In bullous pemphigoid (BP), prolonged treatment with low-dose methotrexate (MTX) may represent an effective strategy to maintain an initial clinical remission achieved by short-duration superpotent topical steroids (STS).).

To evaluate the efficacy and safety of MTX in a real-life setting, a retrospective analysis was conducted in a reference centre for all BP patients treated between 2015 and 2020 with STS and MTX, either in monotherapy (mMTX) or in combination with oral steroids (MTX+OS). The primary endpoints were BP relapse rate and time to relapse during treatment for patients achieving initial disease control (IDC). Secondary endpoints included IDC achievement rate, relapse rate and time to relapse after MTX discontinuation, adverse effect (AE) and mortality rates, number of patients permanently discontinuing MTX owing to AE, number of patients alive and still in complete remission (CR) at the latest updates, and whether they were off treatment (cure rate).

The BP relapse rate during treatment after achievement of IDC was significantly higher in patients treated with mMTX (32.2%) than with MTX+OS (0%) (p = 0.03); mean time to relapse was 10.3 months. The BP relapse rate after MTX discontinuation and the cure rate did not differ significantly between the two groups. One patient (receiving mMTX) died during follow-up and 27.8% of patients experienced at least one AE during the study. The cure rate in patients achieving IDC was 45.2% with mMTX vs. 30% with MTX+OS (p = 0.15).

Our study highlights the value of low-dose mMTX for treating BP in a real-life setting, both for achievement of initial response and for long-term control, with a good overall safety profile and no significant additional mortality risk in elderly subjects. However, relapses appear to have been less frequent during treatment when MTX was initially combined with OS.