How ENSPRYNG is thought to work

ENSPRYNG targets IL-6, which has been implicated in neuromyelitis optica spectrum disorder (NMOSD)1-3

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IL-6, NMOSD, and ENSPRYNG

Watch the video below or scroll to read how IL-6 plays a role in disease development and treatment

ENSPRYNG mechanism of action

ENSPRYNG mechanism of action

Targeting IL-6 with ENSPRYNG as a treatment for aquaporin-4 (AQP4) immunoglobulin, or IgG antibody positive NMOSD patients1

Neuromyelitis optica spectrum disorder, or NMOSD, is a chronic, severely debilitating autoimmune disease of the central nervous system that primarily damages the optic nerves and spinal cord2-7

People with NMOSD experience unpredictable, severe, and recurrent relapses from which they may not fully recover2-9

Relapses cause cumulative, irreversible neurological damage, and even a single episode can lead to blindness, paralysis, or death2-9

NMOSD is often associated with a pathogenic serum IgG antibody against the water channel AQP4 protein found in the central nervous system4

AQP4-IgG antibody is highly specific and found in up to 80% of NMOSD patients’ serum. Prior to 2019, there was no FDA-approved treatment for NMOSD4

Recent research has led to a better understanding of the pathogenesis of NMOSD, including the pivotal role IL-6 plays in driving the inflammatory response2,10

The autoimmune cascade is active in the periphery, where IL-6 promotes T-cell-mediated inflammation by promoting the maturation of T cells into Th17 cells. IL-6 stimulates the differentiation of B cells to plasmablasts, promotes their survival, and enhances AQP4-IgG antibody secretion2,10-12

In addition, IL-6 increases blood-brain barrier permeability, allowing penetration of AQP4-IgG antibodies and proinflammatory cells into the central nervous system2,10-12

This leads to even more IL-6 production by astrocytes and further damage2,10-12

Once in the brain, AQP4-IgG antibodies bind with AQP4 channels on astrocytes, triggering activation of the complement cascade leading to astrocyte injury, oligodendrocyte loss, demyelination, and neuronal loss. IL-6 also recruits neutrophils and eosinophils. This causes bystander damage and activates microglia which produce TNF-alpha and IL-1 beta, cytokines toxic to neurons and nearby cells2,10-12

IL-6 is therefore an important therapeutic target in the treatment of NMOSD2,10

ENSPRYNG, or satralizumab, is the first and only FDA-approved humanized anti-IL-6 receptor monoclonal IgG2 antibody using novel recycling technology for adults with aquaporin-4 antibody positive NMOSD.  It is also the only treatment that can be given subcutaneously1,10,13

While the precise mechanism by which ENSPRYNG exerts therapeutic effects in NMOSD is unknown, it is presumed to involve inhibition of IL-6-mediated signaling via binding through soluble and membrane-bound IL-6 receptors1

ENSPRYNG was engineered to produce several distinguishing characteristics1,10,14,15

One is a Fab fragment, which allows for high-affinity binding to both soluble and membrane-bound IL-61,10,14,15

ENSPRYNG has an engineered IgG2 structure, designed to allow for neonatal Fc-receptor recycling1,10,14,16

Unlike some conventional monoclonal antibodies that bind to antigen once before being rapidly degraded by the cell, ENSPRYNG is transported back into the bloodstream to bind more antigen through a process called antigen recycling1,10,14,16

This allows for a longer duration of ENSPRYNG antibody circulation and prolonged plasma half-life. The clinical significance of this is unknown1,10,14-16

To summarize, by inhibiting IL-6 signaling, ENSPRYNG is thought to help decrease IL-6 mediated autoimmune T- and B-cell activation, as well as differentiation of B cells into AQP4-IgG-secreting plasmablasts1,10

In turn, this targets inflammation, blood-brain barrier permeability, and astrocyte injury—all key drivers of NMOSD disease1,2,10

ENSPRYNG Important Safety Information

Indication

ENSPRYNG is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.

