Network meta-analysis-based comparison of first-line steroid-sparing adjuvants in the treatment of pemphigus vulgaris and pemphigus foliaceus

Background: Steroid-sparing adjuvants may enhance oral glucocorticoid benefits in pemphigus treatment. Selecting the optimal therapeutic option among various first-line steroid-sparing adjuvants is often a clinical challenge due to the lack of head-to-head clinical trials. Objective: To determine the best first-line steroid-sparing adjuvants for pemphigus treatment. Methods: Randomized controlled trials comparing different steroid-sparing adjuvants in patients with pemphigus were identified through a systematic literature search and subjected to a network meta-analysis. The primary outcomes were the proportion of remission and the mean cumulative glucocorticoid dose. Results: Ten trials involving 592 patients were analyzed. Among the 7 steroid-sparing adjuvants evaluated, rituximab was the most effective for achieving remission and was more effective than steroid alone (odds ratio, 14.35; 95% confidence interval [CI], 4.71-43.68). Rituximab, azathioprine, and cyclophosphamide pulse therapy enabled the reduction of the cumulative glucocorticoid doses compared to the use of steroid alone: mean differences, -11,830.5 mg (95% CI, -14,089.48 to -9571.52), - 3032.48 mg (-4700.74 to -1364.22), and -2469.54 mg (-4128.42 to -810.66), respectively. Limitations: The results were driven primarily by a small number of studies, and the effect estimates are imprecise because of indirect comparisons. Conclusion: Network meta-analysis showed that rituximab appears to be an efficacious, well tolerated steroid-sparing adjuvant for pemphigus.