Inebilizumab: A Comprehensive Monograph on a First-in-Class CD19-Directed Cytolytic Antibody

I. Inebilizumab: A Profile of a First-in-Class CD19-Directed Cytolytic Antibody

1.1. Nomenclature and Regulatory Identification

[Inebilizumab is a high-affinity, humanized monoclonal antibody that represents a significant advancement in the targeted therapy of specific B-cell-mediated autoimmune disorders. To ensure precise identification across clinical, research, and regulatory domains, the molecule is designated by several names and unique identifiers.]

[Its proprietary or brand name is UPLIZNA®.][1][ The United States Adopted Name (USAN) is formally designated as]

inebilizumab-cdon[.][4][ The four-letter, non-meaningful suffix "-cdon" is a convention established by the U.S. Food and Drug Administration (FDA) to distinguish the originator biologic from potential future biosimilars, a critical detail for ensuring accurate pharmacovigilance and attribution of clinical data. The International Nonproprietary Name (INN), recognized globally, is]

inebilizumab[.][5][ During its development, the compound was also known by the codes MEDI-551 and AMG 335.][4]

[For scientific and regulatory tracking, inebilizumab is assigned the following identifiers:]

• DrugBank ID:[ DB12530 ][1]
• CAS (Chemical Abstracts Service) Number:[ 1299440-37-1 ][1]
• Anatomical Therapeutic Chemical (ATC) Code:[ L04AG10, classifying it under the category of immunosuppressants and specifically as a monoclonal antibody.][1]
• KEGG (Kyoto Encyclopedia of Genes and Genomes) ID:[ D11757.][1]

1.2. Molecular Architecture and Physicochemical Characteristics

[Inebilizumab is a biologic, or biotech, therapeutic, specifically categorized as a protein-based therapy.][8][ The FDA considers it a]

first-in-class medication[ due to its novel mechanism of action in its approved indications.][1]

[Its molecular structure is that of a ]humanized, afucosylated immunoglobulin G1 kappa (IgG1κ) monoclonal antibody[.][5][ The "humanized" designation indicates that the antibody's framework regions are derived from human sequences, with only the antigen-binding complementarity-determining regions (CDRs) being of murine origin. This structural design is critical for minimizing the potential for immunogenicity and improving overall tolerability and safety when administered to patients, a significant advantage over earlier chimeric antibodies.][11][ The term "afucosylated" refers to a specific glycoengineering modification in which the fucose sugar moiety is removed from the Fc region of the antibody, a design feature that profoundly enhances its cytotoxic function.][8]

[Inebilizumab is produced using recombinant DNA technology in a Chinese Hamster Ovary (CHO) cell line.][13][ Its chemical formula is]

[C6504​H10080​N1732​O2044​S44​, with a molecular weight of approximately 146-149 kDa, which is characteristic of an IgG monoclonal antibody.][4][ This large molecular size dictates its pharmacokinetic behavior, confining it primarily to the vascular and interstitial compartments and precluding renal clearance.]

[The drug product, UPLIZNA®, is supplied as a sterile, preservative-free, clear to slightly opalescent, and colorless to slightly yellow solution in single-dose vials containing 100 mg of inebilizumab-cdon in 10 mL (10 mg/mL).][4][ The formulation includes excipients such as L-histidine, sodium chloride, trehalose dihydrate, and polysorbate 80, and is buffered to a pH of 6.0.][4]

[The designation of inebilizumab as "first-in-class" is of substantial importance. It signifies the introduction of a new therapeutic strategy—CD19-directed B-cell depletion—for its approved indications. This novelty was a key factor in the drug receiving special regulatory designations, including Orphan Drug and Breakthrough Therapy status, which are intended to expedite the development and review of treatments for serious conditions with unmet medical needs.][5][ From a clinical perspective, its first-in-class status means that its pivotal clinical trials were not merely confirmatory but were foundational, establishing the entire evidence base for this specific mechanism in neuromyelitis optica spectrum disorder (NMOSD) and Immunoglobulin G4-related disease (IgG4-RD). Consequently, clinicians adopting this therapy must familiarize themselves with a unique efficacy and safety profile rather than extrapolating from experience with other drug classes.]

II. Pharmacological Profile: Mechanism of Action and Disposition

2.1. Pharmacodynamics: Precision Targeting of the B-Cell Lineage

[The therapeutic effect of inebilizumab is derived from its highly specific and potent interaction with the CD19 antigen, leading to the depletion of a broad spectrum of B-cells implicated in autoimmune pathology. Its molecular design represents a strategic evolution in B-cell depleting therapy, directly addressing the mechanistic limitations of prior agents.]

2.1.1. The Role of CD19 in Autoimmune Pathogenesis

[Inebilizumab's sole molecular target is the ]B-lymphocyte antigen CD19[, a 95 kDa transmembrane glycoprotein that is a critical co-receptor for the B-cell receptor (BCR) and plays a pivotal role in B-cell activation and differentiation.][7][ A key feature of CD19 is its broad and sustained expression across the B-cell lineage, from early pre-B cells through to mature B-lymphocytes and, crucially, on antibody-secreting]

plasmablasts[ and a subset of plasma cells.][5]

[This expression pattern is central to its therapeutic rationale in specific autoimmune diseases:]

• In Neuromyelitis Optica Spectrum Disorder (NMOSD):[ The pathogenesis of AQP4-IgG seropositive NMOSD is driven by autoantibodies against the aquaporin-4 water channel on astrocytes. These pathogenic antibodies are produced primarily by an expanded population of CD19-positive plasmablasts.][8][ By targeting CD19, inebilizumab directly addresses a primary cellular source of the autoantibodies that mediate neuronal damage.][11]
• In Immunoglobulin G4-Related Disease (IgG4-RD):[ The fibroinflammatory pathology of IgG4-RD is believed to be driven by the activity of CD19-positive B-cells, including plasmablasts and plasma cells, which contribute to tissue damage through the secretion of autoantibodies and pro-inflammatory cytokines.][16]

[The choice of CD19 as a target is a deliberate advancement over therapies targeting the CD20 antigen, such as rituximab. While CD20 is an effective target on many B-cells, its expression is lost as B-cells differentiate into plasmablasts and plasma cells.][17][ These CD20-negative, antibody-secreting cells can therefore "escape" CD20-directed therapies, potentially leading to breakthrough disease activity.][21][ Because CD19 expression is maintained on these critical cell types, inebilizumab offers a more comprehensive depletion of the B-cell populations responsible for autoantibody production, providing a clear mechanistic advantage.][5]

2.1.2. Molecular Engineering for Enhanced Cytotoxicity

[Inebilizumab is a cytolytic antibody, meaning its primary function is to induce the death of the cells to which it binds.][8][ This is achieved predominantly through a powerful effector mechanism known as]

Antibody-Dependent Cellular Cytotoxicity (ADCC)[.][5][ In this process, after inebilizumab binds to the CD19 antigen on a B-cell, its Fc (fragment crystallizable) region acts as a beacon for effector immune cells, particularly Natural Killer (NK) cells, which possess Fc receptors (FcγRIIIa) on their surface. The engagement of the antibody's Fc region with these receptors activates the NK cell, triggering the release of cytotoxic granules containing perforin and granzymes, which perforate the B-cell membrane and induce apoptosis, leading to cell lysis.][18]

[The potency of this ADCC mechanism is significantly amplified by a specific molecular design feature: ]afucosylation[. Inebilizumab is glycoengineered to remove the fucose sugar from the N-glycans in its Fc region.][5][ This modification markedly increases the binding affinity of the Fc region for the FcγRIIIa receptor on NK cells, resulting in a more robust and efficient ADCC response.][11][ This bioengineering strategy maximizes the B-cell killing capacity of the antibody. While ADCC is the primary mechanism, some evidence also suggests a potential contribution from Complement-Dependent Cytotoxicity (CDC), whereby the antibody activates the classical complement pathway, leading to the formation of a membrane attack complex and subsequent cell lysis.][17]

2.1.3. Immunological Consequences of B-Cell Depletion

[The administration of inebilizumab results in rapid, profound, and durable depletion of circulating CD19-positive B-cells.][23][ Clinical trial data demonstrated that B-cell counts fell below the lower limit of normal in 100% of treated patients by the fourth week of therapy.][11][ The depth of this depletion appears to be clinically relevant; post hoc analyses of the N-MOmentum trial revealed that patients who achieved a greater degree of B-cell depletion (defined as ≤4 cells/μL) after the initial dosing period had significantly lower annualized attack rates (AAR) over the long term.][10][ This finding establishes B-cell count not merely as a marker of drug activity but as a potential pharmacodynamic surrogate for clinical efficacy, providing a quantifiable biological target for the therapy.]

