What is the use of mycophenolate mofetil (MMF) in patients with Interstitial Lung Disease (ILD) and Non-Specific Interstitial Pneumonia (NSIP) pattern who also have Chronic Kidney Disease (CKD)?

Mycophenolate Mofetil in ILD with NSIP Pattern and CKD

Mycophenolate mofetil (MMF) is recommended as a first-line treatment for interstitial lung disease (ILD) with non-specific interstitial pneumonia (NSIP) pattern in patients with chronic kidney disease (CKD), but requires dose reduction to 1g daily or less in end-stage renal disease patients due to increased risk of adverse effects. 1, 2

Efficacy in ILD with NSIP Pattern

• MMF is conditionally recommended as a first-line treatment option for systemic autoimmune rheumatic disease-associated ILD (SARD-ILD) by the American College of Rheumatology (ACR) and American College of Chest Physicians (CHEST) 2023 guidelines 1
• MMF is particularly effective for ILD with NSIP pattern, showing stabilization or improvement in forced vital capacity (FVC) 3
• Recent evidence demonstrates that combination of rituximab and MMF is superior to MMF alone in patients with ILD and NSIP pattern, with a between-group difference in FVC of 3.60% (95% CI 0.41-6.80; p=0.0273) 3

Dosing Considerations in CKD

• Standard dosing of MMF for ILD is typically 2g daily (1g twice daily) 4
• In patients with end-stage renal disease (ESRD), MMF requires significant dose reduction due to increased risk of adverse effects 2
• For ESRD patients, a lower dose not exceeding 1g daily is recommended with closer monitoring for side effects 2
• Patients with moderate CKD may tolerate intermediate doses, requiring individualized titration based on tolerability and laboratory monitoring 2, 4

Monitoring in CKD Patients

• More frequent monitoring of complete blood count is essential in CKD patients on MMF due to increased risk of severe anemia and leukopenia 2
• Regular assessment of gastrointestinal symptoms is necessary as these may require dose reduction or treatment discontinuation 2, 4
• Baseline and periodic liver function tests should be performed to monitor for hepatotoxicity 1
• For patients with CKD, renal function should be closely monitored, though MMF itself has minimal nephrotoxicity compared to other immunosuppressants 4

Advantages Over Alternative Therapies

• MMF has a more favorable side effect profile compared to cyclophosphamide, which is an alternative first-line agent for ILD 5, 6
• MMF allows for reduction or discontinuation of prednisone without worsening of symptoms or objective progression of disease 6
• In a study of 10 patients with autoimmune-related ILD treated with MMF, improvements were seen in alveolitis, symptoms, quality of life, and activity levels, with 4 of 5 patients able to discontinue oxygen 6
• Unlike calcineurin inhibitors (tacrolimus, cyclosporine), MMF does not cause significant nephrotoxicity, making it particularly suitable for patients with CKD 1, 4

Potential Adverse Effects to Monitor

• Gastrointestinal symptoms (diarrhea, nausea, vomiting) are the most common adverse effects and may be more pronounced in CKD patients 2, 4
• Bone marrow suppression, particularly anemia and leukopenia, occurs more frequently and severely in patients with renal impairment 2
• Risk of infections may be increased, particularly when combined with other immunosuppressants 3
• Regular monitoring of blood counts is essential, with more frequent monitoring recommended for CKD patients 1, 2

Treatment Algorithm for ILD with NSIP Pattern in CKD

1. Initial Assessment:

   • Confirm NSIP pattern through HRCT and/or lung biopsy 1
   • Assess severity of CKD (eGFR, creatinine) 2
   • Evaluate baseline pulmonary function tests (PFTs) and oxygen requirements 7

2. Dosing Strategy:

   • For mild-moderate CKD: Start with 500mg twice daily, titrate to 1g twice daily as tolerated 4
   • For severe CKD or ESRD: Start with 500mg daily, maximum 1g daily (500mg twice daily) 2

3. Monitoring Schedule:

   • CBC with differential: Weekly for first month, then every 2 weeks for second month, monthly thereafter 1, 2
   • Liver function tests: Monthly for first 3 months, then every 3 months 1
   • PFTs: Every 3-6 months to assess response 7
   • Symptoms assessment: At each visit for GI side effects, infections, and respiratory status 2, 6

4. Response Assessment:

   • If stable or improved after 6 months: Continue current dose 6
   • If inadequate response: Consider adding rituximab if tolerated 3
   • If worsening despite treatment: Consider alternative therapies such as nintedanib 1

5. Management of Adverse Effects:

   • For severe anemia or leukopenia: Reduce dose or temporarily discontinue 2
   • For significant GI symptoms: Reduce dose or divide into smaller, more frequent doses 2, 4
   • For infections: Temporarily discontinue until resolution 3