Uplizna: Uses, Dosage & Side Effects

What Is Uplizna and What Is It Used For?

Uplizna contains the active substance inebilizumab, a humanized, affinity-optimized, afucosylated immunoglobulin G1 kappa (IgG1κ) monoclonal antibody. As a monoclonal antibody, inebilizumab is a highly specialized protein engineered to recognize and bind to a specific molecular target on cells. The target for inebilizumab is CD19, a cell surface antigen that is broadly expressed across the B-cell lineage, from early pre-B cells through mature B cells and into antibody-secreting plasmablasts. This broad targeting distinguishes Uplizna from therapies that target CD20, which is expressed on a narrower range of B-cell developmental stages and notably absent from plasmablasts.

The afucosylation of the inebilizumab antibody is a deliberate engineering choice that enhances its ability to engage Fcγ receptors on natural killer (NK) cells and macrophages. This results in significantly enhanced antibody-dependent cellular cytolysis (ADCC) and antibody-dependent cellular phagocytosis (ADCP) compared with conventional fucosylated antibodies. The net effect is more efficient and thorough depletion of CD19-expressing B cells from the circulation and tissues, which translates into a more profound reduction in the production of pathogenic autoantibodies.

Neuromyelitis Optica Spectrum Disorder (NMOSD)

NMOSD is a rare, severe autoimmune disorder that primarily affects the optic nerves and spinal cord, although it can also involve the brain and brainstem. In approximately 70–80% of patients, NMOSD is driven by autoantibodies directed against aquaporin-4 (AQP4), a water channel protein expressed on astrocytes in the central nervous system. These anti-AQP4 antibodies, produced by B cells and plasmablasts, trigger complement activation and inflammatory cascades that lead to astrocyte destruction, demyelination, and neuronal damage. The clinical manifestations of NMOSD include optic neuritis (causing vision loss or blindness), transverse myelitis (causing weakness, paralysis, and sensory disturbances), and area postrema syndrome (causing intractable nausea, vomiting, and hiccups).

NMOSD follows a relapsing course in most patients, and each relapse can cause permanent, cumulative neurological damage. Without effective treatment, patients may experience severe disability, including blindness and paralysis. The disease disproportionately affects women (approximately 9:1 female-to-male ratio) and is more common in individuals of African, Asian, and Hispanic descent. The annual incidence is estimated at 0.5–4 per million people worldwide, with a prevalence of approximately 1–10 per 100,000 depending on the population studied.

Uplizna was evaluated in the pivotal N-MOmentum trial (also known as Study 1), a randomized, double-blind, placebo-controlled study that enrolled 231 adults with NMOSD. In this trial, 213 of the 231 participants (92%) were AQP4-antibody positive. Uplizna demonstrated a statistically significant reduction in the risk of NMOSD attacks (relapses): only 12% of patients in the Uplizna group experienced an attack compared with 39% of patients receiving placebo during the randomized controlled period, representing a 77% reduction in the risk of relapse (hazard ratio 0.227, p < 0.0001). In the AQP4-antibody-positive subgroup, the risk reduction was even more pronounced, with a 77% relative risk reduction. Open-label extension data have demonstrated sustained efficacy over 4 years of continuous treatment.

IgG4-Related Disease (IgG4-RD)

IgG4-related disease is a chronic, immune-mediated fibroinflammatory condition that can affect virtually any organ system. Commonly involved organs include the pancreas (autoimmune pancreatitis), salivary glands (sialadenitis), lacrimal glands (dacryoadenitis), bile ducts (sclerosing cholangitis), kidneys (tubulointerstitial nephritis), retroperitoneum (retroperitoneal fibrosis), and aorta (aortitis). The hallmark pathological features of IgG4-RD include dense lymphoplasmacytic infiltration rich in IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. Many patients have elevated serum IgG4 levels, although this is not universally present.

B cells play a central role in the pathogenesis of IgG4-RD. They drive the disease through antigen presentation, cytokine production, and differentiation into IgG4-secreting plasmablasts. The accumulation of these cells in affected tissues contributes directly to organ inflammation, fibrosis, and functional impairment. Left untreated, IgG4-RD can lead to irreversible organ damage including pancreatic insufficiency, renal failure, and biliary obstruction.

Uplizna was evaluated for IgG4-RD in a randomized, double-blind, placebo-controlled trial that demonstrated significant reductions in disease flares compared with placebo. The B-cell depleting mechanism of inebilizumab effectively reduces the burden of IgG4-producing plasmablasts, leading to decreased tissue inflammation and prevention of new organ involvement.

What Should You Know Before Taking Uplizna?

