Type 1 interferons: A target for immune-mediated inflammatory diseases (IMIDs)

Article Rheumatology

Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial

Eric Morand et al.

Summary: Deucravacitinib treatment showed higher response rates for SRI-4 and other endpoints compared to placebo, with an acceptable safety profile, in adult patients with active SLE.

ARTHRITIS & RHEUMATOLOGY (2023)

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Article Rheumatology

2022 EULAR points to consider for the measurement, reporting and application of IFN-I pathway activation assays in clinical research and practice

Javier Rodriguez-Carrio et al.

Summary: This study developed evidence-based points to consider for the measurement and reporting of IFN-I assays in clinical research. The study provides recommendations on terminology, assay characteristics, and reporting practices, as well as explores the clinical applications of IFN-I assays in diagnosis and outcome assessments.

ANNALS OF THE RHEUMATIC DISEASES (2023)

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Article Rheumatology

OP0139 EFFICACY AND SAFETY OF ABBV-599 HIGH DOSE (ELSUBRUTINIB 60 MG AND UPADACITINIB 30 MG) AND UPADACITINIB MONOTHERAPY FOR THE TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS: A PHASE 2, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

J. T. Merrill et al.

ANNALS OF THE RHEUMATIC DISEASES (2023)

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Review Immunology

Systemic Lupus Erythematosus Pathogenesis: Interferon and Beyond

Simone Caielli et al.

Summary: Autoreactive B cells and interferons play important roles in the development of systemic lupus erythematosus (SLE). Recent studies on genetics and immune monitoring of SLE patients have provided new insights into the underlying mechanisms, including novel gene mutations affecting B cell activation and clearance of interferogenic nucleic acids. Mitochondria have been identified as inducers or amplifiers of SLE through various mechanisms, leading to the release of interferogenic nucleic acids and activation of immune cells. Specific autoantibodies associated with monogenic lupus or triggering interferogenic amplification loops have been discovered. Additionally, atypical B cells and novel T helper cell subsets have been proposed to contribute to the generation of SLE autoantibodies. These findings offer opportunities for improved monitoring and personalized therapy for SLE patients.

ANNUAL REVIEW OF IMMUNOLOGY (2023)

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Article Dermatology

Rapid efficacy of anifrolumab across multiple subtypes of recalcitrant cutaneous lupus erythematosus parallels changes in discrete subsets of blood transcriptomic and cellular biomarkers

Lucy M. Carter et al.

Summary: In a prospective real-world cohort study, anifrolumab showed rapid efficacy and significant quality-of-life impact across multiple subtypes of refractory cutaneous lupus. The response was associated with suppression of blood interferon signatures and normalization of circulating monocyte subsets.

BRITISH JOURNAL OF DERMATOLOGY (2023)

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Review Pharmacology & Pharmacy

Clinical Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Anifrolumab

Weifeng Tang et al.

Summary: The type I interferon (IFN) signaling pathway is implicated in systemic lupus erythematosus (SLE) and anifrolumab, a monoclonal antibody targeting this pathway, has been approved for the treatment of moderate to severe SLE patients. The approved dosing regimen is 300mg intravenously every 4 weeks. Studies have shown that anifrolumab treatment is associated with significant improvements in disease activity and has an acceptable safety profile. Pharmacokinetic and pharmacodynamic analyses have identified covariates for anifrolumab exposure and clearance, and the relationship between serum exposure and clinical responses, safety risks, and the type I IFN gene signature (21-IFNGS) has been evaluated. In this review, the clinical pharmacokinetics, pharmacodynamics, and immunogenicity of anifrolumab are discussed, along with the results of population-pharmacokinetics and exposure-response analyses.

CLINICAL PHARMACOKINETICS (2023)

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Review Rheumatology

New biologics and targeted therapies in systemic lupus: From new molecular targets to new indications. A systematic review

Renaud Felten et al.

