Saphnelo (anifrolumab-fnia) / BMS, AstraZeneca - LARVOL DELTA

Increased type I interferon signaling is a hallmark of idiopathic multicentric castleman disease (ASH 2025) - "While there is an FDA-approved anti-interleukin-6 (IL-6) therapy, siltuximab, whichis effective in 34-50% of iMCD patients, disease etiology and pathophysiology remains largely unknown.While mTOR inhibition with sirolimus is effective in a subset of patients, the cell types and immunesignaling pathways dysregulated in iMCD are poorly understood. Together,our spatial transcriptomics data indicate that IFN-I is significantly upregulated specifically in germinalcenter regions of iMCD lymph nodes.These data demonstrate that IFN-I signaling is increased in the lymph nodes of iMCD patients acrossmultiple cell types, likely in the germinal center. Since IFN-I can lead to mTOR activation through PI3Ksignaling, it is possible that elevated IFN-I contributes to the elevated mTOR signature observed in iMCD.Given that IFN-I is significantly elevated in both circulation and LNs of iMCD patients, targeting INF-alphawith Anifrolumab may be a potential therapy for treatment refractory..."

Clinical • Epstein-Barr Virus Infections • Inflammation • Rare Diseases • CD4 • CD8 • IFNA1 • IL6 • STAT1

TET2 mutations drive cell-autonomous type I interferon production and selective advantage through TRIM4 silencing (ASH 2025) - "DExH-box helicase 58 (DHX58), one of the 190proteins identified by our proteomics analyses and a positive regulator of the MAVS pathway, wasconfirmed by knockout experiments to mediate the aberrant IFN production by TET2-deficient HSPCs.These results support a model whereby TET2 deficiency and consequent TRIM4 silencing activate type IIFN production through decrease in proteasome-mediated degradation of DHX58. Finally, we show thatIFNAR1 blockade by the FDA-approved monoclonal antibody anifrolumab alleviates the clonal advantageof TET2-deficient T cells expressing a CD19-targeted CAR.In summary, we report secretion of type I IFN by TET2-mutant HSPCs as the cause of a pro-inflammatorylocal microenvironment that favors the expansion of mutant cells; we discover TRIM4 silencing as acritical effector of TET2 deficiency; we characterize TRIM4 as a novel negative regulator of type I IFNinduction through degradation of DHX58; and we propose a new pharmacologic approach to..."

IO biomarker • Hematological Disorders • Hematological Malignancies • Lymphoma • T Cell Non-Hodgkin Lymphoma • Targeted Protein Degradation • ASXL1 • CD19 • CD34 • DNMT3A • IFNA1 • IFNAR1 • MYD88 • STING • TET2 • TRIM4

Systemic Lupus Erythematosus: Ophthalmological Safety Considerations of Emerging and Conventional Therapeutic Agents. (PubMed, Int J Mol Sci) - "With the advent of targeted immunomodulatory agents, the therapeutic landscape of SLE has expanded beyond conventional drugs such as hydroxychloroquine and corticosteroids toward biologics and small molecules designed to interfere with specific immunological pathways...In contrast, recently approved or investigational therapies-such as belimumab, anifrolumab, voclosporin, dual BAFF/APRIL inhibitors, rituximab, JAK inhibitors, CD40/CD40L blockade, CD38 inhibition, and mesenchymal stromal cell-based strategies-have limited but evolving safety data, with potential ocular adverse events spanning inflammatory, vascular, neuro-ophthalmic, and structural domains...These findings highlight the need for systematic ophthalmological surveillance in patients receiving immunomodulatory therapies for SLE. Early recognition and timely management of ocular toxicity are crucial to safeguarding visual function and optimizing long-term therapeutic outcomes in this vulnerable patient..."

Journal • Review • Cataract • Glaucoma • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Ophthalmology • Retinal Disorders • Systemic Lupus Erythematosus • CD40LG

Successful treatment of severe systemic lupus erythematosus with anifrolumab: a single-center observational study. (PubMed, Reumatologia) - "All 10 patients with severe manifestations, including neuro-SLE, lupus nephritis and APS-SLE, showed significant clinical improvement following ANF therapy, as evidence by reduced SLEDAI-2K scores. Anifrolumab appears to be a promising and safe therapeutic option for patients with severe SLE based on real-world data."

