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Acetylcholinesterase inhibitor treatment for myasthenia gravis

Evidence Summaries

Level of Evidence = A

Acetylcholinesterase inhibitors are effective in improving sypmtoms in myasthenia gravis.

A Cochrane review 1 included one study with a total of 10 subjects with myasthenia gravis (MG). It used acetylcholinesterase inhibitor, intranasal neostigmine, including 3 participants with ocular and 7 with generalised myasthenia gravis. Symptoms of myasthenia gravis (measured as improvement in at least one muscle function) improved in nine of the 10 participants after the two-week neostigmine treatment phase. No participant improved after the placebo phase (RR 19.00, 95% CI 1.25 to 287.92).

An observational study 2 compared pyridostigmine with neostigmine in 14 participants, and concluded that pyridostigmine was more effective over a follow-up period of one year "because of its superior ability to control myasthenic phenomena and the absence of side-effects after prolonged use".

Similar conclusions came from an analysis of 295 participants with MG 3 , where only 12 out of 69 participants who compared neostigmine with pyridostigmine, preferred neostigmine.

A total of 95 participants with MG were followed for 10 years to evaluate the long-term effects of prednisolone, thymectomy, or both, and compared with a group on acetylcholinesterase inhibitor (AchEI) 4 . Only 15% of the participants on AChEI alone showed improvement 10 years after the onset of MG vs. more than 60% of those treated with other treatments. The study was retrospective and no statistical analysis was performed.

Task force of the European Federation of Neurological Societies (EFNS) 5 reported that "there are no placebo controlled randomised studies of these drugs, but case reports, case series and daily clinical experience demonstrate an objective and marked clinical effect. Although there is inadequate evidence for a formal recommendation, the Task force agreed that AchEI drug should be the first-line treatment of all forms of MG". AchEI may cause general and systemic side effects. General side effects include bradycardia, colicky pain, hypersalivation and headache.

Comment: The quality of evidence is upgraded by large magnitude of effect.

In myasthenia gravis the response to acetylcholinesterase inhibitors in observational studies is probably so clear that a randomised controlled trial depriving participants in a placebo arm of treatment would be difficult to justify.

References

1. Mehndiratta MM, Pandey S, Kuntzer T. Acetylcholinesterase inhibitor treatment for myasthenia gravis. Cochrane Database Syst Rev 2014;10():CD006986.  [PMID:25310725].

2. Schwarz H. Mestinon (pyridostigmine bromide) in myasthenia gravis. Can Med Ass J 1956; 75:98-100

3. Simpson JF, Westerberg MR, Magee KR. Simpson JF, Westerberg MR, Magee KR. Myasthenia gravis. An analysis of 295 cases. Acta Neurol Scand 1966;42():Suppl 23:1-27.  [PMID:5957970]

4. Seto M, Motomura M, Takeo G et al. Treatment of myasthenia gravis: a comparison of the natural course and current therapies. Tohoku J Exp Med 1993;169(1):77-86.  [PMID:8211972]

5. Skeie GO, Apostolski S, Evoli A et al. Guidelines for the treatment of autoimmune neuromuscular transmission disorders. Eur J Neurol 2006;13(7):691-9.  [PMID:16834699]


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Citation

"Acetylcholinesterase Inhibitor Treatment for Myasthenia Gravis." Evidence-Based Medicine Guidelines, Duodecim Medical Publications Limited, 2019. Evidence Central, evidence.unboundmedicine.com/evidence/view/EBMG/457462/all/Acetylcholinesterase_inhibitor_treatment_for_myasthenia_gravis.
Acetylcholinesterase inhibitor treatment for myasthenia gravis. Evidence-Based Medicine Guidelines. Duodecim Medical Publications Limited; 2019. https://evidence.unboundmedicine.com/evidence/view/EBMG/457462/all/Acetylcholinesterase_inhibitor_treatment_for_myasthenia_gravis. Accessed August 18, 2019.
Acetylcholinesterase inhibitor treatment for myasthenia gravis. (2019). In Evidence-Based Medicine Guidelines. Available from https://evidence.unboundmedicine.com/evidence/view/EBMG/457462/all/Acetylcholinesterase_inhibitor_treatment_for_myasthenia_gravis
Acetylcholinesterase Inhibitor Treatment for Myasthenia Gravis [Internet]. In: Evidence-Based Medicine Guidelines. Duodecim Medical Publications Limited; 2019. [cited 2019 August 18]. Available from: https://evidence.unboundmedicine.com/evidence/view/EBMG/457462/all/Acetylcholinesterase_inhibitor_treatment_for_myasthenia_gravis.
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TY - ELEC T1 - Acetylcholinesterase inhibitor treatment for myasthenia gravis ID - 457462 BT - Evidence-Based Medicine Guidelines UR - https://evidence.unboundmedicine.com/evidence/view/EBMG/457462/all/Acetylcholinesterase_inhibitor_treatment_for_myasthenia_gravis PB - Duodecim Medical Publications Limited DB - Evidence Central DP - Unbound Medicine ER -