Contraindications

You must not receive Uplizna if any of the following apply to you:

• Allergy to inebilizumab or any excipient: If you are allergic to inebilizumab or any of the other ingredients in Uplizna (histidine, histidine hydrochloride monohydrate, polysorbate 80, sodium chloride, trehalose dihydrate, or water for injections), you must not receive this medication.
• Active severe infection: Including active hepatitis B virus (HBV) infection. You must be screened for hepatitis B before starting treatment. If you have active hepatitis B, Uplizna must not be administered until the infection is adequately treated.
• Active or untreated latent tuberculosis (TB): You should be screened for tuberculosis before starting Uplizna. If latent TB is detected, it must be treated before initiating Uplizna therapy.
• History of progressive multifocal leukoencephalopathy (PML): PML is a rare but serious brain infection caused by the John Cunningham (JC) virus. If you have ever been diagnosed with PML, you must not receive Uplizna.
• Severe immunodeficiency: If you have been told that you have severe problems with your immune system, Uplizna is contraindicated as it would further suppress immune function.
• Active cancer: If you currently have cancer, Uplizna must not be used.

Warnings and Precautions

Before starting Uplizna, discuss the following with your healthcare provider:

• Current or recent infections: If you have or think you have an infection, inform your doctor. Active infections should be resolved before starting Uplizna treatment.
• Previous immunosuppressive therapy: If you have ever taken, are currently taking, or plan to take medications that affect the immune system (such as rituximab, azathioprine, mycophenolate, or corticosteroids), tell your doctor. These medications, combined with Uplizna, may increase the risk of infections.
• Hepatitis B or C: If you have ever had hepatitis B, are a carrier of the hepatitis B virus, or have ever had hepatitis C, your doctor will need to assess your risk before starting treatment. Hepatitis B screening is mandatory before initiating Uplizna.
• Vaccinations: You should receive all necessary vaccinations at least 4 weeks before starting Uplizna treatment. Live or live-attenuated vaccines should not be given during treatment or while B cells are depleted. Inactivated vaccines may be given during treatment, but their effectiveness may be reduced.

Infusion-Related Reactions

Uplizna can cause infusion-related reactions (IRRs), which may occur during or within 24 hours after the infusion. Symptoms can include headache, nausea, drowsiness, shortness of breath, fever, muscle pain, rash, and palpitations. To reduce the risk of IRRs, you will receive premedication consisting of a corticosteroid (such as methylprednisolone 100 mg IV), an antihistamine (such as diphenhydramine), and an antipyretic (such as paracetamol/acetaminophen) approximately 30 to 60 minutes before each infusion. A healthcare professional will monitor you during the infusion and for at least one hour afterwards.

If an infusion-related reaction occurs, the infusion may be slowed, temporarily stopped, or permanently discontinued depending on the severity of the reaction. In clinical trials, IRRs were reported in approximately 12% of patients treated with Uplizna, compared with 3% with placebo. Most reactions were mild to moderate and manageable with standard symptomatic treatment.

Children and Adolescents

Uplizna is not approved for use in children and adolescents under 18 years of age. The safety and efficacy of inebilizumab have not been studied in pediatric patients. NMOSD and IgG4-RD in the pediatric population may require different treatment approaches, and healthcare providers should consider age-appropriate alternatives.

Pregnancy and Breastfeeding

Uplizna should not be used during pregnancy. As a monoclonal antibody (IgG1), inebilizumab is expected to cross the placental barrier, particularly during the second and third trimesters, and may affect the developing immune system of the fetus. If you can become pregnant, you should use effective contraception while receiving Uplizna and for at least 6 months after your last infusion. If your doctor recommends stopping treatment, continue contraception for this 6-month period.

It is not known whether inebilizumab is excreted in human breast milk. Human immunoglobulin G (IgG) antibodies are known to be present in breast milk. If you are breastfeeding, you should discuss with your healthcare provider whether the benefits of breastfeeding outweigh the potential risks before starting Uplizna treatment.

Driving and Operating Machinery

Uplizna is not expected to affect your ability to drive or operate machinery. However, drowsiness has been reported as an infusion-related reaction. If you experience drowsiness after an infusion, refrain from driving or operating machinery until this resolves.

Sodium Content

Uplizna contains 48 mg of sodium per infusion (three vials), which is equivalent to approximately 2% of the WHO-recommended maximum daily sodium intake for an adult. This should be taken into consideration by patients on a sodium-restricted diet.

How Does Uplizna Interact with Other Drugs?

As a monoclonal antibody, inebilizumab is eliminated through general protein catabolism rather than through cytochrome P450 (CYP) enzyme-mediated metabolism in the liver. This means that pharmacokinetic drug-drug interactions with conventional small-molecule medications are unlikely. However, there are important pharmacodynamic interactions to be aware of, particularly with other immunomodulatory and immunosuppressive therapies.

