual therapies, with careful attention to monitoring for adverse effects.