A 40-year-old woman with myasthenia gravis (anti-AChR antibody positive, Osserman class IIb) has failed to achieve remission with pyridostigmine and prednisolone. She has no thymoma on CT. Which biologic mechanism correctly describes the action of eculizumab in refractory generalised MG?
- A Blocks FcRn receptor, accelerating catabolism of anti-AChR IgG antibodies
- B Depletes B-cells via anti-CD20 monoclonal antibody activity
- C Inhibits IL-6 receptor, reducing autoantibody production
- D Inhibits complement C5, preventing formation of membrane attack complex (MAC) at NMJ ✓
Explanation
Eculizumab is a humanised monoclonal antibody targeting complement protein C5, approved for refractory anti-AChR-positive generalised MG (REGAIN trial, 2017). Anti-AChR antibodies activate the classical complement pathway, leading to formation of the membrane attack complex (C5b-9/MAC) at the neuromuscular junction, causing destruction of the postsynaptic membrane and acetylcholine receptor loss. Eculizumab prevents C5 cleavage into C5a and C5b, thereby blocking MAC formation. FcRn receptor blockade (mechanism of efgartigimod and rozanolixizumab) accelerates IgG catabolism — different mechanism. Rituximab depletes CD20+ B-cells. Tocilizumab blocks IL-6.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.