Rheumatology

Systemic Lupus Erythematosus

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Systemic Lupus Erythematosus: From Pathophysiology to Treatment

conference reporter by Anca D. Askanase, MD, MPH
Overview

Treatments for systemic lupus erythematosus (SLE) derived from understanding the disease pathophysiology were first approved by the US Food and Drug Administration (FDA) 13 years ago. Researchers and clinicians at the 2024 Congress of Clinical Rheumatology (CCR) West presented data on new and emerging treatments that were developed from past research on the pathophysiology of SLE.

 

Following these proceedings, featured expert Anca D. Askanase, MD, MPH, was interviewed by Conference Reporter Associate Editor-in-Chief Christopher Ontiveros, PhD. Dr Askanase’s clinical perspectives on these findings are presented here.

“In a way, the vast majority of SLE drugs are derived from a better understanding of the pathophysiology of lupus.”
— Anca D. Askanase, MD, MPH

The concept of looking at pathophysiology to find therapeutic targets is not novel in lupus. In fact, it has been more than 20 years since the field of rheumatology started focusing on deriving therapeutic targets from the pathophysiology of SLE.

 

At CCR West 2024, Richard A. Furie, MD, gave an extraordinary tour de force talk about studying the pathophysiology of SLE, understanding it, and using it to develop therapeutic options. As Dr Furie highlighted in his presentation, B cells are a very attractive target in lupus, as these cells are responsible for autoantibody production and act as a big player in the onset and perpetuation of the disease. Thinking about targeting B cells makes a lot of intellectual sense. The first drug to be approved by the FDA for the treatment of SLE, belimumab (the anti–B lymphocyte stimulator protein monoclonal antibody), was derived from knowledge of pathophysiology.

 

Belimumab is a targeted therapy success story in that it went through the hurdles of being the first FDA-approved SLE targeted therapy in 2011. After its approval, subsequent studies further established its efficacy in different patient types. It was the first SLE drug with a big safety registry and the first to obtain FDA approval in lupus nephritis. Since its initial approval, long-term extension data and postmarketing surveillance of belimumab have also accumulated a body of evidence suggesting that the drug is effective and safe for the treatment of lupus. Studies also suggest that belimumab is a disease-modifying drug, which means that there is more interest in using it earlier in the treatment of lupus.

 

The second FDA-approved targeted therapy for SLE was the type I interferon receptor inhibitor anifrolumab. Anifrolumab was evaluated in the phase 2b MUSE trial (also known as the CD1013 study) and the phase 3 TULIP-1 and TULIP-2 trials. Like for belimumab, data on the safety and efficacy of anifrolumab, as well as long-term extension data, have been well established. In fact, post hoc analyses of the long-term extension studies were presented as poster sessions at CCR West 2024 and further substantiate the efficacy of anifrolumab and its potential as a disease modifier. One study found that anifrolumab is associated with higher rates of attainment of the lupus low disease activity state, and the other study found that anifrolumab allowed a greater number of patients to reduce steroid use vs placebo.

 

While belimumab and anifrolumab are currently the only FDA-approved targeted therapies for SLE, other drugs are under investigation for lupus, including the anti-CD40 ligand dapirolizumab pegol, the TYK2 inhibitor deucravacitinib, and the BDCA2-targeted antibody litifilimab. One particularly interesting investigational approach that was discussed by Dr Furie in his presentation at CCR West 2024 is to restore IL-2, a cytokine with an important role in the balance between the protective and negative effects of T cells. Restoring IL-2 may help restore T-cell homeostasis and stimulate regulatory T cells, which are generally low in patients with lupus. Finally, everyone is excited about the early data on the use of CAR T-cell therapies, which are also based on the pathophysiology of lupus. In a way, the vast majority of SLE drugs are derived from a better understanding of the pathophysiology of lupus.

References

Chatham WW, Furie R, Saxena A, et al. Long-term safety and efficacy of anifrolumab in adults with systemic lupus erythematosus: results of a phase II open-label extension study. Arthritis Rheumatol. 2021;73(5):816-825. Published correction appears in Arthritis Rheumatol. 2021;73(8):1570.

 

Dixit N, Fanton C, Langowski JL, et al. NKTR-358: a novel regulatory T-cell stimulator that selectively stimulates expansion and suppressive function of regulatory T cells for the treatment of autoimmune and inflammatory diseases. J Transl Autoimmun. 2021;4:100103. doi:10.1016/j.jtauto.2021.100103

 

Furie RA, Bruce IN, Kalunian KC, et al. Glucocorticoid reduction and withdrawal in patients with systemic lupus erythematosus receiving long-term anifrolumab treatment [poster]. Poster presented at: 2024 Congress of Clinical Rheumatology West; September 26-29, 2024; San Diego, CA.

 

Furie RA, Morand EF, Bruce IN, et al; TULIP-1 Study Investigators. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol. 2019;1(4):e208-e219. doi:10.1016/S2665-9913(19)30076-1

 

Furie R, Khamashta M, Merrill JT, et al; CD1013 Study Investigators. Anifrolumab, an anti-interferon-α receptor monoclonal antibody, in moderate-to-severe systemic lupus erythematosus. Arthritis Rheumatol. 2017;69(2):376-386. doi:10.1002/art.39962

 

Furie R. Novel treatments for systemic lupus erythematosus and lupus nephritis (can lupus be cured?). Oral presentation presented at: 2024 Congress of Clinical Rheumatology West; September 26-29, 2024; San Diego, CA.

 

Morand EF, Furie R, Tanaka Y, et al; TULIP-2 Trial Investigators. Trial of anifrolumab in active systemic lupus erythematosus. N Engl J Med. 2020;382(3):211-221. doi:10.1056/NEJMoa1912196

 

Morand EF, van Vollenhoven R, Furie RA, et al. Lupus low disease activity state attainment and reduced glucocorticoid use in patients with SLE in the TULIP-LTE trial of anifrolumab [poster]. Poster presented at: 2024 Congress of Clinical Rheumatology West; September 26-29, 2024; San Diego, CA.

 

 

This information is brought to you by Engage Health Media and is not sponsored, endorsed, or accredited by the Congress of Clinical Rheumatology.

Anca D. Askanase, MD, MPH

Director, Columbia University Lupus Center
Professor of Medicine, Division of Rheumatology
Columbia University College of Physicians and Surgeons
New York, NY

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