Immunomodulators in Bullous Pemphigoid

Introduction to Treatment Options

The British Association of Dermatologists recommends mycophenolate mofetil (0.5-1 g twice daily) or azathioprine (up to 2.5 mg/kg daily) as adjunctive therapy for patients with bullous pemphigoid who are unresponsive to or experiencing significant side effects from corticosteroids, with mycophenolate mofetil being preferred when hepatotoxicity is a concern and azathioprine when cost or infection risk are priorities 1, 2

For patients with bullous pemphigoid, mycophenolate mofetil achieves remission in 100% of patients with a median time of 42 days, and has less hepatotoxicity but more infections compared to azathioprine 1, 2
Azathioprine achieves remission in 100% of patients with a median time of 28.6 days, which is faster than mycophenolate mofetil, and has a different toxicity profile 1, 2
The British Association of Dermatologists states that there is currently insufficient evidence to recommend routine addition of azathioprine to systemic steroids for initial control of bullous pemphigoid, and immunomodulators should only be considered when response to corticosteroids has been inadequate or side effects are troublesome 1

Methotrexate (maximum 15 mg weekly) can be considered as a third-line option for patients with bullous pemphigoid who have failed standard immunomodulators, with a strength of recommendation D (level 4 evidence) 2
Rituximab (375 mg/m² weekly for 4 weeks) can be considered for refractory bullous pemphigoid, achieving a satisfactory response in 78% and complete clearance in 55% of recalcitrant cases, and should be considered when all standard immunomodulators have failed 6

Regular monitoring of complete blood counts and liver function is mandatory for patients on azathioprine, and thiopurine methyltransferase activity should be checked before starting to minimize myelosuppression risk 1
The British Association of Dermatologists recommends reducing treatment whenever disease has been well controlled for a month or more to avoid over-treatment, and notes that high doses of immunosuppressants may put elderly patients at risk of life-threatening adverse effects more dangerous than the bullous pemphigoid itself 3, 4

There is no high-quality evidence that proves adding any immunomodulator to corticosteroids is superior to corticosteroids alone for inducing remission in bullous pemphigoid, and the evidence for all immunomodulators in bullous pemphigoid is weak (Level 4 evidence, Recommendation D) 1, 7