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10-03-2013 | Immunology | Article

Rituximab may provide functional cure for pemphigus

Abstract

Free abstract

medwireNews: Rituximab can induce long-term complete remission (CR) in patients with the chronic autoimmune disease pemphigus, show study findings.

Half of patients who started the monoclonal antibody remained in CR 6 years later, and most of those no longer required treatment, report Philippe Musette (University of Normandy, Rouen, France) and colleagues.

Pemphigus, which causes severe blistering of the skin, is thought to be caused by the production of pathogenic autoantibodies that target two desmosomal proteins involved in keratinocyte adhesion, desmoglein 1, and desmoglein 3.

Although B-cell depletion by rituximab has been effective against pemphigus in the short term, the long-term effect of the treatment has not been properly assessed until now, says the team.

In the current study, the researchers report on the clinical course of 22 patients treated with rituximab for severe pemphigus, over a 6-year follow-up period.

The researchers report that 21 (95%) patients achieved disease control, with complete regrowth of epithelium and/or healing of mucosal lesions after a mean of 3.1 months. However, 17 patients relapsed and required a second cycle of rituximab. Of these individuals, three died after a median survival of 29 months, leaving 19 who could be evaluated at 6 years.

Eleven of these patients achieved CR, including nine who had ceased treatment and two who were receiving minimal treatment. The remaining eight individuals were still receiving prednisone (>10 mg/day) due to active disease and were classified as having incomplete remission (IR).

Analysis of the IR and CR groups using enzyme-linked immunosorbant assay showed that levels of anti-desmoglein 1 and anti-desmoglein 2 significantly decreased, from 112 IU and 152 IU, respectively, at baseline to 23 IU and 71 IU, respectively, at 6 months. At 24 months of follow up, the respective levels were 23 IU and 115 IU, with no further significant variation in levels observed between months 24 and 79.

As reported in Science Translational Medicine, the mean number of CD19+ B lymphocytes measured at the end of the study period remained much lower than at baseline, a finding which the researchers say is "somewhat surprising considering the short half-life of rituximab."

The team says this long-lasting effect is most likely linked to the observed changes in B-cell subpopulations after rituximab treatment, which included a significant change in the naïve/memory B-cell ratio and the expansion of transitional B cells and interleukin (IL)-10-secreting regulatory B cells in patients who had CR.

Indeed, patients in CR had a significantly higher mean number of transitional B cells and of IL-10-secreting B cells than patients in IR.

"It is likely that these cells could be involved in the long-lasting decrease of the anti-desmoglein antibody response in pemphigus patients," writes the team.

"This study demonstrates that rituximab therapy can not only induce prolonged clinical remissions… but also, in some cases, provide a functional cure for pemphigus."

By Sally Robertson, medwireNews Reporter

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