Abstract: Eleven studies with a total of 404 participants (337 pemphigus vulgaris, 27 pemphigus foliaceus and 40 not specified ) were identified. The quality of included studies was not high, the majority of studies did not report allocation concealment, and power was limited by very small sample sizes. Interventions assessed included prednisolone dose regimen, pulsed dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate, plasma exchange, topical epidermal growth factor and traditional Chinese medicine. Ten studies included participants with newly diagnosed or newly active recurrent disease, and one trial included participants in maintenance phase. There was sufficient data for 4 meta-analyses, each pooling results of two studies only. For the majority of interventions, results were inconclusive. We found some interventions to be superior for certain outcomes, although we were unable to conclude which treatments are superior overall. Mycophenolate was more effective in achieving disease control than azathioprine (1 study; n=40; RR 0.72; 95% CI 0.52 to 0.99, NNT 3.7). There was evidence of a steroid-sparing benefit of azathioprine (1 study; n=57; MWD -3919 mg prednisolone; 95% CI -6712 to -1126) and cyclophosphamide (1 study; n=54; MWD -3355 mg prednisolone; 95% CI -6144 to -566) compared to glucocorticoids alone. Topical epidermal growth factor decreased time to control (1 study; n=20; HR 2.35; 95% CI 1.62 to 3.41). There is inadequate information available at present to ascertain the optimal therapy for pemphigus vulgaris or pemphigus foliaceus. Further research is required, especially to assess the optimal glucocorticoid dose, the role of adjuvant immunosuppressive medications, and long-term adverse events to improve harm:benefit analyses.

Plain-language summary: This review included data from 11 clinical trials involving 404 participants. The studies had very small numbers of participants, so can provide only limited information. Ten different active treatments were studied, including prednisolone, pulsed oral dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate, plasma exchange, topical epidermal growth factor and traditional Chinese medicine. This review found insufficient information to conclude which is the most effective and safest treatment plan. We found that mycophenolate mofetil appears to be more effective than azathioprine in controlling disease, although no difference was seen in remission. We found that taking azathioprine and cyclophosphamide decreased the amount of glucocorticoids required. Topical epidermal growth factor decreased time required for lesions to heal by 6 days (median). We found no difference in withdrawal due to adverse events in any study, although differing adverse event profiles were observed for each intervention. We were not able to conclude which treatments are superior overall. Multiple treatments are available for pemphigus vulgaris and pemphigus foliaceus and there is a variation in dosage plan and combination of drugs used, which makes choice of treatment schedule complex. In addition, response to treatment can vary between individuals. Treatments need to be chosen after careful consideration of the potential benefits and side effects, in the context of the individual's other medical conditions. This review found insufficient information to conclude which is the most effective and safest treatment regimen. Further studies are required to determine the optimal treatment regimen, especially to assess the optimal glucocorticoid dose, the role of adjuvant immunosuppressive medications, and long-term adverse events to improve harm:benefit analyses.