Combined treatment with immunoadsorption and rituximab leads to fast and prolonged clinical remission in difficult-to-treat pemphigus vulgaris
ABSTRACT 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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ABSTRACT: This systematic review aimed to (1) explore the patient-reported outcome measures (PROMs) currently used in the oral mucosal disease literature and report on the type and context of the use of these instruments and (2) provide a future direction for PROMs in Oral Medicine practice and research. A systematic review of published English-language articles relating to the use of PROMs in the oral mucosal diseases literature was performed in November 2013. In total, 131 articles met the inclusion criteria; these articles addressed the following oral mucosal conditions: lichen planus (75); recurrent aphthous stomatitis (30); mucous membrane pemphigoid/pemphigus vulgaris (14); orofacial granulomatosis (1); and multiple oral mucosal diseases (11). The most commonly used instruments were visual analog scales (VAS) and the oral health impact profile (OHIP). Limited progress has been achieved with use of PROMs in Oral Medicine in the last few decades in both clinical practice and a research setting. With the engagement of allied medical disciplines in PROM usage and the promotion of PROMs by national health care bodies globally, advancement of PROMs is imperative for Oral Medicine. Exposure through the World Workshop on Oral Medicine (WWOM), along with potential involvement in the Core Outcome Measures in Effectiveness Trials (COMET) or other such initiatives, will enable worldwide collaboration to promote the development and utilization of valid and reliable PROMs in oral medicine, and improve patient care. Copyright © 2015 Elsevier Inc. All rights reserved.03/2015; DOI:10.1016/j.oooo.2015.01.023
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ABSTRACT: Approximately 500 treatment recalcitrant pemphigus vulgaris patients have been treated with rituximab. They were treated according to the lymphoma protocol (N=224) or rheumatoid arthritis protocol (RAP) (N=209) patients. Others were treated with modifications or combinations of the two. The mean duration of follow up with the lymphoma protocol was 28.9months and 21.9 in the rheumatoid arthritis protocol. The majority of the patients received corticosteroids and immunosuppressive therapy before, during, and after rituximab therapy. A clinical remission on therapy was observed in 90%-95% of patients within less than six weeks. A complete resolution occurred within three to four months. A small percentage of patients were able to stay in clinical remission without the need for additional systemic therapy. The incidence of relapse was at least 50%. The number of patients who required additional rituximab was 60% to 90%. A majority of patients in clinical remission post rituximab therapy, were still on CS and ISA, albeit at lower doses. Serious adverse events were reported in a mean of five patients (range 2-9), the most important was infection and frequently resulting in septicaemia. The mortality rate related to rituximab was a mean of 2 patients (range 1-3). Hence, the preliminary conclusions that can be drawn are that rituximab is an excellent agent to induce early remission. The protocols that were used were not ideal for producing a prolonged and sustained remission without additional therapy. The advantages and specificity of targeting B-cells demonstrate that rituximab is one of the best biological agents, currently available for treating recalcitrant pemphigus. Its further use is encouraged. Future research needs to focus on modifying, improving and possibly adding additional agents, so that prolonged and sustained remissions can be obtained by its use. Copyright © 2014 Elsevier B.V. All rights reserved.Autoimmunity Reviews 12/2014; 14(4). DOI:10.1016/j.autrev.2014.12.002 · 7.10 Impact Factor
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ABSTRACT: To determine the efficacy and safety of interventions for pemphigus vulgaris (PV). We conducted a systematic review from 2003 to 2013 according to the Cochrane Collaboration methodology. Randomized controlled trials (RCTs) or controlled clinical trials (CCTs) and observational studies were conducted along with diagnosis confirmed by clinical, histopathologic, and immunofluorescence criteria. Primary outcomes were disease remission and mortality; several relevant secondary outcomes were also included. Fourteen RCTs or CCTs and 110 observational studies were included in the final analyses. RCTs or CCTs demonstrated considerable heterogeneity in outcome measures, and all had a high risk of bias for at least 1 of 8 domains. Of the studies, 96.8% (120) described the use of oral corticosteroids. Azathioprine and mycophenolate-mofetil were the most commonly cited treatments. An increasing number of studies described biologic therapies (rituximab, intravenous immunoglobulin [IVIg]). Evidence supporting recent comprehensive treatment guidelines was reviewed. We found persisting wide variations in treatment practice and inadequate quality of research supporting optimal PV treatment. Copyright © 2015 Elsevier Inc. All rights reserved.Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 03/2015; DOI:10.1016/j.oooo.2015.01.022 · 1.46 Impact Factor