Abstract
Systemic lupus erythematosus (SLE) is a complex autoimmune disease of unknown etiology and limited available therapeutic options frustrating both clinicians and patients. However, recent advances in the understanding of disease mechanisms have given rise to numerous studies on specific approaches to SLE treatment. The purpose of this review is to explain the rationale for new treatments and results of the first clinical studies. We will focus on agents which deplete B cells (anti-CD20, anti-CD22), block cytokines (TNF α, Il 6), inhibit B/T cells interaction (CTLA-4Ig, anti-CD40L), or are even expected to reconstruct physiologic immunotolerance. Although preliminary results seemed promising, two randomized clinical trials with rituximab (EXPLORER and LUNAR study) failed to prove efficacy. Data analysis continues to explain the reasons. Trial design, subject population, limitations of the outcome measure instrument and site qualification have been questioned. Future studies are likely to focus on specific organ involvement or treatment combinations with other immunosuppressive agents.
Keywords: B cells, systemic lupus erythematosus, rituximab, epratuzumab, BLyS, LJP 394, anti-cytokine therapy, monoclonal antibodies, clinical trials
Mini-Reviews in Medicinal Chemistry
Title: Target Therapies in Systemic Lupus Erythematosus: Current State of the Art
Volume: 10 Issue: 10
Author(s): E. Wiesik-Szewczyk, J.K. Lacki, W. Feleszko and M. Olesinska
Affiliation:
Keywords: B cells, systemic lupus erythematosus, rituximab, epratuzumab, BLyS, LJP 394, anti-cytokine therapy, monoclonal antibodies, clinical trials
Abstract: Systemic lupus erythematosus (SLE) is a complex autoimmune disease of unknown etiology and limited available therapeutic options frustrating both clinicians and patients. However, recent advances in the understanding of disease mechanisms have given rise to numerous studies on specific approaches to SLE treatment. The purpose of this review is to explain the rationale for new treatments and results of the first clinical studies. We will focus on agents which deplete B cells (anti-CD20, anti-CD22), block cytokines (TNF α, Il 6), inhibit B/T cells interaction (CTLA-4Ig, anti-CD40L), or are even expected to reconstruct physiologic immunotolerance. Although preliminary results seemed promising, two randomized clinical trials with rituximab (EXPLORER and LUNAR study) failed to prove efficacy. Data analysis continues to explain the reasons. Trial design, subject population, limitations of the outcome measure instrument and site qualification have been questioned. Future studies are likely to focus on specific organ involvement or treatment combinations with other immunosuppressive agents.
Export Options
About this article
Cite this article as:
Wiesik-Szewczyk E., Lacki J.K., Feleszko W. and Olesinska M., Target Therapies in Systemic Lupus Erythematosus: Current State of the Art, Mini-Reviews in Medicinal Chemistry 2010; 10 (10) . https://dx.doi.org/10.2174/138955710792007187
DOI https://dx.doi.org/10.2174/138955710792007187 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Drugs and mitochondria
Mitochondria play a central role in the life and death of cells. They are not merely the center for energy metabolism but are also the headquarters for different catabolic and anabolic processes, calcium fluxes, and various signaling pathways. Mitochondria maintain homeostasis in the cell by interacting with reactive oxygen-nitrogen species ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer’s, Parkinson’s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Triggering of Apoptosis and Pro-Inflammatory Cytokines in NK Cells: Regulation by Cyclosporin A
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Monoclonal Antibodies: New Therapeutic Agents for Autoimmune Hemolytic Anemia?
Endocrine, Metabolic & Immune Disorders - Drug Targets Control of Autoimmune Diseases by the B7-CD28 Family Molecules
Current Pharmaceutical Design Ubiquitin Ligases as Key Elements for the Modulation of the Immune Response: An Insight in the Pathogenesis of Autoimmunity
Current Rheumatology Reviews CCR1 Chemokine Receptor Antagonist
Current Pharmaceutical Design Development of Bruton’s Tyrosine Kinase Inhibitors for Rheumatoid Arthritis
Current Medicinal Chemistry Impact and Therapeutic Potential of PPARs in Alzheimers Disease
Current Neuropharmacology Acquired Hemophilia as Initial Presentation in a Patient with Systemic Lupus Erythematosus
Current Rheumatology Reviews Chaperonopathies and Chaperonotherapy. Hsp60 as Therapeutic Target in Cancer: Potential Benefits and Risks
Current Pharmaceutical Design New Insights on the Possible Role of Mast Cells in Aspirin-Induced Asthma
Current Molecular Pharmacology Use of MHC II Structural Features in the Design of Vaccines for Organ-Specific Autoimmune Diseases
Current Pharmaceutical Design The Interleukin-17/Interleukin-22 Innate Axis in the Gut as a New Drug Target in Allergic-Inflammatory and Autoimmune Diseases. A Working Hypothesis
Endocrine, Metabolic & Immune Disorders - Drug Targets Epigenetic Modifications of the Nuclear Factor Kappa B Signalling Pathway and its Impact on Inflammatory Bowel Disease
Current Pharmaceutical Design Computational Studies Applied to Anti-inflammatory Drug Discovery: A Review
Current Organic Chemistry Antibody - Fc Receptor Interactions in Antimicrobial Functions
Current Immunology Reviews (Discontinued) Invariant Natural Killer T Cell-Based Therapy of Autoimmune Diseases
Current Immunology Reviews (Discontinued) Targeted Therapies – Many Ways to (the Peace of) Rome
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Toll-Like Receptor Signaling Mechanisms Involved in Dendritic Cell Activation: Potential Therapeutic Control of T Cell Polarization
Current Pharmaceutical Design Mechanisms of Neutrophil-mediated Disease: Innovative Therapeutic Interventions
Current Pharmaceutical Design Therapeutic Monitoring of Immunotherapies in Autoimmune Diseases
Current Pharmaceutical Design