Authors: Sarah Anwar Almulla , Mohammad Abdullah Alnoaim , Abdulaziz Abdullah Albanyan , Ali Mohammad Alshakhs , Azzam Nabil Almulhim , Nour Hassan Aljamaan , Waad Abdulelah Alduraywish , Abdulaziz Abdullah Alarfaj , Heba Alojail

Abstract

Background: Long-term corticosteroid use remains central to managing autoimmune blistering diseases (AIBDs) but carries substantial toxicity, prompting wider use of steroid-sparing agents ranging from conventional immunosuppressants to biologics. Comparative evidence on the efficacy and safety of these agents remains heterogeneous.

Methods: We systematically searched PubMed, Web of Science, and Scopus for studies published from 2015 to 2025 evaluating steroid-sparing therapies in pemphigus and bullous pemphigoid. After duplicate removal and two-reviewer screening against predefined eligibility criteria, nine studies totaling 396 patients (randomized trials, prospective comparisons, and retrospective cohorts) were included. Methodological quality was appraised using ROBINS-I for non-randomized studies and Cochrane RoB2 for randomized trials.

Results: Rituximab (RTX) was associated with higher long-term remission and faster corticosteroid tapering than conventional immunosuppressants, but with a higher rate of serious adverse events (approximately 15% to 22% vs. 10% to 15%). Short-term dexamethasone-cyclophosphamide pulse therapy performed comparably to RTX in some studies, though its long-term safety remains a concern. Among conventional agents, mycophenolate mofetil enabled faster steroid tapering than azathioprine. Risk of bias was moderate to serious across the non-randomized studies and ranged from some concerns to high risk across the three randomized trials; considerable heterogeneity in design and outcome reporting limits direct comparison across studies.

Conclusion: RTX was associated with more durable disease control than conventional agents in this set of studies, but the certainty of this finding is limited by the moderate-to-high risk of bias and small number of included studies. Treatment selection should be individualized based on disease severity, comorbidities, cost, and access, and future research should prioritize standardized, long-term, pragmatic comparative trials.

Keywords: Autoimmune Blistering Diseases; Steroid-Sparing Therapy; Immunosuppressive Agents; Rituximab; Pemphigus Vulgaris; Bullous Pemphigoid.