Inebilizumab is an intravenous CD19-directed cytolytic humanized afucosylated IgG1 monoclonal antibody indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody-positive. In a randomized, double-blind, placebo-controlled trial of patients with NMOSD who were anti-AQP4 antibody-positive (n = 213) or anti-AQP4 antibody-negative (n = 17), the time to first adjudicated relapse was significantly longer in patients treated with inebilizumab compared to placebo (relative risk reduction 73%; HR 0.272; p less than 0.0001). In the anti-AQP4 antibody-positive population, there was a 77.3% relative reduction (HR 0.227; p less than 0.0001). There was no evidence of a benefit in patients who were anti-AQP4 antibody-negative. Compared to patients given placebo, inebilizumab-treated patients who were anti-AQP4 antibody-positive had reduced annualized rates of hospitalizations (0.11) vs. placebo (0.5). Infusion-related reactions have been reported with inebilizumab. These reactions are most common with the first infusion but may also occur during subsequent infusions. Administration of inebilizumab requires an experienced clinician with access to appropriate medical support to manage potential severe reactions, such as serious infusion reactions. To reduce the risk of an infusion reaction, premedication with a corticosteroid, an antihistamine, and an antipyretic is 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.
Intravenous Administration
-Before every inebilizumab infusion, determine whether there is an active infection. In case of an active infection, delay inebilizumab administration until the infection resolves.
-Administration of inebilizumab requires an experienced clinician with access to appropriate medical support to manage potential severe reactions, such as serious infusion reactions.
-To reduce the risk of an infusion reaction, administer premedication with a corticosteroid (methylprednisolone 80 to 125 mg IV or equivalent) 30 minutes before the inebilizumab infusion and an antihistamine (diphenhydramine 25 to 50 mg PO or equivalent) and an antipyretic (acetaminophen 500 to 650 mg PO or equivalent) 30 to 60 minutes before the inebilizumab infusion.
-Monitor patients closely for at least 1 hour after the completion of the infusion.
Dilution
-Do not shake inebilizumab vials.
-Withdraw 10 mL from each of the 3 inebilizumab vials contained in the carton.
-Transfer a total of 30 mL into a 250 mL IV bag of 0.9% Sodium Chloride Injection. Do not use other diluents.
-Gently invert the infusion bag to mix the diluted solution. Do not shake the solution.
-Administer the prepared solution immediately.
-Storage: Discard any unused portion remaining in the vials. If not administered immediately, store the infusion solution for a maximum of 24 hours under refrigeration at 2 to 8 degrees C (36 to 46 degrees F) or 4 hours at room temperature of 20 to 25 degrees C (68 to 77 degrees F). Do not freeze.
Intermittent IV Infusion
-Ensure the prepared infusion solution is at room temperature before the start of the IV infusion.
-Administer through an IV line containing a sterile, low-protein binding 0.2 or 0.22-micron in-line filter.
-Administer the dose IV via an infusion pump at an increasing rate to completion over approximately 90 minutes. Infuse at 42 mL/hour for the first 30 minutes, 125 mL/hour for the next 30 minutes, and then 333 mL/hour until completion.
An increased risk of infections has been observed with other B-cell-depleting therapies. During a randomized, placebo-controlled clinical trial, urinary tract infection (cystitis) was reported in 11% of inebilizumab-treated patients (n = 161) compared to 10% of patients given placebo (n = 52). Across both the randomized and open-label treatment, urinary tract infection (20%), naso-pharyngitis (13%), upper respiratory tract infection (8%), and influenza (7%) were among the most common infections reported in inebilizumab-treated patients. Delay inebilizumab administration in patients with an active infection until the infection is resolved. There have been no cases of hepatitis B virus (HBV) reactivation in patients treated with inebilizumab, but patients with chronic HBV infection were excluded from clinical trials. Risk of HBV reactivation has been observed with other B-cell-depleting antibodies. Also, progressive multifocal leukoencephalopathy (PML) is an opportunistic viral infection of the brain caused by the JC virus that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. Although no confirmed cases of PML were identified in inebilizumab clinical trials, JC virus infection resulting in PML has been observed in patients treated with other B-cell-depleting antibodies and other therapies that affect immune competence. In inebilizumab clinical trials, 1 subject died after the development of new brain lesions for which a definitive diagnosis could not be established, though the differential diagnosis included an atypical neuromyelitis optica spectrum disorder (NMOSD) relapse, PML, or acute disseminated encephalomyelitis. At the first sign or symptom suggestive of PML, withhold inebilizumab and perform an appropriate diagnostic evaluation. MRI findings may be apparent before clinical signs or symptoms. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on 1 side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.