[A direct and expected consequence of depleting a broad range of B-cells, including antibody-producing plasmablasts, is a progressive and potentially prolonged reduction in serum immunoglobulin levels, a condition known as ]hypogammaglobulinemia[.][1][ Both total and individual immunoglobulin isotypes, particularly IgG and IgM, can decline with continued treatment.][11][ This effect necessitates careful monitoring, as it can increase the risk of infections.]

[Ultimately, the therapeutic effect of inebilizumab in its approved indications is presumed to arise from these immunological changes. In NMOSD, the destruction of AQP4-IgG-producing plasmablasts leads to lower levels of pathogenic autoantibodies in the central nervous system (CNS), thereby mitigating astrocyte damage, reducing inflammation, and slowing neuronal injury.][8][ In IgG4-RD, the depletion of CD19+ cells is thought to suppress the production of inflammatory cytokines and autoantibodies, thereby reducing the fibroinflammatory processes that cause organ damage.][16]

2.2. Pharmacokinetics: Absorption, Distribution, Metabolism, and Elimination (ADME)

[The pharmacokinetic profile of inebilizumab is characteristic of a large therapeutic monoclonal antibody and provides the scientific basis for its long-term dosing schedule.]

• Absorption:[ As an intravenously administered drug, inebilizumab has 100% bioavailability, with the entire dose entering the systemic circulation immediately.][8][ Following the recommended initial dosing regimen (300 mg on Day 1 and Day 15), the mean maximum plasma concentration (] [Cmax​) after the second dose was reported to be 108 μg/mL.][8]
• Distribution:[ Inebilizumab exhibits a pharmacokinetic profile consistent with a two-compartment model.][10][ Its volume of distribution is small, reflecting its confinement to the vascular and interstitial spaces. Population pharmacokinetic analyses estimate a central volume of distribution of approximately 2.95 L and a peripheral volume of distribution of 2.57 L.][8]
• Metabolism:[ Inebilizumab is a protein and is therefore not metabolized by hepatic cytochrome P450 (CYP) enzymes. This characteristic confers a very low potential for classical pharmacokinetic drug-drug interactions with small-molecule drugs that are substrates, inducers, or inhibitors of CYP pathways.][10][ Instead, it is expected to be degraded via general protein catabolism into smaller peptides and amino acids by proteolytic enzymes within the reticuloendothelial system, the same pathway that eliminates endogenous immunoglobulins.][8]
• Elimination:[ The elimination of inebilizumab is biphasic and complex, involving both a linear, first-order pathway and a time-dependent, nonlinear pathway.][10][ The nonlinear component is attributed to target-mediated drug disposition (TMDD), or receptor-mediated clearance. In this process, inebilizumab binds to CD19 on B-cells, and the entire complex is internalized and degraded, effectively clearing the drug from circulation. As treatment progresses and the population of CD19+ B-cells is depleted, this clearance pathway becomes saturated. This saturation leads to a decrease in the overall clearance rate of inebilizumab over time. This dynamic interplay between pharmacodynamics and pharmacokinetics creates a self-potentiating effect: as the drug effectively eliminates its target, it simultaneously reduces one of its own clearance mechanisms, leading to sustained drug concentrations and a prolonged duration of B-cell depletion. This elegant relationship is the scientific foundation for the convenient six-month maintenance dosing interval.][3]
• Half-Life and Clearance:[ The mean terminal elimination half-life of inebilizumab is approximately ]18 days[.][8][ The estimated systemic clearance is low, at approximately 0.19 L/day (188 mL/day).][8]

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Table 1: Summary of Inebilizumab Physicochemical and Pharmacokinetic Properties

Parameter	Value/Description	Source(s)
Proprietary Name	UPLIZNA®	1
Non-Proprietary Name	inebilizumab-cdon	4
Drug Class	CD19-directed Cytolytic Antibody; Selective Immunosuppressant	8
Molecular Structure	Humanized, afucosylated IgG1κ monoclonal antibody	5
Molecular Weight	Approx. 146-149 kDa	4
Target	B-lymphocyte antigen CD19	7
Mechanism of Action	B-cell depletion via enhanced Antibody-Dependent Cellular Cytotoxicity (ADCC)	5
Administration Route	Intravenous (IV) infusion	1
Bioavailability	100% (IV administration)	8
Mean Cmax​ (after 2nd 300 mg dose)	108 μg/mL	8
Volume of Distribution	Central: ~2.95 L; Peripheral: ~2.57 L	10
Metabolism Pathway	Proteolytic catabolism	8
Elimination Pathway	Biphasic: Linear (proteolysis) and nonlinear (target-mediated) clearance	10
Terminal Half-Life	Approx. 18 days	8
Systemic Clearance	Approx. 0.19 L/day	8

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III. Clinical Development and Efficacy in Neuromyelitis Optica Spectrum Disorder (NMOSD)

[The approval of inebilizumab for NMOSD was a landmark event, providing a highly effective, targeted therapy for a disease with significant morbidity. The clinical development program, centered on the pivotal N-MOmentum trial, robustly demonstrated its efficacy in the specific patient population for which it is indicated.]

3.1. The Pathophysiology of AQP4-IgG Seropositive NMOSD

[NMOSD is a rare, severe, and relapsing autoimmune disease of the CNS that preferentially targets the optic nerves and spinal cord, leading to attacks of optic neuritis and transverse myelitis.][1][ These attacks result in cumulative and often irreversible neurological disability, including blindness and paralysis.][1][ The immunopathology of the most common form of the disease is defined by the presence of pathogenic autoantibodies—specifically, immunoglobulin G (IgG)—directed against the]

aquaporin-4 (AQP4) water channel[.][31][ AQP4 is highly expressed on the foot processes of astrocytes, which are critical support cells in the CNS.][8][ The binding of AQP4-IgG to these channels initiates a destructive inflammatory cascade, primarily through activation of the classical complement pathway. This leads to astrocyte cytotoxicity, breakdown of the blood-brain barrier, infiltration of inflammatory cells (such as neutrophils and eosinophils), and subsequent secondary demyelination and neuronal loss.][1][ This well-defined, B-cell-driven pathophysiology provides a clear and compelling rationale for therapies that deplete the B-cell populations responsible for producing AQP4-IgG.]

3.2. The Pivotal N-MOmentum Trial (NCT02200770): Design and Endpoints

[The efficacy and safety of inebilizumab for NMOSD were established in the N-MOmentum trial, a large, global Phase 2/3 study.][1]

• Study Design:[ The trial was a multicenter, double-blind, randomized (in a 3:1 ratio), placebo-controlled study with a subsequent open-label extension (OLE) period.][1][ It was conducted at 82 sites across 24 countries.][1]
• Population:[ A total of 230 adult participants with a diagnosis of NMOSD were enrolled. The majority of the cohort, 213 participants, were seropositive for AQP4-IgG. A smaller, exploratory cohort of 17 AQP4-IgG seronegative patients was also included.][1][ Baseline demographics, including age, disease duration, and disability scores, were generally well-balanced between the treatment arms.][34]
• Intervention:[ Participants were randomized to receive either inebilizumab 300 mg via intravenous infusion on Day 1 and Day 15 or matching placebo infusions.][36]
• Randomized Controlled Period (RCP):[ The primary efficacy analysis was conducted over a 197-day (approximately 6.5 months) randomized controlled period.][1][ The trial was stopped early by an independent data monitoring committee because of a clear demonstration of efficacy.][37][ This is a relatively uncommon event in clinical trials and signifies a treatment effect that is both large in magnitude and statistically unambiguous.]
• Primary Endpoint:[ The primary efficacy endpoint was the time to the onset of the first adjudicated NMOSD attack on or before Day 197.][1]
• Key Secondary Endpoints:[ The trial also assessed several other clinically meaningful outcomes, including the change from baseline in the Expanded Disability Status Scale (EDSS) score, the number of NMOSD-related inpatient hospitalizations, and the number of total active MRI lesions.][10]

3.3. Primary and Secondary Efficacy Outcomes in the Randomized Controlled Period

[The results from the N-MOmentum trial demonstrated a profound therapeutic benefit for inebilizumab in the AQP4-IgG seropositive population.]

