Anifrolumab is a type 1 interferon receptor antagonist approved for the treatment of moderate to severe systemic lupus erythematosus (SLE) in adult patients who are receiving standard therapy. Standard SLE therapy includes corticosteroids, antimalarials, NSAIDs, and/or immunosuppressants (e.g., azathioprine, mycophenolate, or methotrexate). The most common adverse effects in clinical trials were upper respiratory tract infections, nasopharyngitis, and infusion-related reactions. Serious and sometimes fatal hypersensitivity reactions and infections have been reported in patients receiving biologic immunosuppressive agents, including anifrolumab. Similar to other immunosuppressive agents, there is a risk of new malignancy with anifrolumab therapy. Coadministration of anifrolumab and other biologic therapies, such as B-cell-targeted therapies, is not recommended.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Anifrolumab is a clear to opalescent, colorless to slightly yellow solution. Do not use the solution if it is cloudy, discolored, or contains particulate matter.
-Do not shake the vial.
Intravenous Administration
Preparation
-From a 50 or 100 mL infusion bag containing 0.9% Sodium Chloride Injection, withdraw and discard 2 mL of solution.
-Withdraw 2 mL of solution from the anifrolumab vial and add it to the infusion bag. Gently invert the bag to mix the solution. Do not shake.
-Discard any unused anifrolumab solution that remains in the vial; vials are single-use only.
-Storage: Once diluted, the infusion may be stored at room temperature of 15 to 25 degrees C (59 to 77 degrees F) for up to 4 hours or under refrigeration at 2 to 8 degrees C (36 to 46 degrees F) for up to 24 hours. Protect from light. Do not freeze.
Intravenous infusion
-If the diluted solution has been stored under refrigeration, allow the solution to reach room temperature prior to administration.
-Only healthcare providers prepared to manage hypersensitivity reactions, including anaphylaxis and infusion-related reaction, should administer anifrolumab.
-Prior to IV administration, consider premedication for prophylaxis against infusion and hypersensitivity reactions in patients with a history of these types of reactions.
-Infuse intravenously over 30 minutes through an infusion line containing a sterile, low-protein binding 0.2 to 15 micron in-line or add-on filter.
-Following completion of the infusion, flush the entire infusion line with 25 mL of 0.9% Sodium Chloride Injection to ensure the complete dose has been administered.
-Do not coadminister with other agents through the same IV line.
Patients receiving immunosuppressive agents, such as anifrolumab, may develop an infection, which can be serious and fatal. The overall incidence of infection in the 52-week clinical trials was 69.7% with anifrolumab and 55.4% with placebo, which corresponds to exposure-adjusted incidence rates (EAIR) of 141.8 and 99.9 per 100 patient years, respectively. The incidence of serious infections was 4.8% with anifrolumab and 5.6% with placebo; the EAIR was 5.4 and 6.6 per 100 patient years, respectively. The most common serious infection reported during the 52-week study period was pneumonia; however, during the long-term extension study (an additional 3 years of treatment), the most common serious infections were COVID-19 and pneumonia. Fatal infections occurred in 0.4% of anifrolumab patients compared to 0.2% of placebo patients. Herpes zoster infection occurred in 6.1% of anifrolumab patients and 1.3% of placebo patients, which corresponded to an EAIR of 6.9 and 1.5 per 100 patient years, respectively. There have been reports of herpes zoster infection with multidermatomal involvement and disseminated presentation. Two of the 28 anifrolumab patients who developed herpes zoster experienced disseminated disease and required hospitalization; no placebo patients experienced disseminated disease. Other infections reported in clinical trials were upper respiratory tract infection (34% anifrolumab vs. 23% placebo, including nasopharyngitis and pharyngitis), bronchitis (11% vs. 5.2%, including, viral bronchitis and tracheobronchitis), and respiratory tract infection (2.8% vs. 0.6%, including bacterial and viral respiratory tract infections). Cough was reported in 5% of anifrolumab patients and 3.2% of placebo patients.
