Clinical Trial: Rituximab in the Treatment of Patients With Bullous Pemphigoid

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Rituximab in the Treatment of Patients With Bullous Pemphigoid

Brief Summary: This study will determine the safety of treatment of bullous pemphigoid in patients resistant to therapy with systemic corticosteroids, with rituximab plus systemic corticosteroids.

Detailed Summary:

Bullous pemphigoid (BP) is an autoimmune blistering disease characterized clinically by the presence of severely itchy, tense blisters located over the trunk and extremities. BP is the most common of the autoimmune blistering diseases with an incidence of approximately 10 per 1,000,000 population(1;2). In addition, BP occurs more frequently in the elderly. Routine histopathology reveals a sub-epidermal blister most often with large numbers of eosinophils. Direct immunofluorescence of the skin of patients with BP reveals a linear band of C3 and IgG at the basement membrane zone. Examination of the sera of patients shows the presence of a circulating anti-basement membrane zone autoantibody. This antibody has been found to be directed against a 180 kd protein of the basement membrane zone type XVII collagen (BPAg2) and against a 230 kd protein (BPAg1) found in the epidermal hemi-desmosome(3;4).

BP is a severe disease most often requiring therapy with high dose systemic corticosteroids (0.75 - 1.0 mg/kg/day) often for months(5). In addition, relapses are common and the additional use of immunosuppressive drugs such as azathioprine, methotrexate, cyclosporine A and others are needed to minimize the dose of systemic corticosteroids. The 1-year mortality of BP has been estimated to range from 10 - 30%(1;6). Currently treatment of patients with BP consists of initial use of systemic corticosteroids (0.75 - 1.0 mg/kg/day). Control of symptoms and new blister formation is most often achieved within 1 month and systemic corticosteroids are then tapered. As many as 33 - 50% of patients may not be able to be tapered to clinically acceptable levels of systemic corticosteroids, requiring the addition of systemic immunosuppression often with azathioprine. Approximately 66% of patients require long term treatment with immunosuppressive medication to maintain control of their blistering.(
Sponsor: Duke University

Current Primary Outcome: Primary Safety Endpoint [ Time Frame: 1 year ]

The primary safety endpoint is the occurrence of treatment emergent adverse events including infections, infusion reactions and disease progression. These were determined by clinical evaluation and laboratory questions. Disease progression is defined as development of new blisters despite therapy. These are reported as the number of participants with a study related SAE.


Original Primary Outcome: To determine the safety of rituximab for treatment of patients with bullous pemphigoid.

Current Secondary Outcome:

  • Number of Days to Cessation of New Blister [ Time Frame: 1 year ]
    The first study visit in which patient reported and was confirmed to have no new blister or lesion formation .
  • Systemic Corticosteroid Dose of 25% of Starting Dose or 10 mg/Day by Week 24 [ Time Frame: 24 weeks ]
    Subject systemic corticosteroid dosage at week 24 was 25% of starting dose or 10 mg/day of prednisone or less
  • IgG Anti Bullous Pemphigoid (BP) 180 Measured in Units by ELISA at Week 24. [ Time Frame: Week 0 and at 24 weeks ]
    IgG antibodies against BP 180 measured in units (by ELISA) for each participant at week 0 compared to value at week 24,
  • B Cell Number at Week 24 [ Time Frame: Week 0 and at 24 weeks ]
    Peripheral blood B cell number at week 24 compared to B cell number at week 0


Original Secondary Outcome: Deterine # of days to cessation of new blister formation; reduce prednisone to 25% of initial dose by week 24; reduce bullous pemphigoid antibody

Information By: Duke University

Dates:
Date Received: February 1, 2006
Date Started: March 2005
Date Completion:
Last Updated: April 9, 2013
Last Verified: September 2012