Contraindications

ENSPRYNG is contraindicated in patients with a known hypersensitivity to satralizumab or any of the inactive ingredients, an active hepatitis B infection, or active or untreated latent tuberculosis

Warnings and Precautions

Infections

An increased risk of infections, including serious and potentially fatal infections, has been observed in patients treated with IL-6 receptor antagonists, including ENSPRYNG. The most common infections reported in a randomized clinical trial of patients treated with ENSPRYNG who were not on other chronic immunosuppressant therapies, and that occurred more often than in patients receiving placebo, were nasopharyngitis (12%) and cellulitis (10%). The most common infections in patients who were on an additional concurrent immunosuppressant, and that occurred more often than in patients receiving placebo, were nasopharyngitis (31%), upper respiratory infection (19%), and pharyngitis (12%). Delay ENSPRYNG administration in patients with an active infection, including localized infections, until the infection is resolved.

Hepatitis B Virus (HBV) Reactivation

Risk of HBV reactivation has been observed with other immunosuppressant therapies. Patients with chronic HBV infection were excluded from clinical trials. Perform HBV screening in all patients before initiation of treatment with ENSPRYNG.  Do not administer ENSPRYNG to patients with active hepatitis. For patients who are chronic carriers of HBV [HBsAg+] or are negative for HBsAg and positive for HB core antibody [HBcAb+], consult liver disease experts before starting and during treatment with ENSPRYNG.

Tuberculosis

Tuberculosis has occurred in patients treated with other IL-6 receptor antagonists. Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating ENSPRYNG. Consider anti-tuberculosis therapy prior to initiation of ENSPRYNG in patients with a history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Consult infectious disease experts regarding whether initiating anti-tuberculosis therapy is appropriate before starting treatment. Patients should be monitored for the development of signs and symptoms of tuberculosis with ENSPRYNG, even if initial tuberculosis testing is negative.

Vaccinations

Live or live-attenuated vaccines should not be given concurrently with ENSPRYNG because clinical safety has not been established. Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of ENSPRYNG for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of ENSPRYNG for non-live vaccines.

Elevated Liver Enzymes

Mild and moderate elevations of liver enzymes have been observed in patients treated with ENSPRYNG at a higher incidence than in patients receiving placebo. ALT and AST levels should be monitored every 4 weeks for the first 3 months of treatment, followed by every 3 months for one year, and thereafter, as clinically indicated.

Decreased Neutrophil Counts

Decreases in neutrophil counts were observed in patients treated with ENSPRYNG at a higher incidence than placebo. Neutrophil counts should be monitored 4 to 8 weeks after initiation of therapy, and thereafter at regular clinically determined intervals.

Hypersensitivity Reactions

Hypersensitivity reactions, including rash, urticaria, and fatal anaphylaxis, have occurred with other IL-6 receptor antagonists.

Use in Specific Populations

Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ENSPRYNG during pregnancy. Healthcare providers are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-833-277-9338.

There are no adequate data on the developmental risk associated with the use of ENSPRYNG in pregnant women. In an animal reproduction study, no adverse effects on maternal animals or fetal development were observed in pregnant monkeys and their offspring, with administration of ENSPRYNG at doses up to 50 mg/kg/week. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2 – 4% and 15 – 20%, respectively. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

Lactation

No information is available on the presence of ENSPRYNG in human milk, the effects of ENSPRYNG on the breastfed infant, or the effects of ENSPRYNG on milk production. ENSPRYNG was excreted in the milk of lactating monkeys administered ENSPRYNG throughout pregnancy. Human IgG is excreted in human milk and the potential for absorption in the infant is unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ENSPRYNG and any potential adverse effects on the breastfed infant from ENSPRYNG or from the underlying maternal condition.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of ENSPRYNG did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. However, population pharmacokinetic analyses in patients with NMOSD did not show that age affected the pharmacokinetics of ENSPRYNG. In general, caution should be used when dosing the elderly, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Most Common Adverse Reactions

The most common adverse reactions (≥15% in either trial) were nasopharyngitis (31%), headache (27%), upper respiratory tract infection (19%), rash (17%), arthralgia (17%), extremity pain (15%), gastritis (15%), fatigue (15%), and nausea (15%).

