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Multiple Sclerosis (MS) is a degenerative autoimmune disorder affecting the myelin sheath in the brain. The gMS®Dx blood test is a breakthrough tool which was designed as a companion to the magnetic resonance imaging (MRI) scan in order to expedite the diagnosis of Relapsing Remitting MS (RRMS) in suspected MS cases at first neurological event and Clinical Isolated Syndrome (CIS) patients. The gMS®Dx test enables early treatment as required by the American Academy of Neurology (AAN) Guidelines, while replacing repeated MRI scans and avoidance of additional diagnostic office visits and tests.
MS AAN diagnosis Guidelines
The diagnosis of MS is often time consuming and difficult since there is no definitive test to diagnose MS. Patients with typical symptoms correspond to demyelinating clinical events, as well as patients with atypical symptoms of MS for which other neurological diseases could not be diagnosed, are considered as suspected MS patients. The diagnosis of MS relies on the integration of evidence to disease dissemination in time and space (Poser et al., 1983). Epidemiology studies (Fisniku et al., 2008, Tintoré et. al, 2006) show that only 11-19% of suspected cases will have a confirmed diagnosis of clinically definite MS (CDMS) within one year of first presentation and it can take up to 20 years to confirm a CDMS diagnosis in 67% of first presentation MS patients. McDonald criteria formally integrate first neurological event clinical data with MRIdata, provides low sensitivity of 41% at high specificity of 91% (McDonald et al., 2001, Polman et al., 2005). AAN Guidelines (≥3 white matter lesions on a T2-weighted MRI) predict 80% of CIS patients with a high risk for conversion to CDMS within 7 to 10 years. New T2 lesions or new Gd enhancement lesions at repeated MRI scan, three or more months after a baseline MRI assessment, is highly predictive of the subsequent development of CDMS (Frohman EM et al 2003; Guideline Summary NGC-3154).
MS AAN Treatment Guidelines
The current standard of care for treatment of RRMS is to use Disease Modifying Therapies (DMT) such as beta-interferon (INFB 1a or INFB 1b) in MS and in CIS patients suggestive of MS (i.e. high risk to convert CDMS) or glatiramer acetate in RRMS as soon as a patient is diagnosed with MS (Goodin DS et al., 2002; Guideline Summary NGC-3144).
The gMS®Dx Blood Test
For patients who do not meet with the AAN Guidelines or with McDonald criteria, baseline MRI provides only 64% sensitivity and 67% specificity for Barkhof dissemination in space (DIS) and 46.9% sensitivity and 87.5% specificity for dissemination in time (DIT) (Rovira et al., 2009). Therefore, repeated MRI scans are required to complete the diagnosis of RRMS to enable AAN treatment Guidelines. The gMS®Dx blood test which measures the level of IgM antibodies to the glycan structure GAGA4, and normalized according to the total IgM antibody level, is the first validated serum based test which is highly specific to rule-in RRMS patients at first neurological event. Several studies on over 1,352 MS patients, healthy controls and patients with other neurological disorders that mimic MS show that when using the gMS®Dx test once, at the first neurological presentation, it is able to identify RRMS at a high specificity of 92.8%, thus enabling to confirm MS diagnosis and meet AAN treatment Guidelines. As a companion tool to MRI, cut-off values were set at high specificity to yield mid-level sensitivity of 53.9%. Therefore, it is not recommended to replace baseline MRI scans, but to save repeated MRI scans after baseline (Data on file at Glycominds Laboratory, CA License Number: CLF00340032).
The gMS®Dx Test is performed exclusively by Glycominds Laboratory Services at our CLIA approved lab in Simi Valley, California (CA License Number: CLF00340032. There are currently no approved billing codes for this test which is why it is billed using the CPT Code 84999. As the only provider of this test we ask that you adjudicate our claims based on the patients in network rates as there is not an option for the patient to use a network provider.
References
▪ Guideline Summary NGC-3154: The utility of MRI in suspected MS: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.
Bibliographic Source:
Frohman EM, Goodin DS, Calabresi PA, Corboy JR, Coyle PK, Filippi M, Frank JA, Galetta SL, Grossman RI, Hawker K, Kachuck NJ, Levin MC, Phillips JT, Racke MK, Rivera VM, Stuart WH. The utility of MRI in suspected MS: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2003;61:602-611.
▪ Guideline Summary NGC-3144: Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment
Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines.
Bibliographic Source(s):
Goodin DS, Frohman EM, Garmany GP Jr, Halper J, Likosky WH, Lublin FD, Silberberg DH, Stuart WH, van den Noort S. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology 2002;58:169-178.
▪ Dalton CM, Brex PA, Miszkiel KA, Hickman SJ, MacManus DG, Plant GT, Thompson AJ, Miller DH. Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis. Ann Neurol. 2002;52:47-53.
▪ Fisniku LK, Brex PA, Altmann DR, Miszkiel KA, Benton CE, Lanyon R, Thompson AJ, Miller DH. Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain. 2008;131:808-817.
▪ McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121-127.
▪ Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O'Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005;58:840-846.
