touchNEUROLOGY touchNEUROLOGY
Start activity
 
Video Take CE/CME Test
Neuroimmunology, Neuromuscular Diseases CE/CME accredited

touchPANEL DISCUSSION
A visually engaging discussion designed to emulate a ‘live’ panel experience and provide clinicians with practical expert insights to address their clinical challenges. Useful tips below will show how to navigate the activity. Close

The complement system in NMOSD and MG: A target for therapeutic benefit?

  • Downloads including slides are available for this activity in the Toolkit
Learning Objectives

After watching this activity, participants should be better able to:

  • Describe the role of complement in the pathophysiology of NMOSD and MG
  • Evaluate markers of complement activation as diagnostic and prognostic biomarkers in NMOSD and MG
  • Discuss recently approved and experimental inhibitors of the complement system for the treatment of NMOSD and MG
Overview

In this activity, three experts discuss the evidence for complement involvement in neuromyelitis optica spectrum disorder (NMOSD) and myasthenia gravis (MG) pathogenesis, the markers of complement activation, as well as the latest data for complement therapeutics.

This activity is jointly provided by USF Health and touchIME. read more

Target Audience

Neurologists (including neuromuscular disease specialists), immunologists (including neuro-immunologists) and ophthalmologists involved in the management of patients with neurological disorders, including NMOSD and MG.

Disclosures

USF Health adheres to the Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity. The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

Faculty

Prof. Said Beydoun discloses: Advisory board fees Alexion Pharmaceuticals, Alnylam Pharmaceuticals, Amylyx Pharmaceuticals, Argenx, Biogen, Ionis Pharmaceuticals, Mitsubishi Tanabe Pharma, Octapharma, Takeda and UCB; Grants/research support from Abcuro, Amylyx Pharmaceuticals, Genentech, Healey MGH, Regeneron Pharmaceuticals, Sanofi and UCB; Speaker’s bureau fees from Alexion Pharmaceuticals, Alnylam Pharmaceuticals, Amylyx Pharmaceuticals, Argenx Pharmaceuticals, Grifols and Takeda.

Dr Pushpa Narayanaswami discloses: Advisory board fees from Alexion Pharmaceuticals, Argenx, Dianthus Therapeutics, Janssen and UCB; Consultancy fees from GSK; Grants/research fees from Alexion Pharmaceuticals; Financial support from Sanofi (relationship terminated); Stockholder in Momenta Pharmaceuticals, Pfizer and Viatris (relationship terminated).

Prof. Heinz Wiendl discloses: Advisory board fees from Alexion Pharmaceuticals, Argenx, Bristol Myers Squibb, Janssen, Merck, Novartis and Sandoz; Consultant fees from Actelion, Argenx, BD, Biogen, EMD Serono, Fondazione, Gossamer Bio, Idorsia, Immunic Therapeutics, Immunovant, Lundbeck, Merck, NexGen, Novartis, PSI CRO, Roche, Sanofi and UCB; Grants/research support from Alexion Pharmaceuticals, Amicus Therapeutics, Argenx, Biogen, CSL Behring, F. Hoffmann-La Roche, Genzyme, Merck, Novartis, Roche and UCB.

Content reviewer

Niraja S. Suresh, MD, has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Contributors

Kathy Day has no financial interests/relationships or affiliations in relation to this activity.

USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

If you have questions regarding credit please contact cpdsupport@usf.edu.

Accreditations

Physicians

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

USF Health designates this enduring material for a maximum of 0.75 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

Advanced Practice Providers

Physician Assistants may claim a maximum of 0.75 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

Date of original release: 17 August 2023. Date credits expire: 17 August 2024.

If you have any questions regarding credit please contact cpdsupport@usf.edu.

This activity is CE/CME accredited

To obtain the CE/CME credit(s) from this activity, please complete this post-activity test.

Claim Credit

Topics covered in this activity

Neuroimmunology / Neuromuscular Diseases
REGISTER NOW FOR FREE ACCESS TO
  • 1000+ topical and insightful peer-reviewed journal articles
  • 100+ hours of bite-sized congress highlights
  • 10 major therapy areas packed with the latest scientific advances
  • 150+ specialties offering learn-on-the-go medical education
  • + Concise email updates and newsletters so you never miss out
Register For Free Now
Claim Credit
touchPANEL DISCUSSION
The complement system in NMOSD and MG: A target for therapeutic benefit?
0.75 CE/CME credit

Question 1/5
Which statement describes a key difference between the pathophysiology of NMOSD and MG?

C, serum complement protein; CNS, central nervous system; MG, myasthenia gravis; NMJ, neuromuscular junction; NMOSD, neuromyelitis optica spectrum disorder.