Journal • Observational data • Genetic Disorders • Glomerulonephritis • Hematological Disorders • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Psychiatry • Rheumatology • Systemic Lupus Erythematosus

Update on cutaneous lupus erythematosus pathogenesis, diagnosis and management. (PubMed, J Eur Acad Dermatol Venereol) - "Antimalarials, particularly hydroxychloroquine, remain the cornerstone of systemic therapy. Second-line or third-line agents such as methotrexate, retinoids, dapsone, thalidomide and lenalidomide are recommended in refractory cases. Biological therapies, including belimumab and anifrolumab, are approved in the setting of SLE. Promising results from recent trials of targeted therapies including inhibitors of plasmacytoid dendritic cells, TLR7/8 and TYK2 are paving the way for novel treatment strategies in CLE."

Journal • Review • Cutaneous Lupus Erythematosus • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • TLR7 • TYK2

Anifrolumab for refractory chilblain lupus erythematosus. (PubMed, Int J Womens Dermatol) - No abstract available

Journal • Immunology • Inflammatory Arthritis • Lupus

The Anifrolumab PRIM Program (clinicaltrials.gov) - P=N/A | N=240 | Not yet recruiting | Sponsor: AstraZeneca | Initiation date: Sep 2025 ➔ Apr 2026

Trial initiation date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Indirect comparative efficacy and safety of belimumab vs. anifrolumab in systemic lupus erythematosus and lupus nephritis: a meta-analysis of randomized trials. (PubMed, Z Rheumatol) - "Belimumab confers greater benefit in terms of SRI‑4 response for SLE, while anifrolumab is more effective for corticosteroid tapering and immunologic parameter normalization. In LN, the comparative efficacy remains uncertain. Both agents exhibit similar safety profiles, but anifrolumab is associated with an increased risk of herpes zoster. Differences in study design, inclusion criteria, and assessment protocols among included trials may limit direct comparability."

Journal • Retrospective data • Glomerulonephritis • Herpes Zoster • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus • Varicella Zoster

RF - New treatments in dermatomyositis: present and future. (PubMed, Actas Dermosifiliogr) - No abstract available

Journal • Dermatomyositis • Immunology • Myositis

A Spatial Keratinocyte–Fibroblast–Myeloid Axis Amplifies Type I Interferon–Driven Photosensitivity in Cutaneous Lupus and Dermatomyositis (ISDS 2025) - "UVB exposure of non-lesional DM skin induces rapid infiltration of these cells, an effect absent in healthy controls and blocked by IFN-I receptor blockade (anifrolumab) in vivo...Together, our findings define a feed-forward circuit in which keratinocyte stress, IFN-I priming, and fibroblast chemotaxis converge to drive myeloid cell accumulation and sustained inflammation. This keratinocyte–fibroblast–myeloid axis represents a critical mechanism of photosensitivity in autoimmune skin disease and suggests MMP9+ CD14+ myeloid cells as promising targets for therapeutic intervention."

Cutaneous Lupus Erythematosus • Dermatitis • Dermatology • Dermatomyositis • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Myositis • CCL2 • CD14 • CXCL12 • IFNB1 • MMP9 • TNFA

A RANDOMIZED, PARALLEL-GROUP, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 3 STUDY OF THE TYPE I INTERFERON RECEPTOR ANTIBODY, ANIFROLUMAB, IN SYSTEMIC SCLEROSIS: DESIGN AND RATIONALE OF THE DAISY TRIAL (SSWC 2024) - P3 | "The DAISY trial will evaluate the efficacy of anifrolumab as a first-in-class treatment option, targeting IFN-I pathway activation, for patients with limited or diffuse cutaneous SSc. Selecting revised-CRISS-25 as the primary endpoint captures the heterogeneity of SSc by enabling measurement of improvement and worsening of a broad set of disease activity domains beyond lung function and skin, including clinician- and patient-reported outcomes. An additional strength includes an open-label period for long-term exposure, providing up to two years of on-drug data."

