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Liu et al. Developing treatment guidance for myasthenia gravis

INTRODUCTION which was established and refined by RAND and the
University of California, Los Angeles (UCLA) in the
Myasthenia gravis (MG) is a neuromuscular 1980s.
transmission disorder. The incidence of MG ranges
between 0.3-2.8 per 100,000, affecting more than The first meeting was held in February 2013 in
700,000 people worldwide. The prognosis for patients Durham, North Carolina, to make decisions on cardinal
[1]
with MG has been improved tremendously in recent definitions that were going to be instrumental for
years due to the increasing use of immunomodulating subsequent guidance treatment statements: goals of
treatments. However, there is no optimal treatment treatment, minimal manifestations, remission, ocular
approach for all patients due to disease heterogeneity, MG, impending and manifest myasthenic crises and
thus an internationally recognized standard of care for refractory MG. Definitions without consensus were
MG is still missing. modified upon the panelists’ suggestions and shared
with the panel for subsequent voting rounds.
The MG symptoms and the “morning light evening
heavy” characters were first described as early as The first draft of the MG guidance treatment statements
[2]
1672 by British clinician Thomas Willis, whereas the was prepared by the two executive chairmen and
cause of the disease remained a mystery until the the Harvard University service providers, based
1960s. At that time, MG was described as the result on recent publications and guidelines from the US,
of antibodies binding to the neuromuscular junction, Denmark, Norway, Germany, Japan, Netherlands,
most commonly against the acetylcholine receptor. United Kingdom and Europe. [6-11] The following three
[3]
However, up to date management of MG still remains assumptions were agreed a priori: (1) treatment costs
a great challenge. [4] and availability would not be considered; (2) clinical
examination is performed by experienced physicians
There are many reasons behind the need to develop for the evaluation of neuromuscular disease; (3) the
an international consensus guideline for MG MGFA Clinical Classification refers to the state of the
management. Firstly, early expert treatments can patient at the time of evaluation. Guidance statements
significantly improve the prognosis of a MG patient, as were developed for the following seven topics: MG
some physicians have not seen enough MG patients symptomatic and immunosuppressive (IS) treatment,
to be familiar with all its cardinal features. This is due IV immunoglobulin (IVIg) and plasma exchange
to MG low incidence and heterogeneity. Secondly, (PLEX), impending and manifest myasthenic crisis,
uncontrolled clinical trials may be potentially biased, thymectomy, juvenile MG (JMG), muscle-specific
while the few successful randomized controlled tyrosine kinases (MuSK) antibody-positive MG and
trials (RCTs) cannot be generalized to assess the MG in pregnancy.
effectiveness and safety of multi-regimens, and to
select the best treatment for each patient. Thus, it is The consensus guidance statements were refined
critically important that experts share their knowledge using a quantitative evaluation system of the RAM
and competence to improve the management of MG. program. Initial and revised statements were voted
Such expert-developed guidelines not only will help and commented on anonymously at least three
the clinician, but will also represent a unique resource times during the process. The facilitator (Dr. Pushpa
for third-party payers such as insurance companies, Narayanaswami) was the only person who made
governmental health organizations and institutional announcements about the statements and collected
review boards. votes and feedbacks. Dr. Narayanaswami was
not allowed to vote or participate in discussions
METHODS and feedbacks to ensure the maximum objectivity
of the process. The chairmen gathered the votes
In October 2013, a Task Force of the Myasthenia anonymously and revised the statements, seeking for
Gravis Foundation of America (MGFA) assembled a ultimate consensus. A second face-to-face meeting
panel of 15 internationally recognized MG experts, and panel discussion was held in March 2014 after the
chaired by Donald Sanders of the Duke University and first round of vote. The second and third round of votes
Gil Wolfe of State University of New York at Buffalo, were solicited after statements revision to reflect all
and moderated by Pushpa Narayanaswami of Harvard panelists’ comments and experiences. After all three
University. The main goal of this panel was to develop rounds, consensus was reached on all definitions and
treatment guidance statements based on formalized guidance statements. So far, this represents the first
consensus. The guideline development employed official international MG treatment guidance and as
the RAND/UCLA Appropriateness Method (RAM), [5] such it was published in its final form on June 29, 2016
Neuroimmunology and Neuroinflammation ¦ Volume 4 ¦ March 30, 2017 55