Therapeutic Strategies in Pemphigus Vulgaris and Foliaceus: A Systematic Review and Network Meta-analysis and a Retrospective Cohort Study

Abstract

Abstract

Background Pemphigus is a life-threatening autoimmune bullous disorder of the skin and has been difficult to manage due to its chronic and, at times, unpredictable nature. Pemphigus vulgaris and foliaceus are the most common types and can be difficult to manage. Selecting optimal therapy can be challenging, especially due to the dearth of head-to-head trials of pharmacologic interventions.

Objective To evaluate and compare the odds of remission and adverse events in patients of pemphigus vulgaris and foliaceus treated with different therapeutic agents. Methods We conducted a network meta-analysis of randomized trials in patients of pemphigus vulgaris and foliaceus, identified through a systematic review. The odds of disease remission amongst various therapeutic agents were evaluated via a frequentist network meta-analysis.

Results The network meta-analysis evaluated 11 trials involving 717 patients, evaluating 6 different therapeutic agents with a cumulative 8 different dosages, forming 8 different nodes of the network for the primary outcome of remission. Rituximab was the most effective in inducing remission ranking, which was the highest amongst the network of comparisons.

Limitations The results were derived from only 11 studies with small sample sizes, and the effect estimates can be imprecise because of indirect comparisons. Conclusion In a network meta-analysis of 11 trials examining different pharmacologic interventions for the treatment of pemphigus, rituximab was the most likely to induce disease remission.

Abstract Background Pemphigus vulgaris and pemphigus foliaceus are rare dermatologic diseases. Often, more severe cases require treatment with multiple agents concurrently. Despite the use of combination therapy in clinical practice, there is a lack of published data or guidance regarding how or when to effectively and safely implement combination therapy for pemphigus. Objective To evaluate remission and adverse events in patients with pemphigus vulgaris and pemphigus foliaceus who receive monotherapy (mycophenolate mofetil (MMF) OR rituximab) compared to combination therapy (MMF & rituximab). Methods We conducted a retrospective cohort analysis of patients with pemphigus vulgaris and foliaceus receiving care in the Departments of Dermatology at Massachusetts General Hospital (MGH) and Beth Israel Deaconess Medical Center (BIDMC) from July 2018 to July 2023. We studied 100 patients treated with either MMF or rituximab and grouped them into those who received the drugs alone and those who received the drugs in combination. We used unadjusted and adjusted logistic regression models to estimate the odds ratio of adverse events and remission in monotherapy compared to combination therapy group. Results A total of 100 patients who were treated with either mycophenolate mofetil or rituximab were included in the analysis. There were 48 patients in the monotherapy group and 52 patients in the combination therapy group. The primary outcome of adverse events, evaluated as odds of adverse event adjusted for age and sex, was significantly lower in the monotherapy group compared to the combination-therapy group (Odds ratio = 0.41 (0.17-0.95) (p=0.03). Induction

of remission, evaluated as odds of remission adjusted for age and sex, showed no statistically significant difference in the monotherapy group compared to the combination-therapy group (Odds ratio = 0.62 (0.27-1.41)) (p=0.25). Conclusion The two groups had no significant difference in the odds of inducing remission. In contrast, the odds of an adverse event were significantly lower in the monotherapy group than in the multi-therapy group.