• Primary Outcome:[ In the AQP4-IgG seropositive cohort, treatment with inebilizumab led to a statistically significant and clinically profound ]77% reduction in the risk of experiencing an NMOSD relapse[ compared to placebo.][1][ The hazard ratio (HR) was 0.227 (95% Confidence Interval [CI]: 0.121, 0.423), with a p-value of <0.0001.][34]
• Relapse-Free Rates:[ This risk reduction translated into a dramatic difference in the proportion of patients remaining attack-free. During the RCP, only 11.2% of AQP4-IgG positive patients treated with inebilizumab had an adjudicated attack, in stark contrast to 42.3% of patients in the placebo group.][37]
• Efficacy in Seronegative Patients:[ A critical finding from the trial was the lack of a demonstrable benefit in the small cohort of AQP4-IgG seronegative participants.][1][ This result was instrumental in defining the precise patient population for whom the drug is indicated and suggests that the underlying pathophysiology of seronegative NMOSD may be distinct and less dependent on the CD19+ B-cell lineage. This underscores the essential role of accurate serological testing in guiding therapeutic decisions for NMOSD.]
• Secondary Outcomes:[ The benefits of inebilizumab extended across multiple secondary endpoints. Compared to placebo, treatment was associated with a significantly reduced risk of disability worsening as measured by the EDSS, a lower number of NMOSD-related hospitalizations, and a reduction in the number of new or enlarging T2 hyperintense lesions on MRI.][10][ Furthermore, in patients who did experience an attack, inebilizumab treatment was shown to reduce the severity of the attack and was associated with lower levels of serum biomarkers of astrocytic (sGFAP) and neuronal (sNfL) injury.][45]

3.4. Long-Term Efficacy and Durability of Response: Insights from the Open-Label Extension (OLE)

[The durability of inebilizumab's effect was assessed in the open-label extension (OLE) of the N-MOmentum trial, into which 94% of participants (216 of 230) chose to enroll after completing the RCP.][47][ This near-universal crossover from both the original inebilizumab and placebo groups serves as a powerful, patient- and physician-driven validation of the drug's perceived benefit. In the OLE, all participants received inebilizumab 300 mg every six months.]

• Sustained Efficacy:[ The profound reduction in attack risk observed in the RCP was sustained over long-term follow-up. Data extending to at least four years of treatment showed that the vast majority of patients remained attack-free. In one analysis, 87.7% of patients who were originally randomized to inebilizumab and 83.4% of those who switched from placebo remained attack-free for up to four years in the OLE.][47]
• Progressive Improvement in Efficacy:[ Long-term data suggest that the therapeutic benefit of inebilizumab may even increase after the first year of treatment. The annualized attack rate (AAR) was observed to decrease with each subsequent year of therapy, with the majority of on-treatment attacks occurring within the first year.][38][ This pattern suggests that while peripheral B-cell depletion is rapid, the full immunological and clinical benefits—potentially involving the clearance of long-lived pathogenic cells and the quieting of established CNS inflammation—may take longer to fully manifest.]
• Long-Term Disability and Real-World Evidence:[ Throughout the multi-year OLE, disability scores as measured by the EDSS remained stable or showed improvement, indicating that long-term treatment effectively prevents the accumulation of irreversible neurological damage.][46][ These robust findings from the clinical trial setting have been corroborated by retrospective real-world studies, which have similarly shown significant reductions in ARR, EDSS scores, and MRI lesion activity in patients treated with inebilizumab in routine clinical practice.][50]

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Table 2: Design and Key Efficacy Outcomes of the N-MOmentum Trial (AQP4-IgG+ Cohort)

Parameter	Details/Results	Source(s)
Study Phase	Phase 2/3	1
Design	Multicenter, double-blind, randomized (3:1), placebo-controlled	33
Population	213 adult patients with AQP4-IgG+ NMOSD	1
Intervention	Inebilizumab 300 mg IV on Day 1 and Day 15	36
Comparator	Placebo	36
Randomized Controlled Period	197 days (approx. 6.5 months)	1
Primary Endpoint	Time to first adjudicated NMOSD attack	1
Primary Outcome	77% reduction in the risk of relapse (HR: 0.227; p<0.0001)	1
% Relapse-Free at Day 197	Inebilizumab: 88.8% vs. Placebo: 57.7%	37
Hospitalization Reduction	Significantly reduced vs. placebo	10
Disability Worsening Reduction	Significantly reduced vs. placebo	10
MRI Lesion Reduction	Significantly reduced vs. placebo	10
Long-Term OLE Outcome	Approx. 85% of patients remained attack-free for up to 4 years	47

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IV. Efficacy in Immunoglobulin G4-Related Disease (IgG4-RD)

[The successful application of inebilizumab has expanded beyond neuroinflammatory disorders with its landmark approval for Immunoglobulin G4-Related Disease (IgG4-RD). This development has established a new standard of care for a complex systemic condition and broadened the therapeutic scope of CD19-directed therapy.]

4.1. The Role of B-Cells and Plasmablasts in IgG4-RD

[IgG4-RD is a chronic, progressive, immune-mediated disease characterized by fibroinflammatory lesions that can infiltrate and damage virtually any organ system, often affecting multiple organs simultaneously.][16][ The disease course is marked by unpredictable flares that can lead to irreversible fibrosis and permanent organ dysfunction.][16][ The pathophysiology is understood to be driven by an aberrant immune response involving CD19-expressing B-cells, plasmablasts, and plasma cells, which are thought to promote inflammation and fibrosis through the secretion of cytokines and pathogenic antibodies.][16][ This B-cell-centric pathology provided a strong scientific rationale for investigating a potent B-cell depleting agent like inebilizumab.]

4.2. The MITIGATE Trial: Efficacy in Reducing Disease Flares

[The approval of inebilizumab for IgG4-RD was a pivotal moment for patients with this condition, as it became the ]first and only FDA-approved therapy[ for the disease in April 2025.][1][ This indication received Breakthrough Therapy Designation from the FDA, recognizing the high unmet medical need.][16]

• Study Design:[ The approval was based on the positive results of the MITIGATE trial (NCT04540497), the first randomized, double-blind, placebo-controlled, multicenter Phase 3 study conducted in patients with IgG4-RD.][16]
• Primary Endpoint:[ The trial's primary endpoint was the time to the first treated and adjudicated IgG4-RD flare over a 52-week placebo-controlled period.][16]
• Primary Outcome:[ The trial met its primary endpoint with overwhelming success. Treatment with inebilizumab resulted in a statistically significant and clinically dramatic ]87% reduction in the risk of an IgG4-RD flare[ compared to placebo (HR 0.13, p<0.001).][16]
• Flare Rates:[ The proportion of patients experiencing a flare was markedly different between the groups: only 10.3% of participants in the inebilizumab arm had a flare, compared to 59.7% of those in the placebo arm.][19]
• Secondary Outcomes:[ The benefits of inebilizumab were also evident in key secondary endpoints. A significantly higher proportion of patients treated with inebilizumab achieved a state of flare-free, treatment-free complete remission at the end of the 52-week study period (57.4%) compared to those on placebo (22.4%).][16][ This indicates that inebilizumab not only prevents flares but also allows for the successful withdrawal of other therapies, particularly long-term corticosteroids, which are associated with significant toxicity.]

[The profound efficacy demonstrated in the MITIGATE trial validates the central role of the CD19+ B-cell/plasmablast axis in the pathogenesis of IgG4-RD. This success has effectively redefined the treatment landscape, establishing inebilizumab as the new standard of care and providing Level 1 evidence for a targeted biologic therapy in a disease previously managed with non-specific immunosuppressants.]

V. Comprehensive Safety and Tolerability Assessment

[The safety profile of inebilizumab has been well-characterized through its extensive clinical development program. The observed adverse events are largely predictable consequences of its potent B-cell depleting mechanism of action, allowing for a proactive risk mitigation strategy through mandated screening and monitoring.]

5.1. Adverse Reaction Profile from Clinical Trials

[The safety of inebilizumab was evaluated in the randomized, placebo-controlled periods and long-term open-label extensions of the N-MOmentum (NMOSD) and MITIGATE (IgG4-RD) trials.]

• In NMOSD (N-MOmentum Trial):[ During the 28-week RCP, the overall rate of adverse events was similar between the inebilizumab and placebo groups.][10][ The most common adverse reactions reported in at least 10% of patients treated with inebilizumab and at a higher rate than placebo were] urinary tract infection (UTI)[ (11% vs. 10% for placebo) and ]arthralgia (joint pain)[ (10% vs. 4% for placebo).][1][ Other commonly reported events included headache (8% vs. 8%) and back pain (7% vs. 4%).][1]
• In IgG4-RD (MITIGATE Trial):[ The most common adverse reactions (≥10% and greater than placebo) were ]urinary tract infection[ and ]lymphopenia[ (a decrease in lymphocyte count, an expected pharmacologic effect).][26]
• Long-Term Safety (OLE):[ Data from the NMOSD OLE, with follow-up extending beyond four years, did not reveal any new safety signals.][10][ The most frequently reported adverse events over the long term were UTI (26%) and nasopharyngitis (21%).][41][ Importantly, the rate and severity of infections did not appear to increase with prolonged duration of treatment, suggesting that the risk remains stable over time.][38]
• Hepatotoxicity:[ Inebilizumab is considered an unlikely cause of clinically significant liver injury. In registration trials, the incidence of serum ALT elevations was comparable between the inebilizumab and placebo groups, and no cases of clinically apparent drug-induced liver injury have been reported since its approval.][15]

[The consistency of the safety profile across two different diseases (NMOSD and IgG4-RD) reinforces the conclusion that the observed adverse events are primarily driven by the drug's mechanism of action on the immune system, rather than an interaction with a specific disease pathology. This makes the risk profile highly predictable and allows for the confident application of safety management strategies across its indications.]

5.2. Warnings and Precautions: A Guide to Risk Mitigation

[The prescribing information for inebilizumab includes several important warnings and precautions, each linked to a specific risk mitigation strategy. The administration of inebilizumab is therefore not a simple infusion but a comprehensive clinical management program requiring careful pre-treatment assessment and ongoing monitoring.]

5.2.1. Management of Infusion-Related Reactions (IRRs)

• Risk:[ Inebilizumab can cause infusion-related reactions, which may be serious and can include symptoms such as headache, nausea, somnolence, dyspnea, fever, myalgia, and rash.][3][ Severe hypersensitivity reactions, including anaphylaxis, are possible.][3]
• Incidence:[ IRRs occurred in 9.3% of NMOSD patients and 7.4% of IgG4-RD patients during the initial course of therapy in clinical trials, with reactions being most common during the first infusion.][3]
• Mitigation Strategy:[ To reduce the frequency and severity of IRRs, ]premedication is mandatory[ before every infusion. The standard premedication regimen consists of an intravenous corticosteroid (e.g., methylprednisolone), an oral antihistamine (e.g., diphenhydramine), and an oral antipyretic (e.g., acetaminophen), administered 30-60 minutes prior to the start of the infusion.][15][ Patients must be closely monitored during the infusion and for at least one hour after its completion.][52][ In the event of a life-threatening reaction, the infusion must be stopped immediately and permanently.][3]

5.2.2. Infectious Risks: Opportunistic Infections, PML, and Viral Reactivation

• General Infection Risk:[ As a potent B-cell depleting agent, inebilizumab causes immunosuppression and increases the risk of infections.][8][ The most common infections observed in clinical trials were UTI, nasopharyngitis, and upper respiratory tract infections.][11][ Administration of inebilizumab should be delayed in patients with an active infection until it is resolved.][11]
• Progressive Multifocal Leukoencephalopathy (PML):[ PML is a rare and often fatal demyelinating brain disease caused by the reactivation of the John Cunningham (JC) virus. While no confirmed cases of PML were identified in inebilizumab clinical trials, it is a known risk associated with other B-cell depleting therapies and is therefore listed as a serious warning.][1][ Clinicians must maintain a high index of suspicion for any new or worsening neurological symptoms.]
• Hepatitis B Virus (HBV) Reactivation:[ Inebilizumab can cause the reactivation of latent HBV infection, which can lead to fulminant hepatitis, liver failure, and death.][1]
• Mitigation:[ ]Screening for HBV (HBsAg and anti-HBc) is mandatory for all patients prior to initiating therapy[.][15][ Patients with active HBV are contraindicated. For patients who are carriers or have evidence of past infection, consultation with a liver disease expert is required before and during treatment.]
• Tuberculosis (TB) Reactivation:[ There is a risk of reactivating latent tuberculosis.][1]
• Mitigation:[ ]Screening for latent TB is required for all patients prior to treatment initiation[.][15][ Patients with active or untreated latent TB are contraindicated. Consultation with an infectious disease expert is recommended for patients with a positive screen or risk factors.]

5.2.3. Monitoring and Management of Hypogammaglobulinemia

• Risk:[ As an expected pharmacodynamic effect, inebilizumab treatment can lead to a progressive and prolonged decline in serum immunoglobulin levels (hypogammaglobulinemia), which may increase the risk of serious or recurrent infections.][1]
• Mitigation:[ ]Quantitative serum immunoglobulin levels must be measured at baseline and monitored periodically[ throughout treatment and after discontinuation until B-cell repletion is confirmed.][15][ If a patient develops a serious opportunistic infection or recurrent infections in the context of low immunoglobulin levels, discontinuation of inebilizumab should be considered.][60]

5.3. Contraindications and Use in Specific Populations

• Contraindications:[ Inebilizumab is absolutely contraindicated in patients with ][3][:]
• [A history of a life-threatening infusion reaction to inebilizumab.]
• [Active hepatitis B infection.]
• [Active or untreated latent tuberculosis.]
• Pregnancy and Lactation:[ Based on its mechanism of action and animal data, inebilizumab may cause fetal harm, specifically B-cell lymphopenia in the offspring.][26][ Females of reproductive potential must be advised of this risk and are required to use effective contraception during treatment and for 6 months after the final dose.][1][ It is not known if inebilizumab is excreted in human breast milk.][58]

5.4. Drug Interaction Profile

• Other Immunosuppressants:[ The concomitant use of inebilizumab with other immunosuppressive drugs, including systemic corticosteroids, has not been formally studied but is expected to increase the overall risk of infection due to additive immunosuppressive effects.][11][ Caution is advised when combining therapies.]
• Vaccines:[ The administration of ]live or live-attenuated vaccines is not recommended[ during inebilizumab treatment and should be avoided until B-cell repletion has occurred. This is due to both the risk of causing infection from the vaccine virus and the likelihood of a blunted or inadequate immune response to the vaccine.][1][ All necessary vaccinations, particularly live vaccines, should be completed at least 4 weeks prior to starting inebilizumab.][58]

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Table 3: Summary of Common and Serious Adverse Reactions from Pivotal Trials

Adverse Event	Incidence in NMOSD Trial (Inebilizumab %)	Incidence in NMOSD Trial (Placebo %)	Incidence in IgG4-RD Trial (Inebilizumab %)	Incidence in IgG4-RD Trial (Placebo %)	Key Management/Mitigation Strategy	Source(s)
Common Reactions
Urinary Tract Infection	11	10	12	7	Standard antimicrobial therapy; delay infusion for active infection.	26
Arthralgia (Joint Pain)	10	4	-	-	Symptomatic management.	26
Infusion-Related Reaction	9.3	11	7.4	4.5	Mandatory premedication; monitoring; rate adjustment or discontinuation.	3
Headache	8	8	-	-	Symptomatic management.	55
Lymphopenia	-	-	19	3	Expected effect; monitor lymphocyte counts.	26
Serious Risks
Serious Infections	Rate similar to placebo in RCP	Rate similar to placebo in RCP	18	9	Delay therapy for active infection; monitor for signs/symptoms.	19
HBV Reactivation	Not observed in trials	Not observed in trials	Not observed in trials	Not observed in trials	Mandatory pre-treatment screening; consult specialists for carriers.	15
PML	Not observed in trials	Not observed in trials	Not observed in trials	Not observed in trials	Maintain high clinical vigilance for new/worsening neurological signs.	15
Hypogammaglobulinemia	Progressive decline	No decline	Progressive decline	No decline	Monitor serum Ig levels; consider discontinuation for recurrent infections.	3

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VI. Clinical Application and Administration

[The practical application of inebilizumab requires strict adherence to its approved indications, patient selection criteria, and a detailed administration protocol designed to maximize efficacy and ensure patient safety.]

