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Understanding MMN

Explore the mechanisms driving MMN and the clinical measures used to evaluate disease activity

DISEASE STATE EDUCATION

Understanding MMN

Explore the mechanisms driving MMN and the clinical measures used to evaluate disease activity

 

Decoding MMN pathophysiology

Overview of antibody involvement in MMN

Diverse autoantibodies targeting gangliosides have been observed in MMN.1  

Antibodies of the IgG, IgM, and IgA classes have been detected in patients with MMN; common targets of these autoantibodies include gangliosides GM1 and GM2.1

Additional studies have identified autoantibodies targeting other neural antigens, including the mixture of GM1 with galactocerebroside or the disulfated heparin disaccharide NS6S.2

Classes of autoantibodies found in MMN:1

IgG

IgM

IgM

IgA

Targets of anti-ganglioside autoantibodies:1

Class and target

Percentage of patients with MMN

Anti-GM1 IgM

43%

Anti-GM1 IgA

5%

Anti-GM1 IgG and IgA

1%

Anti-GD1b and anti-GM1 IgM

9%

Anti GM2 IgM

6%

Anti-GD1a, GalNAc-GD1a, GM1b, Gt1a, GQ1b, or SGPG IgM, IgA or IgG

0%

Proposed involvement of IgM autoantibodies and complement activation in MMN

IgM autoantibodies targeting GM1 found in the central and peripheral nervous system have been detected in 40–60% of patients with MMN using current diagnostic tests.2,3,4,5

Patients seropositive for IgM autoantibodies targeting GM1 show greater weakness, disability, and axonal loss than patients without these antibodies.1,a

IgM autoantibodies, including those targeting GM1, can activate the complement pathway in a titer-dependent manner, with greater complement activity correlated with more severe muscle weakness and axonal loss.6-8

Proposed pathophysiology of MMN5,9,10

Proposed pathophysiology of MMN

In MMN, IgM antibodies may cause nerve dysfunction by targeting ganglioside GM1, leading to conduction block through direct and complement-driven indirect mechanisms.11

Watch the proposed mechanism of disease in MMN

IgM autoantibodies may result in:10–12

  • Displacement of ion channel clusters
  • Demyelination
  • Activation of the complement pathway, resulting in deposition of MAC and additional membrane and axonal damage

Available evidence suggests that complement activation may play an important role in the pathogenesis of MMN11

Unveiling the essential role of complement6

Mechanistic data

Studies using patient sera suggested that IgM autoantibodies from patients with MMN can activate the complement cascade and that titers of anti-GM1 IgM antibodies correlate with classical complement pathway complex deposition.7,8

In these experiments, normal human sera served as a source of complement factors:

2015 in vitro analysis8

Vlam and colleagues found that anti-GM1 IgM antibodies from the serum of patients with MMN can activate complement and induce the deposition of complement activation products C3b and C5b-9 (the membrane attack complex) in vitro in a titer-dependent manner

2011 in vitro analysis7

Yuki and colleagues found a strong correlation between the deposition of complement factors C1q, C4b, and C3b in vitro and titers of anti-GM1 antibodies from the sera of patients with MMN

Play: Complement Quest

Learn how the classical complement pathway unfolds and save your neuron from immune-mediated damage!

Translating MMN pathophysiology into clinical markers

Correlation between complement activity and MMN disease severity

A study of patients with MMN demonstrated that complement activity correlates with MMN disease severity, as measured by muscle weakness and axonal loss.8,13

Outcome assessment tools in MMN

There are a number of tools available for the assessment of functional, patient-reported, or QoL outcomes in MMN:

