The Future of B-cell Activating Factor Antagonists in the Treatment of Systemic Lupus Erythematosus

William Stohl

doi:10.4078/jrd.2017.24.2.65

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Stohl: The Future of B-cell Activating Factor Antagonists in the Treatment of Systemic Lupus Erythematosus

Review Article

J Rheum Dis 2017;24(2):65-73.

Published online: 31 October 2017

DOI: https://doi.org/10.4078/jrd.2017.24.2.65

The Future of B-cell Activating Factor Antagonists in the Treatment of Systemic Lupus Erythematosus

William Stohl

Division of Rheumatology, Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA

Corresponding to: William Stohl, Division of Rheumatology, Department of Medicine, University of Southern California Keck School of Medicine, 2011 Zonal Avenue, HMR 711, Los Angeles, CA 90033, USA. E-mail: stohl@usc.edu

Received 15 February 201716 February 2017 Accepted 4 March 2017

This is a Free Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

To review B-cell activating factor (BAFF)-antagonist therapy in systemic lupus erythematosus (SLE), literature was searched using the search words and phrases, “BAFF”, “B lymphocyte stimulator (BLyS)”, “a proliferation-inducing ligand (APRIL)”, “B-cell maturation antigen (BCMA)”, “transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI)”, “BLyS receptor 3 (BR3)”, “belimumab”, “atacicept”, “blisibimod”, “tabalumab”, and “lupus clinical trial”. In addition, papers from the author's personal library were searched. BAFF-antagonist therapy in SLE has a checkered past, with four late-stage clinical trials meeting their primary endpoints and four failing to do so. Additional late-stage clinical trials are enrolling subjects to address some of the remaining unresolved questions, and novel approaches are proposed to improve results. The BAFF-centric pathway is a proven therapeutic target in SLE. As the only pathway in the past 50+ years to have yielded an United States Food and Drug Administration-approved drug for SLE, it occupies a unique place in the armamentarium of the practicing rheumatologist. The challenges facing clinicians and investigators are how to better tweak the BAFF-centric pathway and improve on the successes realized.

Keywords: Systemic lupus erythematosus, BAFF, B lymphocyte

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Table 1.

Late-stage randomized clinical trials of BAFF antagonists planned/ongoing in SLE

Agent	Route	Phase	N	Target population	Primary endpoint	Trial number
Belimumab	i.v.	III	464	Lupus nephritis patients	Renal response, week 104	NCT01639339
Belimumab	i.v.	III	709	SLE patients in Asia	SRI-4, week 52	NCT01345253
Belimumab	i.v.	IV	816	Black SLE patients	SRI-4, week 52	NCT01632241
Belimumab	i.v.	II	100	Pediatric SLE patients	SRI-4, week 52	NCT01649765
Belimumab	i.v.	II (open-label)	40	Lupus nephritis patients (RTX+CTX followed by belimumab vs. RTX+CTX followed by placebo)	Grade ≥3 infection by week 48	NCT02260934
Blisibimod	s.c.	III	442	Very active SLE patients (SELENA SLEDAI ≥10)	SRI-6, week 52	NCT01395745
Blisibimod	s.c.	III	350	Very active SLE patients (SELENA SLEDAI ≥10) with or without active nephritis	SRI-6, week 52	NCT02514967
Atacicept	s.c.	IIb	306	SLE patients	SRI-4, week 24	NCT01972568

BAFF: B-cell activating factor, SLE: systemic lupus erythematosus, RTX: rituximab, CTX: cyclophosphamide, SELENA SLEDAI: safety of estrogens in lupus erythematosus national assessment SLE disease activity index, SRI: SLE response index.

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