Overview:
A monoclonal antibody known as Anifrolumab-fnia is an antagonist of the type 1 interferon receptor (IFNAR). It is developed to treat autoimmune diseases like systemic lupus erythematosus (SLE) and lupus nephritis, both of which have type 1 interferon as an underlying etiology. Intravenous (IV) Anifrolumab-fnia received approval from the United States, Food and Drug Administration (US FDA) in July 2021. Adult patients with moderate to severe SLE who were on regular medication were treated with it.
Drug Group:
The drug Anifrolumab injection belongs to the group of drugs known as monoclonal antibodies. It functions by preventing a specific protein in SLE patients from acting.
Available Doses and Dosage Forms:
The recommended Anifrolumab dosage is 300 mg (milligrams) given as a 30-minute intravenous infusion once every four weeks.
For Patients:
What Is Systemic Lupus Erythematosus (SLE)?
SLE is an autoimmune disease in which the body's immune system attacks its tissues, causing significant tissue damage and inflammation in the affected organs. The brain, the skin, the lungs, the blood vessels, and the joints are among the organs that it may affect. Lupus cannot be cured, but lifestyle changes and drug treatments can help it become more manageable.
Although the exact origins of SLE are not known, it is thought that hormonal, genetic, and environmental factors may all have a role in the origin of SLE.
Systemic lupus erythematosus (SLE) patients can exhibit a wide variety of symptoms, including joint discomfort or swelling, recurrent fevers, skin rashes, and continuous fatigue. Many adults with SLE experience similar symptoms in periodic bouts known as "flares," which could happen intermittently and be separated by years. Increased disease activity is a feature of these flares. Remission, on the other hand, refers to times when symptoms are less severe or nonexistent. It is crucial to remember that while some people only experience occasional flares followed by lengthy remissions, others may endure more regular SLE flares. Symptom control, reducing flare-ups, and long-term stability can all be achieved by managing the illness with a combination of prescribed medicines, dietary changes, and frequent medical checkups.
In addition to these symptoms, people with this condition may also experience sun sensitivity, oral ulcers, arthritis, lung, heart, and kidney issues, seizures, psychosis, and abnormalities of the blood cells and immune system.
How Does Anifrolumab Work?
Anifrolumab is a monoclonal immunoglobulin gamma 1 kappa (IgG1) antibody that binds specifically to INFAR1 subunit 1. IFNAR1 activity is inhibited by Anifrolumab binding to the receptor. This interruption in IFNAR1, reduces the signals it sends and the genes it activates that cause inflammation in the body.
What Is the Dosage of Anifrolumab?
An intravenous infusion of 300 mg of Anifrolumab should be administered once every four weeks.
What Are the Things to Inform the Doctor Before Taking the Drug?
Any known allergies to Anifrolumab, other medications, or any ingredients in the Anifrolumab injection should be disclosed to one's doctor and pharmacist. It is crucial to supply healthcare providers with a thorough list of all current herbal products, vitamins, dietary supplements, and non-prescription and prescription drugs as it may be helpful in modifying the medication dosages or for close drug monitoring. Mention any prior cancer diagnoses or histories of recurrent infections. Consult the doctor if breastfeeding, pregnant, or trying to get pregnant. Without first consulting the doctor, refrain from getting any immunizations while taking Anifrolumab.
How Is Anifrolumab Administered?
Anifrolumab is given intravenously, often over a 30-minute period every four weeks. The frequency is based on how well the patient responds to the drug. Although it helps with lupus management, it does not provide a cure. For the doctor to determine whether it is working, close observation is essential. To ensure they receive the best care possible, patients are urged to keep their healthcare providers informed of their health and any changes to their condition.
What Are the Side Effects of Anifrolumab-Fnia?
Anifrolumab may cause a number of side effects, some of which need to be reported immediately to a healthcare professional. Headaches, nausea, vomiting, and exhaustion are side effects that, if they worsen or continue, should be brought up with the doctor.
There are further severe side effects that demand urgent medical intervention. These include symptoms of infection including fever, chills, a sore throat, and cough, as well as discomfort in the stomach or intestines, diarrhea, painful or frequent urination, sores on the skin that are red or painful, swelling of the face, tongue, or lips, dizziness, fainting, and breathing issues.
It is crucial to be informed that Anifrolumab may increase the risk of developing particular cancers.
Dietary Considerations:
Maintain a regular diet unless the doctor instructs otherwise.
Missed Dose:
In the event of missing an appointment for Anifrolumab infusion, it is advisable to promptly contact the doctor to reschedule and ensure continuity of treatment.
Overdose:
In case of overdosing, the victim can have a seizure, collapse, or might find breathing difficult. Approach the nearest healthcare in that case.
Storage:
The drug Anifrolumab-fnia is packaged in a little glass vial. It is administered through a vein and is used as an intravenous infusion. There are no preservatives added to the liquid. It appears to be a clear or faintly yellowish liquid. Each vial of the medication contains 300 mg (milligrams) of the drug dissolved in two mL (milliliters) of liquid.
