Systemic Lupus Erythematosus (SLE or lupus) is a complex autoimmune disease that is often difficult to manage. An individual’s genomic activity can influence disease progression and response to standard therapy. Lupus research is revealing new drug targets and enabling the development of targeted therapies that may benefit distinct groups of patients. Anifrolumab is one of the newest treatments targeting an important regulatory family of proteins central to immune defense against viruses, Type-1 interferons (IFN-1).1
The biologic anifrolumab was developed by AstraZeneca and approved for use, in conjunction with standard therapy, by the U.S. Food and Drug Administration on August 2, 2021, for adults with moderate to severe systemic lupus erythematosus.2,3
Clinical data supporting the use of anifrolumab
Anifrolumab gained FDA approval based on the results from its TULIP-1 and TULIP-2 phase 3 clinical trials. Anifrolumab showed broad efficacy with improvement in multiple organ domains.4 Further analysis using demographic data, the IFN-1 gene signature, and clinical presentation revealed that while most patient subgroups responded in a manner consistent with general population studies, IFN-1 high patients saw significant improvements across multiple clinical endpoints with anifrolumab treatment, whereas IFN-1 low patients did not.5
Anifrolumab specifically targets IFN-1
Anifrolumab is a human IgG monoclonal antibody that binds to subunit 1 of the type 1 interferon α receptor.1 This action blocks the downstream signaling cascade initiated by IFN-1, thereby suppressing gene expression and over-stimulation of the innate and adaptive immune responses thought to contribute to lupus symptoms.1
IFN-1 is a master regulator of immune response that initiates a cascade of cellular and chemical inflammatory activities within the innate and adaptive immune responses.6,7,8 For reasons not yet fully understood, some individuals produce chronically high levels of IFN-1 which can lead to the development of lupus.9 It is estimated that 50% of adults with SLE have increased IFN-1 expression.10 High IFN-1 is correlated to greater SLE disease activity and has proven to be an important prognostic indicator for the progression to lupus nephritis and poor response to standard of care.10,11,12
Determining patient IFN-1 status
To determine a patient’s IFN-1 status - whether they are IFN-1 high or IFN-1 low - gene expression testing of downstream interferon stimulated genes is the preferred method.1 Most SLE patients show stable IFN-1 gene expression levels7 in the absence of IFN-1 lowering treatments like anifrolumab or high dose intravenous steroids. Viral infections like influenza and COVID-19 will temporarily raise the IFN-1 levels of patients.
Patients expressing high levels of IFN-1 may benefit from new therapies, including anifrolumab, that are designed to reduce IFN-1 activity for improved management of SLE. Learn more about the significance of IFN-1 and new therapy options for SLE patients in our new white paper.
- Casey KA, Guo X, Smith MA, et al. Type 1 interferon receptor blockade with anifrolumab corrects innate and adaptive immune perturbations of SLE. Lupus Science & Medicine 5:e000286 (2018)
- Saphnelo [anifrolumab-fnia] US prescribing information. Astrazeneca.com (2021) Accessed 29 April 2022
- “What you need to know about Saphnelo,” Lupus Foundation of America. Lupus.org [Accessed June 3, 2022].
- Morand EF, Furie RA, Bruce IN, et al. Efficacy of anifrolumab across organ domains in patients with moderate-to-severe systemic lupus erythematosus: a post-hoc analysis of pooled data from the TULIP-1 and TULIP-2 trials, Lancet Rheumatol 2022; 4:e282-292
- Vital EM, Merrill JT, Morand EF, et al. Anifrolumab efficacy and safety by type I interferon gene signature and clinical subgroups in patients with SLE: post hoc analysis of pooled data from two phase III trials. Ann Rheum Dis.0:1-11 (2022)
- Feng X et al. Association of increased interferon-inducible gene expression with disease activity and lupus nephritis in patients with Systemic Lupus Erythematosus. Arthritis & Rheum. Sept 54(9):2951-62 (2006)
- Northcott M, Jones S, Koelmeyer R, et al. Type 1 interferon status in Systemic Lupus Erythematosus: A longitudinal analysis. Lupus Science & Medicine.9:e000625 (2022)
- Mohamed AAA, Gheita TA. Interferons, B cells and neutrophils: innate and adaptive allies in Systemic Lupus Erythematosus. J Rheumatol Arthritic Dis 3(2): 1-12 (2018)
- Crow MK. Type I interferon in the pathogenesis of lupus. J Immunol. 192(12):5459-5468 (2014) Accessed July 2021.
- Baechler E., et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci USA., pp. Mar 4; 100(5): 2610-5 Epub Feb 25 (2003)
- Arriens C et al. Increased risk of progression to lupus nephritis for lupus patients with elevated interferon signature [abstract]. Arthritis Rheumatol. 71 (suppl 10) (2019)
- Morand E et al., Lupus Low Disease Activity State (LLDAS) attainment discriminates responders in a Systemic Lupus Erythematosus trial: post-hoc analysis of the phase IIB MUSE trial of Anifrolumab. Ann Rheum Dis 77:706-713 (2018)