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NEUROSAE 2018 ANNUAL MEETING EDITION (VOLUME 10, ISSUE 3)
QUESTION 63 OF 100
A 32-year-old woman who has acetylcholine receptor positive myasthenia gravis has been treated with at least one in-patient course of plasma exchange and/or IV gamma globulin annually for the past 3 years. Otherwise she is treated with alternating day dosing of prednisone 60-40 mg. The dose cannot be decreased to daily 40 mg due to worsening symptoms. Despite addition of azathioprine to her regimen, she remains symptomatic and requires scheduled doses of pyridostigmine and outpatient plasma exchanges every 1 to 2 months, as needed. Which of the following is the most appropriate next step in management?
A. Thymectomy **
** = Your answer
All the options presented have been or currently are being studied, but only cyclosporine and thymectomy have shown efficacy in phase III clinical trials in terms of steroid-sparing affect and stability of disease.
Rituximab is B cell monoclonal antibody that may be effective in refractory myasthenia gravis (MG), particularly in MuSK+ MG, as reported by case series and retrospective studies; a large NIH-sponsored clinical trial is now underway in patients with non-thymomatous AChR+MG.
Eculizumab, a monoclonal antibody that binds membrane attack complexes, was beneficial in patients with refractory generalized MG in a small double-blind, placebo-controlled study. Results of a large phase III clinical trial were presented in July 2016, and the drug currently is undergoing FDA review for approval.
Methotrexate did not provide a steroid-sparing benefit in a phase III study in 59 patients with generalized MG.
A large multicenter, international trial of thymectomy in patients with non-thymomatous AChR+MG demonstrated that those who underwent surgery had a lower average MG functional score over a 3-year period than those who received prednisone alone, and they had a lower average requirement for alternate-day prednisone. Fewer subjects in the thymectomy group required azathioprine or hospitalization; treatment-associated complications did not differ significantly between groups.
Thymectomy is an evidence-supported therapeutic option for this patient. Although cyclosporine is effective in its steroid-sparing effect, it is limited by significant toxicity. Rituximab is an option, but currently is not FDA approved for MG, and the ability to access the drug requires insurance coverage, cost considerations, and a risk of extended immune suppression.
* Pasnoor M, He J, Herbelin L, et al. A randomized controlled trial of methotrexate for patients with generalized myasthenia gravis. Neurology. 2016 Jul 5;8(1):57-64.
* Howard JF Jr, Barohn RJ, Cutter GR, et al. A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis. Muscle Nerve. 2013 Jul;48(1):76-84.
* Tindall RS, Phillips JT, Rollins JA, et al. A clinical therapeutic trial of cyclosporine in myasthenia gravis. Ann N Y Acad Sci 1993 June;681:539-551.
* Wolfe GI, Kaminski HJ, Aban IB et al. Randomized trial of thymectomy in myasthenia gravis. N Engl J Med. 2016 Aug 11;375(6):511-522.