▪ Rovira A, Swanton J, Tintoré M, Huerga E, Barkhof F, Filippi M, Frederiksen JL, Langkilde A, Miszkiel K, Polman C, Rovaris M, Sastre-Garriga J, Miller D, Montalban X. Arch Neurol. 2009;66:587-592.
▪ Tintoré M, Rovira A, Río J, Nos C, Grivé E, Téllez N, Pelayo R, Comabella M, Sastre-Garriga J, Montalban X. Baseline MRI predicts future attacks and disability in clinically isolated syndromes. Neurology. 2006;67:968-972.
Multiple Sclerosis (MS) is a degenerative autoimmune disorder affecting the myelin sheet in the brain. MS causes both acute and chronic disability for most patients and often severely affects functioning and quality of life (QOL). The gMS®Pro EDSS Test is a breakthrough tool to identify Clinically Isolated Syndrome (CIS) patients suggestive of MS and relapsing form of MS patients at risk for rapid disease progression. Using this blood test enables physicians to predict patients at risk for rapid Expanded Disability Status Scale (EDSS) progression and therefore justifiably escalate for more aggressive therapy associated with severe side effects. Thus, avoiding disease progression and accumulation of irreversible disability and lost of QOL.
The challenge of heterogeneity in MS disease progression
The effect of MS progression is widely variable across patients. About 50% of patients reach the following disability milestones: loss of employment (10 years after diagnosis), need for assistive walking devices (15 years), and inability to walk (25 years). Additional impacts can include loss of arm function, loss of cognitive function, fatigue, weakness, pain, tremor, vision problems, urinary dysfunction, bowel dysfunction, muscle spasticity, swallowing disorders, sexual dysfunction, depression, anxiety, and others. The heterogeneity of MS poses a challenge for the development of clinical guidelines, because very different types of clinical interventions may be needed for different patients. Neurologists have defined four main types of courses of MS. They are directly pertinent for clinical guidelines because therapies effective for one course are often not effective for others (AHRQ-Expert Commentaries December 8, 2008).
MS AAN Treatment Guidelines
The current standard of care for treatment of RRMS is to use 1st line of Disease Modifying Therapies (DMT) such as beta-interferon (INFB 1a or INFB 1b) in MS and in Clinical Isolated Syndrome (CIS) suggestive of MS (i.e. high risk to convert to clinically definite MS) or glatiramer acetate in RRMS as soon as a patient is diagnosed with MS or CIS suggestive of MS (Goodin DS et al., 2002; Guideline Summary NGC-3144). Natalizumab (Tysabri) is an approved drug in the U.S. Food and Drug Administration (FDA) which improves measures of disease severity such as the EDSS progression rate and the T2-hyperintense and T1-hypointense lesion burden seen on magnetic resonance imaging (MRI) in patients with relapsing MS. However, there is an increased risk of developing progressive multifocal leukoencephalopathy (PML) in natalizumab treated patients (Goodin DS et al, 2008; Guideline Summary NGC-6705). More recently the FDA approved fingolimod capsules (Gilenya) for the treatment of patients with relapsing form of MS to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability. However, Gilenya may cause serious side effects including: slow heart rate (bradycardia or bradyarrhythmia) and serious infections (Gilenya product insert).
The gMS®Pro EDSS Blood Test
The gMS®Pro EDSS Test measures the level of IgM antibodies to a panel of glycan structures including GAGA2, 3, 4, 6. Several studies on over 462 CIS and MS patients show that the level of antibodies to a panel of GAGA molecules under the classification rule called gMS-Classifier1, identifies MS patient at risk for rapid confirmed (irreversible) EDSS progression. Hazard ratio of 2.05 for CIS patients suggestive of MS and 10.5 for relapsing form of MS (Data on file at Glycominds Laboratory, CA License Number: CLF00340032).
The gMS®Pro EDSS Test is performed exclusively by Glycominds Laboratory Services at our CLIA approved lab in Simi Valley, California (CA License Number: CLF00340032. There are currently no approved billing codes for this test which is why it is billed using the CPT Code 84999. As the only provider of this test we ask that you adjudicate our claims based on the patients in network rates as there is not an option for the patient to use a network provider.
References
▪ U.S. Department of Health and Human Services, Agency of Healthcare Research and Quality, Expert Commentaries December 8, 2008.
Bibliographic Source(s): Michael G. Trisolini, PhD, MBA
▪ Guideline Summary NGC-3144: Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment
Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines.
Bibliographic Source(s)
Goodin DS, Frohman EM, Garmany GP Jr, Halper J, Likosky WH, Lublin FD, Silberberg DH, Stuart WH, van den Noort S. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology 2002 Jan 22;58(2):169-78.
▪ Guideline Summary NGC-6705: Assessment: the use of natalizumab (Tysabri) for the treatment of multiple sclerosis (an evidence-based review). Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.
Bibliographic Source(s)
Goodin DS, Cohen BA, O'Connor P, Kappos L, Stevens JC. Assessment: the use of natalizumab (Tysabri) for the treatment of multiple sclerosis (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2008 Sep 2;71(10):766-73.
▪ Gilenya product insert, Novartis Pharmaceuticals Corporation, East Hanover, (NJ 07936, T2010-81/t2010-82 5002679)
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