Infusion-related reactions were one of the most frequently reported adverse reactions in anifrolumab clinical trials. Mild to moderate infusion-related reactions were reported in 9.4% of anifrolumab patients and 7.1% of placebo patients, corresponding to an exposure-adjusted incidence rates (EAIR) of 3.2 and 0.7 per 100 patient years, respectively. The most common infusion-related reactions were headache, nausea, vomiting, fatigue, and dizziness. In clinical studies, hypersensitivity reactions occurred in 2.8% of anifrolumab patients and 0.6% of placebo patients, corresponding to EAIR of 3.2 and 0.7 per 100 patient years, respectively. Close patient monitoring is recommended, as hypersensitivity reactions may present as infusion reactions. If the patient develops a serious infusion-related reaction or hypersensitivity reaction, immediately discontinue anifrolumab administration and initiate appropriate therapy.
In clinical trials, serious hypersensitivity reactions, including angioedema (n = 2) and anaphylaxis or anaphylactoid reactions, were reported in 0.6% (3/459) of anifrolumab patients. If a serious infusion-related or hypersensitivity reaction, including anaphylaxis, occurs, immediately discontinue anifrolumab administration and initiate appropriate therapy.
The impact of anifrolumab therapy on the development of new primary malignancy is not known, but, similar to other immunosuppressant agents, anifrolumab may increase the risk for the development of malignancies. During clinical studies, malignancies (excluding non-melanoma skin cancer) were reported in 0.7% of anifrolumab patients and 0.6% if placebo patients; exposure-adjusted incidence rates (EAIR) of 0.7 and 0.7 per 100 patient years, respectively. Malignant neoplasm (including non-melanoma skin cancers) was reported in 1.3% and 0.6% of anifrolumab and placebo patients, respectively, which corresponded to an EAIR of 1.3 and 0.7 per 100 patient years, respectively. Malignancies reported in more than 1 patient treated with anifrolumab included breast cancer and squamous cell carcinoma.
As with all therapeutic proteins, there is a potential for antibody formation against anifrolumab. In the clinical trials and long-term extension study, anti-anifrolumab antibodies were detected in 2.6% (n = 9/350) of patients who received the recommended anifrolumab dosing regimen for up to 4 years. The clinical relevance of these anti-anifrolumab antibodies is not known. The detection of antibodies is dependent on the sensitivity and specificity of the assay, and the incidence of positive antibodies may be influenced by assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. Therefore, the incidence of antibody formation to anifrolumab cannot be directly compared to other products.
Anifrolumab use carries a risk of serious hypersensitivity reactions, including anaphylaxis, and infusion-related reactions. Anifrlolumab is contraindicated in patients with a history of anaphylaxis with anifrolumab. Administration of anifrolumab requires an experienced clinician prepared to manage hypersensitivity reactions, including anaphylaxis and infusion-related reactions. Consider premedication in patients with a history these reactions. If a serious infusion-related or hypersensitivity reaction develops during anifrolumab administration, immediately interrupt the infusion and initiate appropriate therapy. Angioedema has also been reported with anifrolumab use.
Avoid initiation of anifrolumab therapy in patients with any clinically significant active infection until the infection resolves or is adequately treated. Serious and sometimes fatal infections (including COVID-19) have been reported in patients receiving immunosuppressive therapy, including anifrolumab. Consider risks and benefits of anifrolumab prior to initiating therapy in patients with a chronic infection, a history of recurrent infections, or known risk factors for infection. Anifrolumab therapy was associated with an increased risk of respiratory infections and herpes zoster, including disseminated herpes zoster, during clinical trials. Monitor patients for the development of signs and symptoms of clinically significant infection. Consider interruption of anifrolumab therapy in patients who develop an infection or are not responding to standard anti-infective therapy until the infection resolves.
