What is the role of Mycophenolate (Cellcept) mofetil in treating systemic sclerosis with interstitial lung disease (ILD)?

From the Guidelines

Mycophenolate mofetil is a first-line immunosuppressive therapy for systemic sclerosis-associated interstitial lung disease (SSc-ILD), with a recommended dosage of 1,000 to 3,000 mg daily, and should be considered for long-term treatment to maintain disease stability. The treatment effect of mycophenolate mofetil on SSc-ILD has been supported by recent guidelines, including the 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic diseases 1. This guideline conditionally recommends mycophenolate over other listed therapies for the treatment of SSc-ILD.

Key Points for Treatment

• Mycophenolate mofetil works by inhibiting lymphocyte proliferation and fibroblast activity, reducing inflammation and fibrosis in lung tissue.
• Clinical evidence shows it can stabilize or improve lung function, particularly forced vital capacity (FVC), and slow disease progression 1.
• Patients should have regular monitoring of complete blood counts, liver function, and pulmonary function tests during treatment.
• Common side effects include gastrointestinal disturbances, increased infection risk, and potential bone marrow suppression.
• Mycophenolate mofetil is contraindicated during pregnancy due to teratogenic effects, so effective contraception is essential for women of childbearing potential.

Combination Therapy

The use of mycophenolate mofetil in combination with other therapies, such as nintedanib, has also been considered for the treatment of SSc-ILD. The treatment effect of nintedanib on the annual rate of FVC decline was numerically greater in participants who were not taking mycophenolate mofetil at baseline, suggesting a potential benefit of combination therapy 1. However, the decision to use combination therapy should be based on individual patient factors and disease severity.

Monitoring and Follow-Up

Regular monitoring and follow-up are crucial for patients with SSc-ILD treated with mycophenolate mofetil. This includes monitoring of lung function, complete blood counts, and liver function, as well as assessment for potential side effects. The treatment flow chart for SSc-ILD, as outlined in the EULAR recommendations, provides a useful guide for clinicians in making treatment decisions and monitoring patient response 1.

From the Research

Role of Mycophenolate Mofetil in Treating Systemic Sclerosis with Interstitial Lung Disease (ILD)

• Mycophenolate mofetil (MMF) is used to treat systemic sclerosis-related interstitial lung disease (SSc-ILD) due to its immunosuppressive properties 2, 3, 4.
• Studies have shown that MMF can slow the decline in lung function in patients with SSc-ILD, with some patients experiencing stabilization or improvement in lung function 2, 3, 4.
• The efficacy of MMF in treating SSc-ILD has been compared to other immunosuppressive therapies, such as cyclophosphamide (CYC), azathioprine (AZA), and methotrexate (MTX) 5, 6.
• A meta-analysis found that MMF was associated with functional stabilization in patients with SSc-ILD, with no significant difference in forced vital capacity (FVC)% or diffusion capacity of the lung for carbon monoxide (DLco)% predicted 4.
• Another study found that MMF had a higher probability of preventing the deterioration of DLco compared to other therapies, while CYC plus AZA had a higher probability of preventing the deterioration of FVC 5.
• A systematic review and meta-analysis found that the efficacy of MMF with respect to FVC and DLco improvement was comparable to that of CYC, and MMF was preferred due to fewer adverse events 6.

Key Findings

• MMF is well-tolerated and can slow the decline in lung function in patients with SSc-ILD 2, 3, 4.
• MMF has been shown to be effective in stabilizing or improving lung function in patients with SSc-ILD, with some studies suggesting it may be comparable to CYC in terms of efficacy 5, 6.
• MMF may have a lower risk of adverse events compared to other immunosuppressive therapies, such as CYC 6.

Treatment Outcomes

• Studies have reported improvements in FVC and DLco in patients with SSc-ILD treated with MMF 2, 3, 6.
• MMF has been shown to be effective in preventing the deterioration of lung function in patients with SSc-ILD, with some studies suggesting it may be more effective than other therapies in preventing the deterioration of DLco 5.
• The optimal dose and duration of MMF treatment for SSc-ILD are not well-established, but studies have reported effective treatment with doses ranging from 1-3 g/day 2, 3.