What is the recommended dose of mycophenolate mofetil (MMF) for a patient with Systemic Lupus Erythematosus (SLE) nephritis?

Mycophenolate Mofetil Dosing for SLE Nephritis

For induction therapy of Class III/IV lupus nephritis, use mycophenolate mofetil 2-3 grams daily (or mycophenolic acid 1.44-2.16 grams daily), with 3 grams daily preferred for severe disease with crescents or rising creatinine, followed by maintenance dosing of 1.5-2 grams daily (750-1000 mg twice daily) for at least 36 months total. 1, 2

Induction Therapy Dosing (First 6 Months)

Standard Dosing by Disease Severity

• Class III/IV without crescents: Either 2 or 3 grams daily of MMF is acceptable 1, 2
• Class III/IV with crescents: 3 grams daily is strongly preferred 1, 2
• Proteinuria with recent significant rise in creatinine: 3 grams daily is preferred 1, 2
• Class V pure membranous lupus nephritis: 2-3 grams daily combined with prednisone 0.5 mg/kg/day 2

Race/Ethnicity-Based Adjustments

Non-Asian patients should target 3 grams daily as the maximum dose for optimal efficacy 1, 2. This recommendation is based on the ALMS trial showing similar improvement rates across Caucasians, Asians, and other races (primarily African Americans and Hispanics) at these doses 1.

Asian patients may achieve equivalent efficacy with only 2 grams daily 1, 2. A Taiwanese study demonstrated that doses as low as 0.5-1 gram daily combined with glucocorticoids produced a 65.7% response rate (14.3% complete remission, 51.4% partial remission) with excellent tolerability 3. A Chinese multicenter trial using 0.5-2 grams daily (mean 1.26 grams daily) showed significant reduction in proteinuria from 4.24 g/day to 1.54 g/day at 6 months 4.

Mycophenolic Acid Equivalents

If using enteric-coated mycophenolic acid (MPA) instead of MMF:

• Induction: 1.44-2.16 grams daily (720-1080 mg twice daily) 1, 2
• The exact equivalency remains somewhat controversial, but 740-1080 mg MPA twice daily is roughly equivalent to 2-3 grams total daily MMF 1

Maintenance Therapy Dosing (After 6 Months)

After completing induction, reduce to maintenance doses 1, 2:

• MMF: 750-1000 mg twice daily (1.5-2 grams total daily) 1, 2
• MPA: 540-720 mg twice daily (1.08-1.44 grams total daily) 1, 2

Continue maintenance therapy for at least 36 months total (induction plus maintenance combined) 1, 2. This extended duration is critical for preventing relapses.

Combination Therapy Requirements

All mycophenolate dosing must be combined with glucocorticoids 1, 2:

• Start with IV methylprednisolone 0.25-0.5 g/day for up to 3 days 5
• Follow with oral prednisone 0.5-0.6 mg/kg/day (maximum 40 mg/day) 1, 5
• Rapidly taper to ≤5 mg/day by 12 weeks and <2.5 mg/day by 6 months 1, 5

Therapeutic Drug Monitoring

Consider therapeutic drug monitoring to optimize outcomes 2, 6:

• Target MPA-AUC₀₋₁₂ of 60-90 mg*h/L 2, 6
• A concentration-controlled study showed that dose adjustments targeting this range resulted in 87.5% of patients achieving partial or complete remission at 12 months 6
• While not yet standard practice, monitoring can address the high inter-individual variability in MPA exposure 6

Evidence Quality and Comparative Efficacy

The recommendation for MMF is based on high-quality evidence showing equivalence or superiority to cyclophosphamide 1, 7, 8. A 2005 trial demonstrated MMF superiority over IV cyclophosphamide for complete remission (22.5% vs 5.8%, P=0.005) with fewer severe infections 7. However, the larger 2009 ALMS trial showed similar response rates between MMF (56.2%) and IV cyclophosphamide (53.0%) without detecting significant superiority 8.

MMF is particularly preferred for African American and Hispanic patients, who respond less well to IV cyclophosphamide than Caucasian or Asian patients 1.

Common Pitfalls to Avoid

• Do not use lower than 2 grams daily in non-Asian patients unless tolerance issues arise, as this may compromise efficacy 1, 2
• Do not continue high induction doses beyond 6 months without transitioning to maintenance dosing 1, 2
• Do not discontinue therapy before 36 months total duration unless intolerance or treatment failure occurs 1, 2
• Do not omit glucocorticoids, as monotherapy with MMF is inadequate 1
• Do not forget to taper glucocorticoids aggressively to minimize toxicity while maintaining the MMF 1, 5

Alternative Considerations

If MMF is not tolerated, azathioprine 2 mg/kg/day can be used as maintenance therapy after induction, though it may be associated with inferior efficacy 1. For refractory disease or nephrotic-range proteinuria, consider adding a calcineurin inhibitor (particularly tacrolimus) to MMF as multitarget therapy 2, 9.