A comparison of prednisolone plus oral azathioprine or oral cyclophosphamide versus prednisolone alone for the treatment of mild pemphigus

Abstract

Background: Pemphigus is a rare bullous autoimmune disorder. Systemic corticosteroids are the mainstay of therapy and are usually given in combination with adjuvant immunosuppressive agents to reduce the cumulative corticosteroids dose and adverse effects, however there is no controlled studies on individual therapeutic regimens in mild pemphigus.

Objective: To demonstrate the efficacy, safety and corticosteroids-sparing effect of oral cyclophosphamide or azathioprine for the treatment of mild pemphigus.

Material and Methods: A prospective randomized non-blinded experimental study 22 patients with mild pemphigus. They were randomized in to 2 groups, 11 for each by simple randomization method. The first group were received daily oral prednisolone alone. The second group were received daily oral prednisolone plus oral cyclophosphamide or azathioprine. At each follow up visit, the prednisolone dosage was subsequently reduced until discontinue followed by 6 and  12 weeks  follow up to measure number of patients who achieve complete remission, time to achieve  remission, recurrent and relapsing rate, cumulative prednisolone dose and side effects of the treatments. The number of new blister formation and level of anti-Dsg3 and/or anti-Dsg1auto-antibodies by ELISA method are used for evaluation.

Results: There were 22 patients included in this study, but 3 patients from the combined group were excluded due to their poor compliance. The remaining 19, 13 were female, 6 were male in 18-78 years of age (average 47.7 years). There were 7 cases with pemphigus foliaceus, 12 with pemphigus vulgaris and 2 of them have been treated with prednisolone. At the end of the study, the number of patients who achieved complete remission was 63.6% (7/11) in the prednisolone group and 75% (6/8) in the combined group (P = 1) correlate with the reduction of anti-Dsg 3 and/or anti-Dsg 1 auto-antibodies titers. The average time to complete remission in the prednisolone group were 255.14 (215 – 267 days) and in the combined group were 266.66 (266 – 267 days) (P = 0.125). One patient from the combined group had disease relapse between treatment. Three patients from the prednisolone group had disease recurred after stop treatment with average time 8.3 weeks. The average cumulative prednisolone dose were 2648.5 (1750 – 3600 mg) in the first group and 2300 (2100 – 2625 mg) in the combined group (P = 0.191). Acne, weight gain and cushigoid appearance were the adverse effects noted in both group. Hypertension, hyperglycemia and oral candidiasis were found only in prednisolone group. Nausea and vomiting were found only in combined group

Conclusions: The combination of daily oral prednisolone plus oral cyclophosphamide or azathioprine seems to have higher rate of complete remission, lower recurrent rate, longer disease free interval  and also demonstrate steroid sparing effect without serious adverse effects from immunosuppressive agents.