Summary: Despite available therapies, persistently active and corticosteroid-dependent Systemic Lupus Erythematosus (SLE) represent a significant therapeutic challenge. This systematic review provides an updated view of targeted therapies currently in clinical development in SLE, with a special focus on the most promising ones.

JOINT BONE SPINE (2023)

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Letter Dermatology

Assessment of Clinical Response to Anifrolumab in Patients With Refractory Discoid Lupus Erythematosus

Katharina Shaw et al.

Summary: This case series investigates the effectiveness of anifrolumab as a treatment option for patients with lupus erythematosus.

JAMA DERMATOLOGY (2023)

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Review Rheumatology

Association between type I interferon pathway activation and clinical outcomes in rheumatic and musculoskeletal diseases: a systematic literature review informing EULAR points to consider

Javier Rodriguez-Carrio et al.

Summary: This article provides a systematic review of assays measuring IFN-I pathway activation and summarizes the potential clinical utility in various rheumatic and musculoskeletal diseases. The results show that IFN-I pathway activation is associated with disease diagnosis, disease activity assessment, prognosis, response to treatment, and assay responsiveness. However, the heterogeneity in techniques and technical conditions are major limitations.

RMD OPEN (2023)

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Letter Dermatology

Rapid efficacy of anifrolumab in refractory cutaneous lupus erythematosus

Francois Chasset et al.

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY (2023)

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Letter Rheumatology

Serum interferon-α levels and IFN type I-stimulated genes score perform equally to assess systemic lupus erythematosus disease activity

Francois Chasset et al.

ANNALS OF THE RHEUMATIC DISEASES (2022)

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Article Rheumatology

Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis

David Jayne et al.

Summary: This study evaluated the efficacy and safety of anifrolumab, a type I interferon receptor antibody, in patients with active lupus nephritis. The results showed that anifrolumab IR had numerical improvements over placebo in several endpoints, including complete renal response. However, the primary endpoint of improvement in 24-hour urine protein-creatinine ratio was not met.

ANNALS OF THE RHEUMATIC DISEASES (2022)

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Article Rheumatology

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

Eric F. Morand et al.

Summary: This post-hoc analysis aimed to evaluate the efficacy of anifrolumab on organ domain-specific SLE disease activity. The results demonstrated that anifrolumab treatment improved multiple organ systems in SLE patients, particularly the musculoskeletal system, mucocutaneous system, and immunological system.

LANCET RHEUMATOLOGY (2022)

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Article Rheumatology

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

Edward M. Vital et al.

Summary: This study characterizes the efficacy and safety of anifrolumab in patients with moderate-to-severe SLE. It shows that anifrolumab has consistent efficacy and safety across different subgroups of patients. However, the limited sample size in some subgroups limits the conclusions about treatment benefit with anifrolumab.

ANNALS OF THE RHEUMATIC DISEASES (2022)

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Article Medicine, General & Internal

Phase 2 Trial of Iberdomide in Systemic Lupus Erythematosus

Joan T. Merrill et al.

Summary: This phase 2 trial investigated the efficacy of Iberdomide, a drug for systemic lupus erythematosus (SLE). The results indicated that the 0.45 mg dose of Iberdomide showed a higher treatment response compared to the placebo group at 24 weeks.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Article Biochemical Research Methods

Scoring personalized molecular portraits identify Systemic Lupus Erythematosus subtypes and predict individualized drug responses, symptomatology and disease progression

Daniel Toro-Dominguez et al.

Summary: This study developed MyPROSLE, an omic-based analytical workflow, to measure the molecular characteristics of individual patients and support therapeutic decisions. Through analysis of nearly 6100 lupus patients and 750 healthy samples, it was found that dysregulation of certain gene-modules is strongly associated with specific clinical manifestations, relapses, long-term remission, and drug response. Therefore, MyPROSLE can accurately predict these clinical outcomes.

BRIEFINGS IN BIOINFORMATICS (2022)

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Article Multidisciplinary Sciences

Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells

Bhuwan Khatri et al.

Summary: This study identifies ten novel genetic risk regions associated with Sjogren's disease, implicating genes involved in immune and salivary gland function.

