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International consensus guidance for management of myasthenia gravis


Published Ahead of Print on June 29, 2016 as 10.1212/WNL.0000000000002790
International consensus guidance formanagement of myasthenia gravisExecutive summary Donald B. Sanders, MD* ABSTRACTGil I. Wolfe, MD* Objective: To develop formal consensus-based guidance for the management of myasthenia Michael Benatar, MD, gravis (MG).
Methods: In October 2013, the Myasthenia Gravis Foundation of America appointed a Task Force to develop treatment guidance for MG, and a panel of 15 international experts was convened. The Nils E. Gilhus, MD RAND/UCLA appropriateness methodology was used to develop consensus guidance state- ments. Definitions were developed for goals of treatment, minimal manifestations, remission, ocu- lar MG, impending crisis, crisis, and refractory MG. An in-person panel meeting then determined Janice M. Massey, MD 7 treatment topics to be addressed. Initial guidance statements were developed from literature summaries. Three rounds of anonymous e-mail votes were used to attain consensus on guidance Hiroyuki Murai, MD statements modified on the basis of panel input.
Michael Nicolle, MDJacqueline Palace, BM, Results: Guidance statements were developed for symptomatic and immunosuppressive treat- ments, IV immunoglobulin and plasma exchange, management of impending and manifest myas- David P. Richman, MD thenic crisis, thymectomy, juvenile MG, MG associated with antibodies to muscle-specific Jan Verschuuren, MD tyrosine kinase, and MG in pregnancy.
Pushpa Narayanaswami, Conclusion: This is an international formal consensus of MG experts intended to be a guide for clinicians caring for patients with MG worldwide. Neurology® 2016;87:1–7 Correspondence to AChR 5 acetylcholine receptor; ChEI 5 cholinesterase inhibitor; CTCAE 5 Common Terminology Criteria for Adverse Events; FDA 5 Food and Drug Administration; IS 5 immunosuppressive; IVIg 5 IV immunoglobulin; JMG 5 juvenile myas- thenia gravis; MG 5 myasthenia gravis; MGFA 5 Myasthenia Gravis Foundation of America; MMS 5 minimal manifestationstatus; MuSK 5 muscle-specific tyrosine kinase; PIS 5 Post-Intervention Status; PLEX 5 plasma exchange; RAM 5 RAND/UCLA Appropriateness Method; RCT 5 randomized controlled trial.
Acquired myasthenia gravis (MG) is a disorder of neuromuscular transmission, resulting frombinding of autoantibodies to components of the neuromuscular junction, most commonlythe acetylcholine receptor (AChR). The incidence ranges from 0.3 to 2.8 per 100,000,1 andit is estimated to affect more than 700,000 people worldwide.
The increasing use of immunomodulating therapies has been a major factor in improving the prognosis for patients with MG in recent years.2 The various treatment options must be weighedin the context of individual patient factors.
Editorial, page 350 Why do we need MG guidance treatment statements? Although there is widespread agreement on the use of many Supplemental data treatments for MG, there is no internationally accepted standard of care. Because MG is heterogeneous, no one *These authors contributed equally to this work.
From the Department of Neurology (D.B.S., J.M.M.), Duke University Medical Center, Durham, NC; Department of Neurology (G.I.W.), Universityat Buffalo School of Medicine and Biomedical Sciences, State University of New York; Department of Neurology (M.B.), University of Miami, MillerSchool of Medicine, FL; Department of Neurology (A.E.), Catholic University, Rome, Italy; Department of Clinical Medicine (N.E.G.), University ofBergen, Norway; Department of Neurology (I.I.), Hospital Santa Creu i Sant Pau, Universitat Autònoma de Barcelona; CIBERER U762 (I.I.),Barcelona, Spain; Departments of Pediatrics and Neurology (N.K.), Northwestern Feinberg School of Medicine, Chicago, IL; Neurologische Klinik(A.M.), Universitätsklinikum Erlangen; Hertie Institute for Clinical Research (A.M.), University of Tübingen, Germany; Department of NeurologicalTherapeutics (H.M.), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Clinical Neurological Sciences (M.N.),Western University, London, Canada; Department of Clinical Neurology (J.P.), John Radcliffe Hospital, Oxford University Hospitals Trust, Oxford,UK; Department of Neurology (D.P.R.), University of California, Davis, CA; Department of Neurology (J.V.), Leiden University Medical Centre,Leiden, the Netherlands; and Department of Neurology, Beth Israel Deaconess Medical Center/Harvard Medical School (P.N.), Boston, MA.