Neutrophil counts between 1 to 1.5 x 109/L were observed in 6.9% of inebilizumab-treated patients compared to 1.9% of patients given placebo. Neutrophil counts between 0.5 to 1 x 109/L were observed in 1.9% of inebilizumab-treated patients compared to no patients given placebo. At the end of the 6.5-month randomized, placebo-controlled trial period, 12% of inebilizumab-treated patients (n = 161) had a neutrophil count below the limit of normal (neutropenia) compared to 4.2% of patients given placebo (n = 52), and 5.3% of inebilizumab-treated patients had a lymphocyte count below the limit of normal (lymphopenia) compared to 4.2% of patients given placebo. There may be a progressive and prolonged hypogammaglobulinemia or decline in the concentrations of total and individual immunoglobulins such as immunoglobulins G and M (IgG and IgM) with continued inebilizumab treatment. At the end of the 6.5 month randomized, placebo-controlled trial period, the total immunoglobulin concentration was reduced by approximately 8% from baseline for inebilizumab-treated patients compared to an increase of 6% in patients given placebo. The mean decreases from baseline in immunoglobulin G (IgG) and immunoglobulin M (IgM) were approximately 4% and 32%, respectively, in inebilizumab-treated patients, whereas IgG was increased by 6% and IgM was increased by approximately 13% in patients given placebo. The proportion of patients treated with inebilizumab who had IgG concentrations below the lower limit of normal at year 1 was 6.6% and at year 2 was 13%. The proportion of patients treated with inebilizumab who had IgM concentrations below the lower limit of normal at year 1 was 31% and at year 2 was 42%. Monitor the concentrations of quantitative serum immunoglobulins during treatment with inebilizumab, especially in patients with opportunistic or recurrent infections, and until B-cell repletion after discontinuation of therapy. Consider discontinuing inebilizumab therapy if a patient with low immunoglobulin G or M develops a serious opportunistic infection or recurrent infections, or if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins.
As with all therapeutic proteins, there is the potential for immunogenicity and antibody formation. During a randomized, placebo-controlled trial, treatment-emergent antibodies (those that appeared or significantly increased from baseline after administration of inebilizumab), were detected in 5.6% of inebilizumab-treated patients. Although these data do not demonstrate an impact of anti-inebilizumab antibody development on the efficacy or safety of inebilizumab in these patients, the available data are too limited to make definitive conclusions.
During a randomized, placebo-controlled trial, back pain was reported in 7% of inebilizumab-treated patients (n = 161) compared to 4% of patients given placebo (n = 52); arthralgia occurred in 10% of inebilizumab-treated patients compared to 4% of patients given placebo. Across both the randomized and open-label treatment, arthralgia was reported in 11% of patients.
During a randomized, placebo-controlled trial, headache was reported in 8% of inebilizumab-treated patients (n = 161) and patients given placebo (n = 52). Across both the randomized and open-label treatment, headache was reported in 10% of patients.
During a randomized, placebo-controlled clinical trial, infusion-related reactions, which can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash, or other signs or symptoms, were observed with the first course of inebilizumab (n = 161) in 9.3% of patients. Across both the randomized and open-label treatment, infusion reaction was reported in 12% of patients. Infusion reactions were most common with the first infusion but were also observed during subsequent infusions. To reduce the risk of an infusion reaction, administer premedication with a corticosteroid, an antihistamine, and an antipyretic. Monitor patients closely for at least 1 hour after the completion of the infusion. For life-threatening reactions, immediately and permanently stop inebilizumab and administer appropriate supportive treatment. For less severe reactions, management may include temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment.
