What is the role of Anifrolumab in treating lupus nephritis?

Anifrolumab in Lupus Nephritis: Current Role and Recommendations

Anifrolumab is not currently recommended as a first-line therapy for lupus nephritis due to limited evidence of efficacy and an FDA limitation of use specifically stating it has not been evaluated in severe active lupus nephritis. 1

Current Status and Evidence

• The FDA label for anifrolumab (SAPHNELO) explicitly states: "The efficacy of SAPHNELO has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Use of SAPHNELO is not recommended in these situations." 1

• The phase II TULIP-LN trial evaluated anifrolumab in lupus nephritis patients but did not meet its primary endpoint of change in 24-hour urine protein-creatinine ratio (UPCR) at week 52 compared to placebo. 2

• However, the intensified regimen (IR) of anifrolumab (900 mg for first 3 doses, then 300 mg) showed numerical improvements over placebo in complete renal response (45.5% vs 31.1%), though this was not statistically significant. 2

Position in Treatment Algorithm

First-Line Therapy for Lupus Nephritis

• First-line therapy for active lupus nephritis should be:
  • Mycophenolic acid analogs (MPAA) with glucocorticoids 3
  • OR cyclophosphamide with glucocorticoids 3
  • OR calcineurin inhibitors (voclosporin, tacrolimus, cyclosporine) in specific cases with preserved kidney function and nephrotic-range proteinuria 3

For Refractory Lupus Nephritis

• For patients who fail to respond after 6 months of treatment with glucocorticoids plus MMF or cyclophosphamide, the American College of Rheumatology recommends:

  • Switch from cyclophosphamide to MMF, or from MMF to cyclophosphamide 3
  • Consider rituximab in patients whose nephritis fails to improve after 6 months of one induction therapy 3

• The KDIGO 2024 guidelines recommend the following for refractory disease:

  • Consider switching to an alternative recommended treatment regimen 3
  • Consider addition of rituximab or other biologic therapies 3
  • Consider extended course of IV pulse cyclophosphamide 3

Potential Role for Anifrolumab in Lupus Nephritis

• The 2-year extension of the TULIP-LN trial showed that more patients on the intensified regimen attained complete renal response at Week 104 compared with basic regimen or placebo (27.3% vs 18.6% and 17.8%), suggesting potential long-term benefits. 4

• The EULAR systematic literature review noted that in the TULIP-LN study, the intensified regimen showed better complete response rates compared to placebo (45.5% vs 31.1%), particularly in the intensified dosing regimen. 3

• Safety concerns include an increased incidence of herpes zoster infection with anifrolumab compared to placebo (16.7% vs 8.2%). 2

Practical Considerations

• Anifrolumab works by binding to the type I interferon receptor (IFNAR), inhibiting type I IFN signaling and blocking inflammatory and immunological processes. 1

• When considering anifrolumab, it's important to note that patients with UPCR >2 mg/mg were excluded from clinical trials, and the drug is not cleared renally. 1

• Case reports suggest that combination therapy with voclosporin and anifrolumab may be effective in patients with both lupus nephritis and discoid lupus erythematosus, potentially allowing for steroid-free remission. 5

Recommendations for Clinical Practice

• For patients with active lupus nephritis, start with standard first-line therapies (MMF/MPA with glucocorticoids or cyclophosphamide with glucocorticoids). 3

• For refractory disease, consider switching between MMF and cyclophosphamide or adding rituximab before considering anifrolumab. 3

• If considering anifrolumab for refractory lupus nephritis despite the FDA limitation:

  • The intensified regimen (900 mg for first 3 doses, then 300 mg) showed better outcomes than the basic regimen. 2
  • Monitor closely for herpes zoster infections, which occurred at higher rates with anifrolumab. 2

• Consider clinical trials or other emerging therapies like obinutuzumab for patients with truly refractory disease. 6

Conclusion

While anifrolumab shows some promise in the treatment of lupus nephritis based on secondary endpoints and extension studies, its FDA label specifically does not recommend its use in severe active lupus nephritis. Standard therapies remain the first-line approach, with rituximab being a more established option for refractory disease. Further research is needed to definitively establish anifrolumab's role in lupus nephritis treatment.