Go to for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
The Article Processing Charge was paid by the Myasthenia Gravis Foundation of America.
This is an open access article distributed under the terms of the which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
2016 American Academy of Neurology ª 2016 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
treatment approach is best for all patients. Few physi- treatment guidelines,4–9 supplemented by other cians treat enough patients with MG to be comfort- able with all available treatments. Given its Guidance statements were developed for the heterogeneity, the few randomized controlled trials (RCTs) in MG have limited generalizability, while uncontrolled trials are limited by potential bias.
Hence, an effort to develop consensus among interna- 2. IV immunoglobulin (IVIg) and plasma exchange tional experts was undertaken to guide clinicians worldwide on the multifaceted approach to managing 3. Impending and manifest myasthenic crisis MG. This summary condenses the extensive back- ground information in the full guidance statements, 5. Juvenile MG (JMG) available on the Neurology® Web site at 6. MG with antibodies to muscle-specific tyrosine Panel constitution and method of expert consensus. In October 2013, a Task Force of the Myasthenia 7. MG in pregnancy Gravis Foundation of America (MGFA) convened Voting process for consensus guidance treatment a panel of 15 international experts in MG to develop statements. We used the RAND/UCLA Appropriate- treatment guidance statements based on formalized ness Method (RAM) for formal consensus to quantify consensus. The panel was chosen to represent the agreement.10 RAM uses a multi-round modified breadth of knowledge and experience and a wide vari- Delphi process to obtain a quantitative assessment ety of opinions from MG experts internationally.
that reflects the judgment of an expert group.
Development of preliminary definitions. The panel initially Appropriateness refers to the relative benefit vs voted on definitions that formed the foundation for sub- harm of the intervention. We obtained anonymous sequent guidance treatment statements: goals of treat- votes and feedback on each draft statement from the ment, remission, ocular MG, impending and manifest panelists, who rated each for appropriateness on a 9- myasthenic crises, and refractory MG.
point scale (1–3 inappropriate, 4–6 uncertain, and 7– The Task Force co-chairs (D.B.S., G.I.W.) 9 appropriate). Panelists responded by e-mail to the drafted initial definitions based on available litera- facilitator, who tallied the votes and collated the ture.3 These were sent by e-mail to the panelists, discussions. Following each round of voting, who were asked to vote yes or no on each, and to statements were modified by the Task Force co- provide modifications if they did not agree. Panelists chairs and facilitator based on the panel feedback.
were instructed not to discuss the definitions among Statements that did not achieve consensus within 3 themselves, and to send their votes only to the facil- rounds were excluded.
itator (P.N.). A simple consensus was used ($80% of For statements on symptomatic and IS therapies panelists voting yes).
and thymectomy, an initial round of e-mail voting Definitions not achieving consensus were modi- was followed by a meeting in Durham, North fied based on the panelists' suggestions and the mod- Carolina, on March 1, 2014. During this meeting, ified definitions and discussions were shared with the statements that had undergone prior voting by panel for subsequent voting rounds.
e-mail were refined with panel input, and a secondround of voting was completed. All subsequent voting Development of guidance treatment statements. The was by e-mail.
following were agreed upon a priori: The level of appropriateness and presence of agree- ment were determined for each statement as per RAM.10 1. Treatment costs and availability would not be con- sidered, as it is not possible to make international RESULTS All definitions below obtained simple con- consensus statements specific for all countries.
sensus and all guidance statements below were agreed 2. Clinical examination is assumed to have been per- upon as being appropriate by the panel. Literature formed by physicians skilled in the evaluation of summaries and tables for medication dosing guidance and medication cautions are available as supplemental 3. The MGFA Clinical Classification, including remission, refers to the state of the patient at the time of evaluation.