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

For additional safety information, please see the full Prescribing Information and Medication Guide.

References

  1. ENSPRYNG [prescribing information]. South San Francisco, CA: Genentech, Inc. 2022.
  2. Traboulsee A, Greenberg BM, Bennett JL, et al. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicenter, placebo-controlled phase 3 trial. Lancet Neurol. 2020;19(6):402-412. doi:10.1016/S1474-4422(20)30078-8
  3. Kawachi I, Lassmann H. Neurodegeneration in multiple sclerosis and neuromyelitis optica. J Neurol Neurosurg Psychiatry. 2017;88(2):137-145. doi:10.1136/jnnp-2016-313300
  4. Jarius S, Wildemann B, Paul F. Neuromyelitis optica: clinical features, immunopathogenesis and treatment. Clin Exp Immunol. 2014;176(2):149-164. doi:10.1111/cei.12271
  5. Yamamura T, Kleiter I, Fujihara K, et al. Trial of satralizumab in neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(22):2114-2124. doi:10.1056/NEJMoa1901747
  6. Huda S, Whittam D, Bhojak M, et al. Neuromyelitis optica spectrum disorders. Clin Med (Lond). 2019;19(2):169-176. doi:10.7861/clinmedicine.19-2-169
  7. Chihara N, Aranami T, Sato W, et al. Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica. Proc Natl Acad Sci USA. 2011;108(9):3701-3706. doi:10.1073/pnas.1017385108
  8. Knapp RK, Hardtstock F, Wilke T, et al. Evaluating the economic burden of relapses in neuromyelitis optica spectrum disorder: a real-world analysis using German claims data. Neurol Ther. 2021;11(1):247-263. doi:10.1007/s40120-021-00311-x
  9. Carnero Contentti E, Rojas JI, Cristiano E, et al. Latin American consensus recommendations for management and treatment of neuromyelitis optica spectrum disorders in clinical practice. Mult Scler Relat Disord. 2020;45:102428. doi:10.1016/j.msard.2020.102428
  10. Heo Y-A. Satralizumab: first approval. Drugs. 2020;80(14):1477-1482. https://doi.org/10.1007/s40265-020-01380-2
  11. Takeshita Y, Obermeier B, Cotleur AC, et al. Effects of neuromyelitis optica-IgG at the blood-brain barrier in vitro. Neurol Neuroimmunol Neuroinflamm. 2016;4(1):e311. doi:10.1212/NXI.0000000000000311
  12. Obermeier B, Daneman R, Ransohoff RM. Development, maintenance and disruption of the blood-brain barrier. Nat Med. 2013;19(12):1584-1596. doi:10.1038/nm.3407
  13. Rajan K. Satralizumab wins FDA approval for NMOSD. American Academy of Ophthalmology. Published August 18, 2020. Accessed August 10, 2022. https://www.aao.org/headline/satralizumab-wins-fda-approval-nmosd
  14. Chugai Pharmaceutical Co, LTD. SMART-Ig. Accessed August 10, 2022. https://www.chugai-pharm.co.jp/english/ir/rd/technologies/files/eChugaiProprietaryTechnologies.pdf
  15. Igawa T, Tsunoda H, Kuramochi T, Sampei Z, Ishii S, Hattori K. Engineering the variable region of therapeutic IgG antibodies. MAbs. 2011;3(3):243-252. doi:10.4161/mabs.3.3.15234
  16. Data on file. Genentech, Inc. South San Francisco, CA

A chronic, debilitating autoimmune disease3-8

Unpredictable, severe relapses can cause cumulative, irreversible neurologic damage3-10

  • Even a single episode can lead to blindless, paralysis, or death

NMOSD is often associated with a pathogenic serum IgG antibody against the water channel aquaporin 4, or AQP4, protein found in the CNS5

  • Up to 80% of patients have AQP4-IgG antibody in their serum

Interleukin 6 (IL-6) plays a pivotal role in driving inflammation2,3

IL-6 is a pleiotropic cytokine produced by a variety of cell types

The first and only FDA-approved anti-IL-6 receptor monoclonal antibody for NMOSD1