  • Grip strength can be used to evaluate muscle weakness14
  • The Martin Vigorimeter is a hydraulic instrument used to measure isometric strength using a compressible rubber ball15
  • Measurements are repeated three times15
  • MMN-RODS is a disease-specific assessment tool used to evaluate activity limitations in patients with MMN
  • MMN disease-specific items are mainly related to fine motor hand activities and upper limb function
  • It is composed of 25 items that are scored 0 (unable to perform), 1 (able to perform, but with difficulty), or 2 (able to perform without difficulty), with a total possible score ranging from 0 to 50
  • The raw scores are transformed to logits and then to a centile metric, ranging from 0 to 100, to determine the final MMN-RODS score
  • HRPQ can be used to evaluate health-related productivity and work productivity
  • It was originally developed as a self-administered outcome measure in patients with Parkinson’s disease
  • The HRPQ provides data related to missed hours at work or educational activities and reduced effectiveness during any attempted work
  • The FSS was developed to assess fatigue and consists of a short questionnaire that requires the participant to rate their own level of fatigue from the previous week
  • Nine items are rated from 1 to 7, depending on how the patient felt the statement applied to them over the previous week. A low value indicates that the patient disagrees with the question, whereas a high value indicates agreement
  • The EQ-5D-5L VAS can be used to evaluate participants’ overall assessment of their health on a scale of 1 to 100
  • The endpoints are labeled “the best health you can imagine” and “the worst health you can imagine”
  • PGI-C can be used to measure participants’ impressions of overall disease improvement
  • The PGI-C is a patient-reported outcome, measuring a patient’s belief about the efficacy of their treatment on a 7-point scale
  • The GNDS measures disability in 12 domains
  • Disability in each domain is measured using a 6-step severity scale, ranging from 0 (normal status) to 5 (total loss of function – maximal help required)
  • MRC sum scores are used to evaluate muscle strength
  • The muscle groups evaluated can be tested against gravity, with both proximal and distal muscle groups included
  • Each muscle group, tested on both sides, is scored from 0 (paralysis) to 5 (normal strength)
  • The 9-HPT is regarded as the gold standard in quantitatively evaluating fine motor dexterity
  • The 9-HPT measures the number of seconds it takes a participant to place nine pegs into a peg board and then remove them
  • TSQM can be used to evaluate treatment satisfaction21
  • It was originally developed to measure patient satisfaction/experience with their medication using four dimensions/subscales: effectiveness (items 1–3), side effects (items 4–8), convenience (items 9–11), and global satisfaction (items 12–14)22
  • The scores for each dimension/subscale are transformed and range from 0 to 100, with higher numbers indicating greater patient satisfaction with treatment/medication22
  • EQ-5D-5L can be used to evaluate QoL
  • The EQ-5D-5L is composed of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression
  • Responses are recorded based on five levels of severity: no problems, slight problems, moderate problems, severe problems, and unable to/extreme problems
  • CAP-PRI can be used to evaluate disease-specific QoL
  • It was specifically developed for patients with chronic, immune-mediated polyneuropathies
  • The CAP-PRI addresses several life domains (physical and social functioning, pain, and emotional well-being)
  • There are 15 items, scored as: 0 (not at all), 1 (a little bit), or 2 (a lot)
  • The PGI-S score can be used to evaluate the participant’s belief about the severity of their MMN
  • The PGI-S asks participants to rate their symptom or disease severity on a verbal scale ranging from “not present” to “extremely severe”
  • PGI-S measurements are typically administered at multiple timepoints
  • The INCAT score is an ordinal scale scored from 0 to 10, with higher scores indicating greater disability

Footnotes:
aData from a cross-sectional study of 88 patients in the Netherlands from January through December 2017; 81% had definite MMN, 18% probable, 1% possible; 73% were male; median age was 52 (27–78) years.1

Abbreviations:
C=complement factor; CAP-PRI=Chronic Acquired Polyneuropathy Patient-Reported Index; EQ-5D-5L=EuroQoL 5-Dimension, 5-Level; FSS=Fatigue Severity Scale; GalNAc=N-acetylgalactosamine; GD=disialoganglioside; GM=monosialoganglioside; GNDS=Guy’s Neurological Disability Scale; GQ=quadsialoganglioside; Gt=trisialoganglioside; 9-HPT=9 Hole Peg Test; HRPQ=Health Related Productivity Questionnaire; HRQOL=Health-Related Quality of Life; Ig=immunoglobulin; INCAT=Inflammatory Neuropathy Cause and Treatment; MAC=membrane attack complex; MMN=multifocal motor neuropathy; MMN-RODS=Rasch-built Overall Disability Scale for multifocal motor neuropathy; MRC=Medical Research Council; PGI-C=Patient Global Impression of Change; PGI-S=Patient Global Impression of Severity; PROM=Patient Reported Outcome Measure; QoL=quality of life; SGPG=sulfoglucuronyl paragloboside; TSQM=Treatment Satisfaction Questionnaire for Medication; VAS=Visual Analogue Scale.

