Combined treatment with immunoadsorption and rituximab leads to fast and prolonged clinical remissions in difficult to treat pemphigus

Department of Dermatology and Allergology, Philipps-Universität, D-35043 Marburg, Germany.
British Journal of Dermatology (Impact Factor: 4.28). 11/2011; 166(4):844-52. DOI: 10.1111/j.1365-2133.2011.10732.x
Source: PubMed


Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune bullous disorder which is characterized by blisters and erosions of the skin and mucous membranes. A frequently applied first-line therapy for PV consists of systemic corticosteroids (CS) combined with immunosuppressive agents. In refractory cases, novel therapeutic strategies such as immunoadsorption (IA) and the anti-CD20 antibody rituximab (Rtx) aim at directly interfering with pathogenic autoantibodies (auto-Abs).
To investigate the long-term efficacy of IA in combination with Rtx in patients with difficult-to-treat PV, we assessed the clinical response to treatment by monitoring the Autoimmune Bullous Skin Disorder Intensity Score, IgG auto-Abs against desmoglein 1 and 3 (Dsg1 and Dsg3) and the dose of systemic CS.
We retrospectively analysed clinical and serological parameters of 10 patients with difficult-to-treat PV who received IA at 4-week intervals, followed by Rtx either twice at 1000 mg or four times at 375mg m(-2) . During a 12-month follow-up period, CS were tapered according to the individual clinical status.
Six months after the first IA treatment eight of 10 patients were in complete remission on therapy while one patient showed a partial response and one patient was unresponsive to the treatment. At 12 months, six of eight patients were in complete remission on therapy, one patient showed stable disease and one patient had relapsed. Overall, anti-Dsg3 IgG and anti-Dsg1 IgG auto-Abs correlated well with the clinical activity and systemic CS were tapered gradually.
The present findings show that the combination of IA and Rtx induces rapid clinical remission and long-term control in difficult-to-treat pemphigus.

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    • "Overall, anti-Dsg3 IgG and anti-Dsg1 IgG auto-Abs correlated well with the clinical activity. These findings suggest that the combination of IA and rituximab induces rapid clinical remission and long term control in difficult-to-treat pemphigus.[40] "
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    ABSTRACT: Background: Rituximab has been reported to be effective in various small case series of patients with severe and/or refractory pemphigus. However, no systematic evaluation is available to corroborate this observation. The aim of this study was to systematically determine efficacy and safety of rituximab in treatment-resistant pemphigus. Patients and Methods: Multicenter retrospective, observational study of 36 patients with severe pemphigus vulgaris (n = 33) and pemphigus foliaceus (n = 3) treated with rituximab before August 31(st) , 2008 and enrolled in a national observational registery between December 2008 and June 2009. Results: Within a mean period of observation of 11 (1-37) months, 21 (58 %) pemphigus patients showed complete, 13 (36 %) partial, and 2 (6 %) no response to rituximab treatment. This correlates with a mean improvement of the visual analog scale for well-being of 34 (20-60) at baseline to 75 (40-95) at the last control visit. In 4 (11 %) patients, severe adverse events were recorded including 1 (3 %) serious infection. Conclusions: Data collected in this systematic registry indicate that rituximab is an effective and relatively safe adjuvant treatment option for refractory pemphigus. To further extend our knowledge on efficacy and safety of this drug, controlled prospective trials are required.
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