The most clinically significant interaction concern relates to the co-administration of Uplizna with other immunosuppressive agents. Because Uplizna depletes B cells and suppresses humoral immunity, combining it with other medications that suppress the immune system may lead to additive or synergistic immunosuppression, increasing the risk of serious infections. Careful consideration and monitoring are required when transitioning from or combining with other immunosuppressive therapies.

If you are transitioning to Uplizna from another immunosuppressive therapy, your doctor will assess the appropriate washout period to minimize the risk of cumulative immunosuppression. The duration of the washout depends on the half-life and mechanism of the previous treatment. For example, transitioning from rituximab may require waiting until B-cell counts begin to recover, while transitioning from shorter-acting oral immunosuppressants may require a shorter interval.

Always inform your doctor about all medications, herbal supplements, and over-the-counter products you are currently using or have recently used. While conventional medications are unlikely to interact with Uplizna pharmacokinetically, a complete medication history helps ensure comprehensive monitoring and appropriate clinical management.

What Is the Correct Dosage of Uplizna?

Uplizna is administered exclusively as an intravenous (IV) infusion by a healthcare professional experienced in the management of patients with NMOSD or IgG4-RD. It is not available for self-administration. Each dose requires three vials of Uplizna (each containing 100 mg of inebilizumab in 10 mL), which are diluted in 250 mL of sodium chloride 0.9% infusion solution before administration.

Adults

The infusion is typically administered over approximately 90 minutes for the first two infusions, with a gradual increase in infusion rate if tolerated. Subsequent maintenance infusions may be given over a shorter duration (approximately 60 minutes) if previous infusions were well tolerated. The infusion rate should be reduced or the infusion temporarily interrupted if infusion-related reactions occur.

Premedication Protocol

To reduce the risk and severity of infusion-related reactions, the following premedication should be administered approximately 30 to 60 minutes before each Uplizna infusion:

• Corticosteroid: Methylprednisolone 100 mg IV (or equivalent)
• Antihistamine: Diphenhydramine 50 mg IV or oral (or equivalent H1 antihistamine)
• Antipyretic: Paracetamol (acetaminophen) 500–1000 mg oral

Children and Adolescents

Uplizna is not approved for use in patients under 18 years of age. The safety and efficacy of inebilizumab have not been established in the pediatric population. No dosing recommendations are available for this age group.

Elderly Patients

No dose adjustment is required for elderly patients. Clinical experience in patients aged 65 and over is limited, but no overall differences in safety or efficacy have been observed in the available data. As with any immunosuppressive therapy in elderly patients, careful monitoring for infections is advisable given the natural decline in immune function with age.

Renal and Hepatic Impairment

No dose adjustment is necessary for patients with mild to moderate renal or hepatic impairment. Uplizna has not been specifically studied in patients with severe renal or hepatic impairment. Since monoclonal antibodies are cleared by general protein catabolism rather than by renal or hepatic metabolism, clinically significant effects of organ impairment on inebilizumab clearance are not expected.

Missed Dose

If you miss a scheduled Uplizna infusion, contact your doctor as soon as possible to reschedule. The missed dose should be administered as soon as practicable. Do not wait until the next scheduled dose. After receiving the missed dose, subsequent infusions should be scheduled every 6 months from the date of the most recent infusion. Maintaining the regular infusion schedule is important for sustained B-cell depletion and disease control.

Overdose

There is limited experience with overdose of inebilizumab. In the event of an overdose, the patient should be closely monitored for signs of adverse reactions, particularly infusion-related reactions and infections. There is no specific antidote for inebilizumab. Treatment of overdose is supportive, with monitoring of vital signs and clinical status. Given the mechanism of action (B-cell depletion), monitoring of B-cell counts and immunoglobulin levels should be performed, and prophylactic measures against infection may be warranted.

What Are the Side Effects of Uplizna?

Like all medicines, Uplizna can cause side effects, although not everyone who receives it will experience them. Your doctor will discuss the potential side effects and their management before starting treatment. The safety profile of Uplizna is based on data from the pivotal N-MOmentum clinical trial, its open-label extension study, the IgG4-RD clinical trial, and post-marketing surveillance.

Because Uplizna depletes B cells and can lower immunoglobulin levels, the most clinically significant side effects relate to increased susceptibility to infections. Your healthcare team will monitor your immunoglobulin levels and blood counts regularly during treatment to help manage this risk. If immunoglobulin levels fall below a certain threshold, your doctor may consider supplemental immunoglobulin therapy or adjustments to the treatment schedule.