Inebilizumab is contraindicated in patients with active hepatitis B virus (HBV) infection, confirmed by positive results for surface antigen [HBsAg] and anti-HBV tests, or active or untreated latent tuberculosis. Perform HBV screening in all patients before initiation of inebilizumab treatment. Do not administer inebilizumab to patients with active hepatitis. Consult liver disease experts before starting and during treatment with inebilizumab for patients who are negative for HBsAg and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+]. There have been no cases of HBV reactivation in patients treated with inebilizumab, but patients with chronic HBV infection were excluded from clinical trials. Risk of HBV reactivation has been observed with other B-cell-depleting antibodies. Evaluate for active tuberculosis and test for latent infection before initiating treatment with inebilizumab. Consider anti-tuberculosis therapy before treatment initiation in patients with a history of latent active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but with risk factors for tuberculosis infection. Consult infectious disease experts before initiating treatment with inebilizumab for patients with active tuberculosis or positive tuberculosis screening without a history of appropriate treatment. Also, perform testing for quantitative serum immunoglobulins before starting inebilizumab treatment. For patients with hypogammaglobulinemia, consult immunology experts before starting treatment with inebilizumab. Monitor the concentrations of quantitative serum immunoglobulins during treatment with inebilizumab, especially in patients with opportunistic or recurrent infections, and until B-cell repletion after discontinuation of therapy. Delay inebilizumab administration in patients with an active infection until the infection has resolved. Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroid therapy, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Administer all immunizations according to immunization guidelines at least 4 weeks before initiation of inebilizumab. Vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion. In a neonate or infant with in utero exposure to inebilizumab, do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts in the infant. Depletion of B-cells in the exposed infant may increase the risks from live or live-attenuated vaccines. Non-live vaccines, as indicated, may be administered before recovery from B-cell and immunoglobulin concentration depletion; however, consider consultation with a qualified specialist to assess whether a protective immune response was mounted.
Inebilizumab is contraindicated for use in patients with a history of life-threatening infusion-related reactions to inebilizumab. Infusion-related reactions are most common with the first infusion but may also occur during subsequent infusions. Administration of inebilizumab requires an experienced clinician with access to appropriate medical support to manage potential severe reactions, such as serious infusion reactions. To reduce the risk of an infusion reaction, administer premedication with a corticosteroid, an antihistamine, and an antipyretic. Monitor patients closely for at least 1 hour after the completion of the infusion. For life-threatening reactions, immediately and permanently stop inebilizumab and administer appropriate supportive treatment. For less severe reactions, management may include temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment.
There are no adequate data on the developmental risk associated with the use of inebilizumab during human pregnancy. Inebilizumab is a humanized IgG1 monoclonal antibody, and immunoglobulins are known to cross the placental barrier. Based on animal data, inebilizumab can cause fetal harm due to B-cell lymphopenia and reduce antibody response in offspring exposed to inebilizumab even after B-cell repletion. Transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other B-cell depleting antibodies during pregnancy. B-cell concentrations in infants after maternal exposure to inebilizumab have not been studied in clinical trials, and the potential duration of B-cell depletion in such infants, and the impact of B-cell depletion on vaccine safety and effectiveness, is unknown. In animal studies, administration of inebilizumab to mice throughout organogenesis and lactation resulted in depletion of B cells and persistent reductions in immune function (even after repletion of B cells and lasting into adulthood) in offspring.
There are no data on the presence of inebilizumab in human milk, the effects on a breast-fed infant, or the effects on milk production. Inebilizumab is a humanized IgG1 monoclonal antibody, and human IgG is excreted in human milk. The potential for absorption of inebilizumab to lead to B-cell depletion in the breast-fed infant is unknown. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for inebilizumab and any potential adverse effects on the breast-fed infant from inebilizumab or from the underlying maternal condition.