1. Goals for the treatment of MG. MGFA Task Force A formal systematic review of the literature was Post-Intervention Status (PIS) classification Minimal not performed. The Task Force co-chairs and facilita- Manifestation Status (MMS) or better,3 with no more tor drafted initial guidance statements based on liter- than grade 1 Common Terminology Criteria for ature cited in recent national and regional MG Adverse Events (CTCAE) medication side effects.11 Neurology 87 July 26, 2016 ª 2016 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
MMS: The patient has no symptoms or functional 2. A nonsteroidal IS agent should be used alone when limitations from MG but has some weakness on corticosteroids are contraindicated or refused.
examination of some muscles. This class recognizes A nonsteroidal IS agent should be used initially that some patients who otherwise meet the definition in conjunction with corticosteroids when the risk of remission have mild weakness.
of steroid side effects is high based on medical CTCAE grade 1 medication side effects: asymp- comorbidities. A nonsteroidal IS agent should be tomatic or only mild symptoms; intervention not added to corticosteroids when: a. Steroid side effects, deemed significant by the 2. Definition of remission. The patient has no symp- patient or the treating physician, develop; toms or signs of MG. Weakness of eyelid closure is b. Response to an adequate trial (table e-1) of cor- accepted, but there is no weakness of any other mus- ticosteroids is inadequate; or cle on careful examination. Patients taking cholines- c. The corticosteroid dose cannot be reduced due terase inhibitors (ChEIs) every day with reasonable to symptom relapse.
evidence to support symptomatic benefit are therefore 3. Nonsteroidal IS agents that can be used in MG excluded from this category.
include azathioprine, cyclosporine, mycophenolate 3. Definition of ocular MG (based on dysfunction due to mofetil, methotrexate, and tacrolimus. The follow- MG at a specified point in time, and not dependent upon the ing factors should be considered in selecting duration of disease). MGFA Class I3: Any ocular muscle among these agents: weakness. May have weakness of eye closure.
a. There is widespread variation in practice with Strength in all other facial, bulbar, and limb muscles respect to choice of IS agent since there is little is normal. (It is recognized that some patients report literature comparing them.
fatigue when strength testing is normal. The physi- b. Expert consensus and some RCT evidence sup- cian should use clinical judgment in attributing port the use of azathioprine as a first-line IS fatigue to generalized MG in the absence of objec- agent in MG.
tive nonocular weakness).
c. Evidence from RCTs supports the use of cyclo- 4. Definition of impending myasthenic crisis. Rapid clin- sporine in MG, but potential serious adverse ical worsening of MG that, in the opinion of the effects and drug interactions limit its use.
treating physician, could lead to crisis in the short d. Although available RCT evidence does not sup- term (days to weeks).
port the use of mycophenolate and tacrolimus in 5. Definition of manifest myasthenic crisis (the concept of MG, both are widely used, and one or both are crisis focuses on the clinical implications—it represents a seri- recommended in several national MG treatment ous, life-threatening, rapid worsening of MG and potential airway compromise from ventilatory or bulbar dysfunction).
4. Patients with refractory MG should be referred to MGFA Class V3: Worsening of myasthenic weakness a physician or a center with expertise in manage- requiring intubation or noninvasive ventilation to ment of MG. In addition to the previously men- avoid intubation, except when these measures are tioned IS agents, the following therapies may also employed during routine postoperative management be used in refractory MG: (the use of a feeding tube without intubation places a. Chronic IVIg and chronic PLEX (see IVIg and the patient in MGFA Class IVB3).
6. Definition of refractory MG. PIS3 is unchanged or b. Cyclophosphamide; worse after corticosteroids and at least 2 other IS c. Rituximab, for which evidence of efficacy is agents, used in adequate doses for an adequate dura- building, but for which formal consensus could tion, with persistent symptoms or side effects that limit not be reached.
functioning, as defined by patient and physician.
