SELECTED ARTICLES FROM THE RECENT LITERATURE 2006

11/9/06

Treatment of pemphigus vulgaris with rituximab

Summary
Background – Pemphigus vulgaris (PV) is a severe, potentially fatal, autoimmune blistering disease. Current therapy with corticosteroids (CS), immunosuppressive agents and IV immunoglobulin (Ig) control PV in some, but not all, cases.

Findings – Ahmed et al of the New England Baptist Hospital in Boston, MA evaluated 11 patients with severe PV, not sufficiently controlled with the drugs listed above. The patients were then treated with 2 cycles of rituximab (Ritux), an anti-CD20 monoclonal antibody, 375 mg/kg plus one infusion of IV Ig (2 Gm per kg body weight). This was followed by monthly infusions of Ritux and IV Ig.

There was a prompt remission of PV lesions in 9 of the 11 patients treated with Ritux, lasting 22-37 months. Levels of IgG4 anti-keratinocyte antibodies also decreased markedly with Ritux treatment, with levels of such antibodies subsequently correlated with PV clinical disease activity. Circulating B cell levels also decreased markedly.

Reference
N Eng J Med 2006;355:1772-79

Editor's Comments
I have reviewed this report because it helps to point out wide spectrum of putatively auto-immune diseases in which Ritux is being tried therapeutically. The mechanism(s) underlying any beneficial effects of Ritux treatment are still not defined. In almost all cases, circulating B cells decrease to almost undetectable levels. Yet effects of Ritux treatment on the serum levels of relevant autoantibodies have varied among different studies, possibly reflecting varying proportions of such autoantibodies which are produced by CD20-positive B cells and CD20-negative plasma cells.

It would be of considerable interest to determine whether there is loss of efficacy of repeated Ritux treatments of PV with time and whether loss of efficacy is associated with development of host antibody responses against the Ritux monoclonal antibody (called a HACA by some investigators).

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