Inebilizumab is associated with reproductive risk. Discuss contraception requirements with the patient. Advise females of reproductive potential to use effective contraception while receiving inebilizumab and for 6 months after the last infusion of inebilizumab. Instruct patients that if they are pregnant or plan to become pregnant while taking inebilizumab to inform their health care provider.
General dosing information:
-Perform hepatitis B virus (HBV) infection screening in all patients before inebilizumab initiation. Inebilizumab is contraindicated in patients with active HBV infection, confirmed by positive results for surface antigen [HBsAg] and anti-HBV tests. Consult liver disease experts before starting and during treatment with inebilizumab for patients who are negative for HBsAg and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+].
-Evaluate for active tuberculosis and test for latent infection before initiating treatment with inebilizumab. Consult infectious disease experts before initiating treatment with inebilizumab for patients with active tuberculosis or positive tuberculosis screening without a history of appropriate treatment.
-Perform testing for quantitative serum immunoglobulins before starting inebilizumab treatment. Consult immunology experts before starting treatment with inebilizumab for patients with low serum immunoglobulins.
-Delay inebilizumab administration in patients with an active infection until the infection has resolved.
For the treatment of anti-aquaporin-4 (AQP4) antibody positive neuromyelitis optica spectrum disorder (NMOSD):
Intravenous dosage:
Adults: 300 mg IV every 2 weeks for 2 doses, then 300 mg IV every 6 months starting 6 months from the first infusion.
Maximum Dosage Limits:
-Adults
300 mg/dose IV.
-Geriatric
300 mg/dose IV.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Albuterol; Budesonide: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Azelastine; Fluticasone: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Bacillus Calmette-Guerin Vaccine, BCG: (Major) Administer all immunizations according to immunization guidelines at least 4 weeks before initiation of inebilizumab. Vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion. In a neonate or infant with in utero exposure to inebilizumab, do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts in the infant. Depletion of B-cells in the exposed infant may increase the risks from live or live-attenuated vaccines.
Beclomethasone: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Betamethasone: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Budesonide: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Budesonide; Formoterol: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Chikungunya Vaccine, Live: (Major) Administer all immunizations according to immunization guidelines at least 4 weeks before initiation of inebilizumab. Vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion. In a neonate or infant with in utero exposure to inebilizumab, do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts in the infant. Depletion of B-cells in the exposed infant may increase the risks from live or live-attenuated vaccines.
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.
Ciclesonide: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Corticosteroids: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Cortisone: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Deflazacort: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
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.
Dexamethasone: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Fludrocortisone: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Flunisolide: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Fluticasone: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Fluticasone; Salmeterol: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Fluticasone; Vilanterol: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Formoterol; Mometasone: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Hydrocortisone: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Intranasal Influenza Vaccine: (Major) Administer all immunizations according to immunization guidelines at least 4 weeks before initiation of inebilizumab. Vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion. In a neonate or infant with in utero exposure to inebilizumab, do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts in the infant. Depletion of B-cells in the exposed infant may increase the risks from live or live-attenuated vaccines.
Live Vaccines: (Major) Administer all immunizations according to immunization guidelines at least 4 weeks before initiation of inebilizumab. Vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion. In a neonate or infant with in utero exposure to inebilizumab, do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts in the infant. Depletion of B-cells in the exposed infant may increase the risks from live or live-attenuated vaccines.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Administer all immunizations according to immunization guidelines at least 4 weeks before initiation of inebilizumab. Vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion. In a neonate or infant with in utero exposure to inebilizumab, do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts in the infant. Depletion of B-cells in the exposed infant may increase the risks from live or live-attenuated vaccines.
Measles/Mumps/Rubella Vaccines, MMR: (Major) Administer all immunizations according to immunization guidelines at least 4 weeks before initiation of inebilizumab. Vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion. In a neonate or infant with in utero exposure to inebilizumab, do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts in the infant. Depletion of B-cells in the exposed infant may increase the risks from live or live-attenuated vaccines.