While the precise mechanism through which ENSPRYNG exerts therapeutic effects in NMOSD is unknown, it is presumed to involve inhibition of IL-6-mediated signaling via binding through soluble and membrane-bound IL-6 receptors.1

ENSPRYNG was engineered to produce several distinguishing characteristics. One is a Fab fragment, which allows for high-affinity binding to both soluble and membrane-bound IL-6.1,2,13,14

ENSPRYNG has an engineered IgG2 structure designed to allow for neonatal Fc-receptor recycling. Unlike some conventional monoclonal antibodies that bind to antigen once before being rapidly degraded by the cell, ENSPRYNG is transported back into the bloodstream to bind more antigen through a process called antigen recycling. This allows for a long duration of ENSPRYNG antibody circulation and prolonged plasma half-life. The clinical significance of this is unknown.1,2,13-15

IL-6 levels may be indicative of NMOSD relapse16

Relationship between serum IL-6 levels and relapses*

Chart detailing that higher baseline IL-6 levels correlated with the risk of clinical relapse.

During a 2-year follow-up, higher baseline IL-6 levels correlated with risk of clinical relapse

Box limits=25th and 75th percentiles; Horizontal bars=median; Vertical=range.
*IL-6 levels were assessed at baseline in patients with neuromyelitis optica (NMO) (n=20) who were in clinical remission and not receiving maintenance treatment. After a 2-year follow-up period, patients were stratified by those without clinical relapse (“Relapses (-)”; n=9) and those who had at least 1 relapse (“Relapses (+)”; n=11). Baseline IL-6 levels were compared between NMO groups and healthy controls (n=20).

Clinical studies icon
Risk reduction

Relapse reduction results at 96 weeks

Indication

ENSPRYNG is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.

Contraindications

ENSPRYNG is contraindicated in patients with a known hypersensitivity to satralizumab or any of the inactive ingredients, an active hepatitis B infection, or active or untreated latent tuberculosis.

Warnings and Precautions

Infections
An increased risk of infections, including serious and potentially fatal infections, has been observed in patients treated with IL-6 receptor antagonists, including ENSPRYNG. The most common infections reported in a randomized clinical trial of patients treated with ENSPRYNG who were not on other chronic immunosuppressant therapies, and that occurred more often than in patients receiving placebo, were nasopharyngitis (12%) and cellulitis (10%). The most common infections in patients who were on an additional concurrent immunosuppressant, and that occurred more often than in patients receiving placebo, were nasopharyngitis (31%), upper respiratory infection (19%), and pharyngitis (12%). Delay ENSPRYNG administration in patients with an active infection, including localized infections, until the infection is resolved.

Hepatitis B Virus (HBV) Reactivation
Risk of HBV reactivation has been observed with other immunosuppressant therapies. Patients with chronic HBV infection were excluded from clinical trials. Perform HBV screening in all patients before initiation of treatment with ENSPRYNG. Do not administer ENSPRYNG to patients with active hepatitis. For patients who are chronic carriers of HBV [HBsAg+] or are negative for HBsAg and positive for HB core antibody [HBcAb+], consult liver disease experts before starting and during treatment with ENSPRYNG.

Tuberculosis
Tuberculosis has occurred in patients treated with other IL-6 receptor antagonists. Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating ENSPRYNG. Consider anti-tuberculosis therapy prior to initiation of ENSPRYNG in patients with a history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Consult infectious disease experts regarding whether initiating anti-tuberculosis therapy is appropriate before starting treatment. Patients should be monitored for the development of signs and symptoms of tuberculosis with ENSPRYNG, even if initial tuberculosis testing is negative.

Vaccinations
Live or live-attenuated vaccines should not be given concurrently with ENSPRYNG because clinical safety has not been established. Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of ENSPRYNG for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of ENSPRYNG for non-live vaccines.

Elevated Liver Enzymes
Mild and moderate elevations of liver enzymes have been observed in patients treated with ENSPRYNG at a higher incidence than in patients receiving placebo. ALT and AST levels should be monitored every 4 weeks for the first 3 months of treatment, followed by every 3 months for one year, and thereafter, as clinically indicated.