Clinical • P3 data • Fibrosis • Immunology • Inflammatory Arthritis • Interstitial Lung Disease • Lupus • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis • IFNA1 • IFNAR2

Real-World Use of Anifrolumab for Articular Involvement in Systemic Lupus Erythematosus: A Monocentric Case Series and Systematic Review. (PubMed, J Pers Med) - "The results underscore anifrolumab's potential as a valuable treatment option for joint manifestations of SLE, addressing an unmet clinical need in routine practice. This evidence may assist clinicians in selecting the most suitable therapeutic approach based on predominant clinical features, thus enhancing personalized treatment strategies in SLE."

Journal • Real-world evidence • Review • Immunology • Inflammatory Arthritis • Lupus • Rheumatology • Systemic Lupus Erythematosus

A TLR7/9-IFNα-LDHB axis drives vital NET release and compromises antibacterial defense in lupus. (PubMed, bioRxiv) - "Combined treatment with hydroxychloroquine (HCQ) and interferon-alpha/beta receptor (IFNAR) blockade restores LDHB expression, NET homeostasis, and bacterial clearance in lupus-prone mice. Neutrophils from SLE patients exhibit similar defects, which are reversed by HCQ and the IFNAR-blocking antibody anifrolumab. These findings identify a clinically actionable immunometabolic checkpoint linking chronic autoimmune signaling to defective antibacterial defense in SLE."

IO biomarker • Journal • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • IFNA1 • IFNAR1 • LDHB • TLR7

Beyond the Usual: A Rare Case of Lupus Podocytopathy and FSGS (KIDNEY WEEK 2025) - "She was prescribed hydroxychloroquine (HCQS) but was non-compliant...She improved and was discharged on prednisone, with outpatient plans for tacrolimus...This case highlights treatment challenges due to medication intolerance. Emerging therapies like anifrolumab show promise."

Clinical • Anemia • Cardiovascular • Chronic Kidney Disease • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Arthritis • Leukopenia • Lupus • Lupus Nephritis • Musculoskeletal Diseases • Musculoskeletal Pain • Nephrology • Orthopedics • Pneumonia • Pulmonary Disease • Pulmonary Embolism • Renal Disease • Respiratory Diseases • Rheumatology • Systemic Lupus Erythematosus • Thrombocytosis

A de novo dominant-negative PSMB8 mutation causes severe CANDLE/PRAAS due to arrested proteasome biogenesis. (PubMed, Ann Rheum Dis) - "The DN-PSMB8 p.G209R variant broadens the clinical and mechanistic PRAAS spectrum by causing 20S proteasome maturation arrest and uncovering a convergence between mitochondrial dysfunction and the ISR. Our findings implicate cytopenia in a pattern of vascular pathology, including PSVD of the liver. We further identify PKR and GCN2 as key mediators of maladaptive IFN-I responses and potential therapeutic targets."

Journal • Hematological Disorders • Hepatology • Infectious Disease • Inflammation • Interferonopathies • Metabolic Disorders • PSMB8

LAVENDER: A Phase III Study to Investigate the Efficacy and Safety of Anifrolumab in Adults With Chronic and/or Subacute Cutaneous Lupus Erythematosus (clinicaltrials.gov) - P3 | N=302 | Recruiting | Sponsor: AstraZeneca | N=460 ➔ 302 | Trial completion date: Dec 2027 ➔ Aug 2027 | Trial primary completion date: Dec 2027 ➔ Nov 2026

Enrollment change • Trial completion date • Trial primary completion date • Cutaneous Lupus Erythematosus • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • IFNG

Real-World Data on Voclosporin for the Treatment of Lupus Nephritis, Including Use of Concomitant Biologic Therapies: Analysis of the Enlight-LN Registry (KIDNEY WEEK 2025) - P | "There were 83 (36.2%) patients on voclosporin who concomitantly received treatment with a biologic including belimumab (28.4%), rituximab (4.8%), anifrolumab (3.9%) and obinutuzumab (1.3%). This is notable given the unique and possibly synergistic effects of these agents on the immune system. Additional analysis of the registry data will provide further clinical and mechanistic insights into the use of these multi-targeted therapeutic approaches."