5. IS agent dosage and duration of treatment a. Once patients achieve treatment goals, the cor- Consensus guidance treatment statements.
ticosteroid dose should be gradually tapered. In Symptomatic and IS treatment of MG.
1. Pyridostigmine should be part of the initial treat- many patients, continuing a low dose of cortico- ment in most patients with MG. Pyridostigmine steroids long-term can help to maintain the dose should be adjusted as needed based on symp- treatment goal.
toms. The ability to discontinue pyridostigmine can b. For nonsteroidal IS agents, once treatment goals be an indicator that the patient has met treatment have been achieved and maintained for 6 goals and may guide the tapering of other therapies.
months to 2 years, the IS dose should be tapered Corticosteroids or IS therapy should be used in all slowly to the minimal effective amount. Dosage patients with MG who have not met treatment goals adjustments should be made no more frequently after an adequate trial of pyridostigmine.
than every 3–6 months (table e-1).
Neurology 87 July 26, 2016 ª 2016 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
c. Tapering of IS drugs is associated with risk of in patients with significant respiratory or bulbar relapse, which may necessitate upward adjust- dysfunction. Corticosteroids or other IS agents ments in dose. The risk of relapse is higher in are often started at the same time to achieve a sus- patients who are symptomatic, or after rapid taper.
tained clinical response. (Because corticosteroids d. It is usually necessary to maintain some immu- may cause transient worsening of myasthenic nosuppression for many years, sometimes for weakness, it may be appropriate to wait several days for PLEX or IVIg to have a beneficial effect 6. Patients must be monitored for potential adverse before starting corticosteroids).
effects and complications from IS drugs. Changing 3. Although clinical trials suggest that IVIg and PLEX to an alternative IS agent should be considered if are equally effective in the treatment of impending adverse effects and complications are medically sig- or manifest myasthenic crisis, expert consensus nificant or create undue hardship for the patient.
suggests that PLEX is more effective and worksmore quickly. The choice between the 2 therapies IVIg and PLEX.
depends on patient comorbidity (e.g., PLEX can- 1. PLEX and IVIg are appropriately used as short- not be used in sepsis and IVIg is contraindicated in term treatments in patients with MG with life- hypercoagulable states, renal failure, or hypersensi- threatening signs such as respiratory insufficiency tivity to immunoglobulin) and other factors, or dysphagia; in preparation for surgery in patients including availability. A greater risk of hemody- with significant bulbar dysfunction; when a rapid namic and venous access complications with PLEX response to treatment is needed; when other treat- should also be considered in the decision (many ments are insufficiently effective; and prior to complications of PLEX are related to route of beginning corticosteroids if deemed necessary to access and may be minimized by using peripheral prevent or minimize exacerbations.
rather than central venous access).
2. The choice between PLEX and IVIg depends on individual patient factors (e.g., PLEX cannot be Thymectomy in MG.
used in patients with sepsis and IVIg cannot be used 1. In non-thymomatous MG, thymectomy is per- in renal failure) and on the availability of each.
formed as an option to potentially avoid 3. IVIg and PLEX are probably equally effective in or minimize the dose or duration of immunother- the treatment of severe generalized MG.
apy, or if patients fail to respond to an initial trial of 4. The efficacy of IVIg is less certain in milder MG or immunotherapy or have intolerable side-effects in ocular MG.
from that therapy. Because of the long delay in 5. PLEX may be more effective than IVIg in MuSK- onset of effect, thymectomy for MG is an elective procedure. It should be performed when the 6. The use of IVIg as maintenance therapy can be con- patient is stable and deemed safe to undergo a pro- sidered for patients with refractory MG or for those in cedure where postoperative pain and mechanical whom IS agents are relatively contraindicated.
factors can limit respiratory function.