Immunosuppressive therapy has been associated with an increased risk of new primary malignancy. The impact of anifrolumab treatment on the potential development of malignancies is not known. Consider the risks and benefits of anifrolumab prior to initiating therapy in patients with known risk factors for the development or reoccurrence of malignancy. In patients who develop a malignancy, consider risks and benefits of continued treatment with anifrolumab.
Avoid vaccination with live or live-attenuated vaccines in patients receiving anifrolumab. Update immunizations, according to current immunization guidelines, prior to initiating anifrolumab therapy.
The limited human data with anifrolumab use during human pregnancy are insufficient to determine whether there is a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcome. Monoclonal IgG antibodies are known to be actively transported across the placenta as pregnancy progresses; therefore, fetal anifrolumab exposure may be greater during the third trimester of pregnancy. There are maternal and fetal risks associated with the underlying maternal condition, systemic lupus erythematosus (SLE). In a study of cynomolgus monkeys that received intravenous anifrolumab 30 mg/kg or 60 mg/kg intravenously every 2 weeks from gestation day 20 through 1-month postpartum (approximately lactation day 28), there was no evidence of anifrolumab related maternal toxicity, embryo-fetal toxicity, or postnatal developmental effects. In addition, anifrolumab was not found to have an effect on T-cell-dependent antibody response in infants up to day 180 post birth. The no observed adverse effect level (NOAEL) for maternal and developmental toxicity was identified as anifrolumab 60 mg/kg, which is approximately 28 times the maximum recommended human dose (MRHD) on an AUC basis. Mean anifrolumab serum concentrations in infants were approximately 4.2% to 9.7% of the respective maternal concentrations and were up to 22-times the concentrations in maternal milk, suggesting placental anifrolumab transfer. There is a pregnancy registry that monitors outcomes in women exposed to anifrolumab during pregnancy; information about the registry can be obtained by calling 1-877-693-9268.
No data are available regarding the presence of anifrolumab in human milk, effects on the breastfed child, or the effects on milk production. Maternal IgG is known to be present in human milk. If anifrolumab is transferred into human milk, the effects of local gastrointestinal exposure or systemic exposure in the breast-fed infant are unknown. Anifrolumab was detected in the milk of cynomolgus monkeys; however, due to species-specific differences in lactation physiology, these animal data may not predict drug concentrations in human milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, the risk of potential adverse effects on the breast-fed infant from the underlying maternal condition, and the risk of an untreated or inadequately treated maternal condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.
For the treatment of moderate to severe systemic lupus erythematosus (SLE) in combination with standard therapy:
Intravenous dosage:
Adults: 300 mg IV infused over 30 minutes every 4 weeks. If a dose is missed, administer anifrolumab as soon as possible while maintaining a minimum interval of 14 days between infusions. LIMITATION OF USE: Anifrolumab has not been evaluated and is not recommended in patients with severe active lupus nephritis or severe active central nervous system lupus.
Maximum Dosage Limits:
-Adults
300 mg IV every 4 weeks.