Clinical • Real-world • Real-world evidence • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Systemic Lupus Erythematosus

Anifrolumab Use in Patients with Lupus Nephritis Is Associated with Decreased Progression to ESRD (KIDNEY WEEK 2025) - "Conclusion In this real-world data study, we illicit that the use of Anifrolumab in LN patients has decreased association with ESRD. Further prospective studies are required to ascertain the use of Anifrolumab in the prevention of ESRD in LN patients."

Clinical • Cardiovascular • Chronic Kidney Disease • Diabetes • Glomerulonephritis • Hypertension • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Metabolic Disorders • Nephrology • Renal Disease

Advanced Therapies and the Unmet Need in Systemic Lupus Erythematosus Patients: Results From a Real-World Study in the United States and Germany (ISPOR-EU 2025) - "OBJECTIVES: We aimed to examine the unmet need in patients with systemic lupus erythematosus (SLE) receiving advanced therapies (ATs). Data were drawn from the Adelphi Real World Lupus Disease Specific Programme™, a cross-sectional survey of rheumatologists and their patients with SLE (plus additional SLE patients receiving anifrolumab) in Germany and the United States (US) from July 2024 - January 2025... Although ATs appear to support steroid sparing, there is unmet need for AT patients in polypharmacy and QoL impact, despite being treated with an advanced therapy."

Clinical • Metastases • Real-world • Real-world evidence • Fatigue • Immunology • Inflammatory Arthritis • Lupus • Rheumatology • Systemic Lupus Erythematosus

Anifrolumab as a Glucocorticoid-Sparing Agent in MRI-Negative Myelitis Associated with Neuropsychiatric Lupus: A Case Report. (PubMed, Mod Rheumatol Case Rep) - "The patient received high-dose intravenous glucocorticoids (GCs) and intravenous cyclophosphamide as induction therapy, after which anifrolumab was introduced; GCs were rapidly tapered with sustained neurological improvement. MRI-negative myelitis is a rare and diagnostically challenging NPSLE phenotype that requires a high index of suspicion. This case suggests that anifrolumab may have GC-sparing potential as part of maintenance management following induction therapy in selected patients, warranting further investigation."

Journal • CNS Disorders • Immunology • Inflammatory Arthritis • Lupus • Psychiatry • Systemic Lupus Erythematosus

Dual Targeted Therapy with Baricitinib and Anifrolumab in Infantile Spondyloenchondrodysplasia with Immune Dysregulation. (PubMed, J Clin Immunol) - No abstract available

Journal

Anifrolumab for refractory dermatomyositis: Experience from a Spanish cohort. (PubMed, Eur J Intern Med) - No abstract available

Journal • Dermatomyositis • Immunology • Myositis

Anifrolumab in Systemic Lupus Erythematosus With Severe Hematological Manifestations: A Spanish Multicenter Study. (PubMed, J Rheumatol) - "The revised text is "severe leukopenia (leukocyte count < 2 × 109/L)." This correction applies only to the October 1 First Release. The correct text appears in the print and online issues."

Clinical • Journal • Hematological Disorders • Immunology • Inflammatory Arthritis • Leukopenia • Lupus • Systemic Lupus Erythematosus

Discoid lupus erythematosus and its progression to systemic lupus erythematosus across age groups: a systematic review. (PubMed, J Med Life) - "Treatment relied mainly on topical corticosteroids (44.4% pediatric; 51.6% adult) and hydroxychloroquine (11.1% pediatric; 28.7% adult), while newer therapies such as lenalidomide and anifrolumab showed potential benefits. Overall, DLE demonstrates a strong female predominance and a substantial likelihood of progression to SLE, particularly in younger patients with autoantibody positivity."

Journal • Review • Cutaneous Lupus Erythematosus • Discoid Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus • Pediatrics • Rheumatology • Systemic Lupus Erythematosus

Subacute skin lesions in systemic lupus erythematosus: an impressive and well-tolerated response to anifrolumab. (PubMed, An Bras Dermatol) - No abstract available

Journal • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus