Diagnosing NMOSD vs MS

Misdiagnosis of NMOSD as MS leaves patients vulnerable to potentially permanent disability1

NMOSD patient, Carla

NMOSD patient, Carla

Graphic-image Graphic-image Graphic-image

NMOSD and MS share similar diagnostic criteria, but there are key differences evident on
MRI4-7

NMOSD vs MS differential diagnosis table in the domain of transverse myelitis, with both MS and NMOSD presenting in spasms, limb weakness, sensation loss, paralysis, and loss of bladder/bowel function, but with MS MRI showing longitudinal, short‐length spinal cord lesions and NMOSD MRI showing LETM involving >50% of the spinal cord, centrallyNMOSD vs MS differential diagnosis table in the domain of transverse myelitis, with both MS and NMOSD presenting in spasms, limb weakness, sensation loss, paralysis, and loss of bladder/bowel function, but with MS MRI showing longitudinal, short‐length spinal cord lesions and NMOSD MRI showing LETM involving >50% of the spinal cord, centrally

NMOSD vs MS differential diagnosis table in the domain of optic neuritis, with MS presenting in vision loss and unilateral optic neuritis in MRI, and NMOSD presenting in vision loss, blindness, and unilateral or bilateral optic neuritis in MRINMOSD vs MS differential diagnosis table in the domain of optic neuritis, with MS presenting in vision loss and unilateral optic neuritis in MRI, and NMOSD presenting in vision loss, blindness, and unilateral or bilateral optic neuritis in MRI

NMOSD vs MS differential diagnosis table in the domain of brain and brain stem, with MS not presenting through hiccups, nausea, or vomiting and an MRI of ovoid, white-matter lesions, and NMOSD presenting as hiccups, nausea, and vomiting, and an MRI showing periventricular and circumventricular lesionsNMOSD vs MS differential diagnosis table in the domain of brain and brain stem, with MS not presenting through hiccups, nausea, or vomiting and an MRI of ovoid, white-matter lesions, and NMOSD presenting as hiccups, nausea, and vomiting, and an MRI showing periventricular and circumventricular lesions

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Learn about AQP4-IgG testing for diagnosing NMOSD

aTreatments for MS that can exacerbate NMOSD include interferon-beta, natalizumab, and S1P receptor modulators.4,8

bSymptom of area postrema syndrome.

LETM, longitudinally extensive transverse myelitis; MS, multiple sclerosis; NMOSD, neuromyelitis optica spectrum disorder; S1P, sphingosine 1-phosphate.

Tx Recommendations

INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATION

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

IMPORTANT SAFETY INFORMATION

UPLIZNA is contraindicated in patients with:

  • A history of life-threatening infusion reaction to UPLIZNA
  • Active hepatitis B infection
  • Active or untreated latent tuberculosis

WARNINGS AND PRECAUTIONS

Infusion Reactions: UPLIZNA can cause infusion reactions, which can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash, or other symptoms. Infusion reactions were most common with the first infusion but were also observed during subsequent infusions. Administer pre-medication with a corticosteroid, an antihistamine, and an anti-pyretic.

Infections: The most common infections reported by UPLIZNA-treated patients in the randomized and open-label periods included urinary tract infection (20%), nasopharyngitis (13%), upper respiratory tract infection (8%), and influenza (7%). Delay UPLIZNA administration in patients with an active infection until the infection is resolved.

Increased immunosuppressive effects are possible if combining UPLIZNA with another immunosuppressive therapy.

The risk of Hepatitis B Virus (HBV) reactivation has been observed with other B-cell-depleting antibodies. Perform HBV screening in all patients before initiation of treatment with UPLIZNA. Do not administer to patients with active hepatitis.

Although no confirmed cases of Progressive Multifocal Leukoencephalopathy (PML) were identified in UPLIZNA clinical trials, JC virus infection resulting in PML has been observed in patients treated with other B-cell-depleting antibodies and other therapies that affect immune competence. At the first sign or symptom suggestive of PML, withhold UPLIZNA and perform an appropriate diagnostic evaluation.

Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating UPLIZNA.

Vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation, until B-cell repletion.

Reduction in Immunoglobulins: There may be a progressive and prolonged hypogammaglobulinemia or decline in the levels of total and individual immunoglobulins such as immunoglobulins G and M (IgG and IgM) with continued UPLIZNA treatment. Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with UPLIZNA until B-cell repletion especially in patients with opportunistic or recurrent infections.