Decreased Neutrophil Counts
Decreases in neutrophil counts were observed in patients treated with ENSPRYNG at a higher incidence than placebo. Neutrophil counts should be monitored 4 to 8 weeks after initiation of therapy, and thereafter at regular clinically determined intervals.

Hypersensitivity Reactions
Hypersensitivity reactions, including rash, urticaria, and fatal anaphylaxis, have occurred with other IL-6 receptor antagonists.

Use in Specific Populations

Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ENSPRYNG during pregnancy. Healthcare providers are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-833-277-9338.

There are no adequate data on the developmental risk associated with the use of ENSPRYNG in pregnant women. In an animal reproduction study, no adverse effects on maternal animals or fetal development were observed in pregnant monkeys and their offspring, with administration of ENSPRYNG at doses up to 50 mg/kg/week. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2 – 4% and 15 – 20%, respectively. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.


Lactation
No information is available on the presence of ENSPRYNG in human milk, the effects of ENSPRYNG on the breastfed infant, or the effects of ENSPRYNG on milk production. ENSPRYNG was excreted in the milk of lactating monkeys administered ENSPRYNG throughout pregnancy. Human IgG is excreted in human milk and the potential for absorption in the infant is unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ENSPRYNG and any potential adverse effects on the breastfed infant from ENSPRYNG or from the underlying maternal condition.

Pediatric Use
Safety and effectiveness in pediatric patients have not been established.

Geriatric Use
Clinical studies of ENSPRYNG did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. However, population pharmacokinetic analyses in patients with NMOSD did not show that age affected the pharmacokinetics of ENSPRYNG. In general, caution should be used when dosing the elderly, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Most Common Adverse Reactions

The most common adverse reactions (≥15% in either trial) were nasopharyngitis (31%), headache (27%), upper respiratory tract infection (19%), rash (17%), arthralgia (17%), extremity pain (15%), gastritis (15%), fatigue (15%), and nausea (15%).

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

For additional safety information, please see the full Prescribing Information and Medication Guide.

    • ENSPRYNG [prescribing information]. South San Francisco, CA: Genentech, Inc. 2022.

      ENSPRYNG [prescribing information]. South San Francisco, CA: Genentech, Inc. 2022.

    • Heo Y-A. Satralizumab: first approval. Drugs. 2020;80(14):1477-1482. https://doi.org/10.1007/s40265-020-01380-2

      Heo Y-A. Satralizumab: first approval. Drugs. 2020;80(14):1477-1482. https://doi.org/10.1007/s40265-020-01380-2

    • Traboulsee A, Greenberg BM, Bennett JL, et al. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol. 2020;19(5):402-412. doi:10.1016/S1474-4422(20)30078-8

      Traboulsee A, Greenberg BM, Bennett JL, et al. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol. 2020;19(5):402-412. doi:10.1016/S1474-4422(20)30078-8

    • Kawachi I, Lassmann H. J Neurol Neurosurg Psychiatry. 2017;88:137–145. doi:10.1136/jnnp-2016-313300

      Kawachi I, Lassmann H. J Neurol Neurosurg Psychiatry. 2017;88:137–145. doi:10.1136/jnnp-2016-313300

    • Jarius S, Wildemann D, Paul F. Neuromyelitis optica: clinical features, immunopathogenesis and treatment. Clinical and Experimental Immunology. 2014;176:149–164. doi:10.1111/cei.12271

      Jarius S, Wildemann D, Paul F. Neuromyelitis optica: clinical features, immunopathogenesis and treatment. Clinical and Experimental Immunology. 2014;176:149–164. doi:10.1111/cei.12271

    • Yamamura T, Kleiter I, Fujihara K, et al. Trial of satralizumab in neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(22):2114-2124.

      Yamamura T, Kleiter I, Fujihara K, et al. Trial of satralizumab in neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(22):2114-2124.

