Current Tx for blistering disorders lacks evidence-based science
EXPERT ANALYSIS AT PDA 2016
The standard of treatment for autoimmune blistering diseases is prednisone 0.7-2 mg/kg. Nonsteroidal immunosuppressive agents are also helpful, including methotrexate, azathioprine, cyclophosphamide, and mycophenolate mofetil. Emerging evidence suggests that rituximab is the drug of choice for PV and PF, and should be the first-line therapy. Rituximab is a chimeric monoclonal antibody that targets CD20–positive B lymphocytes. “It removes cells that are ready to transform into autoantibody-producing short-lived plasma cells,” Dr. Woodley said. “The depletion lasts 6-12 months.”
Another new development in BP is the use of omalizumab, a monoclonal antibody to IgE. “Omalizumab inhibits the IgE antibody binding to the BP180,” Dr. Woodley said.
“It’s thought that the BP180 antigen is released from basal keratinocytes into the high papillary dermis. In BP patients, there are numerous mast cells at that location. IgE binds to the mast cells, which have IgE receptors on their surface, and in the presence of the BP180 antigen, forms dimers on the mast cells, and causes them to release inflammatory cytokines, some of which recruit eosinophils. This is likely why BP is such an inflammatory disorder. You cannot follow the IgE levels; you have to follow the eosinophils. The IgE is still high, but it’s nullified and inactive.”
Other biologics that have been successfully used in PV, PF, and BP include tumor necrosis factor–alpha inhibitors and rituximab (Rituxan). Common dosing for rituximab is 325 mg/m2 per week for 4 weeks. Infusion reactions are the most common side effect, he said, but other reported adverse reactions include infections, transient hypogammaglobulinemia, neutropenia, deep vein thrombosis, and pulmonary embolism. “The incidence of side effects seems to be going down, because we are now premedicating patients with antihistamines and IV hydrocortisone before giving them rituximab,” Dr. Woodley noted.
The development of progressive multifocal leukoencephalopathy has also been reported with the use of rituximab. “This is exceedingly rare with rituximab but has been described, and this is what keeps doctors who use this drug awake at night,” he said.
Elderly patients with mild BP sometimes can get by without using immunosuppressive agents to manage their disease. One option is potent topical steroids plus niacinamide 0.5-2 g after each meal as an anti-inflammatory B vitamin. “Doxycycline 100 mg b.i.d. also works to inhibit neutrophils,” he said. “Antihistamines can also be helpful, and some French dermatologists have found total body clobetasol to be useful.”
Dr. Woodley disclosed that he holds patents on human recombinant type VII collagen. He is also a consultant for Shire Pharmaceuticals and a speaker for Biofusion.