For Doctors:
Indication:
Systemic lupus erythematosus (SLE) in adult patients who are receiving standard therapy and have moderate to severe disease is approved for treatment with Anifrolumab-fnia.
Dose:
Anifrolumab should be given intravenously once every four weeks in a dose of 300 mg.
Dosing Considerations:
For injection, use a single-dose vial containing 300 mg (milligrams) per 2 mL (milliliter) (150 mg/mL) of a clear to opalescent, colorless to slightly yellow solution.
What Are the Pharmacological Aspects of Anifrolumab-Fnia?
Description:
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Molecular Weight - 148 kDa (kilodalton).
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pH - 5.9
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Composition - Each vial contains 300 mg (150 mg/mL) of Anifrolumab-fnia, L-histidine hydrochloride monohydrate (6 mg), polysorbate 80 (1 mg), L-histidine (3 mg), trehalose dihydrate (98 mg), L-lysine hydrochloride (18 mg), and water for Injection.
Mechanism of Action:
A human IgG1 monoclonal antibody called Anifrolumab-fnia is renowned for having a strong affinity and specificity for subunit 1 of the type I interferon receptor (IFNAR). It effectively blocks the biological activity of type I interferons (IFNs) by binding to IFNAR1, which suppresses the signaling of IFNs. Additionally, IFNAR1 is internalized as a result of this antibody, which lowers the amount of this receptor subunit that is accessible for assembly on the cell surface. Anifrolumab-fnia obstructs IFN-mediated signaling as a result, which inhibits IFN-responsive gene expression as well as subsequent inflammatory and immunological processes. Additionally, it prevents plasma cell differentiation and normalizes peripheral T-cell subsets by inhibiting type I IFNs. Anifrolumab-fnia has potential as a treatment for systemic lupus erythematosus (SLE), a condition in which high type I IFN levels play a substantial role in the pathophysiology of the illness and afflict 60–80 percent of adult patients with active SLE.
Pharmacodynamics: Anifrolumab-fnia was given to SLE patients as an intravenous infusion at a dose of 300 mg every four weeks for 52 weeks. In particular, it caused a significant neutralization (80 percent) of a type 1 IFN gene signature in people with high levels of type 1 IFN inducible genes from week four to Week 52. However, it is important to note that after stopping Anifrolumab-fnia at the end of the 52-week treatment period, this effect recovered to baseline within eight to 12 weeks.
Pharmacokinetics: Adult patients and healthy volunteers were evaluated whilst taking the medicine Anifrolumab-fnia, which is used to treat SLE (a form of lupus). Its behavior in the body when administered in dosages ranging from 100 mg to 1000 mg every four weeks is complicated, which means the increase in its level in the body does not correspond to the dose increase. For instance, an increased dose does not necessarily translate into an increased exposure. When 300 mg was administered consistently, it took the body 85 days to achieve a steady level. At steady state, the highest concentration (Cmax) rose 1.36 times more than the initial dose, whereas the minimum concentration (Ctrough) increased 2.49 times greater.
Toxicity:
An increase in carcinogenicity has been observed in rodent models with IFNAR1 inhibition, while Anifrolumab-fnia's ability to cause cancer and genotoxicity has not been evaluated. The potential clinical importance is still unknown. Animals have not been specifically used in studies of effects on male and female fertility. There were no unfavorable effects on fertility-related indicators such as spermatogenesis, menstrual cycle, semen analysis, or reproductive organ parameters in nine-month toxicity trials in cynomolgus monkeys at doses up to 50 mg/kg (milligram per kilogram) intravenously once weekly (approximately 58 times the MRHD maximum recommended human dose).
Clinical Studies:
An open extension study on Anifrolumab followed adult patients for three years who had previously participated in a clinical trial called MUSE. In the MUSE trial, these patients received either Anifrolumab or a placebo for 48 weeks, followed by a 12-week observation period. Anifrolumab is a medication given through an IV route. All participants in this extension study got 1000 mg of Anifrolumab intravenously every four weeks at first. Nevertheless, the dosage was subsequently decreased to 300 mg every four weeks based on what was discovered from the MUSE trial, taking into account both the advantages and disadvantages of the drug.
Any adverse events that the patients encountered were observed and recorded by the researchers throughout the trial. Each month, they performed this. The SLE Disease Activity Index, health-related quality of life (HRQoL), and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), pharmacodynamics, were used in the study to examine other indicators of the activity of the chronic autoimmune disease systemic lupus erythematosus (SLE). This was carried out in order to comprehend the medication's impact on the condition better.
This study hence proved that Anifrolumab has a strong safety track record when used as a treatment over a long length of time. Additionally, it regularly results in improvements in blood test outcomes for systemic lupus erythematosus (SLE), quality of life (HRQoL), and SLE activity. This implies that Anifrolumab is a safe and efficient long-term treatment for SLE.