References:
1. Cats EA, et al. Neurology. 2010;75(9):818-825. doi: 10.1212/WL.060133181f0738e; 2. Nobile-Orazio E, et al. J Neurol Neurosurg Psychiatry. 2014;85(7):754-758. doi:10.1136/jnnp-2013-305755; 3. Delmont E, et al. J Neuroimmunol.2015;278:159-161. doi:10.1016/j.jneuroim.2014.11.001; 4. Guo Z, et al. Int J Mol Sci. 2023;24(11x9558. doi:10.3390/ljms24119558; 5. Loser V, et al. Front Neurol. 2024;15:1495205. doi:10.3389/fneur.2024,1495205; 6. Krijgsman D, et al. Neurol Neuroimmunol Neuroinflamm. 2026;13(1):e200482. doi:10.1212/NXI.0000000000200482; 7. Yuki N, et al. J Neurol Neurosurg Psychiatry. 2011;82(1):87-91. doi:10.1136/jnnp.2010.205856;  8. Vlam L, et al. Neurol Neurommunol Neuroinflamm. 2015;2(4):e119. doi:10.1212/ NXI.0000000000000119; 9. Sathe A, Cusick JK. Biochemistry, Immunoglobulin M.[Updated 2022 Dec 19), In: StatPearls [Internet). Treasure Island (FL): StatPearls Publishing; Jan 2025. Available at: www.ncbi.nlm_.nih.gov/books/NBK555995/ (Accessed: November 2025); 10. Vlam L, et al. Nat Rev Neurol. 2011;8(1):48-58. doi:10.1038/nreurol.2011.175; 11. Harschnitz O, et al.J Clin Immunol. 2014;34(suppl1):S112-S119. doi:10.1007/s10875-014-0026-3; 12. Beadon K, et al. Curr Opin Neurol. 2018;31(5):559-564. doi:10.1097/WCO.0000000000000605; 13. Querol L et al. Nat Rev Neurol. 2017;13(9):533-547. dol:10.1038/nmeurol.2017.84; 14. Lee SY, et al. Ann Rehabil Med. 2021;45(3):167-169. dol:10.5535/arm.21106; 15. Neumann S, et al, In Vivo. 2017;31(5):917-924. doi: 10.21873/invivo.11147; 16. Kleyweg RP, et al. Muscle Nerve. 1991;14(11)1103-1109. doi:10.1002/mus.880141111; 17. Vanhoutte EK, et al. J Peripher Nerv Syst. 2015;20(3):296-305. doi:10.1111/jns.12141; 18. Vanhoutte EK. Peripheral neuropathy outcome measures standardisation(PeriNomS) study part 2: getting consensus. Doctoral Thesis. Maastricht University; 2015; 19. Moreno-Morente G, et al. Int J Environ Res Public Health. 2022; 19(16):10080. doi:10.3390/ijerph191610080; 20. Kumar RN, et al.J Occup Environ Med.2003;45(8):899-907. doi:10.1097/01.jom.0000083039.56116.79; 21. Atkinson MJ, et al. Health Qual Life Outcomes. 2004;2:12. doi:10.1186/1477-7525-2-12; 22. Liberato ACS, et al. Value Health Reg Issues. 2020;23:150-156. doi:10.1016/j.vhri.2020.07.578; 23. Krupp LB, et al. Arch Neurol. 1989;46(10)1121-1123. doi:10.1001/archneur.1989.00520460115022; 24. Shirley Ryan AbilityLab. Fatigue Severity Scale. Available at: www.sralab.org/sites/default/files/2017-06/sleep-Fatigue-Severity-Scale.pdf (Accessed: March 2026); 25. EUROQOL EQ-5D-5L user guide version 4.0. 2025. Available at: https://euroqol-domain.ams3.digitaloceanspaces.com/wp-content/uploads/2025/01/12124516/EQ-5D-5L-Userguide-2025-04.pdf (Accessed: March 2026); 26. Gwathmey KG, et al. Muscle Nerve. 2016;54(1)9-17. dol:10.1002/mus.24985; 27. Eremenco S, et al. Qual of Life Res.2022;31(12):3501-3512. dol:10.1007/s11136-022-03180-5; 28. Sharrack B, Hughes RAMult Scler.1999;5(4):223-233. doi:10.1177/135245859900500406; 29. Allen JA, et al. JAMA Neurol. 2020; 77(9):1159-1166; doi:10.1001/jamaneurol.2020.0781.

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