Topical Steroids Alone or Associated With Methotrexate in Bullous Pemphigoid

Overview

This controlled multi-center randomized clinical trial, with direct individual benefit, will compare efficacy and safety of two strategies in non-localized BP care: a combined regimen using initial superpotent topical steroids associated with methotrexate for 4 weeks followed by methotrexate alone for 8 months and superpotent topical steroids alone maintained 9 months (current standard of care). The expected result is an equivalence between the two compared strategies in terms of safety and efficacy, MTX monotherapy during the maintenance phase being easier to manage and therefore associated with better compliance than topical steroids with less cutaneous side effects and most cost-effective.

Bullous pemphigoid (BP) is a rare mucocutaneous autoimmune bullous disorder (incidence \<1/10000 / year in France) that mostly affects elderly patients. Its mortality rate is as high as 20 to 40% at one year. A study initiated by the French group for bulllous disorders devoted to the study of autoimmune bullous diseases the study of autoimmune bullous diseases and which is an international leader on this issue, has previously demonstrated the efficacy and relatively good tolerance of superpotent topical corticosteroids in BP.However, the use of superpotent topical corticosteroids is flawed with practical difficulties (home-based care by nurses once or twice a day to administer treatment, this for several months) and its cost is significantly higher than that an oral steroid treatment as a consequence. On the other hand, there is probably a non-negligible systemic absorption of superpotent topicalsteroid responsible for potentially serious side effects similar to those encountered with systemic corticosteroids. Finally, a protracted treatment with superpotent topical steroid most often causes skin atrophy with deleterious consequences.It would then be of interest to be able to significantly reduce the duration of use of topical steroids through an early-associated systemic treatment relying on an easy-to-use and relatively safe molecule that would maintain the disease under control after an initial clinical remission has been achieved by initial and time-limited use of superpotent topical steroids. Methotrexate (MTX) could be an interesting candidate in this regard, with a low-level and tolerable short- and middle-term toxicity if small doses are used (10-15 mg / week) while its long-term safety is usually irrelevant in elderly patients. Its use and monitoring are relatively easy and a number of international publications, including two recent French ones, have shown efficacy in this setting including a relaying strategy after initial use of superpotent topical steroids in BP treatment, in preliminary open studies .These encouraging results prompt to propose a controlled multi-center randomized clinical trial, with direct individual benefit, comparing efficacy and safety of a treatment regimen using superpotent topical steroids alone maintained 9 months (current standard of care) to a mixed initial treatment combining applications of superpotent topical steroids associated with methotrexate for 4 weeks followed by methotrexate alone for 8 additional months in non-localized BP. In both arms, the total treatment duration will then be 9 months. The two arms of the study will be:Arm A: daily applications of topical clobetasol propionate at a dose of 10 to 30 g / day depending on the patient's weight and the initial number of new blisters per day, associated with methotrexate (MTX) received either orally or subcutaneously at a dose of 12.5 mg / week in patients weighing less than 60 kg and with creatinine clearance greater than 50 ml / min (planned dose reduction to 10 mg / week in patients less than 60 kg or with a creatinine clearance less than 50 ml / min) for four weeks followed by oral or subcutaneous methotrexate alone at the same dose during following 8 monthsArm B: daily applications of topical clobetasol propionate at a dose of 10 to 30 g / day depending on the patient's weight and the initial number of new blisters per day maintained until 14 days after full disease control followed by the same daily dose applied every other day for a month and then twice a week for a month and then once a week until the end of the 9th month.The primary endpoint will be the actuarial survival rate at one year in both groups and secondary endpoints will be the initial control rate of the disease, the number of serious side effects during treatment and the number of relapses during treatment.The expected result is an equivalence between the two compared strategies in terms of safety and efficacy, MTX monotherapy during the maintenance phase being easier to manage and therefore associated with better compliance than topical steroids with less cutaneous side effects and most cost-effective.This study will enroll 150 patients per arm and will include a follow up of 9 months with 9 visits per patient.