DefinitionThis section has been translated automatically.
Pharmacodynamics (Effect)This section has been translated automatically.
Anifrolumab is a human immunoglobulin G1-kappa monoclonal antibody that binds with high specificity and affinity to subunit 1 of the type I interferon receptor(IFNAR1). Activation of INFAR1 and INFAR2 leads to phosphorylation of STAT1 and STAT2, which are translocated to the nucleus with interferon-regulatory factor 9(IRF9) to activate the interferon-stimulated response element (ISRE). Activation of ISRE leads to the expression of many pro-inflammatory and immunomodulatory proteins, as well as the activation of a positive feedback loop that produces more type 1 interferons .
Binding of anifrolumab to IFNAR1blocks type I IFN signal transduction and thus the biological activity of type I interferons. In addition, anifrolumab induces internalization of IFNAR1, thereby reducing the number of receptors on the cell surface, leaving less IFNAR1 available for receptor binding.
Blockade of receptor-mediated type I IFN signal transduction inhibits interferon-stimulated gene expression and downstream inflammatory and immunologic processes. Inhibition of type I IFN blocks plasma cell differentiation and normalizes peripheral T cell subsets, restoring the balance between adaptive and innate immunity, which is dysregulated in SLE, for example.
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Field of application/useThis section has been translated automatically.
Anifrolumab is intended for intravenous use. After dilution with 0.9% sodium chloride infusion solution (9 mg/ml), Saphnelo is given as an infusion over 30 minutes using an infusion tubing containing a sterile 0.2 or 0.22 micrometer in-line filter with low protein binding.
IndicationThis section has been translated automatically.
Indicated as add-on therapy for the treatment of adult patients with moderate to severe, active autoantibody-positive systemic lupus erythematosus (SLE) who are already receiving standard therapy. Chloroquine and hydroxychloroquine are considered basic medications in SLE. For arthralgias and arthritides, NSAIDs, glucocorticoids, methotrexate, leflunomide, or belimumab are used. If the nervous system is affected or life is at risk, systemic steroids, cyclophosphamide, or rituximab are used.
There is a case report of successful use of the drug in Köhlmeier-Degos disease.
Pregnancy/nursing periodThis section has been translated automatically.
To date, there is very limited experience (less than 300 pregnancy outcomes) with the use of anifrolumab in pregnant women. The use of anifrolumab during pregnancy and in women of childbearing potential who are not using contraception is therefore not recommended unless the potential benefit justifies the potential risk.
Dosage and method of useThis section has been translated automatically.
The recommended dose of Saphnelo is 300 mg of anifrolumab given as an intravenous infusion every 4 weeks for a duration of 30 minutes.
If there is a history of infusion-related reactions, a premedication consisting of an antihistamine may be given prior to infusion.
Undesirable effectsThis section has been translated automatically.
The most commonly reported adverse events that occurred in controlled clinical trials with anifrolumab were:
- Upper respiratory tract infections (34%)
- bronchitis (11%)
- infusion-related reactions (9.4%)
- herpes zoster (6.1%)
ContraindicationThis section has been translated automatically.
Anifrolumab must not be used in case of hypersensitivity to the active substance or any of the other ingredients of the drug.
PreparationsThis section has been translated automatically.
Note(s)This section has been translated automatically.
Other monoclonal antibodies targeting the type 1 interferon pathway that are currently being investigated in clinical trials as potential treatments for systemic lupus erythematosus include rontalizumab and sifalimumab.