Mucosal involvement is a risk factor for poor clinical outcomes and relapse in patients with pemphigus treated with rituximab

Cho, Soo Ick; Kim, Ji Won; Lim, Ji Soo; Chung, Jin Ho

doi:10.1111/dth.12814

Cited by 10 publications

(7 citation statements)

References 16 publications

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“…Also in this study, later B-cell repopulation was found in patients experiencing a late relapse compared to patients experiencing an early relapse (209). By contrast, in a retrospective study including 40 pemphigus patients treated with RTX, mucosal involvement was found to be associated with a poor clinical outcome and relapse (210).…”

Section: Treatmentmentioning

confidence: 99%

Pemphigus: Current and Future Therapeutic Strategies

et al. 2019

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Pemphigus encompasses a heterogeneous group of autoimmune blistering diseases, which affect both mucous membranes and the skin. The disease usually runs a chronic-relapsing course, with a potentially devastating impact on the patients' quality of life. Pemphigus pathogenesis is related to IgG autoantibodies targeting various adhesion molecules in the epidermis, including desmoglein (Dsg) 1 and 3, major components of desmosomes. The pathogenic relevance of such autoantibodies has been largely demonstrated experimentally. IgG autoantibody binding to Dsg results in loss of epidermal keratinocyte adhesion, a phenomenon referred to as acantholysis. This in turn causes intra-epidermal blistering and the clinical appearance of flaccid blisters and erosions at involved sites. Since the advent of glucocorticoids, the overall prognosis of pemphigus has largely improved. However, mortality persists elevated, since long-term use of high dose corticosteroids and adjuvant steroid-sparing immunosuppressants portend a high risk of serious adverse events, especially infections. Recently, rituximab, a chimeric anti CD20 monoclonal antibody which induces B-cell depletion, has been shown to improve patients' survival, as early rituximab use results in higher disease remission rates, long term clinical response and faster prednisone tapering compared to conventional immunosuppressive therapies, leading to its approval as a first line therapy in pemphigus. Other anti B-cell therapies targeting B-cell receptor or downstream molecules are currently tried in clinical studies. More intriguingly, a preliminary study in a preclinical mouse model of pemphigus has shown promise regarding future therapeutic application of Chimeric Autoantibody Receptor T-cells engineered using Dsg domains to selectively target autoreactive B-cells. Conversely, previous studies from our group have demonstrated that B-cell depletion in pemphigus resulted in secondary impairment of T-cell function; this may account for the observed long-term remission following B-cell recovery in rituximab treated patients. Likewise, our data support the critical role of Dsg-specific T-cell clones in orchestrating the inflammatory response and B-cell activation in pemphigus. Monitoring autoreactive T-cells in patients may indeed provide further information on the role of these cells, and would be the starting point for designating therapies aimed at restoring the lost immune tolerance against Dsg. The present review focuses on current advances, unmet challenges and future perspectives of pemphigus management.

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Section: Treatmentmentioning

confidence: 99%

Pemphigus: Current and Future Therapeutic Strategies

et al. 2019

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“…However, some patients are better RTX responders. Mucosal involvement not only is an indicator of poor clinical response but also accompanies a 4.6 times higher risk of disease relapse 31,32 . B‐cell repopulation, low CD4+ T‐cell count (<400 cells/μl), and positive anti‐Dsg1/3 are reported as risk factors for relapse after RTX treatment 24 .…”

Section: Rituximab For Treatment Of Pemphigus: a Brief Literature Reviewmentioning

confidence: 99%

Rituximab in practice: Clinical evaluation of patients with pemphigus after rituximab administration

Mahmoudi

Tavakolpour

Balighi

et al. 2020

Dermatologic Therapy

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Pemphigus Vulgaris (PV) is a rare autoimmune blistering disease, which mainly causes mucosal and/or cutaneous lesions. In June 2018, FDA approved Rituximab (RTX)—a B‐cell depleting agent—for the management of patients with moderate‐to‐severe pemphigus. Although the majority of patients respond well to this drug, some do not reach complete remission with a single cycle of RTX. In this review, following an overview of RTX and its clinical outcomes, we have focused on the possible outcomes after RTX therapy in patients with PV. The response is defined into four main categories; complete responders, partial responders, nonresponders, and paradoxical reactions, based on three possibilities of reaching the consolidation phase after 3 months, reaching remission until 6 months, and the ability of corticosteroid tapering in 6 months after RTX administration. Concerning the safety of RTX, three categories of infusion reactions, short and long‐term side effects are discussed. Additionally, we have suggested approaches for the evaluation of clinical and serological responses at different critical time‐points, including 1, 2, 3, and 6 months after RTX administration. Finally, available markers to predict the response to RTX and research gaps in the field of RTX therapy have been summarized.

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“…According to recent studies, mucosal involvement is correlated with severity of the disease (PDAI) but also with the risk of relapse. In fact, in the study by Cho et al [8] , the risk of relapse was 4.626 times higher in patients with mucosal lesions than patients without mucosal involvement. In addition, patients with isolated oral disease responded less to treatment with rituximab and relapsed more frequently, moreover, the risk of relapse in these patients was equivocal in both sexes, concluding that pemphigus vulgaris would be more likely to relapse than pemphigus foliaceous, in addition to a higher risk of relapse as the disease begins with mucosal involvement.…”

Section: Discussionmentioning

confidence: 91%

Untitled

2022

Int. J. Appl. Dent. Sci.

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Mucosal involvement is a risk factor for poor clinical outcomes and relapse in patients with pemphigus treated with rituximab

Cited by 10 publications

References 16 publications

Pemphigus: Current and Future Therapeutic Strategies

Pemphigus: Current and Future Therapeutic Strategies

Rituximab in practice: Clinical evaluation of patients with pemphigus after rituximab administration

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