6.1. Approved Indications and Patient Selection Criteria

[Inebilizumab is approved by the FDA for two distinct indications:]

1. Neuromyelitis Optica Spectrum Disorder (NMOSD):[ For the treatment of NMOSD in ]adult patients who are seropositive for anti-aquaporin-4 (AQP4) antibodies[.][3][ The efficacy of inebilizumab has not been established in AQP4-IgG seronegative patients, making accurate serological testing a prerequisite for treatment initiation.]
2. Immunoglobulin G4-Related Disease (IgG4-RD):[ For the treatment of IgG4-RD in ]adult patients[.][8]

6.2. Dosing Regimen and Intravenous Administration Protocol

[The dosing and administration of inebilizumab are standardized for both approved indications and involve an initial loading phase followed by a long-term maintenance schedule.]

• Initial Dose:[ The treatment is initiated with a loading dose consisting of a ]300 mg intravenous infusion on Day 1[, followed two weeks later by a ]second 300 mg intravenous infusion on Day 15[.][15]
• Maintenance Doses:[ Subsequent doses consist of a ]single 300 mg intravenous infusion administered every 6 months[, starting 6 months after the first infusion.][3]
• Preparation:[ Each 300 mg dose requires three 100 mg/10 mL single-dose vials. A total volume of 30 mL is withdrawn and must be diluted in a 250 mL intravenous bag of 0.9% Sodium Chloride Injection, USP. No other diluents should be used. The diluted solution should be mixed by gentle inversion, not by shaking.][4]
• Infusion Procedure:[ The prepared solution is administered as an intravenous infusion over a total period of approximately 90 minutes. The infusion rate is titrated according to a specific schedule to improve tolerability:]
• [0 to 30 minutes: 42 mL/hour]
• [31 to 60 minutes: 125 mL/hour]
• [61 minutes to completion: 333 mL/hour] [The infusion must be administered through an intravenous line containing a sterile, low-protein-binding 0.2 or 0.22 micron in-line filter.57]
• Post-Infusion Monitoring:[ Following the completion of the infusion, patients must be monitored by a healthcare professional for at least one hour for any signs or symptoms of an infusion-related reaction.][52]

6.3. Pre-Treatment Screening and Vaccination Guidelines

[A comprehensive series of assessments is mandatory before initiating inebilizumab therapy to identify contraindications and mitigate potential risks.]

• Required Screening:[ Before the first dose, all patients must undergo ][15][:]
• Hepatitis B Virus (HBV) Screening:[ Including tests for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc).]
• Tuberculosis (TB) Screening:[ To test for latent TB infection.]
• Quantitative Serum Immunoglobulins:[ To establish a baseline for monitoring potential hypogammaglobulinemia.]
• Vaccination Guidelines:[ A patient's vaccination status must be reviewed and updated prior to starting treatment.]
• Timing:[ All necessary immunizations, particularly ]live or live-attenuated vaccines, must be administered at least 4 weeks before the first inebilizumab infusion[.][57][ This window allows for an adequate immune response to develop before B-cell depletion occurs.]
• Contraindicated Vaccines During Treatment:[ The use of live or live-attenuated vaccines is not recommended during inebilizumab treatment and should be deferred until B-cell counts have recovered after discontinuation of the drug.][1]

VII. Regulatory History and Future Directions

[Inebilizumab's journey from laboratory research to a multi-indication approved therapy has been marked by strategic development, expedited regulatory pathways, and ongoing investigation into its broader therapeutic potential.]

7.1. Key Milestones in FDA Approval and Global Registration

[The development of inebilizumab originated from foundational research at Cellective Therapeutics, led by Thomas Tedder, and was advanced through clinical development by MedImmune and Viela Bio.][1][ The product was later acquired by Amgen, which now holds the marketing authorization.][6]

[Recognizing its potential to address significant unmet needs in rare diseases, regulatory agencies granted inebilizumab several special designations that facilitated its development and review:]

• For NMOSD:[ It received ]Orphan Drug designation[ in February 2016 and ]Breakthrough Therapy designation[ in April 2019 from the FDA.][1]
• For IgG4-RD:[ It was granted ]Breakthrough Therapy Designation[ by the FDA.][16]

[The FDA approval timeline for its two indications is as follows:]

• NMOSD:[ UPLIZNA was first approved in the United States on June 11, 2020, for the treatment of AQP4-IgG seropositive NMOSD in adults.][1]
• IgG4-RD:[ The indication was expanded to include the treatment of IgG4-RD in adults on April 3, 2025.][1]

[Beyond the United States, inebilizumab has also received marketing authorization in other major regions, including the European Union (April 2022) and Canada (December 2023).][1]

7.2. Investigational Studies and Potential for Expanded Indications

[The potent and broad B-cell depleting mechanism of inebilizumab has prompted its investigation in a range of other autoimmune and B-cell-mediated conditions.]

• Myasthenia Gravis (gMG):[ Inebilizumab has demonstrated promising results in gMG. Data from a Phase 3 trial showed superior efficacy compared to placebo in patients with seropositive generalized MG.][73][ The FDA has granted it Orphan Drug Designation for this indication, suggesting a potential future approval.][16]
• Multiple Sclerosis (MS) and Systemic Lupus Erythematosus (SLE):[ The drug has been evaluated in early-phase studies for relapsing MS, and its mechanism makes it a rational candidate for further investigation in other B-cell-driven diseases like SLE.][10]
• B-Cell Malignancies:[ Early clinical development included Phase 1 dose-escalation studies in patients with relapsed or refractory advanced B-cell malignancies, demonstrating its cytolytic potential beyond autoimmune disease.][74]
• Pediatric NMOSD:[ A Phase 2 clinical trial (NCT05549258) is currently recruiting to evaluate the safety and efficacy of inebilizumab in pediatric patients with NMOSD, which could potentially expand its use to a younger population.][76]
• Long-Term Safety:[ A Phase 4 study (NCT06180278) is underway to continue monitoring the long-term safety of inebilizumab in NMOSD, with a specific focus on the dynamics of immunoglobulin levels and B-cell counts during chronic treatment and after discontinuation.][77]

VIII. Inebilizumab in the NMOSD Therapeutic Landscape: A Comparative Analysis

[The approval of inebilizumab, followed by eculizumab and satralizumab, has transformed the management of AQP4-IgG+ NMOSD from a reliance on off-label immunosuppressants to an era of highly effective, targeted biologic therapies. Each of these agents intervenes at a distinct point in the disease's pathophysiological cascade, offering clinicians a strategic choice based on mechanism, efficacy, administration profile, and safety considerations.]

[The core pathophysiology of AQP4-IgG+ NMOSD can be conceptualized as a three-stage process: (1) ]Production[ of pathogenic autoantibodies by B-cells and plasmablasts; (2) ]Promotion[ of this process and overall inflammation by cytokines like IL-6; and (3) ]Execution[ of tissue damage via complement activation triggered by the autoantibodies. The three approved therapies target each of these stages specifically.]

• Inebilizumab (Uplizna®):[ Targets the ]production[ stage. As a CD19-directed cytolytic antibody, it eliminates a broad spectrum of B-cells, including the plasmablasts that are the primary source of AQP4-IgG, thereby removing the root cause of the autoimmune attack.][8][ Its pivotal N-MOmentum trial demonstrated a 77% reduction in relapse risk versus placebo.][1][ It is administered as an intravenous infusion every 6 months for maintenance.][3]
• Eculizumab (Soliris®):[ Targets the final ]execution[ stage. It is a terminal complement C5 inhibitor that prevents the formation of the pro-inflammatory C5a and the lytic membrane attack complex (MAC), which is directly responsible for astrocyte destruction.][79][ It does not affect B-cell numbers or autoantibody levels but blocks their downstream destructive capacity. Its pivotal PREVENT trial showed a 94% reduction in relapse risk.][79][ However, it carries a significant administration burden, requiring an intravenous infusion every 2 weeks for maintenance.][83]
• Satralizumab (Enspryng®):[ Targets the ]promotion[ stage. It is an interleukin-6 (IL-6) receptor antagonist. IL-6 is a key cytokine that promotes the differentiation of B-cells into antibody-secreting cells and enhances blood-brain barrier permeability.][85][ Its pivotal SAkuraStar trial demonstrated a 74% relapse risk reduction as monotherapy in AQP4+ patients.][88][ It offers the convenience of subcutaneous self-injection but requires administration every 4 weeks.][90]

[While direct head-to-head trials are lacking, all three agents have demonstrated high efficacy in preventing NMOSD relapses. Therefore, the choice of therapy often hinges on non-efficacy factors. An anchored matching-adjusted indirect comparison (MAIC) analysis suggested that inebilizumab may be associated with a more favorable risk of attack and better long-term quality-of-life outcomes compared to the other agents, though such indirect comparisons must be interpreted with caution due to inherent methodological limitations.][92]

[The most significant differentiators are the route of administration and dosing frequency, which have profound implications for treatment burden and patient preference. Inebilizumab's biannual infusion schedule represents the lowest dosing frequency among the approved options, a major advantage for patients seeking to minimize healthcare interactions. In contrast, satralizumab offers the flexibility of at-home subcutaneous administration, while eculizumab's frequent intravenous infusions present the highest treatment burden. The distinct safety profiles, particularly the specific risk of meningococcal infection with eculizumab, also play a critical role in shared decision-making.]

