Novel Therapies for Pemphigus Vulgaris

Altman, Emily

doi:10.1007/s40257-020-00544-w

Cited by 12 publications

(8 citation statements)

References 178 publications

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“…Given the complexity of pemphigus pathology with the involvement of innate immunity, T cells, B cells, and autoantibodies, it is not surprising that various therapies beyond those targeting autoantibody-producing B cells are also being investigated [reviewed in ( 20 )]. It remains to be determined how potent these approaches are, individually and collectively, and whether complete elimination of corticosteroids and broad immunosuppressants can be achieved.…”

Section: Discussionmentioning

confidence: 99%

“…Autoantigen uptake and presentation by APCs, fueled by the autoantibodies themselves through Fc-receptors [classical FcγR ( 17 ) but also the neonatal Fc receptor (FcRn) ( 18 )] and/or complement-mediated uptake ( 19 ), may also reinforce inflammation and autoantibody production. Various therapeutic approaches targeting disparate immune components are therefore extensively tested in autoimmune diseases including pemphigus ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

FcRn Antagonism Leads to a Decrease of Desmoglein-Specific B Cells: Secondary Analysis of a Phase 2 Study of Efgartigimod in Pemphigus Vulgaris and Pemphigus Foliaceus

et al. 2022

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BackgroundImmunoglobulin G (IgG) levels are maintained by the IgG-recycling neonatal Fc-receptor (FcRn). Pemphigus vulgaris and pemphigus foliaceus are debilitating autoimmune disorders triggered by IgG autoantibodies against mucosal and epidermal desmogleins. Recently, a phase 2 clinical trial (NCT03334058; https://clinicaltrials.gov/NCT03334058) was completed in participants with pemphigus using efgartigimod, an FcRn inhibitor, in combination with prednisone. Efgartigimod demonstrated an early effect on diease activity and was well tolerated. In addition to the safety and efficacy assessment, clinical trials present an opportunity to gain more insights into the mechanism of disease, the mode of action of treatment, and potential for corticosteroid-sparing activity.ObjectiveThe aim of our study was to assess the impact of FcRn antagonism by efgartigimod on immunological parameters known to be directly involved in pemphigus pathology, such as cellular and serological responses.MethodsWe investigated total and antigen-specific IgG subclass level kinetics during and after treatment, assessed antigen-specific B-cell responses, followed T- and B-cell immunophenotypes, and analyzed how different immunophenotypes link to clinical response.ResultsTreatment resulted in reduction of total IgG as well as autoreactive IgG antibody levels. Surprisingly, unlike total IgG and vaccine- or natural-infection-elicited IgG, which returned to baseline levels after stopping efgartigimod treatment, autoreactive antibody levels remained low in several study participants. Efgartigimod showed no effect on total leukocytes, neutrophils, monocytes, or lymphocytes in patients treated with extended efgartigimod therapy. Intriguingly, antigen-specific analyses revealed a loss of desmoglein-specific B cells in several participants responding to efgartigimod, in line with prolonged reduction of pathogenic IgG levels.ConclusionsEfgartigimod treatment of participants with pemphigus improved their conditions and exerted an immunomodulatory effect beyond the blockade of IgG recycling. Further studies in larger populations with an appropriate placebo control are needed to confirm these potentially important observations to establish long-term clinical responses in autoimmune diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

FcRn Antagonism Leads to a Decrease of Desmoglein-Specific B Cells: Secondary Analysis of a Phase 2 Study of Efgartigimod in Pemphigus Vulgaris and Pemphigus Foliaceus

et al. 2022

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“…It can trigger apoptosis and eliminate B cells by facilitating mediating antibody and complement-dependent cytotoxicity. 7 RTX was first proposed in the early 2000s for the treatment of refractory or recurrent PV and patients with contraindications to glucocorticoids. 8 Subsequent observations in multiple studies have shown that first-line use of RTX in combination with glucocorticoids is more effective than prednisone alone in patients with moderate-to-severe pemphigus, which helps to rapidly reduce the dose of glucocorticoids and fewer adverse events.…”

Section: Rituximab For Covid-19 Vaccine-associated Pemphigus Vulgarismentioning

confidence: 99%

Rituximab for COVID-19 Vaccine-Associated Pemphigus Vulgaris

Hui

Wang

Cheng

et al. 2023

American Journal of Therapeutics

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“…Despite the great improvement in the prognosis of patients with pemphigus, there have always been concerns about the high cost of these medications. 81 A pharmacoeconomic study on patients with PV found that IVIg therapy would approximately halve the long-term cost compared to conventional therapy. 82 Similarly, RTX, which is even cheaper than IVIg, results in an effective decrease in health care costs, owing to reducing admissions, length of stay, and treatment-related adverse events.…”

Section: Economic Burdenmentioning

confidence: 99%

Burden of pemphigus vulgaris with a particular focus on women: A review

Kianfar

Dasdar

Mahmoudi

et al. 2022

International Journal of Women’s Dermatology

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Pemphigus vulgaris is a chronic autoimmune mucocutaneous blistering disorder. Apart from the disease itself, other aspects of patients’ life, including psychological, social, and financial, can be affected. Women are particularly more disposed to the impact of the disease due to their physiological characteristics, the specific periods of pregnancy and lactation as well as their social and familial role. In this review, we summarized the burden of pemphigus vulgaris on various aspects of women’s lives. It is essential to understand these problems and provide appropriate support for patients with such a burdensome disease.

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Novel Therapies for Pemphigus Vulgaris

Cited by 12 publications

References 178 publications

FcRn Antagonism Leads to a Decrease of Desmoglein-Specific B Cells: Secondary Analysis of a Phase 2 Study of Efgartigimod in Pemphigus Vulgaris and Pemphigus Foliaceus

FcRn Antagonism Leads to a Decrease of Desmoglein-Specific B Cells: Secondary Analysis of a Phase 2 Study of Efgartigimod in Pemphigus Vulgaris and Pemphigus Foliaceus

Rituximab for COVID-19 Vaccine-Associated Pemphigus Vulgaris

Burden of pemphigus vulgaris with a particular focus on women: A review

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