EVALUATING CLINICAL AND SEROLOGICAL OUTCOMES OF SINGLE HIGH(1000MG) VERSUS LOW DOSE (500MG) RITUXIMAB IN PATIENTS WITH PEMPHIGUS : A RANDOMIZED , COMPARATIVE STUDY

This study aims to evaluate the clinical, serological efficacy, and safety of single high-dose (1000mg) versus low-dose (500mg) rituximab in the treatment of pemphigus vulgaris (PV) in the Indian population. Pemphigus is a potentially life-threatening autoimmune blistering disorder, traditionally treated with corticosteroids and immunosuppressants (ISA). However, the introduction of biological therapies, particularly rituximab, has significantly changed the treatment landscape by offering earlier and more sustained remission while reducing steroid dependence and associated side effects.

Rituximab, a CD20 monoclonal antibody, has been widely used in pemphigus for over two decades, but there is no standardized dosing regimen. The FDA approval for rituximab in pemphigus is based on dosing regimens from rheumatoid arthritis (RA) and lymphoma protocols. The lymphoma protocol (375mg/m² weekly for four weeks) and the RA protocol (two doses of 1g, two weeks apart) have shown efficacy, but given that pemphigus involves a lower abnormal B-cell burden compared to lymphoproliferative disorders, these higher doses may be unnecessary.

Several studies have explored the use of lower doses of rituximab (500mg and even ultra-low 200mg) in pemphigus, with positive outcomes. A study by Xingizhou et al. demonstrated that a single 500mg dose induced clinical and immunological remission for up to 52 weeks in all 19 patients. Similarly, Irene Russo et al. and Giuliani et al. found no relapse in pemphigus patients treated with ultra-low-dose rituximab (200mg). Additionally, Schoergenhofer et al. reported that two 100mg infusions were sufficient to suppress B-cells for three months. Despite these promising findings, no Indian studies have directly compared the efficacy of single high-dose (1000mg) versus low-dose (500mg) rituximab.

This prospective, randomized controlled trial will enroll pemphigus patients and randomly assign them to two groups:

• Group A: Single high-dose rituximab (1000mg)
• Group B: Single low-dose rituximab (500mg)

Both groups will receive initial corticosteroid treatment based on S2K guidelines:

• Mild pemphigus: 0.5–1mg/kg prednisone
• Moderate to severe pemphigus: 1–1.5mg/kg prednisone

Steroid tapering will follow a standardized protocol, with adjustments if disease control is inadequate. The total cumulative steroid dose (TCD) will be recorded and compared between the groups.

Outcome Measures:

1. Clinical Response: Evaluated using the Pemphigus Disease Area Index (PDAI), Autoimmune Bullous Disease Quality of Life (ABQOL), and remission status (partial/complete) as defined by the International Pemphigus Committee.
2. Serological Response: Desmoglein 1 (Dsg1) and Desmoglein 3 (Dsg3) titers measured by ELISA at baseline and at six months.
3. Safety Profile: Adverse effects such as infusion reactions and infections will be recorded.

By optimizing rituximab dosing for pemphigus vulgaris, this study aims to balance efficacy with safety and cost-effectiveness. If low-dose rituximab proves to be as effective as the high-dose regimen, it could become a safer and more affordable treatment option for pemphigus patients.