ArticleArthritis research & therapy2014
Dose-escalation of human anti-interferon-α receptor monoclonal antibody MEDI-546 in subjects with systemic sclerosis: a phase 1, multicenter, open label study.
Article in Arthritis research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00930683 (A Phase 1 Multicenter, Open-label Study to Evaluate the Safety and Tolerability of Single and Multiple Intravenous Doses of MEDI-546, a Fully Human Monoclonal Antibody Directed Against Subunit 1 of the Type I Interferon Receptor, in Adult Subjects With Scleroderma), which is not on this map. Cited by 53 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1 Multicenter, Open-label Study to Evaluate the Safety and Tolerability of Single and Multiple Intravenous Doses of MEDI-546, a Fully Human Monoclonal Antibody Directed Against Subunit 1 of the Type I Interferon Receptor, in Adult Subjects With Scleroderma
Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus.Arthritis & rheumatology (Hoboken, N.J.) · 2017Trial
- Suppression of T Cell Activation and Collagen Accumulation by an Anti-IFNAR1 mAb, Anifrolumab, in Adult Patients with Systemic Sclerosis.The Journal of investigative dermatology · 2015Trial
- A symposium update on the key perspectives in systemic sclerosis and systemic lupus erythematosus.Journal of translational autoimmunity · 2026Review
- Real-world safety profile of anifrolumab: An observational disproportionality analysis of the FAERS database.Medicine · 2026Observational
- Anifrolumab-A Potential New Systemic Sclerosis Treatment.Journal of clinical medicine · 2026Review
- Emerging therapies for the treatment of systemic sclerosis.Nature reviews. Rheumatology · 2025Review
- Post-marketing safety signals of anifrolumab in systemic lupus erythematosus: a pharmacovigilance study based on FAERS.BMC rheumatology · 2025Article
- Physiology-based pharmacokinetic model with relative transcriptomics to evaluate tissue distribution and receptor occupancy of anifrolumab.CPT: pharmacometrics & systems pharmacology · 2025Article
- Type I Interferons in Systemic Autoimmune Rheumatic Diseases: Pathogenesis, Clinical Features and Treatment Options.Mediterranean journal of rheumatology · 2024Review
- Systemic sclerosis interstitial lung disease: unmet needs and potential solutions.Nature reviews. Rheumatology · 2024Review
- Type I Interferons in Autoimmunity: Implications in Clinical Phenotypes and Treatment Response.The Journal of rheumatology · 2023Review
- Novel Therapeutic Strategies in the Treatment of Systemic Sclerosis.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Clinical Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Anifrolumab.Clinical pharmacokinetics · 2023Review
- Molecular Mechanisms Behind the Role of Plasmacytoid Dendritic Cells in Systemic Sclerosis.Biology · 2023Review
- Autoantibodies associated with systemic sclerosis in three autoimmune diseases imprinted by type I interferon gene dysregulation: a comparison across SLE, primary Sjögren's syndrome and systemic sclerosis.Lupus science & medicine · 2022Article
- Targeting type I interferon (IFN) signalling in patients with RA with a high type I IFN gene signature.RMD open · 2022Article
- Nonlinear Population Pharmacokinetics of Anifrolumab in Healthy Volunteers and Patients With Systemic Lupus Erythematosus.Journal of clinical pharmacology · 2022Article
- Relationship Between Anifrolumab Pharmacokinetics, Pharmacodynamics, and Efficacy in Patients With Moderate to Severe Systemic Lupus Erythematosus.Journal of clinical pharmacology · 2022Article
- Rapid Response of Refractory Systemic Lupus Erythematosus Skin Manifestations to Anifrolumab-A Case-Based Review of Clinical Trial Data Suggesting a Domain-Based Therapeutic Approach.Journal of clinical medicine · 2022Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
introductionType I interferons (IFNs) are implicated in the pathogenesis of systemic sclerosis (SSc). MEDI-546 is an investigational human monoclonal antibody directed against the type I IFN receptor. This Phase 1 study evaluated the safety/tolerability, pharmacokinetics (PK), immunogenicity, and pharmacodynamics (PD) of single and multiple intravenous doses of MEDI-546 in adults with SSc.
methodsSubjects (≥18 years) with SSc were enrolled in an open-label, dose-escalation study to receive single (0.1, 0.3, 1.0, 3.0, 10.0, or 20.0 mg/kg), or 4 weekly intravenous doses (0.3, 1.0, or 5.0 mg/kg/week) of MEDI-546. Subjects were followed for 12 weeks. Safety assessments included adverse events (AEs), laboratory results, and viral monitoring. Blood samples were collected from all subjects for determination of PK, presence of anti-drug antibodies (ADAs), and expression of type I IFN-inducible genes.
resultsOf 34 subjects (mean age 47.4 years), 32 completed treatment and 33 completed the study. Overall, 148 treatment-emergent AEs (TEAEs) were reported (68.9% mild, 27.7% moderate). TEAEs included one grade 1 infusion reaction (5.0 mg/kg/week multiple dose). Of 4 treatment-emergent serious AEs (skin ulcer, osteomyelitis, vertigo, and chronic myelogenous leukemia (CML)), only CML (1.0 mg/kg/week multiple dose) was considered possibly treatment-related. MEDI-546 exhibited non-linear PK at lower doses. ADAs were detected in 5 subjects; no apparent impact on PK was observed. Peak inhibition of the type I IFN signature in whole blood was achieved within 1 day and in skin after 7 days.
conclusionThe safety/tolerability, PK, and PD profiles observed in this study support further clinical development of MEDI-546.
trial registrationClinicalTrials.gov NCT00930683.
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