MG is usually mediated by AChR antibodies, which can be blocking, modulating or binding.1 Activation of the classical complement pathway occurs when the antibody binds to the AChR.2 This results in MAC formation and damage to the postsynaptic membrane.1 In NMOSD, complement activation leads to C5b-mediated MAC formation. The subsequent astrocyte cell death alongside C5a formation induces release of pro-inflammatory cytokines, leading to further cytotoxicity, demyelination and neuronal tissue damage.3

Abbreviations

AChR, acetylcholine receptor; C, serum complement protein; MAC, membrane attack complex; MG, myasthenia gravis; NMOSD, neuromyelitis optica spectrum disorder.

References

  1. Dresser L, et al. J Clin Med. 2021;10:2235.
  2. Albazli K, et al. Front Immunol. 2020;11:917.
  3. Ponleitner M, Rommer PS. Wien Med Wochenschr. 2022. doi: 10.1007/s10354-022-00987-2.
Question 2/5
Your patient presents with fatigue, pain, stiffness/spasticity, bladder and bowel dysfunction, cognitive/emotional symptoms and visual disturbances. MRI scans reveal NMOSD-typical lesions and signs of ocular disease. What action would you take to make a definitive diagnosis of NMOSD?

AQP4, aquaporin 4; MRI, magnetic resonance imaging; NMOSD, neuromyelitis optica spectrum disorder.

In AQP4 positive disease, the presence of one of the six core clinical characteristics (LETM, optic neuritis, APS, symptomatic brainstem, diencephalic, or cerebral syndromes) with AQP4 antibodies is sufficient to make a diagnosis of NMOSD. Approximately 75% of patients have antibodies against AQP4. In seronegative cases, the criteria are more stringent and MRI requirements must also be fulfilled.

Abbreviations

APS, area postrema syndrome; AQP4, aquaporin 4; LETM, longitudinally extensive transverse myelitis; MRI, magnetic resonance imaging; NMOSD, neuromyelitis optica spectrum disorder.

Reference
Huda S, et al. Clin Med (Lond). 2019;19:169–76.

Question 3/5
You are considering treatment options for your patient who is showing symptoms characteristic of MG. How might a finding of a low AChR antibody titre guide your prognostic and diagnostic decision making?

AChR, acetylcholine receptor; MG, myasthenia gravis.

Diagnosis of MG should be made on a clinical basis, considering the clinical history and physical symptoms.1 Testing for AChR antibodies is very important to help define the disease pathophysiology and validate the diagnosis. While the specificity can be up to 95%, the risk of false positives means antibody testing alone should not be a confirmatory test.1 There is no correlation between titres and severity of MG, and AChR antibody titre has not been shown to be a reliable prognostic biomarker.2

Abbreviations

AChR, acetylcholine receptor; MG, myasthenia gravis.

References

  1. Rousseff RT. J Clin Med. 2021;10:1736.
  2. Fichtner ML, et al. PLoS One. 2022;17:e0264489.
Question 4/5
Your patient with gMG has continued to progress on their current treatment and has asked you if complement inhibitors may help them. What can you tell them about the clinical data of complement inhibitors in gMG?

C5, serum complement component 5; gMG, generalized myasthenia gravis; MG-ADL, myasthenia gravis activities of daily living.

Complement inhibitor therapies that target C5 have shown positive results in trials of gMG.1–3 Eculizumab demonstrated a 75% reduction in exacerbation rate, with sustained MG-ADL improvements.1 Ravulizumab gave improvements in MG-ADL, with improvement seen within 1 week, maintained over 26 weeks compared with placebo,2 while zilucoplan has also demonstrated rapid and clinically meaningful improvements in MG-ADL compared with placebo.3

Abbreviations

C5, serum complement component 5; gMG, generalized myasthenia gravis; MG-ADL, myasthenia gravis activities of daily living.

References

  1. Muppidi S, et al. Muscle Nerve. 2019;60:14–24.
  2. Vu T, et al. NEJM Evid. 2022;1. doi: 10.1056/EVIDoa2100066.
  3. Howard JF, et al. Lancet Neurol. 2023;22:395–406.
Question 5/5
Your patient has previously received treatment for NMOSD, but this was insufficient to control their disease. What action must you take before initiating a complement inhibitor?

NMOSD, neuromyelitis optica spectrum disorder.

C5 inhibition impairs formation of the MAC, which increases the risk of meningococcal infections.1 Patients therefore must be vaccinated against meningococcal disease ≥2 weeks prior to their first dose, or receive prophylactic antibiotics until 2 weeks after vaccination.2 All treatment decisions for NMOSD should consider prior therapies, comorbidities and disease severity.3

Abbreviations

C, serum complement protein; MAC, membrane attack complex; NMOSD, neuromyelitis optica spectrum disorder.

