IVIG With Rituximab vs Rituximab as First Line Treatment of Pemphigus

Conditions

• Pemphigus

Eligibility Criteria

Sex

ALL

Age

18 Years - 75 Years

Healthy Volunteers

Not accepted

Interventions

• Rituximab — DRUG
  Rituximab would be given intravenously. * IV Rituximab is prediluted at a dose of 500mg in 500ml of 0.9% normal saline (i.e. 1:1 dilution, 1 mg/ml) * Initial infusion rate starts at a rate of 50mg/hr (50ml/hr) * If no hypersensitivity/anaphylaxis reaction occurs, increase infusion rate in 50mg/hr (50 ml/hr) increments every 30 minutes * Maximum infusion rate is 400 mg/hr (400 ml/hr) * Subsequent infusion: start at rate of 100mg/hr (100 ml/hr), increase 100mg/hr (100 ml/hr) increments every 30 minutes * Monitor temperature, BP HR, respiratory rate and SpO2 every 30 minutes
• IVIg — OTHER
  IVIg would be given in combination with Rituximab intravenously. Infusion plan of IVIg: 0 min: 50ml/hour 15 min: 75ml/hour 30 min: 100ml/hour 45 min: 125ml/hour 60 min: 150ml/hour 75 min \& beyond: 180ml/hour

Study Details

Pemphigus is a rare acquired autoimmune disease in which immunoglobulin G (IgG) antibodies target desmosomal proteins to produce intraepithelial, and mucocutaneous blisters. It is potentially fatal and the average mortality of pemphigus vulgaris (PV) was 75% before the introduction of corticosteroids in the early 1950s. Traditionally, treatment of pemphigus included high dose systemic corticosteroids with or without adjuvant immunosuppressants. However; the prolonged use of high dose steroids carries significant side effects. A recent randomized trial has proved the efficacy of Rituximab, a monoclonal anti-CD20 antibody against B-lymphocytes, as an efficacious therapy for pemphigus. Early use of rituximab was associated with better clinical outcomes, hence combination treatment of rituximab and intravenous immunoglobulins (IVIG) has shown to be effective for refractory pemphigus cases and can potentially induce long-term complete remission and lower risks infectious complications. In this study, investigators will evaluate the efficacy and safety of early use of rituximab with or without IVIG in patients with moderate to severe pemphigus using protocols that were similar to those previously published, investigators will also aim to measure the impact of health care economics and in doing so, assess the cost and benefits of both treatment arms.

Key Dates

Start date

Jun 20, 2020

Status verified

Jul 2025

Primary completion

Dec 31, 2025

Completion

Jun 30, 2026

Study Design

Enrollment

20 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Rituximab only
  * Rituximab infusion 375mg/m2 body surface area (BSA) weekly for 4 weeks from baseline (week 0, 1, 2, 3) * Rituximab infusion 375mg/m2 BSA weekly for 4 weeks at week 24 (week 24, 25, 26, 27) * Rituximab infusion 375mg/m2 BSA weekly for 2 weeks at week 52 (week 52, 53) * Rituximab infusion 375mg/m2 BSA weekly for 4 weeks at week 76 (week 76, 77) * A total of 12 doses of rituximab will be given in 55 weeks
• Experimental: Rituximab and IVIG
  * Rituximab (375 mg/m2 BSA) once a week for 4 weeks (week 1, 2, 3); * Week 4: Rituximab + IVIG 2g per kg * Week 5, 6, 7: Above treatment repeated for 2nd cycle, infusion of rituximab (375 mg/m2 BSA) once a week for 4 weeks (week 5, 6, 7); * Week 8: Rituximab + IVIG 2g/kg * In months 3, 4, 5, 6, patients received a single infusion of rituximab (375 mg/m2 BSA) plus infusion of 2g/kg IVIG * Thus in 6-month period patients received a total of 12 infusions of rituximab and 7 infusions of IVIG * If a patient was clinically free of disease at end of 6 months, additional infusions of IVIG will be given at week 30, 38, 48, 60 and 76 * A total of 12 doses of rituximab and 12 cycles of IVIG will be given

Primary Outcome Measure

relapse-free complete remission [ Time Frame: From baseline up to 208 weeks ]