Rituximab With Corticosteroids Versus Corticosteroids Plus Azathioprine for Moderate-to-Severe Pemphigus Vulgaris

Overview

This quasi-experimental study aims to compare the effectiveness and safety of rituximab combined with corticosteroids versus the standard regimen of oral corticosteroids plus azathioprine in patients with moderate to severe pemphigus vulgaris. Pemphigus vulgaris is a rare autoimmune blistering disease. Conventional treatment with high-dose corticosteroids and azathioprine, though effective, is associated with significant long-term side effects. Rituximab, a B-cell depleting monoclonal antibody, has emerged as a promising alternative that may achieve higher rates of complete remission, faster disease control, fewer relapses, and reduced cumulative steroid exposure. Patients will be allocated non-randomly into two groups based on clinical suitability, affordability, and preference. Outcomes will be assessed over 12 months, focusing primarily on complete remission rates, with secondary evaluation of time to disease control, relapse rates, cumulative corticosteroid dose, and adverse events. The study seeks to generate local evidence from Pakistan to guide more effective and safer treatment protocols for moderate to severe pemphigus vulgaris.

Pemphigus vulgaris is a rare but serious autoimmune disease in which the body's immune system produces antibodies that attack proteins (desmogleins) responsible for holding skin and mucosal cells together. This leads to painful blisters and erosions on the skin and mucous membranes, particularly in the mouth. If not treated effectively, the condition can cause significant morbidity and, in severe cases, life-threatening complications. For many years the standard approach has involved high-dose oral corticosteroids combined with an immunosuppressive agent such as azathioprine. While this combination can control the disease, prolonged use of corticosteroids frequently results in serious adverse effects, including diabetes, osteoporosis, increased susceptibility to infections, and Cushingoid features. These complications often limit the long-term safety of conventional therapy. Rituximab is a monoclonal antibody that specifically targets CD20-positive B-cells, the cells responsible for producing the harmful autoantibodies. By depleting these cells, rituximab addresses the underlying immunological mechanism of the disease more selectively than broad immunosuppression. Growing evidence from international studies suggests that rituximab, when used with a short course of corticosteroids, can achieve higher rates of sustained remission, reduce the frequency of relapses, and substantially lower the total amount of corticosteroids patients need to take. Despite these promising findings, comparative data from Pakistan and similar resource-constrained settings remain limited. Cost, availability, and local clinical experience still influence treatment choices. A quasi-experimental design is therefore appropriate: patients with moderate to severe disease will be assigned to one of two treatment arms according to clinical suitability, affordability, and informed preference rather than by randomisation. One group will receive rituximab plus corticosteroids; the other will receive the conventional regimen of oral corticosteroids plus azathioprine. Patients will be followed for twelve months. The primary focus will be the proportion of patients who achieve complete clinical remission. Secondary measures will include the time required to achieve disease control, the number and timing of relapses, the cumulative dose of corticosteroids administered, and the frequency and severity of treatment-related adverse events. Disease activity will be monitored using the Pemphigus Disease Area Index (PDAI) at regular intervals. By generating local comparative data, this study aims to clarify whether rituximab-based therapy offers meaningful advantages in effectiveness and safety over the conventional regimen in the Pakistani population, thereby supporting more informed treatment decisions for patients with moderate to severe pemphigus vulgaris.