-Geriatric
300 mg IV every 4 weeks.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No specific studies have been conducted to investigate the effect of hepatic impairment on anifrolumab. Elimination of IgG monoclonal antibodies, such as anifrolumab, is primarily via catabolism; thus, anifrolumab is not expected to undergo hepatic metabolism or be effected by hepatic impairment. In population pharmacokinetic analyses, baseline hepatic function biomarkers (ALT and AST 2 times the upper limit of normal and greater, and total bilirubin) had no clinically relevant effect on anifrolumab clearance. It appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
No specific clinical studies have been conducted to investigate the effect of renal impairment on anifrolumab. In population pharmacokinetic analyses, anifrolumab clearance was similar in patients with normal, mild, and moderate renal impairment (90 mL/min/1.73 m2 and greater, 60 to 89 mL/min/1.73 m2, and 30 to 59 mL/min/1.73 m2, respectively); no patients had severe renal impairment or end-stage renal disease (less than 30 mL/min/1.73 m2). Anifrolumab is not renally cleared, so it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Adalimumab: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including tumor necrosis factor modifiers (TNF blockers). Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Alemtuzumab: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including B-cell targeted therapies such as alemtuzumab. Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Bacillus Calmette-Guerin Vaccine, BCG: (Major) Avoid concurrent use of live vaccines during treatment with anifrolumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving anifrolumab. Before initiation of anifrolumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Belimumab: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including belimumab. Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Certolizumab pegol: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including tumor necrosis factor modifiers (TNF blockers). Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Chikungunya Vaccine, Live: (Major) Avoid concurrent use of live vaccines during treatment with anifrolumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving anifrolumab. Before initiation of anifrolumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cyclophosphamide: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including B-cell targeted therapies such as cyclophosphamide. Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Etanercept: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including tumor necrosis factor modifiers (TNF blockers). Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Golimumab: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including tumor necrosis factor modifiers (TNF blockers). Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Ibritumomab Tiuxetan: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including B-cell targeted therapies such as ibritumomab. Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Infliximab: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including tumor necrosis factor modifiers (TNF blockers). Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Intranasal Influenza Vaccine: (Major) Avoid concurrent use of live vaccines during treatment with anifrolumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving anifrolumab. Before initiation of anifrolumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Live Vaccines: (Major) Avoid concurrent use of live vaccines during treatment with anifrolumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving anifrolumab. Before initiation of anifrolumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Avoid concurrent use of live vaccines during treatment with anifrolumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving anifrolumab. Before initiation of anifrolumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Measles/Mumps/Rubella Vaccines, MMR: (Major) Avoid concurrent use of live vaccines during treatment with anifrolumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving anifrolumab. Before initiation of anifrolumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Obinutuzumab: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including B-cell targeted therapies such as obinutuzumab. Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Ocrelizumab: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including B-cell targeted therapies such as ocrelizumab. Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Ofatumumab: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including B-cell targeted therapies such as ofatumumab. Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Rituximab: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including B-cell targeted therapies such as rituximab. Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Rituximab; Hyaluronidase: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including B-cell targeted therapies such as rituximab. Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Rotavirus Vaccine: (Major) Avoid concurrent use of live vaccines during treatment with anifrolumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving anifrolumab. Before initiation of anifrolumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Major) Avoid concurrent use of live vaccines during treatment with anifrolumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving anifrolumab. Before initiation of anifrolumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Smallpox Vaccine, Vaccinia Vaccine: (Major) Avoid concurrent use of live vaccines during treatment with anifrolumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving anifrolumab. Before initiation of anifrolumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Tumor Necrosis Factor modifiers: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including tumor necrosis factor modifiers (TNF blockers). Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Typhoid Vaccine: (Major) Avoid concurrent use of live vaccines during treatment with anifrolumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving anifrolumab. Before initiation of anifrolumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Varicella-Zoster Virus Vaccine, Live: (Major) Avoid concurrent use of live vaccines during treatment with anifrolumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving anifrolumab. Before initiation of anifrolumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Yellow Fever Vaccine, Live: (Major) Avoid concurrent use of live vaccines during treatment with anifrolumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving anifrolumab. Before initiation of anifrolumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Anifrolumab is a human IgG1 kappa monoclonal antibody that inhibits type I interferon (IFN) signaling by binding, with high specificity and affinity, to subunit 1 of the type I interferon receptor (IFNAR). Type I IFNs are involved in the pathogenesis of systemic lupus erythematosus (SLE) and elevated levels are associated with SLE disease flares. Approximately 60% to 80% of adult patients with active SLE express elevated levels of type I IFN inducible genes. This inhibition of type I IFN blocks the biologic activity of type I IFN, which may result in SLE symptom improvement by reversing immune dysregulation and reducing further tissue damage. Anifrolumab also induces the internalization of IFNAR1, thereby reducing the levels of cell surface IFNAR1 available for receptor assembly. Inhibition of receptor-mediated type I IFN signaling blocks IFN responsive gene expression along with downstream inflammatory and immunological processes. Blockade of plasma differentiation and normalization of peripheral T-cell subsets also occurs with type I IFN inhibition.