---

Table 4: Comparative Analysis of FDA-Approved Therapies for AQP4-IgG+ NMOSD

Feature	Inebilizumab (Uplizna®)	Eculizumab (Soliris®)	Satralizumab (Enspryng®)
Target/Mechanism of Action	CD19-directed B-cell depletion: Eliminates a broad range of B-cells, including autoantibody-producing plasmablasts.8	Terminal Complement C5 Inhibition: Blocks formation of the membrane attack complex (MAC), preventing astrocyte lysis.79	Interleukin-6 (IL-6) Receptor Blockade: Inhibits pro-inflammatory cytokine signaling that drives B-cell differentiation and inflammation.85
Pivotal Trial	N-MOmentum	PREVENT	SAkuraStar (monotherapy)
Relapse Risk Reduction (vs. Placebo)	77% 1	94% 82	74% 88
Administration Route	Intravenous (IV) Infusion	Intravenous (IV) Infusion	Subcutaneous (SC) Injection
Dosing Frequency (Maintenance)	Every 6 months (2 infusions/year) 3	Every 2 weeks (26 infusions/year) 83	Every 4 weeks (13 injections/year) 91
Key Safety Considerations/Warnings	Infusion reactions, infections, hypogammaglobulinemia, PML risk, HBV/TB reactivation screening required.3	Serious meningococcal infections (Boxed Warning), other infections. Vaccination required. REMS program.84	Infections, elevated liver enzymes, decreased neutrophil counts, HBV/TB reactivation screening required.96

---

IX. Conclusion

[Inebilizumab (UPLIZNA®) has been established as a first-in-class, highly effective therapeutic agent for specific B-cell-mediated autoimmune diseases. As a humanized, afucosylated monoclonal antibody, its design is optimized for potent and broad depletion of the B-cell lineage by targeting the CD19 antigen. This mechanism represents a rational and strategic evolution over prior B-cell therapies, as it effectively targets the antibody-secreting plasmablasts that are central to the pathophysiology of its approved indications.]

[In AQP4-IgG seropositive neuromyelitis optica spectrum disorder, the pivotal N-MOmentum trial demonstrated a profound and durable reduction in the risk of relapse, accompanied by benefits in disability, hospitalization rates, and MRI outcomes. The long-term data confirm that this efficacy is sustained, and may even improve, with continued treatment. The finding that deeper B-cell depletion correlates with improved clinical outcomes provides a valuable pharmacodynamic link between the drug's mechanism and its therapeutic effect.]

[The recent approval of inebilizumab for Immunoglobulin G4-related disease, based on the similarly impressive results of the MITIGATE trial, marks a significant expansion of its therapeutic role. It is the first and only therapy approved for this complex fibroinflammatory condition, establishing a new standard of care and validating the CD19+ B-cell axis as a critical driver of the disease.]

[The safety profile of inebilizumab is well-defined and directly related to its potent immunosuppressive mechanism. The primary risks—including infusion reactions, infections, and hypogammaglobulinemia—are predictable and manageable through a comprehensive program of mandatory pre-treatment screening, premedication, and ongoing monitoring.]

[Within the therapeutic landscape for NMOSD, inebilizumab is distinguished by its unique mechanism of action and a highly favorable maintenance dosing schedule of a single intravenous infusion every six months. This low treatment burden, combined with its robust and sustained efficacy, positions inebilizumab as a foundational therapy for AQP4-IgG+ NMOSD and a breakthrough treatment for IgG4-RD. Ongoing research in other autoimmune conditions, such as myasthenia gravis, suggests that the full therapeutic potential of this targeted B-cell depleting strategy may yet be further realized.]