2. The value of thymectomy in the treatment of pre- Impending and manifest myasthenic crisis. Impending and pubertal patients with MG is unclear, but thymec- manifest myasthenic crisis are emergent situations tomy should be considered in children with requiring aggressive management and supportive generalized AChR antibody–positive MG: a. If the response to pyridostigmine and IS therapy Although cholinergic crises are now rare, excessive is unsatisfactory; or ChEI cannot be completely excluded as a cause of b. In order to avoid potential complications of IS clinical worsening. Also, ChEIs increase airway secre- tions, which may exacerbate breathing difficulties.
PLEX and IVIg are the mainstay of management For children diagnosed with seronegative general- in myasthenic crisis.
ized MG, the possibility of a congenital myasthenicsyndrome or other neuromuscular condition should 1. Impending crisis requires hospital admission and be entertained, and evaluation at a center specializing close observation of respiratory and bulbar func- in neuromuscular diseases is of value prior to tion, with the ability to transfer to an intensive care unit if it progresses to manifest crisis. Myastheniccrisis requires admission to an intensive care or 3. With rare exceptions, all patients with MG with step-down unit to monitor for or manage respira- thymoma should undergo surgery to remove the tory failure and bulbar dysfunction.
tumor. Removal of the thymoma is performed to 2. PLEX and IVIg are used as short-term treatment rid the patient of the tumor and may not produce for impending and manifest myasthenic crisis and improvement in MG. All thymus tissue should be Neurology 87 July 26, 2016 ª 2016 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
removed along with the tumor. Further treatment MG in pregnancy.
of thymoma will be dictated by histologic classifi- 1. Planning for pregnancy should be instituted well in cation and degree of surgical excision. Incom- advance to allow time for optimization of myasthenic pletely resected thymomas should be managed clinical status and to minimize risks to the fetus.
after surgery with an interdisciplinary treatment 2. Multidisciplinary communication among relevant approach (radiotherapy, chemotherapy).
specialists should occur throughout pregnancy, 4. In elderly or multimorbid patients with thymoma, during delivery, and in the postpartum period.
palliative radiation therapy can be considered in 3. Provided that their myasthenia is under good con- the appropriate clinical setting. Small thymomas trol before pregnancy, the majority of women can may be followed without treatment unless they be reassured that they will remain stable through- are enlarging or become symptomatic.
out pregnancy. If worsening occurs, it may be 5. Endoscopic and robotic approaches to thymectomy more likely during the first few months after are increasingly performed and have a good track record for safety in experienced centers. Data from 4. Oral pyridostigmine is the first-line treatment dur- randomized, controlled comparison studies are not ing pregnancy. IV ChEIs may produce uterine con- available. Based on comparisons across studies, less tractions and should not be used during pregnancy.
invasive thymectomy approaches appear to yield 5. Thymectomy should be postponed until after preg- similar results to more aggressive approaches.
nancy as benefit is unlikely to occur during 6. Thymectomy may be considered in patients with generalized MG without detectable AChR anti- 6. Chest CT without contrast can be performed safely bodies if they fail to respond adequately to IS ther- during pregnancy, although the risks of radiation apy, or to avoid/minimize intolerable adverse to the fetus need to be carefully considered. Unless effects from IS therapy. Current evidence does there is a compelling indication, postponement of not support an indication for thymectomy in pa- diagnostic CT until after delivery is preferable.
tients with MuSK, LRP4, or agrin antibodies.
7. Prednisone is the IS agent of choice during Juvenile MG (see also Thymectomy in MG, no. 2).
8. Current information indicates that azathioprine 1. Children with acquired autoimmune ocular MG and cyclosporine are relatively safe in expectant are more likely than adults to go into spontaneous mothers who are not satisfactorily controlled with remission. Thus, young children with only ocular or cannot tolerate corticosteroids. Current evidence symptoms of MG can be treated initially with pyr- indicates that mycophenolate mofetil and metho- idostigmine. Immunotherapy can be initiated ifgoals of therapy are not met.
