What are the treatment options for myasthenia gravis if first-line agents fail?

Christopher Zust; John A. Morren

doi:10.3949/ccjm.90a.22022

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TABLE 1

Ranking of therapies for acetylcholine receptor antibody-positive generalized myasthenia gravis

First-line	Pyridostigmine, prednisone, thymectomy^a
Second-line	Azathioprine, mycophenolate mofetil, intravenous immunoglobulin
Third-line	Methotrexate, tacrolimus,^b eculizumab,^c ravulizumab,^c efgartigimod,^c plasmapheresis
Fourth-line	Rituximab, cyclosporine^b
Fifth-line	Cyclophosphamide

↵a For certain patients with acetylcholine receptor antibody-positive generalized myasthenia gravis without thymoma (see reference 5).
↵b May be considered as an early treatment option, depending on clinical context.
↵c Newer agents with emerging data; may be considered as early treatment option for refractory acetylcholine receptor antibody-positive generalized myasthenia gravis, but cost may be prohibitive.
Based on information in references 5 and 6.

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TABLE 2

Clinical features of fatigable weakness in myasthenia gravis by region of involvement

Muscle group/region	Manifestation of fatigable weakness in myasthenia gravis
Ocular	Fluctuating ptosis (often asymmetrical, worsened by sustained upgaze) with or without variable diplopia Ptosis may improve with application of an ice pack to the eyes, ie, the bedside ice-pack test
Bulbar	Dysarthria with or without dysphonia; worse at the end of long conversations, when especially nasal-sounding, “mushy,” or “wet” speech is significant Painless dysphagia, which may include nasal regurgitation, sialorrhea, and frequent throat-clearing, with or without coughing; may range from weak to frank choking Masticatory or chewing weakness; when severe, the mouth may hang open, and the patient may use a hand to close or manipulate the jaw
Facial	Bilateral weakness with “sagging and expressionless” face and a horizontal smile Inability to close eyes firmly Drooling from poorly sealed lips Inability to whistle, pucker lips, or use a straw
Axial Weak	Weak flexion or extension of the neck, “dropped” head when severe Occasional stooped posture with anteroposterior truncal flexion (camptocormia) or lateral trunk flexion (“Pisa syndrome”)
Limb or appendicular	Weakness that affects proximal more than distal upper and lower limb groups Difficulty getting up from low-seated positions, using arms for overhead activities like washing hair; worse with repeated and sustained actions
Respiratory	Orthopnea Dyspnea on exertion or with increased intra-abdominal pressure as when bending forward to tie shoelaces, or when trunk is immersed in a pool Classic features of accessory respiratory muscle use during respiratory distress may be blunted with significant myasthenic weakness of these muscles Decreased counts (< 20) on a single-breath counting test suggest significant respiratory muscle weakness and risk for respiratory failure