Works cited

1. Inebilizumab - Wikipedia, accessed September 3, 2025, https://en.wikipedia.org/wiki/Inebilizumab
2. en.wikipedia.org, accessed September 3, 2025, https://en.wikipedia.org/wiki/Inebilizumab#:~:text=Inebilizumab%2C%20sold%20under%20the%20brand,in%20adults%20and%20IgG4%2DRD.
3. UPLIZNA® (inebilizumab-cdon) | Healthcare Professional Home, accessed September 3, 2025, https://www.upliznahcp.com/
4. UPLIZNA® - msds-amgen-com, accessed September 3, 2025, https://www.msds.amgen.com/uplizna-safety-datasheet
5. APPLICATION NUMBER: - 761142Orig1s000 PRODUCT QUALITY REVIEW(S) - accessdata.fda.gov, accessed September 3, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/761142Orig1s000ChemR.pdf
6. www.drugs.com, accessed September 3, 2025, https://www.drugs.com/inebilizumab.html#:~:text=Inebilizumab%20belongs%20to%20the%20drug,Therapeutics%2C%20a%20subsidiary%20of%20Amgen.
7. Inebilizumab - KEGG DRUG, accessed September 3, 2025, https://www.kegg.jp/entry/D11757
8. Inebilizumab: Uses, Interactions, Mechanism of Action | DrugBank Online, accessed September 3, 2025, https://go.drugbank.com/drugs/DB12530
9. Inebilizumab |CAS 1299440-37-1 - DC Chemicals, accessed September 3, 2025, https://www.dcchemicals.com/product_show-inebilizumab.html
10. Inebilizumab: A Review in Neuromyelitis Optica Spectrum Disorder - PMC - PubMed Central, accessed September 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9550749/
11. Mechanism of Action | UPLIZNA® (inebilizumab-cdon) for HCPs, accessed September 3, 2025, https://www.upliznahcp.com/nmosd/mechanism-of-action
12. Definition of inebilizumab - NCI Drug Dictionary, accessed September 3, 2025, https://www.cancer.gov/publications/dictionaries/cancer-drug/def/inebilizumab
13. Inebilizumab (Anti-CD19) CD markers antibody | Read Reviews & Product Use Citations - Selleck Chemicals, accessed September 3, 2025, https://www.selleckchem.com/products/inebilizumab-anti-cd19.html
14. Uplizna, INN-inebilizumab, accessed September 3, 2025, https://ec.europa.eu/health/documents/community-register/2022/20220629156033/anx_156033_en.pdf
15. Inebilizumab - LiverTox - NCBI Bookshelf, accessed September 3, 2025, https://www.ncbi.nlm.nih.gov/books/NBK605688/
16. UPLIZNA® (INEBILIZUMAB-CDON) IS NOW THE FIRST AND ONLY FDA-APPROVED TREATMENT FOR IGG4-RELATED DISEASE - Amgen, accessed September 3, 2025, https://www.amgen.com/newsroom/press-releases/2025/04/uplizna-inebilizumabcdon-is-now-the-first-and-only-fdaapproved-treatment-for-igg4related-disease
17. Inebilizumab: Advancing Research and Clinical Applications - Assay Genie, accessed September 3, 2025, https://www.assaygenie.com/blog/inebilizumab-advancing-research-and-clinical-applications/
18. IgG4-RD Mechanism of Action | UPLIZNA® (inebilizumab-cdon) for HCPs, accessed September 3, 2025, https://www.upliznahcp.com/igg4-rd/why-uplizna/mechanism-of-action
19. B-Cell Depletion Reduces IgG4 Disease Flare Risk - EMJ, accessed September 3, 2025, https://www.emjreviews.com/allergy-immunology/news/b-cell-depletion-reduces-igg4-disease-flare-risk/
20. Can autoimmune disease be cured by deep CD19+ cell depletion? - Oxford Academic, accessed September 3, 2025, https://academic.oup.com/jimmunol/article/214/6/1075/8090055
21. Inebilizumab for treatment of neuromyelitis optica spectrum disorder in patients with prior rituximab use from the N-MOmentum Study - PubMed, accessed September 3, 2025, https://pubmed.ncbi.nlm.nih.gov/35158461/
22. What is the mechanism of Inebilizumab-cdon? - Patsnap Synapse, accessed September 3, 2025, https://synapse.patsnap.com/article/what-is-the-mechanism-of-inebilizumab-cdon
23. Association between B-cell depletion and attack risk in neuromyelitis optica spectrum disorder: An exploratory analysis from N-MOmentum, a double-blind, randomised, placebo-controlled, multicentre phase 2/3 trial - PMC - PubMed Central, accessed September 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9664402/
24. Pharmacodynamic modelling and exposure-response assessment of inebilizumab in subjects with neuromyelitis optica spectrum disorders - PubMed, accessed September 3, 2025, https://pubmed.ncbi.nlm.nih.gov/35332558/
25. Pharmacodynamic modelling and exposure–response assessment of inebilizumab in subjects with neuromyelitis optica spectrum disorders - PMC - PubMed Central, accessed September 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9545531/
26. Dosing and Prescribing Information | UPLIZNA® (inebilizumab-cdon) HCP, accessed September 3, 2025, https://www.upliznahcp.com/nmosd/dosing-and-infusion-information
27. Efficacy in NMOSD Treatment | UPLIZNA® (inebilizumab-cdon) for HCPs, accessed September 3, 2025, https://www.upliznahcp.com/nmosd/mechanism-of-action/efficacy-nmosd-treatment
28. PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION PrUPLIZNA® Inebilizumab for injection 100 mg / 10 mL (10 mg / mL) s, accessed September 3, 2025, https://pdf.hres.ca/dpd_pm/00080115.PDF
29. Inebilizumab: Uses, Dosage, Side Effects, Warnings - Drugs.com, accessed September 3, 2025, https://www.drugs.com/inebilizumab.html
30. What Is NMOSD? | UPLIZNA® (inebilizumab-cdon), accessed September 3, 2025, https://www.uplizna.com/nmosd/what-is-nmosd
31. Inebilizumab: A Review in Neuromyelitis Optica Spectrum Disorder - PubMed, accessed September 3, 2025, https://pubmed.ncbi.nlm.nih.gov/36070074/
32. Inebilizumab-cdon (Uplizna) - Medical Clinical Policy Bulletins - Aetna, accessed September 3, 2025, https://www.aetna.com/cpb/medical/data/900_999/0975.html
33. N-MOmentum Study | UPLIZNA® (inebilizumab-cdon) for HCPs, accessed September 3, 2025, https://www.upliznahcp.com/nmosd/mechanism-of-action/study-design
34. Sensitivity analysis of the primary endpoint from the N-MOmentum study of inebilizumab in NMOSD - PMC - PubMed Central, accessed September 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC8564264/
35. Sensitivity analysis of the primary endpoint from the N-MOmentum study of inebilizumab in NMOSD - PubMed, accessed September 3, 2025, https://pubmed.ncbi.nlm.nih.gov/33538237/
36. Disability Outcomes in the N-MOmentum Trial of Inebilizumab in Neuromyelitis Optica Spectrum Disorder | Neurology Neuroimmunology & Neuroinflammation, accessed September 3, 2025, https://www.neurology.org/doi/10.1212/NXI.0000000000000978
37. Uplizna® (inebilizumab-cdon) - CarePartners of Connecticut, accessed September 3, 2025, https://www.carepartnersct.com/cpct-pdoc-uplizna-mdmng
38. Safety and efficacy of inebilizumab for the treatment of neuromyelitis optica spectrum disorder: end-of-study results from the open-label period of the N-MOmentum trial - PubMed, accessed September 3, 2025, https://pubmed.ncbi.nlm.nih.gov/38760098/
39. (PDF) Inebilizumab: A Review in Neuromyelitis Optica Spectrum Disorder - ResearchGate, accessed September 3, 2025, https://www.researchgate.net/publication/363359384_Inebilizumab_A_Review_in_Neuromyelitis_Optica_Spectrum_Disorder
40. Subject: Inebilizumab (Uplizna) Injection - Medical Coverage Guideline - Florida Blue, accessed September 3, 2025, https://mcgs.bcbsfl.com/MCG?mcgId=09-J3000-73&pv=false
41. Safety and Efficacy of Inebilizumab for Treating Neuromyelitis Optica Spectrum Disorder: Insights from the N-MOmentum Trial - Safe Therapeutics, accessed September 3, 2025, https://safetherapeutics.com/safety-and-efficacy-of-inebilizumab-for-treating-neuromyelitis-optica-spectrum-disorder/
42. Uplizna® (inebilizumab-cdon): Prescribing Information Overview, accessed September 3, 2025, https://ce.mayo.edu/sites/default/files/Uplizna%20PI%20Based%20Brochure%20FINAL.pdf
43. Analysis of aquaporin-4–immunoglobulin G–seropositive participants taking inebilizumab for 4 years in the N-MOmentum trial - PMC - PubMed Central, accessed September 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9024030/
44. Inebilizumab: A Review in Neuromyelitis Optica Spectrum Disorder, accessed September 3, 2025, https://www.sumairafoundation.org/summaries/inebilizumab-a-review-in-neuromyelitis-optica-spectrum-disorder/
45. Inebilizumab Reduced Severity of Neuromyelitis Optica Spectrum Disorder Attacks, accessed September 3, 2025, https://practicalneurology.com/news/inebilizumab-reduced-severity-of-neuromyelitis-optica-spectrum-disorder-attacks/2469830/
46. Inebilizumab Has Enduring Effect as NMOSD Treatment - NeurologyLive, accessed September 3, 2025, https://www.neurologylive.com/view/inebilizumab-continues-demonstrate-strength-nmosd-treatment
47. Long Term Efficacy Outcomes with Inebilizumab Treatment in NMOSD: the N-MOmentum Trial (2329) - Neurology.org, accessed September 3, 2025, https://www.neurology.org/doi/10.1212/WNL.96.15_supplement.2329
48. Long-term efficacy and safety of inebilizumab in neuromyelitis optica spectrum disorder: Analysis of aquaporin-4-immunoglobulin G-seropositive participants taking inebilizumab for 4 years in the N-MOmentum trial - PubMed, accessed September 3, 2025, https://pubmed.ncbi.nlm.nih.gov/34595983/
49. Updates on N-MOmentum: inebilizumab versus placebo in patients with NMOSD, accessed September 3, 2025, https://www.vjneurology.com/video/qjlheqvjzxo-updates-on-n-momentum-inebilizumab-versus-placebo-in-patients-with-nmosd/
