{"id":643977,"date":"2026-10-12T09:58:08","date_gmt":"2026-10-12T09:58:08","guid":{"rendered":"https:\/\/www.newsbeep.com\/il\/643977\/"},"modified":"2026-10-12T09:58:08","modified_gmt":"2026-10-12T09:58:08","slug":"new-pemphigus-vulgaris-therapies-amj","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/il\/643977\/","title":{"rendered":"New Pemphigus Vulgaris Therapies – AMJ"},"content":{"rendered":"

EMERGING therapies could reshape pemphigus vulgaris treatment for patients who relapse or remain refractory after rituximab<\/a>.<\/p>\n

Rituximab has transformed treatment of the autoimmune blistering disorder, achieving complete remission off therapy in 70% to 90% of patients. However, approximately 20% to 30% either fail to respond or experience relapse, creating a need for treatments that address mechanisms not fully controlled by conventional B-cell depletion.<\/p>\n

Why Pemphigus Vulgaris Relapses After Rituximab<\/p>\n

Several processes may contribute to refractory pemphigus vulgaris. B cells can repopulate after rituximab as levels of B-cell activating factor (BAFF) and a proliferation inducing ligand (APRIL) rise. Long lived plasma cells may also continue producing pathogenic antibodies because they do not express CD20 and therefore escape rituximab.<\/p>\n

Other proposed drivers include IgG4 dominant autoantibodies, innate immune activation, anti-drug antibodies that neutralize rituximab, and localized immune activity within skin and mucosal tissue.<\/p>\n

These mechanisms have prompted investigation of targeted therapies acting at different stages of disease.<\/p>\n

Targeted Therapies Address Different Disease Pathways<\/p>\n

Next generation anti-CD20 therapies, including ofatumumab, ocrelizumab, obinutuzumab, and veltuzumab, aim to improve B-cell depletion while reducing immunogenicity. Ofatumumab currently has the strongest pemphigus evidence within this group, although available data remain largely limited to cohorts and case reports.<\/p>\n

BAFF and APRIL inhibitors offer another approach by targeting signals that support B-cell repopulation and plasma-cell survival. These agents remain experimental in pemphigus but may ultimately be suited to preventing relapse after B-cell depletion.<\/p>\n

Bruton tyrosine kinase inhibitors can interfere with B-cell and Fc receptor signaling without directly depleting B cells. Rilzabrutinib produced rapid disease control and corticosteroid sparing in Phase II testing, although its Phase III trial failed to meet the primary endpoint.<\/p>\n

FcRn antagonists instead accelerate removal of circulating pathogenic IgG. Efgartigimod reduced IgG substantially and produced rapid disease control in Phase II testing, but also missed its Phase III primary endpoint.<\/p>\n

Could Combination Therapy Change Pemphigus Care?<\/p>\n

DSG3-CAAR T-cell therapy represents a more precise strategy, designed to eliminate desmoglein 3 specific pathogenic B cells while preserving the wider B-cell population. Human efficacy data, however, remain awaited.<\/p>\n

Rather than identifying one replacement for rituximab, the review points toward rational combinations. Pairing B-cell depletion with FcRn blockade could remove existing pathogenic antibodies while limiting new production, while BAFF\/APRIL blockade may help prevent post-rituximab repopulation.<\/p>\n

For clinicians, these approaches remain investigational, but they illustrate a shift toward targeting the specific biological mechanisms sustaining refractory pemphigus vulgaris.<\/p>\n

Reference
Ahuja R et al. Targeted therapies in pemphigus vulgaris: Emerging horizons beyond rituximab. J Eur Acad Dermatol Venereol. 2026;DOI:10.1111\/jdv.70773.<\/p>\n

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