What Are the Contraindications of Anifrolumab?
Patients who have experienced anaphylaxis after using Anifrolumab-fnia should not take this drug.
Warnings and Precautions:
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Serious Infections - Patients on immunosuppressive medications, such as Anifrolumab-fnia, have been documented to experience serious and occasionally fatal infections. In studies that were carefully monitored, individuals receiving Anifrolumab-fnia and those receiving a placebo saw similar overall incidences of severe infections. It is crucial to remember that patients receiving Anifrolumab-fnia experienced deadly infections more frequently. Patients with any clinically significant ongoing infection should wait to start Anifrolumab-fnia therapy until the infection has subsided or has received sufficient treatment. Patients should be made aware of how crucial it is to seek medical help if they exhibit any signs or symptoms of an infection that is clinically severe while receiving Anifrolumab-fnia treatment. Close observation is essential if a patient gets infected or does not respond well to the recommended anti-infective therapy. Until the infection has cleared up and the patient's condition has stabilized, it could be important to think about temporarily stopping Anifrolumab-fnia therapy. This strategy tries to strike a balance between the patient's overall health and safety and the therapeutic benefits of Anifrolumab-fnia. Based on the unique circumstances of each patient, a healthcare practitioner should be consulted before deciding whether to stop or continue therapy.
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Hypersensitivity Reactions - It is crucial to carefully weigh the potential benefit and risks of treatment when thinking about using Anifrolumab-fnia in patients with a chronic infection, a history of recurrent infections, or established risk factors for infection. Patients with any clinically significant ongoing infection should wait to start Anifrolumab-fnia therapy until the infection has subsided or has received sufficient treatment. Patients should be made aware of how crucial it is to seek medical help right away if they exhibit any signs or symptoms of an infection that is clinically severe while receiving Anifrolumab-fnia treatment.
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Malignancy - Immunosuppressant use increases the likelihood of developing cancer, and it is unknown whether Anifrolumab-fnia treatment could have a similar effect. Therefore, before administering Anifrolumab-fnia to patients who already have cancer risk factors, it is essential to evaluate each patient's unique benefit-risk profile. When patients do contract cancer while using Anifrolumab-fnia, it is crucial to carefully weigh the ongoing benefits and risks of continuing treatment. Healthcare professionals should be watchful and use their own discretion when handling patients on Anifrolumab-fnia who have worries about cancer.
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Immunization - Prior to beginning Anifrolumab-fnia therapy, patients should update their immunizations in accordance with current immunization recommendations. In patients receiving Anifrolumab-fnia, avoid administering live or live-attenuated vaccinations concurrently.
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Use With Other Biologic Therapies Is Not Advised Concurrently - Combining Anifrolumab-fnia with other biologic treatments, such as B-cell-targeted treatments, has not been researched. As a result, it is not advised to combine Anifrolumab-fnia with biologic therapy.
What Are the Drug Interactions of Anifrolumab-Fnia?
There have been no official studies on drug interactions.
Specific Considerations:
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Pregnancy - To determine the potential risks of serious birth abnormalities, miscarriage, or other negative outcomes linked to the use of Anifrolumab-fnia during pregnancy, insufficient human data are available. Notably, monoclonal IgG antibodies, such as Anifrolumab-fnia, can cross the placenta and may expose the fetus to more substances in the third trimester. It's critical to understand that every pregnancy comes with a standard risk of birth abnormalities, miscarriage, or unfavorable consequences. Healthcare professionals should carefully assess the clinical necessity, potential benefits, and dangers to the fetus when considering the use of Anifrolumab-fnia in pregnant patients.
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Lactating Mothers - There is a lack of information on the possibility of Anifrolumab-fnia having an impact on breastfed newborns. Anifrolumab-fnia was found in the milk of cynomolgus monkeys in studies, however, due to changes in lactation physiology between species, this may not properly predict human outcomes. Human milk contains maternal IgG by nature. There is still some uncertainty regarding the systemic and local effects of Anifrolumab-fnia exposure on breastfed infants. Therefore, when weighing the possible benefits of nursing against the mother's clinical need for the medication and any potential hazards to the breastfed infant, taking into account the underlying maternal illness, healthcare providers may evaluate the use of Anifrolumab-fnia in lactating mothers.
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Pediatric Population - It is unknown whether Anifrolumab-fnia is safe and effective for use in pediatric patients younger than 18 years old.
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Geriatric Population - 20 out of 664 SLE patients that participated in clinical trials and made up three percent of the study group were 65 years of age or older. However, a clear evaluation of whether patients 65 and older demonstrate distinctive responses in comparison to their younger counterparts is impossible due to the little representation of this age group. For the purpose of determining any potential age-related variations in the response to Anifrolumab-fnia, an additional study with a larger sample size of senior patients is required.