Fetal Risk: May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 6 months after stopping UPLIZNA.

Adverse Reactions: The most common adverse reactions (at least 10% of patients treated with UPLIZNA and greater than placebo) were urinary tract infection and arthralgia.

INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATION

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

IMPORTANT SAFETY INFORMATION

UPLIZNA is contraindicated in patients with:

  • A history of life-threatening infusion reaction to UPLIZNA
  • Active hepatitis B infection
  • Active or untreated latent tuberculosis

WARNINGS AND PRECAUTIONS

Infusion Reactions: UPLIZNA can cause infusion reactions, which can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash, or other symptoms. Infusion reactions were most common with the first infusion but were also observed during subsequent infusions. Administer pre-medication with a corticosteroid, an antihistamine, and an anti-pyretic.

Infections: The most common infections reported by UPLIZNA-treated patients in the randomized and open-label periods included urinary tract infection (20%), nasopharyngitis (13%), upper respiratory tract infection (8%), and influenza (7%). Delay UPLIZNA administration in patients with an active infection until the infection is resolved.

Increased immunosuppressive effects are possible if combining UPLIZNA with another immunosuppressive therapy.

The risk of Hepatitis B Virus (HBV) reactivation has been observed with other B-cell-depleting antibodies. Perform HBV screening in all patients before initiation of treatment with UPLIZNA. Do not administer to patients with active hepatitis.

Although no confirmed cases of Progressive Multifocal Leukoencephalopathy (PML) were identified in UPLIZNA clinical trials, JC virus infection resulting in PML has been observed in patients treated with other B-cell-depleting antibodies and other therapies that affect immune competence. At the first sign or symptom suggestive of PML, withhold UPLIZNA and perform an appropriate diagnostic evaluation.

Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating UPLIZNA.

Vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation, until B-cell repletion.

Reduction in Immunoglobulins: There may be a progressive and prolonged hypogammaglobulinemia or decline in the levels of total and individual immunoglobulins such as immunoglobulins G and M (IgG and IgM) with continued UPLIZNA treatment. Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with UPLIZNA until B-cell repletion especially in patients with opportunistic or recurrent infections.

Fetal Risk: May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 6 months after stopping UPLIZNA.

Adverse Reactions: The most common adverse reactions (at least 10% of patients treated with UPLIZNA and greater than placebo) were urinary tract infection and arthralgia.

  1. Mealy MA, Wingerchuk DM, Greenberg BM, Levy M. Epidemiology of neuromyelitis optica in the United States: a multicenter analysis. Arch Neurol. 2012;69(9):1176-1180. doi:10.1001/archneurol.2012.314
  2. Beekman J, Keisler A, Pedraza O, et al. Neuromyelitis optica spectrum disorder: patient experience and quality of life. Neurol Neuroimmunol Neuroinflamm. 2019;6(4):e580. doi:10.1212/NXI.0000000000000580
  3. Mealy MA, Mossburg SE, Kim S-H, et al. Long-term disability in neuromyelitis optica spectrum disorder with a history of myelitis is associated with age at onset, delay in diagnosis/preventive treatment, MRI lesion length and presence of symptomatic brain lesions. Mult Scler Relat Disord. 2019;28:64-68. doi:10.1016/j.msard.2018.12.011
  4. MS signs & symptoms. National Multiple Sclerosis Society. Accessed August 8, 2022. https://www.nationalmssociety.org/Symptoms-Diagnosis/MS-Symptoms
  5. National Organization for Rare Disorders. Neuromyelitis optica spectrum disorder. NORD. Updated 2018. Accessed August 8, 2022. https://rarediseases.org/rare-diseases/neuromyelitis-optica/
  6. Dutra BG, da Rocha AJ, Nunes RH, Maia ACM Jr. Neuromyelitis optica spectrum disorders: spectrum of MR imaging findings and their differential diagnosis. Radiographics. 2018;38(1):169-193. doi:10.1148/rg.2018170141
  7. Pereira WLCJ, Reiche EMV, Kallaur AP, et al. Epidemiological, clinical, and immunological characteristics of neuromyelitis optica: a review.
    J Neurol Sci. 2015;355(1-2):7-17. doi:10.1016/j.jns.2015.05.034
  8. Traub J, Häusser-Kinzel S, Weber MS. Differential effects of MS therapeutics on B cells—implications for their use and failure in AQP4-positive NMOSD patients. Int J Mol Sci. 2020;21:1-30. doi:10.3390/ijms21145021