Methylprednisolone: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Mometasone: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Olopatadine; Mometasone: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Prednisolone: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Prednisone: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Rotavirus Vaccine: (Major) Administer all immunizations according to immunization guidelines at least 4 weeks before initiation of inebilizumab. Vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion. In a neonate or infant with in utero exposure to inebilizumab, do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts in the infant. Depletion of B-cells in the exposed infant may increase the risks from live or live-attenuated vaccines.
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) Administer all immunizations according to immunization guidelines at least 4 weeks before initiation of inebilizumab. Vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion. In a neonate or infant with in utero exposure to inebilizumab, do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts in the infant. Depletion of B-cells in the exposed infant may increase the risks from live or live-attenuated vaccines.
Smallpox Vaccine, Vaccinia Vaccine: (Major) Administer all immunizations according to immunization guidelines at least 4 weeks before initiation of inebilizumab. Vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion. In a neonate or infant with in utero exposure to inebilizumab, do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts in the infant. Depletion of B-cells in the exposed infant may increase the risks from live or live-attenuated vaccines.
Triamcinolone: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Typhoid Vaccine: (Major) Administer all immunizations according to immunization guidelines at least 4 weeks before initiation of inebilizumab. Vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion. In a neonate or infant with in utero exposure to inebilizumab, do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts in the infant. Depletion of B-cells in the exposed infant may increase the risks from live or live-attenuated vaccines.
Varicella-Zoster Virus Vaccine, Live: (Major) Administer all immunizations according to immunization guidelines at least 4 weeks before initiation of inebilizumab. Vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion. In a neonate or infant with in utero exposure to inebilizumab, do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts in the infant. Depletion of B-cells in the exposed infant may increase the risks from live or live-attenuated vaccines.
Yellow Fever Vaccine, Live: (Major) Administer all immunizations according to immunization guidelines at least 4 weeks before initiation of inebilizumab. Vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion. In a neonate or infant with in utero exposure to inebilizumab, do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts in the infant. Depletion of B-cells in the exposed infant may increase the risks from live or live-attenuated vaccines.
Inebilizumab is a CD19-directed humanized afucosylated IgG1 monoclonal antibody. The exact mechanism of action by which inebilizumab exerts its therapeutic effects in neuromyelitis optica spectrum disorder (NMOSD) is not known but is presumed to involve binding to CD19, a cell surface antigen on pre-B and mature B lymphocytes. After cell surface binding to B lymphocytes, inebilizumab results in antibody-dependent cellular cytolysis and B cell depletion.
Inebilizumab is administered via intravenous infusion. Pharmacokinetics are biphasic after intravenous administration. The estimated typical central and peripheral Vd of inebilizumab was 2.95 L and 2.57 L, respectively. Inebilizumab is degraded by proteolytic enzymes distributed throughout the body. The estimated systemic clearance of the first-order elimination pathway is 0.19 L/day. The mean terminal half-life of inebilizumab is 18 days. At low concentrations, inebilizumab is likely subject to CD19-mediated clearance, which decreases with time because of B-cell depletion. Inebilizumab reduces CD20+ B-cell counts in blood by 8 days after infusion. In a randomized, placebo-controlled clinical trial, CD20+ B-cell counts were reduced below the lower limit of normal by 4 weeks in 100% of patients treated with inebilizumab and remained below the lower limit of normal in 94% of patients for 28 weeks after initiation of treatment.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Intravenous Route
The mean maximum concentration of inebilizumab was 108 mcg/mL after the second 300 mg dose on day 15 of treatment. The cumulative AUC of the 26-week treatment period in which neuromyelitis optica spectrum disorder (NMOSD) patients received 2 intravenous administrations 2 weeks apart was 2,980 mcg x day/mL.
-Special Populations
Hepatic Impairment
The effect of hepatic impairment on inebilizumab pharmacokinetics has not been evaluated.
Renal Impairment
The effect of renal impairment on inebilizumab pharmacokinetics has not been evaluated.
Geriatric
There was no significant effect of age on inebilizumab clearance.
Gender Differences
There was no significant effect of gender on inebilizumab clearance.
Ethnic Differences
There was no significant effect of race on inebilizumab clearance.