NATURE COMMUNICATIONS (2022)

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Article Rheumatology

Variability of Primary Sjogren's Syndrome Is Driven by Interferon α and Interferon α Blood Levels Are Associated With the Class II HLA-DQ Locus

Diana Trutschel et al.

Summary: By integrating transcriptomic, proteomic, cellular, and genetic data with clinical phenotypes, this study identified IFNα as a key driver of primary SS variability and its association with HLA gene polymorphisms.

ARTHRITIS & RHEUMATOLOGY (2022)

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Article Medicine, General & Internal

Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus Erythematosus

Richard A. Furie et al.

Summary: Litifilimab, a humanized monoclonal antibody that binds to BDCA2, showed a greater reduction in the number of swollen and tender joints in participants with SLE compared to placebo over a period of 24 weeks. Longer and larger trials are needed to determine the safety and efficacy of litifilimab for the treatment of SLE.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Article Rheumatology

Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases

Guillermo Barturen et al.

Summary: The study identified and validated four clusters, one healthy and three pathological, for systemic autoimmune diseases based on molecular patterns. Patients remained stable within their pathological clusters over time, with distinct molecular signatures characterizing each individual. This reclassification has significant implications for future clinical trials and understanding nonresponse to therapy, indicating a paradigm shift in the understanding of systemic autoimmune diseases.

ARTHRITIS & RHEUMATOLOGY (2021)

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Article Cell Biology

Depleting plasmacytoid dendritic cells reduces local type I interferon responses and disease activity in patients with cutaneous lupus

Jodi L. Karnell et al.

Summary: Plasmacytoid dendritic cells (pDCs) are specialized in producing IFN and regulating immune responses, with persistent activation in autoimmune diseases. VIB7734, a monoclonal antibody, effectively depletes pDCs, reduces IFN activity, and improves clinical disease activity in animal models and patients. Biomarker analysis suggests that VIB7734 may be more effective in individuals with high baseline IFN activity, supporting further development in IFN-associated diseases.

SCIENCE TRANSLATIONAL MEDICINE (2021)

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Article Medicine, General & Internal

Trial of Anifrolumab in Active Systemic Lupus Erythematosus

Eric F. Morand et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Article Rheumatology

Identification of highly active systemic lupus erythematosus by combined type I interferon and neutrophil gene scores vs classical serologic markers

Francois Chasset et al.

RHEUMATOLOGY (2020)

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Article Multidisciplinary Sciences

Functionally impaired plasmacytoid dendritic cells and non-haematopoietic sources of type I interferon characterize human autoimmunity

Antonios Psarras et al.

NATURE COMMUNICATIONS (2020)

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Article Rheumatology

Shared development of targeted therapies among autoimmune and inflammatory diseases: a systematic repurposing analysis

Arthur Petitdemange et al.

THERAPEUTIC ADVANCES IN MUSCULOSKELETAL DISEASE (2020)

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Review Rheumatology

Advances in the treatment of systemic lupus erythematosus: From back to the future, to the future and beyond

Renaud Felten et al.

JOINT BONE SPINE (2019)

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Article Immunology

Tubular cell and keratinocyte single-cell transcriptomics applied to lupus nephritis reveal type I IFN and fibrosis relevant pathways

Evan Der et al.

NATURE IMMUNOLOGY (2019)

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Review Chemistry, Medicinal

Spotlight on anifrolumab and its potential for the treatment of moderate-to-severe systemic lupus erythematosus: evidence to date

Renaud Felten et al.

DRUG DESIGN DEVELOPMENT AND THERAPY (2019)

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Article Medicine, General & Internal

Molecular Profiling of Cutaneous Lupus Lesions Identifies Subgroups Distinct from Clinical Phenotypes

Celine C. Berthier et al.

JOURNAL OF CLINICAL MEDICINE (2019)

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Article Rheumatology

Monitoring Disease Activity in Systemic Lupus Erythematosus With Single-Molecule Array Digital Enzyme-Linked Immunosorbent Assay Quantification of Serum Interferon-

Alexis Mathian et al.