trexate increase the risk of teratogenicity and are 2. Children are at particular risk of steroid side effects, contraindicated during pregnancy. (These agents including growth failure, poor bone mineralization, previously carried Food and Drug Administration and susceptibility to infection, due in part to a delay [FDA] Category C (cyclosporine), D (azathioprine in live vaccinations. Long-term treatment with cor- and mycophenolate mofetil), and X (methotrexate) ticosteroids should use the lowest effective dose ratings. The FDA has recently discontinued this to minimize side effects.
rating system, and replaced it with a summary of 3. Maintenance PLEX or IVIg are alternatives to IS the risks of using a drug during pregnancy and drugs in JMG.
breastfeeding, along with supporting data and "rel-evant information to help health care providers MG with MuSK antibodies.
make prescribing and counseling decisions"12).
1. Many patients with MuSK-MG respond poorly to Although this statement achieved consensus, there was ChEIs, and conventional pyridostigmine doses fre- a strong minority opinion against the use of azathio- quently induce side effects.
prine in pregnancy. Azathioprine is the nonsteroidal 2. Patients with MuSK-MG appear to respond well to IS of choice for MG in pregnancy in Europe but is corticosteroids and to many steroid-sparing IS considered high risk in the United States. This differ- agents. They tend to remain dependent on predni- ence is based on a small number of animal studies and sone despite concomitant treatment with steroid- case reports.
sparing agents.
9. PLEX or IVIg are useful when a prompt, although 3. MuSK-MG responds well to PLEX, while IVIg temporary, response is required during pregnancy.
seems to be less effective.
Careful consideration of both maternal and fetal 4. Rituximab should be considered as an early thera- issues, weighing the risks of these treatments peutic option in patients with MuSK-MG who have against the requirement for use during pregnancy an unsatisfactory response to initial immunotherapy.
and their potential benefits, is required.
Neurology 87 July 26, 2016 ª 2016 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
10. Spontaneous vaginal delivery should be the the manuscript for important intellectual content. I. Illa: acquisition objective and is actively encouraged.
of data, critical revision of the manuscript for important intellectualcontent. N. Kuntz: acquisition of data, drafting/revising the manuscript, 11. Magnesium sulfate is not recommended for critical revision of the manuscript for important intellectual content.
management of eclampsia in MG because of J.M. Massey: acquisition of data, drafting/revising the manuscript, crit- its neuromuscular blocking effects; barbiturates ical revision of the manuscript for important intellectual content.
A. Melms: acquisition of data, critical revision of the manuscript for important intellectual content. H. Murai: acquisition of data, critical revision of the manuscript for important intellectual content. J. Palace: 12. All babies born to myasthenic mothers should acquisition of data, drafting/revising the manuscript, critical revision of be examined for evidence of transient myas- the manuscript for important intellectual content. M. Nicolle: acquisi-tion of data, drafting/revising the manuscript, critical revision of the thenic weakness, even if the mother's myasthe- manuscript for important intellectual content. D.P. Richman: acquisi- nia is well-controlled, and should have rapid tion of data, critical revision of the manuscript for important intellec- access to neonatal critical care support.
tual content. J. Verschuuren: acquisition of data, critical revision of themanuscript for important intellectual content. P. Narayanaswami:study concept and design, acquisition of data, analysis or interpretation DISCUSSION We have developed international guid- of data, drafting/revising the manuscript, critical revision of the man- ance statements for the management of JMG and uscript for important intellectual content, study supervision.
adult MG. We utilized recent national guidelines anda regional European guideline to assemble a foundation of literature, supplementing their comprehensive litera- The authors thank MGFA Board member Jurgen Venitz, MD, PhD, for ture reviews with additional articles identified by panel- providing insight from the patients' perspective.
ists. After reaching agreement on the treatment goals,a 3-round anonymous modified Delphi voting process Supported by a grant from the Myasthenia Gravis Foundation of America was used to obtain consensus on guidance statements.