50. A Real-world Study of Inebilizumab for Neuromyelitis Optica Spectrum Disorders (P9-1.008), accessed September 3, 2025, https://www.neurology.org/doi/abs/10.1212/WNL.0000000000211090
51. First FDA Approval of Its Kind for People Living With IgG4-Related Disease | Amgen, accessed September 3, 2025, https://www.amgen.com/stories/2025/04/first-fda-approval-of-its-kind-for-people-living-with-igg4-related-disease
52. Official Consumer Website | UPLIZNA® (inebilizumab-cdon), accessed September 3, 2025, https://www.uplizna.com/
53. Uplizna (inebilizumab-cdon) is Now the First and Only FDA-Approved Treatment for IgG4-Related Disease - Drugs.com, accessed September 3, 2025, https://www.drugs.com/newdrugs/uplizna-inebilizumab-cdon-now-first-only-fda-approved-igg4-related-6494.html
54. Efficacy and Safety of Inebilizumab in IgG4-Related Disease: Protocol for a Randomized Controlled Trial - PubMed, accessed September 3, 2025, https://pubmed.ncbi.nlm.nih.gov/37792260/
55. NMOSD UPLIZNA® (inebilizumab-cdon) Side Effects, accessed September 3, 2025, https://www.uplizna.com/nmosd/about-uplizna/side-effects
56. Safety and Side Effects | UPLIZNA® (inebilizumab-cdon) for HCPs, accessed September 3, 2025, https://www.upliznahcp.com/nmosd/mechanism-of-action/safety-adverse-events
57. Uplizna (inebilizumab) dosing, indications, interactions, adverse effects, and more, accessed September 3, 2025, https://reference.medscape.com/drug/uplizna-inebilizumab-4000023
58. NMOSD Dosing | UPLIZNA® (inebilizumab-cdon), accessed September 3, 2025, https://www.uplizna.com/nmosd/about-uplizna/how-to-take
59. UPLIZNA® Resources | Amgen By Your Side HCP, accessed September 3, 2025, https://www.amgenbyyourside.com/uplizna/hcp/resources
60. 1 of 21 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use UPLIZNA® safely - accessdata.fda.gov, accessed September 3, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761142s003lbl.pdf
61. Administration | UPLIZNA® (inebilizumab-cdon) HCP, accessed September 3, 2025, https://www.upliznahcp.com/nmosd/dosing-and-infusion-information/administration
62. What is NMOSD? | UPLIZNA® (inebilizumab-cdon) FAQs for HCP, accessed September 3, 2025, https://www.upliznahcp.com/nmosd/access-and-support/frequently-asked-questions
63. Uplizna NDFB, accessed September 3, 2025, https://dss.mo.gov/mhd/cs/advisory/rdac/files/UpliznaNDFB_MO.pdf
64. Uplizna - This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda, accessed September 3, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761142s000lbl.pdf
65. Inebilizumab: Side Effects, Uses, Dosage, Interactions, Warnings - RxList, accessed September 3, 2025, https://www.rxlist.com/inebilizumab/generic-drug.htm
66. nursing.unboundmedicine.com, accessed September 3, 2025, https://nursing.unboundmedicine.com/nursingcentral/view/Davis-Drug-Guide/110946/all/inebilizumab?q=mo#:~:text=Concurrent%20use%20with%20other%20immunosuppressants,to%20initiation%20of%20inebilizumab%20therapy.
67. Inebilizumab injection - Cleveland Clinic, accessed September 3, 2025, https://my.clevelandclinic.org/health/drugs/23627-inebilizumab-injection
68. NMOSD FAQs | UPLIZNA® (inebilizumab-cdon), accessed September 3, 2025, https://www.uplizna.com/nmosd/resources-and-support/faq
69. www.upliznahcp.com, accessed September 3, 2025, https://www.upliznahcp.com/nmosd/mechanism-of-action/safety-adverse-events#:~:text=Symptoms%20can%20include%20headache%2C%20nausea,in%209.3%25%20of%20NMOSD%20patients.
70. NMOSD: What Makes UPLIZNA® Different? | UPLIZNA® (inebilizumab-cdon), accessed September 3, 2025, https://www.uplizna.com/nmosd/about-uplizna
71. Medication Guide UPLIZNA® (up-liz'-nah) (inebilizumab-cdon) injection, for intravenous use What is the most important infor, accessed September 3, 2025, https://www.uplizna.com/-/media/Themes/Horizon/Uplizna/Uplizna/Documents/Uplizna-Medication-Guide.pdf
72. Uplizna (inebilizumab-cdon) FDA Approval History - Drugs.com, accessed September 3, 2025, https://www.drugs.com/history/uplizna.html
73. First-in-Class B-Cell Depleting Agent Promising for Myasthenia Gravis - The Hospitalist, accessed September 3, 2025, https://blogs.the-hospitalist.org/content/first-class-b-cell-depleting-agent-promising-myasthenia-gravis
74. Inebilizumab Completed Phase 1 Trials for Advanced B Cell Malignancies / Hematological Malignancy Treatment | DrugBank Online, accessed September 3, 2025, https://go.drugbank.com/drugs/DB12530/clinical_trials?conditions=DBCOND0065631%2CDBCOND0031698&phase=1&purpose=treatment&status=completed
75. Inebilizumab Completed Phase 2 Trials for Diffuse Large B-Cell Lymphoma (DLBCL) Treatment - DrugBank, accessed September 3, 2025, https://go.drugbank.com/drugs/DB12530/clinical_trials?conditions=DBCOND0028221&phase=2&purpose=treatment&status=completed
76. Inebilizumab Recruiting Phase 2 Trials for Neuromyelitis Optica Spectrum Disorders Treatment | DrugBank Online, accessed September 3, 2025, https://go.drugbank.com/drugs/DB12530/clinical_trials?conditions=DBCOND0067761&phase=2&purpose=treatment&status=recruiting
77. NMO Spectrum Disorder (NMOSD) Active Not Recruiting Phase 4 Trials for Inebilizumab (DB12530) - DrugBank, accessed September 3, 2025, https://go.drugbank.com/indications/DBCOND0067771/clinical_trials/DB12530?phase=4&status=active_not_recruiting
78. Long-term, Open-label, Safety Study of Inebilizumab in Neuromyelitis Optica Spectrum Disorder (NMOSD) | MedPath, accessed September 3, 2025, https://trial.medpath.com/clinical-trial/55f658a5225db5bf/nct06180278-inebilizumab-treatment-nmosd-safety-study
79. Eculizumab Use in Neuromyelitis Optica Spectrum Disorders ..., accessed September 3, 2025, https://www.neurology.org/doi/10.1212/WNL.0000000000209888
80. Eculizumab in the treatment of neuromyelitis optica spectrum ..., accessed September 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10460925/
81. Eculizumab: A Review in Neuromyelitis Optica Spectrum Disorder - PMC - PubMed Central, accessed September 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC7183484/
82. Multiple Sclerosis Minute: Novel Treatment Options for Neuromyelitis Optica Spectrum Disorder - Practical Neurology, accessed September 3, 2025, https://practicalneurology.com/diseases-diagnoses/ms-immune-disorders/multiple-sclerosis-minute-novel-treatment-options-for-neuromyelitis-opticaspectrum-disorder/31844/
83. Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD), accessed September 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10770020/
84. Eculizumab (Soliris) for Neuromyelitis Optica Spectrum Disorder | Cleveland Clinic, accessed September 3, 2025, https://my.clevelandclinic.org/departments/neurological/depts/multiple-sclerosis/ms-approaches/eculizumab
85. 761149Orig1s000 CLINICAL PHARMACOLOGY REVIEW(S) - accessdata.fda.gov, accessed September 3, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/761149Orig1s000ClinPharmR.pdf
86. Review of Satralizumab for Neuromyelitis Optica Spectrum Disorder: A New Biologic Agent Targeting the Interleukin-6 Receptor - PMC - PubMed Central, accessed September 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10978816/
87. Satralizumab: Uses, Interactions, Mechanism of Action | DrugBank Online, accessed September 3, 2025, https://go.drugbank.com/drugs/DB15762
88. Roche's satralizumab significantly reduced relapse risk in second positive phase III study for neuromyelitis optica spectrum, accessed September 3, 2025, https://www.roche.com/media/releases/med-cor-2019-09-12b
89. Genentech's Satralizumab Significantly Reduced Relapse Risk in Second Positive Phase III Study for Neuromyelitis Optica Spectrum Disorder, accessed September 3, 2025, https://www.gene.com/media/press-releases/14808/2019-09-11/genentechs-satralizumab-significantly-re
90. What is the mechanism of Satralizumab? - Patsnap Synapse, accessed September 3, 2025, https://synapse.patsnap.com/article/what-is-the-mechanism-of-satralizumab
91. Satralizumab: Uses, Dosage, Side Effects, Warnings - Drugs.com, accessed September 3, 2025, https://www.drugs.com/satralizumab.html
92. MODELLING THE LONG-TERM EFFECTIVENESS OF INEBILIZUMAB IN THE CURRENT TREATMENT LANDSCAPE IN NMOSD - ISPOR, accessed September 3, 2025, https://www.ispor.org/docs/default-source/intl2023/ispor23sorioposter-pdf.pdf?sfvrsn=ee88940d_0
93. Indirect Comparison of 3 Monoclonal Antibodies to Treat AQP4+ ..., accessed September 3, 2025, https://practicalneurology.com/news/indirect-comparison-of-3-different-monoclonal-antibodies-to-treat-aqp4-nmosd/2470311/
94. Neuromyelitis optica spectrum disorder (NMOSD) | ULTOMIRIS® (ravulizumab-cwvz), accessed September 3, 2025, https://ultomirishcp.com/nmosd
95. HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use SOLIRIS safely and effec - Alexion.US, accessed September 3, 2025, https://alexion.us/-/media/alexion_global/documents/regulatory/north-america/usa/2024/english/soliris_uspi.pdf
96. Satralizumab - Wikipedia, accessed September 3, 2025, https://en.wikipedia.org/wiki/Satralizumab
97. Important Safety Information | ENSPRYNG® (satralizumab), accessed September 3, 2025, https://www.enspryng-hcp.com/side-effects/important-safety-information.html
98. Side Effects & Trial Safety | ENSPRYNG® (satralizumab), accessed September 3, 2025, https://www.enspryng-hcp.com/side-effects/summary.html