ARTHRITIS & RHEUMATOLOGY (2019)

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Article Rheumatology

Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1) a randomised, controlled, phase 3 trial

Richard A. Furie et al.

LANCET RHEUMATOLOGY (2019)

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Article Rheumatology

Photosensitivity and type I IFN responses in cutaneous lupus are driven by epidermal-derived interferon kappa

Mrinal K. Sarkar et al.

ANNALS OF THE RHEUMATIC DISEASES (2018)

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Article Rheumatology

Prediction of autoimmune connective tissue disease in an at-risk cohort: prognostic value of a novel two-score system for interferon status

Md Yuzaiful Md Yusof et al.

ANNALS OF THE RHEUMATIC DISEASES (2018)

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Article Pathology

Type I Interferons in Autoimmune Disease

Mary K. Crow et al.

Annual Review of Pathology-Mechanisms of Disease (2018)

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Article Rheumatology

Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus

Richard Furie et al.

ARTHRITIS & RHEUMATOLOGY (2017)

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Review Immunology

Type I interferonopathies: Mendelian type I interferon up-regulation

Yanick J. Crow

CURRENT OPINION IN IMMUNOLOGY (2015)

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Article Pharmacology & Pharmacy

Targeting Interferons in Systemic Lupus Erythematosus: Current and Future Prospects

Alexis Mathian et al.

DRUGS (2015)

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Article Medicine, Research & Experimental

Anti-BDCA2 monoclonal antibody inhibits plasmacytoid dendritic cell activation through Fc-dependent and Fc-independent mechanisms

Alex Pellerin et al.

EMBO MOLECULAR MEDICINE (2015)

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Review Immunology

Type I interferons in infectious disease

Finlay McNab et al.

NATURE REVIEWS IMMUNOLOGY (2015)

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Article Rheumatology

Modular Transcriptional Repertoire Analyses of Adults With Systemic Lupus Erythematosus Reveal Distinct Type I and Type II Interferon Signatures

Laurent Chiche et al.

ARTHRITIS & RHEUMATOLOGY (2014)

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Article Dermatology

The interferon-regulated gene signature is elevated in subacute cutaneous lupus erythematosus and discoid lupus erythematosus and correlates with the cutaneous lupus area and severity index score

I. Braunstein et al.

BRITISH JOURNAL OF DERMATOLOGY (2012)

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Article Rheumatology

Patients with systemic lupus erythematosus, myositis, rheumatoid arthritis and scleroderma share activation of a common type I interferon pathway

Brandon W. Higgs et al.

ANNALS OF THE RHEUMATIC DISEASES (2011)

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Review Immunology

Autoimmunity and Klinefelter's syndrome: When men have two X chromosomes

Amr H. Sawalha et al.

JOURNAL OF AUTOIMMUNITY (2009)

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Article Hematology

Inteirferon-α promotes abnormal vasculogenesis in lupus:: a potential pathway for premature atherosclerosis

Michael F. Denny et al.

BLOOD (2007)

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Article Rheumatology

Identification of distinct gene expression profiles in the synovium of patients with systemic lupus erythematosus

A. Nzeusseu Toukap et al.

ARTHRITIS AND RHEUMATISM (2007)

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Article Rheumatology

Type I interferon correlates with serological and clinical manifestations of SLE

MC Dall'Era et al.

ANNALS OF THE RHEUMATIC DISEASES (2005)

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Article Genetics & Heredity

Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus

S Sigurdsson et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2005)

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Article Immunology

Interferon and granulopoiesis signatures in systemic lupus erythematosus blood

L Bennett et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2003)

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Article Pathology

Plasmacytoid dendritic cells (natural interferon-α/β-producing cells) accumulate in cutaneous lupus erythematosus lesions

L Farkas et al.

AMERICAN JOURNAL OF PATHOLOGY (2001)

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Type 1 interferons: A target for immune-mediated inflammatory diseases (IMIDs)

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