References

  1. Asavapanumas N, et al. Expert Opin Biol Ther. 2021;21:1073–86.
  2. Frampton JE. Drugs. 2020;80:719–27.
  3. Paul F, et al. Neurol Neuroimmunol Neuroinflamm. 2023;10:e200124.
Back to Activity
Copied to clipboard!
accredited arrow-down-editablearrow-downarrow_leftarrow-right-bluearrow-right-dark-bluearrow-right-greenarrow-right-greyarrow-right-orangearrow-right-whitearrow-right-bluearrow-up-orangeavatarcalendarchevron-down consultant-pathologist-nurseconsultant-pathologistcrosscrossdownloademailexclaimationfeedbackfiltergraph-arrowinterviewslinkmdt_iconmenumore_dots nurse-consultantpadlock patient-advocate-pathologistpatient-consultantpatientperson pharmacist-nurseplay_buttonplay-colour-tmcplay-colourAsset 1podcastprinter scenerysearch share single-doctor social_facebooksocial_googleplussocial_instagramsocial_linkedin_altsocial_linkedin_altsocial_pinterestlogo-twitter-glyph-32social_youtubeshape-star (1)tick-bluetick-orangetick-red tick-whiteticktimetranscriptup-arrowwebinar Sponsored Department Location NEW TMM Corporate Services Icons-07NEW TMM Corporate Services Icons-08NEW TMM Corporate Services Icons-09NEW TMM Corporate Services Icons-10NEW TMM Corporate Services Icons-11NEW TMM Corporate Services Icons-12Salary £ TMM-Corp-Site-Icons-01TMM-Corp-Site-Icons-02TMM-Corp-Site-Icons-03TMM-Corp-Site-Icons-04TMM-Corp-Site-Icons-05TMM-Corp-Site-Icons-06TMM-Corp-Site-Icons-07TMM-Corp-Site-Icons-08TMM-Corp-Site-Icons-09TMM-Corp-Site-Icons-10TMM-Corp-Site-Icons-11TMM-Corp-Site-Icons-12TMM-Corp-Site-Icons-13TMM-Corp-Site-Icons-14TMM-Corp-Site-Icons-15TMM-Corp-Site-Icons-16TMM-Corp-Site-Icons-17TMM-Corp-Site-Icons-18TMM-Corp-Site-Icons-19TMM-Corp-Site-Icons-20TMM-Corp-Site-Icons-21TMM-Corp-Site-Icons-22TMM-Corp-Site-Icons-23TMM-Corp-Site-Icons-24TMM-Corp-Site-Icons-25TMM-Corp-Site-Icons-26TMM-Corp-Site-Icons-27TMM-Corp-Site-Icons-28TMM-Corp-Site-Icons-29TMM-Corp-Site-Icons-30TMM-Corp-Site-Icons-31TMM-Corp-Site-Icons-32TMM-Corp-Site-Icons-33TMM-Corp-Site-Icons-34TMM-Corp-Site-Icons-35TMM-Corp-Site-Icons-36TMM-Corp-Site-Icons-37TMM-Corp-Site-Icons-38TMM-Corp-Site-Icons-39TMM-Corp-Site-Icons-40TMM-Corp-Site-Icons-41TMM-Corp-Site-Icons-42TMM-Corp-Site-Icons-43TMM-Corp-Site-Icons-44TMM-Corp-Site-Icons-45TMM-Corp-Site-Icons-46TMM-Corp-Site-Icons-47TMM-Corp-Site-Icons-48TMM-Corp-Site-Icons-49TMM-Corp-Site-Icons-50TMM-Corp-Site-Icons-51TMM-Corp-Site-Icons-52TMM-Corp-Site-Icons-53TMM-Corp-Site-Icons-54TMM-Corp-Site-Icons-55TMM-Corp-Site-Icons-56TMM-Corp-Site-Icons-57TMM-Corp-Site-Icons-58TMM-Corp-Site-Icons-59TMM-Corp-Site-Icons-60TMM-Corp-Site-Icons-61TMM-Corp-Site-Icons-62TMM-Corp-Site-Icons-63TMM-Corp-Site-Icons-64TMM-Corp-Site-Icons-65TMM-Corp-Site-Icons-66TMM-Corp-Site-Icons-67TMM-Corp-Site-Icons-68TMM-Corp-Site-Icons-69TMM-Corp-Site-Icons-70TMM-Corp-Site-Icons-71TMM-Corp-Site-Icons-72
Close Popup