Rheumatology: Current Research
Open Access

Systemic lupus erythematosus: after 50 years no longer �lost in translation� � the pipeline of therapeutic antibodies is here!

International Conference and Exhibition on Orthopedics & Rheumatology

August 13-15, 2012 Hilton Chicago/Northbrook, USA

C. Michael Neuwelt

Scientific Tracks Abstracts: Rheumatology & Orthopedics

Abstract :

T herapy for Systemic Lupus Erythematosus (SLE) has entered a new age of multiple trials of monoclonal antibodies (MAb), tolerogens, and gene expression to better treatment in this �orphan� disease. Belimumab (Benlysta) in 2011 was the first new drug with Food & Drug Administration (FDA) approval in 50 years! Other B-cell depleting agents include rituximab (a negative randomized controlled trial contrasts extensive open-label experience in refractory cases). Most experts agree that rituximab is an effective synergistic treatment of cyclophosphamide resistant SLE. This synergism of rituximab and cyclophosphamide may be especially true in neuropsychiatric SLE (NP-SLE) in the experience of several centers experienced in NP-SLE. Epratuzamab, which targets CD 22 is in Phase III trials (EMBODY) with impressive Phase II data. Subcutaneous LY2127399, also a B-cell depletor blocks both soluble and membrane bound B-cell activating factor (BAFF). Two MAb against interferon �?±, rontalizumab and sifalimumab are moving quickly through Phase II & IIb trials with promising open label extensions. These treatments reduce SLE activity and interferon �?± leaves a pattern of expression of interferon-regulated genes in SLE and is referred to as the �interferon signature.� This signature is a biomarker of drug effect and SLE gene expression. Unique tolerogens, laquinimod and lupuzor, previously studied in Europe also have promising Phase IIb studies. B11B023, a tumor necrosis factor inhibitor (TNF) - related weak inducer of Apoptosis (TWEAK) is in earlier clinical development. Finally, AMG557 inhibits inducible costimulator (ICOS) which with its sole ligand B7-related protein-1 (B7RP-1), ICOS plays a role in T cell function and lymphocyte costimulation. As we better understand the pathophysiology of SLE and improve trial design, SLE will be no longer be �Lost in Translation.

Biography :

C. Michael Neuwelt, M.D. has been in private practice for 32 years. Dr. Neuwelt has been on the Physician Leadership Council since 2002 for the Lupus Research Institute in New York City. He has been on the Advisory Board for ?Lupus Now? magazine of the Lupus Foundation of America in Washington, D. C. Dr. Neuwelt?s major interests have been SLE and NP-SLE. Topics of research have included health status, genetic epidemiology, and gene expression in SLE. Therapeutic trials include dehydroepiandrosterone (DHEA, Prasterone), LJP 394 (Riquent), Rituximab (general SLE, lupus nephritis, and NP-SLE), Epratuzumab, Ocrelizumab, Interferon alpha monoclonal antibodies rhuMab IFNalpha (Rontalizumab), Medi- 545 (Sifalimumab), Anti CD40L monoclonal antibody, Laquinimod in active nephritis and arthritis, Lupuzor, and MEDI-570 (a Phase 1 ascending dose study assessing serial skin biopsies in SLE). The recent publications of Dr. Neuwelt include: Michelle Petri, MD ; Daniel Wallace, MD ; Alberto Spindler, MD ; Vishala Chindalore, MD ; Kenneth Kalunian, MD ; Eduardo Mysler, MD ; Michael Neuwelt, MD ; Gabriel Robbie, PhD ; Wendy White, PhD ; Yihong Yao, PhD ; Liangwei Wang, MD ; Dominique Ethgen, MD ; Warren Greth, MD, MSc. Safety and Tolerability of Multiple Intravenous Doses of a Fully Human Anti-Interferon-Alpha Monoclonal Antibody (Medi-545) in Patients with SLE (Submission in Process). 2012. Merrill JT, Neuwelt CM, Wallace DJ, et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus (SLE): The Randomized, Double-blind, Phase II/III Systemic Lupus Erythematosus Evaluation of Rituximab Trial. ?Arthritis and Rheumatism,? Vol. 62, No. 1, pp.222-233, January, 2010. Neuwelt CM & Young RG; Managing neuropsychiatric lupus: Top 10 clinical pearls. ?The Journal of Musculoskeletal Medicine,? Vol. 26, Number 4, pp.127-135, 2009. Recent grand rounds include ?Central Nervous System Lupus? at the Oregon Health Sciences University February 15, 2012 and International Symposium include ?Systemic Lupus Erythematosus: After 50 Years No Longer ?Lost in Translation? at the 4th Annual International Congress of Antibodies (ICA-2012) in Beijing, China, March 28, 2012