{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:53:30Z","timestamp":1791284010739,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pemphigus vulgaris is a potentially life\u2010threatening autoimmune blistering disorder driven by pathogenic IgG autoantibodies targeting desmoglein 3 and 1. While rituximab has transformed management\u2014achieving complete remission off\u2010therapy in 70\u201390% of patients\u2014approximately 20\u201330% of patients relapse or fail to respond, defining a critical unmet need. The key drivers of rituximab\u2010refractory disease include post\u2010depletion B\u2010cell repopulation fuelled by elevated BAFF and APRIL, persistence of long\u2010lived plasma cells in bone marrow niches that evade anti\u2010CD20 depletion, IgG4\u2010dominant autoantibodies requiring high complement\u2010dependent cytotoxicity, innate immune amplification via Fc\u03b3\u2010receptor signalling and human anti\u2010chimeric antibody formation neutralizing the drug itself. This review critically evaluates five emerging targeted therapeutic classes addressing these mechanisms. Next\u2010generation anti\u2010CD20 monoclonal antibodies\u2014ofatumumab, ocrelizumab, obinutuzumab and veltuzumab\u2014offer enhanced effector functions, reduced immunogenicity and subcutaneous delivery for rituximab\u2010intolerant or HACA\u2010positive patients, though evidence remains at case and cohort level. BAFF\/APRIL pathway inhibitors, principally telitacicept and ianalumab, target the B\u2010cell survival axis elevated post\u2010rituximab and show promise in pemphigus case reports and extrapolated phase 2\/3 systemic lupus erythematosus data. Bruton tyrosine kinase inhibitors, particularly rilzabrutinib, demonstrated rapid disease control and meaningful steroid\u2010sparing effects in phase 2 trials, though the pivotal PEGASUS phase 3 trial did not meet its primary endpoint. FcRn antagonists, led by efgartigimod, achieve 60\u201370% reduction in circulating IgG within weeks without broad immunosuppression; the phase 3 ADDRESS trial missed its primary endpoint, likely due to corticosteroid confounding rather than biological inefficacy. Finally, DSG3\u2010CAAR T\u2010cell therapy represents the most transformative approach\u2014antigen\u2010specific elimination of pathogenic anti\u2010Dsg3 B cells while preserving normal humoral immunity\u2014with early phase 1 data awaited. Rational combination strategies and refined trial designs will be essential to translate the biological promise of these next\u2010generation agents into clinical practice for patients with refractory pemphigus.<\/jats:p>","DOI":"10.1111\/jdv.70773","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:17:23Z","timestamp":1791281843000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted therapies in pemphigus vulgaris: Emerging horizons beyond rituximab"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3314-1734","authenticated-orcid":false,"given":"Rhea","family":"Ahuja","sequence":"first","affiliation":[{"name":"Department of Dermatology St George Hospital Campus Sydney Australia"},{"name":"Faculty of Medicine University of New South Wales Sydney New South Wales 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