Infusion-related reactions are among the most immediate side effects and can occur during or within 24 hours after any Uplizna infusion. In the N-MOmentum trial, approximately 12% of patients in the Uplizna group experienced infusion-related reactions, compared with 3% in the placebo group. The most common symptoms included headache, nausea, drowsiness, shortness of breath, fever, muscle pain, rash, and palpitations. Premedication with corticosteroids, antihistamines, and antipyretics significantly reduces the incidence and severity of these reactions.

Infections are the most clinically significant adverse effect associated with Uplizna treatment. The B-cell depletion caused by inebilizumab reduces the body’s ability to produce new antibodies and mount effective immune responses to pathogens. Urinary tract infections and upper respiratory infections were the most frequently reported infections in clinical trials. Serious infections, including pneumonia, cellulitis, and sepsis, have been reported in a smaller proportion of patients. Patients should be educated to recognize early signs of infection and seek prompt medical attention.

Decreased immunoglobulin levels (particularly IgG, IgM, and IgA) are an expected pharmacological consequence of B-cell depletion and are monitored regularly during treatment. While most patients maintain immunoglobulin levels above clinically significant thresholds, some patients may develop hypogammaglobulinemia that requires intervention. If immunoglobulin levels fall significantly, your doctor may recommend immunoglobulin replacement therapy, dose delays, or treatment discontinuation depending on the clinical context.

Late-onset neutropenia (a decrease in a type of white blood cell called neutrophils) has been observed, sometimes occurring 4 weeks or more after the last dose of Uplizna. This is generally reversible and may resolve without specific treatment, but severe neutropenia requires monitoring and may necessitate growth factor support or dose adjustments.

How Should You Store Uplizna?

Proper storage of Uplizna is essential to maintain the quality, safety, and efficacy of the medication. As a biological product (monoclonal antibody), inebilizumab is sensitive to temperature extremes, light exposure, and physical stress, all of which can compromise its structural integrity and therapeutic effectiveness. Because Uplizna is administered as an intravenous infusion in a healthcare setting, storage is typically managed by the hospital pharmacy or clinic rather than by the patient directly.

The following storage guidelines apply:

• Refrigerated storage: Store unopened vials in a refrigerator at 2–8 °C (36–46 °F). This is the primary long-term storage condition.
• Protect from light: Keep the vials in the original carton until ready for use to protect the solution from light exposure, which can degrade the protein.
• Do not freeze: Freezing can damage the molecular structure of the monoclonal antibody and render the medication ineffective. If Uplizna has been accidentally frozen, do not use it.
• Do not shake: Avoid vigorous shaking or agitation, which can cause protein aggregation.
• Keep out of reach of children: Store Uplizna in a secure location that children cannot access.
• Check expiration date: Do not use Uplizna after the expiration date printed on the carton and vial label after “EXP.” The expiration date refers to the last day of that month.
• Inspect before use: Before preparation, visually inspect the solution. Uplizna concentrate should be a clear to slightly opalescent, colorless to slightly yellow solution. Do not use if you notice particulate matter or discoloration.
• After dilution: Once diluted in 0.9% sodium chloride for infusion, the prepared solution should be used within a timeframe specified by local guidelines, typically within 4–8 hours at room temperature or up to 24 hours if refrigerated. The diluted solution should not be frozen.

Dispose of any unused medicinal product or waste material in accordance with local requirements. Empty vials and any remaining solution should not be reused.

What Does Uplizna Contain?

Understanding the composition of your medication is important, particularly if you have known allergies or sensitivities to specific pharmaceutical ingredients. Below is a detailed breakdown of what Uplizna contains.

Active Ingredient

The active substance is inebilizumab, a humanized, affinity-optimized, afucosylated IgG1κ monoclonal antibody that binds to CD19 on B cells. Each vial contains 100 mg of inebilizumab in 10 mL of concentrate (corresponding to a concentration of 10 mg/mL). A full therapeutic dose of 300 mg requires the contents of three vials.

Inactive Ingredients (Excipients)

Appearance and Pack Sizes

Uplizna 100 mg concentrate for solution for infusion is a clear to slightly opalescent, colorless to slightly yellow solution. It is supplied in a carton containing 3 single-use glass vials. Each vial contains 100 mg of inebilizumab in 10 mL of concentrate. The three vials provide the full 300 mg dose required for each infusion.

Marketing Authorization Holder and Manufacturer

The marketing authorization holder for the European Union is Amgen Europe B.V. (Breda, Netherlands). The manufacturer is Horizon Therapeutics Ireland DAC (Dun Laoghaire, Ireland). In the United States, Uplizna was originally developed by Viela Bio (subsequently acquired by Horizon Therapeutics, now part of Amgen) and was first approved by the FDA in June 2020 for the treatment of NMOSD in AQP4-antibody-positive adults. The European Commission granted marketing authorization in May 2022. Uplizna has since received approval for IgG4-related disease in additional markets.