A limitation of consensus-based processes is that subconscious or conscious selection of like-minded panel members may result in opinions that are not rep- D. Sanders: consultant for Accordant Health Services, Cytokinetics, resentative of MG experts. This issue was addressed by GlaxoSmithKline, and Jacobus Pharmaceutical Co. G. Wolfe: advisory selecting an international panel with variations in prac- board for Grifols, Baxter, CSL Behring, and Syntimmune; and researchsupport from Alexion. M. Benatar: research support from the FDA tice and by using a formal consensus process.
(R01FD003710), NIH (U01NS084495), and Alexion. A. Evoli: scien- Recognizing the variability of practice patterns and tific award jury member for Grifols. N. Gilhus: speaker's honoraria from availability of treatment modalities, these statements Octopharma, Baxter, and Merck Serono. I. Illa: research funding fromGrifols and speaking fees and travel grants from Genzyme and Pfizer; and are not absolute recommendations for management, consultant for Alexion, UCB, and Grifols. N. Kuntz and J. Massey report but are intended as a guide for the clinician. They no disclosures relevant to the manuscript. A. Melms: advisory board, are also not intended for establishing payment poli- UCB. H. Murai: research funding from Biogen, Novartis, Bayer, Tanabe cies or drug tiering by payers.
Mitsubishi, and the Japan Blood Products Organization. J. Palace: con-sultant for Merck Serono, Biogen Idec, Novartis, Teva, Chugai Pharma, This is a living document that will require updates Alexion, and Bayer Schering; research funding from Merck Serono, No- as the MG treatment theater continues to evolve.
vartis, Biogen Idec, and Bayer Schering. M. Nicolle reports no disclosures Despite the limitations of consensus-based methods, relevant to the manuscript. D. Richman: research funding from the these guidance statements reflect an up-to-date expert Muscular Dystrophy Association, Myasthenia Gravis Foundation ofCalifornia, and the Myasthenia Gravis Foundation of Illinois. J. Verschuuren: consensus to guide clinicians worldwide who strive to research support by NIH, FP7 European grant (#602420), consultant for optimize function and quality of life for their patients Tyr pharma, and arGEN-X. The LUMC receives royalties from IBL for with MG, especially for those who practice in parts of antibody tests. P. Narayanaswami: serves on the Medical and ScientificAdvisory Board, Myasthenia Gravis Foundation of America (MGFA), the world that do not have the resources to develop and Medical Advisory Board, MGFA, New England Chapter. Go to local treatment guidelines. Any future trial of treat- for full disclosures.
ment that provides relevant information will meritreview of these guidance statements.
Received August 25, 2015. Accepted in final form February 19, 2016.
AUTHOR CONTRIBUTIONS Deenen JCW, Horlings CGC, Verschuuren JJGM, D.B. Sanders: study concept and design, grant application and manage- Verbeek ALM. The epidemiology of neuromuscular ment, acquisition of data, analysis or interpretation of data, drafting/ disorders: a comprehensive overview of the literature.
revising the manuscript, critical revision of the manuscript for important J Neuromuscul Dis 2015;2:73–85.
intellectual content, study supervision. G.I. Wolfe: study concept and Grob D, Brunner NG, Namba T, Pagala M. Lifetime course design, acquisition of data, analysis or interpretation of data, drafting/ of myasthenia gravis. Muscle Nerve 2008;37:141–149.
revising the manuscript, critical revision of the manuscript for important Jaretzki A III, Barohn RB, Ernstoff RM, et al. Myasthenia intellectual content, study supervision. M. Benatar: acquisition of data,drafting/revising the manuscript, critical revision of the manuscript for gravis: recommendations for clinical research standards: important intellectual content. A. Evoli: acquisition of data, drafting/ Task Force of the Medical Scientific Advisory Board revising the manuscript, critical revision of the manuscript for important of the Myasthenia Gravis Foundation of America.
intellectual content. N.E. Gilhus: acquisition of data, critical revision of Neurology 87 July 26, 2016 ª 2016 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
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International consensus guidance for management of myasthenia gravis: Executive
Donald B. Sanders, Gil I. Wolfe, Michael Benatar, et al. Neurology published online June 29, 2016 This information is current as of June 29, 2016
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