Treatment of Atopic Dermatitis

Introduction to Mycophenolate Mofetil

• Mycophenolate mofetil (MMF) is an immunosuppressive agent that works through inhibition of purine nucleotide synthesis, reduction of activated lymphocyte proliferation, decreased production of adhesion molecules, increased apoptosis of activated T lymphocytes, and reduction of inducible nitric oxide synthase and oxidative stress, and is conditionally recommended by the American Academy of Dermatology for treating pruritus in patients with refractory moderate to severe atopic dermatitis, with evidence showing effectiveness in 45-85% of patients within 4-8 weeks of treatment 1, 2

Dosage and Administration

• The initial dose of MMF is 1g daily, increased to a maintenance level of 1.5-2g daily, with a dose range of 500mg daily to 3g daily based on severity and patient factors, and is 6-7 times more expensive than azathioprine 2
• MMF should be administered at a dose of 1.5-2 grams per day, with a maximum of 3 grams per day in severe cases, and Asian patients may require lower dosing, up to 2 grams per day, due to evidence suggesting similar efficacy at lower doses 3
• MMF is available as oral suspension, capsules, and tablets, and should be divided into two equal doses given 12 hours apart 4

Efficacy and Recommendations

• The American Academy of Dermatology conditionally recommends MMF for refractory moderate-severe atopic dermatitis, with studies showing effectiveness in this condition, and the American College of Physicians recommends monitoring CBC weekly for the first month after dose changes, assessing for resolution of any toxicity symptoms, and adjusting the dose to maintain therapeutic levels while minimizing adverse effects 1, 5, 6
• Initial response may be delayed, typically 4-8 weeks, and maximum benefit is usually observed after 3-6 months of therapy, with treatment often continued long-term for sustained benefit 4, 3

Safety and Precautions

• Common side effects of MMF include gastrointestinal symptoms such as nausea, diarrhea, and abdominal pain, which occur in 3-34% of patients, and there is an increased susceptibility to viral and bacterial infections, and a theoretical increased risk of cutaneous malignancy and lymphoma with long-term use 2, 4, 6
• MMF is contraindicated in pregnancy and during lactation due to risk of severe congenital malformations, and women of childbearing potential should use two reliable forms of birth control, with consideration of the potential for bidirectional interaction between mycophenolate-containing medications and hormonal contraceptives 4, 2, 7
• Monitoring is recommended, including complete blood count weekly for the first month, then monthly, liver function tests monthly, and watching for signs of infection and gastrointestinal side effects, with the European Society of Clinical Microbiology and Infectious Diseases recommending monitoring for opportunistic infections 4, 6

Therapeutic Drug Monitoring

• The following table summarizes the recommended target MPA levels for different indications:

• Several factors can influence MPA levels, including renal function, serum albumin levels, concurrent medications, gender, liver function, and enterohepatic recirculation, with renal impairment decreasing clearance, and certain medications like tacrolimus increasing MPA levels, and patient characteristics, such as race/ethnicity, can also impact MPA levels 3
• A significantly elevated MPA level can put patients at high risk for toxicity, manifesting as hematologic effects, gastrointestinal effects, infectious complications, and metabolic disturbances, with the American College of Rheumatology recommending monitoring for these adverse effects in patients with elevated MPA levels 6
• The American Society of Transplantation recommends considering temporary dose reduction or interruption of mycophenolate mofetil in patients with significantly elevated MPA levels, with a target MPA level based on clinical context 3
• The British Society for Rheumatology recommends considering switching from mycophenolate mofetil to enteric-coated mycophenolate sodium in patients with gastrointestinal side effects, with equivalent dosing of 720-1080 mg twice daily of mycophenolate sodium ≈ 1-1.5 g twice daily of mycophenolate mofetil, and the European League Against Rheumatism recommends reassessing MPA levels after dose adjustment, typically within 5-7 days, and adjusting the dose to maintain therapeutic levels while minimizing adverse effects 8, 9, 6