    • Huda S, Whittam D, Bhojak M, et al. Neuromyelitis optica spectrum disorders. Clinical Medicine. 2019; 19(2):169–176.

      Huda S, Whittam D, Bhojak M, et al. Neuromyelitis optica spectrum disorders. Clinical Medicine. 2019; 19(2):169–176.

    • Chihara N, Aranami T, Sato W, et al. Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica. Proc Natl Acad Sci USA. 2011;108(9):3701-3706.

      Chihara N, Aranami T, Sato W, et al. Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica. Proc Natl Acad Sci USA. 2011;108(9):3701-3706.

    • Knapp RK, Hardtstock F, Wilke T, et al. Evaluating the economic burden of relapses in neuromyelitis optica spectrum disorder: a real-world analysis using German claims data. Neurol Ther. 2022;11:247-263. https://doi.org/10.1007/s40120-021-00311-x

      Knapp RK, Hardtstock F, Wilke T, et al. Evaluating the economic burden of relapses in neuromyelitis optica spectrum disorder: a real-world analysis using German claims data. Neurol Ther. 2022;11:247-263. https://doi.org/10.1007/s40120-021-00311-x

    • Contentti EC, Rojas JI, Cristiano E, et al. Latin American consensus recommendations for management and treatment of neuromyelitis optica spectrum disorders in clinical practice. Mult Scler Relat Disord. 2020;45:102428. doi: 10.1016/j.msard.2020.102428

      Contentti EC, Rojas JI, Cristiano E, et al. Latin American consensus recommendations for management and treatment of neuromyelitis optica spectrum disorders in clinical practice. Mult Scler Relat Disord. 2020;45:102428. doi: 10.1016/j.msard.2020.102428

    • Takeshita Y, Obermeier B, Cotleur AC, et al. Effects of neuromyelitis optica-IgG at the blood-brain barrier in vitro. Neurol Neuroimmunol Neuroinflamm. 2016;4(1):e311. doi:10.1212/NXI.0000000000000311

      Takeshita Y, Obermeier B, Cotleur AC, et al. Effects of neuromyelitis optica-IgG at the blood-brain barrier in vitro. Neurol Neuroimmunol Neuroinflamm. 2016;4(1):e311. doi:10.1212/NXI.0000000000000311

    • Obermeier B, Daneman R, Ransohoff RM. Development, maintenance and disruption of the blood-brain barrier. Nat Med. 2013;19(12):1584-1596. doi:10.1038/nm.3407

      Obermeier B, Daneman R, Ransohoff RM. Development, maintenance and disruption of the blood-brain barrier. Nat Med. 2013;19(12):1584-1596. doi:10.1038/nm.3407

    • Chugai Pharmaceutical Co, LTD. SMART-Ig. Accessed February 17, 2022. https://www.chugai-pharm.co.jp/english/ir/rd/technologies/files/eChugaiProprietaryTechnologies.pdf

      Chugai Pharmaceutical Co, LTD. SMART-Ig. Accessed February 17, 2022. https://www.chugai-pharm.co.jp/english/ir/rd/technologies/files/eChugaiProprietaryTechnologies.pdf

    • Igawa T, Tsunoda H, Kuramochi T, Sampei Z, Ishii S, Hattori K. Engineering the variable region of therapeutic IgG antibodies. MAbs. 2011;3(3):243-252.

      Igawa T, Tsunoda H, Kuramochi T, Sampei Z, Ishii S, Hattori K. Engineering the variable region of therapeutic IgG antibodies. MAbs. 2011;3(3):243-252.

    • Data on file. Genentech, Inc. South San Francisco, CA.

      Data on file. Genentech, Inc. South San Francisco, CA.

    • Barros PO, Cassano T, Hygino J, et al. Prediction of disease severity in neuromyelitis optica by the levels of interleukin (IL)-6 produced during remission phase. Clin Exp Immunol. 2016;183:480-489.

      Barros PO, Cassano T, Hygino J, et al. Prediction of disease severity in neuromyelitis optica by the levels of interleukin (IL)-6 produced during remission phase. Clin Exp Immunol. 2016;183:480-489.