Clinical Focus: From Mechanism to Management—Novel C5 Inhibitors in Generalized Myasthenia Gravis : Pre-test

1.

How many people with MG do you provide care for in a typical month?

A. 1-4
B. 5-10
C. 11-15
D. 16-20
E. >20
F. Not applicable

2.

For those who practice in academic or community settings, please indicate your practice setting:

A. Academic
B. Community
C. Not applicable

3.

When assessing a patient, which do you characterize as an important persistent unmet need in the long-term care of people with generalized myasthenia gravis (gMG)?

A. Prevention of myasthenic crisis indicates adequate disease control as patients with MG who experience crisis will never achieve good long-term disease control
B. Persistent functional limitations, corticosteroid burden, or reliance on rescue therapy despite conventional treatment may indicate inadequate disease control and a need to reassess management
C. Treatment success should be judged primarily by improvement in clinical scores, even when corticosteroid or rescue-treatment burden remains substantial
D. Administration burden is not clinically relevant when a treatment provides measurable improvement in disease scores

4.

Which of the following most accurately differentiates the currently available component 5 (C5) inhibitors used for AChR antibody–positive gMG?

A. Eculizumab and ravulizumab are self-administered subcutaneous (SC) therapies, whereas zilucoplan requires regular intravenous (IV) infusion
B. Eculizumab uses IV maintenance dosing every 2 weeks, ravulizumab uses less frequent IV maintenance dosing, and zilucoplan is administered by daily self-injection; all require appropriate meningococcal risk-mitigation planning
C. Meningococcal vaccination is required with eculizumab but is unnecessary with ravulizumab and zilucoplan because they use different dosing schedules
D. Differences in placebo-adjusted Myasthenia Gravis-specific Activities of Daily Living scale (MG-ADL) improvement across their individual pivotal trials can be used to rank the 3 agents from most to least effective

5.

A 58-year-old woman with AChR antibody–positive gMG is receiving pyridostigmine, prednisone 15 mg/day, and mycophenolate. Her MG-ADL score is 8, with persistent diplopia, chewing fatigue, dysarthria, and proximal weakness. She has required 2 courses of rescue IV immunoglobulin (IVIg) during the past year. Her goal is more predictable daily function with reduced corticosteroid exposure.

What would you do next for this patient to ensure you are taking the most appropriate step in her management?

A. Continue the current regimen until she experiences a myasthenic crisis because targeted therapy should generally be reserved for crisis prevention
B. Select the C5 inhibitor associated with the largest numerical MG-ADL improvement in its pivotal trial, regardless of differences in trial design or treatment logistics
C. Discuss C5 inhibition as a biologically appropriate targeted option and select the specific agent by integrating route and dosing cadence, meningococcal risk-mitigation requirements, access, treatment burden, and patient preference, with subsequent reassessment of clinical and functional response
D. Select a self-administered SC C5 inhibitor because SC therapy is intrinsically more convenient than IV therapy for all patients

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Clinical Focus: From Mechanism to Management—Novel C5 Inhibitors in Generalized Myasthenia Gravis

Gil I. Wolfe, MD, FAAN

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