B-Cell Targeted Therapeutics in Systemic Lupus Erythematosus: From Paradox to Synergy?

EditorialsDecember 2021B-Cell Targeted Therapeutics in Systemic Lupus Erythematosus: From Paradox to Synergy?Medha Barbhaiya, MD, MPH and Katherine P. Liao, MDMedha Barbhaiya, MD, MPHDivision of Rheumatology, Hospital for Special Surgery, and Departments of Medicine and Population Health Sciences, Weill Cornell Medicine, New York, New YorkSearch for more papers by this author and Katherine P. Liao, MDDivision of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Department of Medicine and Biomedical Informatics, Harvard Medical School, and Rheumatology Section, Veterans Affairs Boston Healthcare System, Boston, MassachusettsSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M21-4124 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Systemic lupus erythematosus (SLE) is a complex, multisystem autoimmune disease characterized by a wide range of clinical manifestations—from rashes and joint swelling to life-threatening organ involvement—and a chronic course subject to unpredictable flares. Few therapeutic agents have been approved by the U.S. Food and Drug Administration for SLE since the 1950s, despite advancements in the understanding of SLE pathophysiology and promising candidates for new therapeutic options. These disappointing results are at least partly attributable to small sample sizes, trial design challenges, and disease heterogeneity.Antinuclear antibodies and antibodies against specific nuclear antigens, such as double-stranded DNA (anti-dsDNA), are hallmarks of ...References1. Merrill JT, Neuwelt CM, Wallace DJ, et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, Phase II/III Systemic Lupus Erythematosus Evaluation of Rituximab trial. Arthritis Rheum. 2010;62:222-33. [PMID: 20039413] doi:10.1002/art.27233 CrossrefMedlineGoogle Scholar2. Rovin BH, Furie R, Latinis K, et al; LUNAR Investigator Group. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum. 2012;64:1215-26. [PMID: 22231479] doi:10.1002/art.34359 CrossrefMedlineGoogle Scholar3. Zhang F, Bae SC, Bass D, et al. A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea. Ann Rheum Dis. 2018;77:355-63. [PMID: 29295825] doi:10.1136/annrheumdis-2017-211631 CrossrefMedlineGoogle Scholar4. Stohl W, Schwarting A, Okada M, et al. Efficacy and safety of subcutaneous belimumab in systemic lupus erythematosus: a fifty-two-week randomized, double-blind, placebo-controlled study. Arthritis Rheumatol. 2017;69:1016-27. [PMID: 28118533] doi:10.1002/art.40049 CrossrefMedlineGoogle Scholar5. Navarra SV, Guzmán RM, Gallacher AE, et al; BLISS-52 Study Group. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377:721-31. [PMID: 21296403] doi:10.1016/S0140-6736(10)61354-2 CrossrefMedlineGoogle Scholar6. Cambridge G, Isenberg DA, Edwards JC, et al. B cell depletion therapy in systemic lupus erythematosus: relationships among serum B lymphocyte stimulator levels, autoantibody profile and clinical response. Ann Rheum Dis. 2008;67:1011-6. [PMID: 17962238] CrossrefMedlineGoogle Scholar7. Carter LM, Isenberg DA, Ehrenstein MR. Elevated serum BAFF levels are associated with rising anti-double-stranded DNA antibody levels and disease flare following B cell depletion therapy in systemic lupus erythematosus. Arthritis Rheum. 2013;65:2672-9. [PMID: 23839909] doi:10.1002/art.38074 CrossrefMedlineGoogle Scholar8. Atisha-Fregoso Y, Malkiel S, Harris KM, et al. Phase II randomized trial of rituximab plus cyclophosphamide followed by belimumab for the treatment of lupus nephritis. Arthritis Rheumatol. 2021;73:121-31. [PMID: 32755035] doi:10.1002/art.41466 CrossrefMedlineGoogle Scholar9. Shipa M, Embleton-Thirsk A, Parvaz M, et al. Effectiveness of belimumab after rituximab in systemic lupus erythematosus. A randomized controlled trial. Ann Intern Med. 2021;174:1647-57. doi:10.7326/M21-2078 Google Scholar10. Teng YKO, Bruce IN, Diamond B, et al. Phase III, multicentre, randomised, double-blind, placebo-controlled, 104-week study of subcutaneous belimumab administered in combination with rituximab in adults with systemic lupus erythematosus (SLE): BLISS-BELIEVE study protocol. BMJ Open. 2019;9:e025687. [PMID: 30898822] doi:10.1136/bmjopen-2018-025687 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Division of Rheumatology, Hospital for Special Surgery, and Departments of Medicine and Population Health Sciences, Weill Cornell Medicine, New York, New YorkDivision of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Department of Medicine and Biomedical Informatics, Harvard Medical School, and Rheumatology Section, Veterans Affairs Boston Healthcare System, Boston, MassachusettsDisclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M21-4124.Corresponding Author: Medha Barbhaiya, MD, MPH, Division of Rheumatology, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021; e-mail, [email protected]edu.This article was published at Annals.org on 26 October 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEffectiveness of Belimumab After Rituximab in Systemic Lupus Erythematosus Muhammad Shipa , Andrew Embleton-Thirsk , Mariea Parvaz , Liliana Ribeiro Santos , Patrick Muller , Kashfia Chowdhury , David A. Isenberg , Caroline J. Doré , Caroline Gordon , Michael R. Ehrenstein , and Metrics December 2021Volume 174, Issue 12Page: 1747-1748KeywordsBiologicsClinical trialsRheumatologySystemic lupus erythematosus ePublished: 26 October 2021 Issue Published: December 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...