Mechanisms of Resistance to Rituximab Used for the Treatment of Autoimmune Blistering Diseases

Autoimmune blistering diseases represent a group of chronic severe, disabling, and potentially fatal disorders of the skin and/or mucous membranes, primarily mediated by pathogenic auto-antibodies. Despite their rarity, these diseases are associated with significant morbidity and mortality and profo...

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Published inLife (Basel, Switzerland) Vol. 14; no. 10; p. 1223
Main Authors Popa, Liliana Gabriela, Dumitras, Ioana, Giurcaneanu, Calin, Berghi, Ovidiu, Radaschin, Diana Sabina, Vivisenco, Cristina Iolanda, Popescu, Marius Nicolae, Beiu, Cristina
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 01.10.2024
MDPI
Subjects
Antibodies
Antigens
Autoantibodies
autoimmune blistering diseases
Autoimmune diseases
Blistering
Cells
Collagen
Cytotoxicity
Disease
Disease resistance
Drug resistance
Drug therapy
Health services
Immunoglobulins
Immunosuppressive agents
Lymphocytes
mechanism of action
Medical research
Medicine, Experimental
Monoclonal antibodies
Morbidity
Mortality
Pemphigus
Quality of life
Remission
Remission (Medicine)
resistance
Review
Rituximab
Skin diseases
Skin resistance
Steroids
Romania
mechanism of action
pemphigus
autoimmune blistering diseases
resistance
rituximab
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Abstract Autoimmune blistering diseases represent a group of chronic severe, disabling, and potentially fatal disorders of the skin and/or mucous membranes, primarily mediated by pathogenic auto-antibodies. Despite their rarity, these diseases are associated with significant morbidity and mortality and profound negative impact on the patient’s quality of life and impose a considerable economic burden. Rituximab, an anti-CD-20 monoclonal antibody, represents the first line of therapy for pemphigus, regardless of severity and a valuable off-label therapeutic alternative for subepidermal autoimmune blistering diseases as it ensures high rates of rapid, long-lasting complete remission. Nevertheless, disease recurrence is the rule, all patients requiring maintenance therapy with rituximab eventually. While innate resistance to rituximab in pemphigus patients is exceptional, acquired resistance is frequent and may develop even in patients with initial complete response to rituximab, representing a real challenge for physicians. We discuss the various resistance mechanisms and their complex interplay, as well as the numerous therapeutic alternatives that may be used to circumvent rituximab resistance. As no therapeutic measure is universally efficient, individualization of rituximab treatment regimen and tailored adjuvant therapies in refractory autoimmune blistering diseases are mandatory.
AbstractList Autoimmune blistering diseases represent a group of chronic severe, disabling, and potentially fatal disorders of the skin and/or mucous membranes, primarily mediated by pathogenic auto-antibodies. Despite their rarity, these diseases are associated with significant morbidity and mortality and profound negative impact on the patient’s quality of life and impose a considerable economic burden. Rituximab, an anti-CD-20 monoclonal antibody, represents the first line of therapy for pemphigus, regardless of severity and a valuable off-label therapeutic alternative for subepidermal autoimmune blistering diseases as it ensures high rates of rapid, long-lasting complete remission. Nevertheless, disease recurrence is the rule, all patients requiring maintenance therapy with rituximab eventually. While innate resistance to rituximab in pemphigus patients is exceptional, acquired resistance is frequent and may develop even in patients with initial complete response to rituximab, representing a real challenge for physicians. We discuss the various resistance mechanisms and their complex interplay, as well as the numerous therapeutic alternatives that may be used to circumvent rituximab resistance. As no therapeutic measure is universally efficient, individualization of rituximab treatment regimen and tailored adjuvant therapies in refractory autoimmune blistering diseases are mandatory.
