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Management of Myasthenia Gravis: International Consensus Guidance

Written By : Dr. Kamal Kant Kohli Published On 2023-01-02T09:30:05+05:30  |  Updated On 2 Jan 2023 10:45 AM IST
Management of Myasthenia Gravis: International Consensus Guidance
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Myasthenia gravis (MG) is a chronic autoimmune disorder in which antibodies destroy the communication between nerves and muscle, resulting in weakness of the skeletal muscles. The disease can strike anyone at any age, but is more frequently seen in young women (age 20 and 30) and men aged 50 and older. The cause of myasthenia gravis is unknown and there is no cure, but early detection and prompt medical management can help people live longer, more functional lives.

American Academy of Neurology (AAN) has released guidelines titled International Consensus Guidance for Management of Myasthenia Gravis in November 2020 and reaffirmed July 14, 2022.

Following are its major recommendations:

1. In nonthymomatous, generalized MG patients with AChR-Ab, aged 18–50 years, thymectomy should be considered early in the disease to improve clinical outcomes and to minimize immunotherapy requirements and the need for hospitalizations for disease exacerbations (median 9, range 2–9). b. Thymectomy should be strongly considered in patients with AChR-Ab+ generalized MG if they fail to respond to an initial adequate trial of immunotherapy or have intolerable side effects from that therapy (median 9, range 5-9).

2. Thymectomy for MG is an elective procedure and should be performed when the patient is stable and deemed safe to undergo a procedure where postoperative pain and mechanical factors can limit respiratory function (median 9, range 8-9).

3. Endoscopic and robotic approaches to thymectomy are increasingly performed and have a good track record for safety in experienced centers. Data from randomized, controlled comparison studies are not available. Based on comparisons across studies, less invasive thymectomy approaches appear to yield similar results to more aggressive approaches (median 9, range 4-9).

4. Thymectomy may be considered in patients with generalized MG without detectable AChR-Ab if they fail to respond adequately to immunosuppressive (IS) therapy or to avoid/minimize intolerable adverse effects from IS therapy. Current evidence does not support an indication for thymectomy in patients with MuSK, low-density lipoprotein receptor-related protein 4, or agrin antibodies (median 9, range 6-9) (table e-3, doi:10.5061/dryad.6hdr7sqxx).

5. Ophthalmoparesis or ptosis in ocular MG that is not responding to anticholinesterase agents should be treated with immunosuppressant agents if symptoms are functionally limiting or troublesome to the patient (median 9, range 7-9).

6. Corticosteroids should be used as the initial IS agent in ocular MG. Steroid-sparing IS agents may be needed when corticosteroids alone are ineffective, contraindicated, or not tolerated (median 9, range 6-9).

7. Data from a single small RCT suggest that low-dose corticosteroids may be effective for ocular MG and may avoid side effects associated with high-dose corticosteroids (median 9, range 4-9).

8. AChR-Ab+ patients with ocular MG who do not respond adequately to acetylcholinesterases and who either prefer not to take IS therapy or have contraindications to or are refractory to IS agents may be offered thymectomy (median 8, range 5–9) (table e-10, doi:10.5061/dryad.6hdr7sqxx).

9. Rituximab should be considered as an early therapeutic option in patients with MuSK-Ab+ MG who have an unsatisfactory response to initial immunotherapy (median 9, range 4-9).

10. The efficacy of RTX in refractory AChR-Ab+ MG is uncertain. It is an option if patients fail or do not tolerate other IS agents (median 8, range 4–9) (tables e-2 and e-7, doi:10.5061/dryad.6hdr7sqxx).

11. Although evidence from RCTs is lacking, oral MTX may be considered as a steroid-sparing agent in patients with generalized MG who have not tolerated or responded to steroid-sparing agents that are better supported by RCT data (median 9, range 5–9) (table e-2, doi:10.5061/dryad.6hdr7sqxx).

12. Eculizumab should be considered in the treatment of severe, refractory, AChR-Ab+ generalized MG (median 9, range 2–9).

13. The role of eculizumab in the treatment of MG is likely to evolve over time. Until further data become available to allow comparisons of cost and efficacy with other treatments, eculizumab should be considered after trials of other immunotherapies have been unsuccessful in meeting treatment goals (median 9, range 5–9).

14. Recommendations of the Advisory Committee on Immunization Practices or other local guidelines regarding immunization against meningococcal meningitis should be followed before treatment with eculizumab (median 9, range 8–9).

15. Future research should include assessment of the duration of eculizumab therapy necessary to achieve and maintain treatment goals, its efficacy in other MG populations (MG with thymoma and seronegative MG), and in other stages of disease (MG crises, exacerbations, and early therapy in nonrefractory AChR-Ab+ MG) (median 8, range 4-9) (table e-2, doi:10.5061/dryad.6hdr7sqxx).

16. The risk of MG and other immune-mediated neurologic illnesses should be discussed with patients who are candidates for ICIs (median 9, range 5-9).

17. At this time, there is no evidence to either support or refute the utility of AChR antibody testing in patients without MG before starting ICIs (median 8, range 7-9).

18. MG associated with ICIs is generally severe, with a high rate of respiratory crises (median 8, range 5–9).

19. Preexisting MG does not constitute an absolute contraindication to the use of ICIs, at least in patients with well-controlled disease (MM status or better). However, in these patients:

 • It may be prudent to avoid combined therapy (anti–CTLA-4 plus anti-PD-1/PD-L1 monoclonal antibodies), given the higher potential for severe irAEs.

 • Close clinical monitoring, particularly of respiratory and bulbar function, is mandatory.

 • Although the therapeutic response to ICIs seems to be less satisfactory in patients receiving immunosuppressants, MG treatment should be maintained and may even be restarted in patients whose MG is in remission before treatment with ICIs (median 8, range 5–9).

20. Early aggressive treatment with high-dose steroids in combination with plasma exchange or IVIg may be required in patients who develop overt MG while on ICIs. The decision to withdraw ICIs is determined by the oncologic status (median 8, range 7–9) (table e-9, doi:10.5061/dryad.6hdr7sqxx).

Reference:

Pushpa Narayanaswami, Donald B. Sanders, Gil Wolfe, Michael Benatar, Gabriel Cea, Amelia Evoli, Nils Erik Gilhus, Isabel Illa, Nancy L. Kuntz, Janice Massey, Arthur Melms, Hiroyuki Murai, Michael Nicolle, Jacqueline Palace, David Richman, Jan Verschuuren Neurology Jan 2021, 96 (3) 114-122; DOI: 10.1212/WNL.0000000000011124

American Academy of NeurologyAANchronic autoimmune disorderAAN guidelinesMyasthenia gravisMGMG patientsRituximab
Source : American Academy of Neurology,AAN
Dr. Kamal Kant Kohli
Dr. Kamal Kant Kohli

Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Email: drkohli@medicaldialogues.in. Contact no. 011-43720751

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