Anifrolumab is administered by intravenous infusion. Based on the more than dose-proportional increases in anifrolumab exposure, as measured by the AUC, over a dose range of 100 mg to 1,000 mg IV once every 4 weeks to systemic lupus erythematosus (SLE) patients, anifrolumab was determined to have non-linear pharmacokinetics. Following administration of anifrolumab 300 mg IV every 4 weeks, the time to steady-state was 85 days and the steady-state Vd is 6.23 L (based on an average SLE patient with a weight of 69.1 kg). Anifrolumab undergoes type I interferon receptor (IFNAR1) mediated drug clearance. Following administration of anifrolumab 300 mg IV every 4 weeks for 52 weeks in patients with SLE, neutralization (80% or greater) of a type I interferon (IFN) gene signature was observed from week 4 to week 52 in the blood samples of patients with elevated levels of type I IFN inducible genes and levels returned to baseline 8 to 12 weeks after anifrolumab discontinuation; clinical relevance of type I IFN gene signature neutralization is not clear. A numerical reduction in anti-dsDNA antibodies was observed over time through week 52 in patients with positive anti-dsDNA antibodies at baseline. In patients with low complement levels, increases in complement levels were observed through week 52 with anifrolumab therapy.
Affected P-gp and Cytochrome P450 isoenzymes: none
-Route-Specific Pharmacokinetics
Intravenous Route
Following anifrolumab 300 mg IV once every 4 weeks, the accumulation ratio was approximately 1.36 for Cmax and 2.49 for Ctrough. The estimated systemic clearance for anifrolumab was 0.193 L/day. Based on population pharmacokinetic analysis of patients who received treatment for 1 year, serum concentrations of anifrolumab were below the limits of detection at approximately 16 weeks after the last dose in 95% of drug recipients.
-Special Populations
Hepatic Impairment
Clinical studies have not been conducted to evaluate the impact of hepatic impairment on anifrolumab; however, IgG1 monoclonal antibodies are primarily eliminated via catabolism and not expected to undergo hepatic metabolism. Thus, changes in hepatic function are not expected to have an impact on anifrolumab clearance. In population pharmacokinetic analyses, baseline hepatic function biomarkers (ALT and AST 2-times the ULN or less, and total bilirubin) had no clinically relevant effect on anifrolumab clearance.
Renal Impairment
Clinical studies have not been conducted to evaluate the impact of renal impairment on anifrolumab; however, it does not undergo renal elimination. Based on pharmacokinetic population analyses, anifrolumab clearance was comparable in systemic lupus erythematosus (SLE) patients with normal, mild, and moderate renal impairment (90 mL/min/1.73 m2 and greater, 60 to 89 mL/min/1.73 m2, and 30 to 59 mL/min/1.73 m2, respectively). There were no SLE patients with severe eGFR reductions or end stage renal disease (less than 30 mL/min/1.73 m2) included in the analyses. Patients with a urine protein/creatinine ration (UPCR) greater than 2 mg/mg were excluded from clinical trials; however, based on population pharmacokinetic analyses, increased UPCR did not have a significant effect on anifrolumab clearance.
Geriatric
Based on pharmacokinetic analysis, age (range: 18 to 69 years) did not affect anifrolumab clearance. Only 3% (n = 20) of the patients enrolled in the pharmacokinetic analyses were aged 65 and older; thus, pharmacokinetic data is limited in this patient population.
Gender Differences
No clinically meaningful differences in systemic clearance of anifrolumab based on gender have been identified.
Ethnic Differences
No clinically meaningful differences in systemic clearance of anifrolumab based on race or ethnicity have been identified.
Obesity
No clinically meaningful differences in systemic clearance of anifrolumab based on body weight have been identified.