Autoimmune blistering diseases represent a group of chronic severe, disabling, and potentially fatal disorders of the skin and/or mucous membranes, primarily mediated by pathogenic auto-antibodies. Despite their rarity, these diseases are associated with significant morbidity and mortality and profound negative impact on the patient's quality of life and impose a considerable economic burden. Rituximab, an anti-CD-20 monoclonal antibody, represents the first line of therapy for pemphigus, regardless of severity and a valuable off-label therapeutic alternative for subepidermal autoimmune blistering diseases as it ensures high rates of rapid, long-lasting complete remission. Nevertheless, disease recurrence is the rule, all patients requiring maintenance therapy with rituximab eventually. While innate resistance to rituximab in pemphigus patients is exceptional, acquired resistance is frequent and may develop even in patients with initial complete response to rituximab, representing a real challenge for physicians. We discuss the various resistance mechanisms and their complex interplay, as well as the numerous therapeutic alternatives that may be used to circumvent rituximab resistance. As no therapeutic measure is universally efficient, individualization of rituximab treatment regimen and tailored adjuvant therapies in refractory autoimmune blistering diseases are mandatory.Autoimmune blistering diseases represent a group of chronic severe, disabling, and potentially fatal disorders of the skin and/or mucous membranes, primarily mediated by pathogenic auto-antibodies. Despite their rarity, these diseases are associated with significant morbidity and mortality and profound negative impact on the patient's quality of life and impose a considerable economic burden. Rituximab, an anti-CD-20 monoclonal antibody, represents the first line of therapy for pemphigus, regardless of severity and a valuable off-label therapeutic alternative for subepidermal autoimmune blistering diseases as it ensures high rates of rapid, long-lasting complete remission. Nevertheless, disease recurrence is the rule, all patients requiring maintenance therapy with rituximab eventually. While innate resistance to rituximab in pemphigus patients is exceptional, acquired resistance is frequent and may develop even in patients with initial complete response to rituximab, representing a real challenge for physicians. We discuss the various resistance mechanisms and their complex interplay, as well as the numerous therapeutic alternatives that may be used to circumvent rituximab resistance. As no therapeutic measure is universally efficient, individualization of rituximab treatment regimen and tailored adjuvant therapies in refractory autoimmune blistering diseases are mandatory.
Audience Academic
Author Giurcaneanu, Calin
Dumitras, Ioana
Radaschin, Diana Sabina
Vivisenco, Cristina Iolanda
Beiu, Cristina
Popa, Liliana Gabriela
Berghi, Ovidiu
Popescu, Marius Nicolae
AuthorAffiliation 3 Department of Allergy and Clinical Immunology, Colentina Clinical Hospital, 19-21 Stefan cel Mare Bd., District 2, 020125 Bucharest, Romania
6 Department of Pediatrics, Grigore Alexandrescu Clinical Emergency Hospital for Children, 30-32 Iancu de Hunedoara Road, 011743 Bucharest, Romania
5 Department of Paediatrics, Carol Davila University of Medicine and Pharmacy, 37 Dionisie Lupu Street, District 1, 020021 Bucharest, Romania
7 Department of Physical and Rehabilitation Medicine, Carol Davila University of Medicine and Pharmacy, 37 Dionisie Lupu Street, District 1, 020021 Bucharest, Romania
4 Department of Dermatology, Dunarea de Jos University of Medicine and Pharmacy, 25 Otelarilor Bd., 800008 Galati, Romania
8 Department of Physical and Rehabilitation Medicine, Dermatology Department, Elias Emergency University Hospital, 17 Marasti Bd., District 1, 011461 Bucharest, Romania
2 Department of Dermatology, Elias Emergency University Hospital, 17 Marasti Bd., District 1, 011461 Bucharest, Ro
AuthorAffiliation_xml – name: 6 Department of Pediatrics, Grigore Alexandrescu Clinical Emergency Hospital for Children, 30-32 Iancu de Hunedoara Road, 011743 Bucharest, Romania
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Issue 10
Keywords mechanism of action
pemphigus
autoimmune blistering diseases
resistance
rituximab
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Snippet Autoimmune blistering diseases represent a group of chronic severe, disabling, and potentially fatal disorders of the skin and/or mucous membranes, primarily...
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StartPage 1223
SubjectTerms Antibodies
Antigens
Autoantibodies
autoimmune blistering diseases
Autoimmune diseases
Blistering
Cells
Collagen
Cytotoxicity
Disease
Disease resistance
Drug resistance
Drug therapy
Health services
Immunoglobulins
Immunosuppressive agents
Lymphocytes
mechanism of action
Medical research
Medicine, Experimental
Monoclonal antibodies
Morbidity
Mortality
Pemphigus
Quality of life
Remission
Remission (Medicine)
resistance
Review
Rituximab
Skin diseases
Skin resistance
Steroids
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Title Mechanisms of Resistance to Rituximab Used for the Treatment of Autoimmune Blistering Diseases
URI https://www.ncbi.nlm.nih.gov/pubmed/39459523
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Volume 14
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