Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy

• Sponsor: University of Alabama at Birmingham (Other)
• Overall Status: Completed
• CT.gov ID: NCT00294658
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS) (NIH)
• Enrollment: 126
• Locations: 70
• Arms: 2
• Duration (Months): 114
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this trial is to determine if thymectomy combined with prednisone therapy is more beneficial in treating non-thymomatous myasthenia gravis than prednisone therapy alone.

Condition or Disease	Intervention/Treatment	Phase
Myasthenia Gravis	Procedure: thymectomy plus prednisone; Drug: prednisone alone	Phase 3

Detailed Description

Myasthenia gravis (MG) is an autoimmune disease involving the thymus in which 85 percent of patients have antibodies to muscle acetylcholine receptors (AchR-Ab) that interfere with neuromuscular transmission. MG frequently causes severe disability that can be life-threatening. Thymectomy-a surgical procedure that removes thymus gland tissue from the chest cavity-has been an established therapy for non-thymomatous MG, or MG without thymoma, for more than 60 years (based on retrospective, non-randomized studies). Corticosteroids are now being used increasingly either as the sole treatment or in combination with thymectomy. Both therapies have associated adverse effects and indications for their use based on randomized trial data are lacking.

The purpose of this 5-year trial is to determine if the surgical procedure, extended transsternal thymectomy (ETTX), combined with prednisone therapy is more beneficial in treating individuals with non-thymomatous MG than prednisone therapy alone. More specifically, this study will determine 1) if ETTX combined with prednisone results in a greater improvement in myasthenic weakness, compared to prednisone alone; 2) if ETTX combined with prednisone results in a lower total dose of prednisone, thus decreasing the likelihood of concurrent and long-term toxic effects, compared to prednisone alone; and 3) if ETTX combined with prednisone enhances quality of life by reducing adverse events and symptoms associated with the therapies, compared to prednisone alone.

Learning that thymectomy results in a meaningful reduction of prednisone dosage or even full withdrawal or reduces side effects related to prednisone would support using the two treatments-thymectomy and prednisone-together. However, if no meaningful reduction of prednisone dosage or side effects is shown, the results would mean that using the two treatments together offers no advantages over prednisone treatment alone.

After an initial screening, study participants will be randomized either to undergo the surgical procedure ETTX and receive prednisone treatment, or to receive prednisone treatment alone without surgery. Participants will be followed for at least 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 126 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Single-Blind, Randomized Study Comparing Thymectomy to No Thymectomy in Non-Thymomatous Myasthenia Gravis (MG) Patients Receiving Prednisone
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Thymectomy plus prednisone Procedure: Extended Transsternal Thymectomy plus prednisone treatment	Procedure: thymectomy plus prednisone; The thymectomy will be performed as soon as possible after randomization.; Other Names: Extended transsternal thymectomy plus prednisone
Placebo Comparator: Prednisone alone Drug: prednisone alone protocol	Drug: prednisone alone; Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.; Other Names: prednisolone

Outcome Measures

Primary Outcome Measures

1. Time-weighted Average Quantitative Myasthenia Gravis Weakness Score Over 3 Years [baseline, month 3, 4, 6 and every 3 months through 36 months]

   Myasthenia Gravis (QMG) test. QMG total scores range from 0 to 39 for a given visit, with higher scores indicating more severe disease. The time weighted average is a calculation that provides an integrated measure of the outcome over the time of followup. The denominator that was used to compute the time-weighted average for the Quantitative Myasthenia Gravis (QMG) score and the prednisone dose was the number of days from randomization to the last visit. Computations used the trapezoidal method where in the QMG score is multiplied by the number of days at this level from one visit to the next and added up over the entire followup experience and divided by the total number of days from randomization.

2. Time-weighted Average Alternate-day Prednisone Dose (mg) Measured Over 3 Years [baseline, month 1 , 2 , 3, 4, 6 and every 3 months through 36 months]

   Participants reported alternate-day prednisone dose (mg) intake from baseline through withdrawn or completed 3 years follow up. The prednisone dosages had been weighted over the days of reporting period.

Secondary Outcome Measures

1. Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Prednisone Use at Enrollment [baseline, month 3, 4, 6 and every 3 months through 36 months]

   Myasthenia Gravis (QMG) test. QMG total scores range from 0 to 39 for a given visit, with higher scores indicating more severe disease.

2. Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Sex [baseline, month 3, 4, 6 and every 3 months through 36 months]

   Myasthenia Gravis (QMG) test. QMG total scores range from 0 to 39 for a given visit, with higher scores indicating more severe disease.

3. Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Age at Disease Onset [baseline, month 3, 4, 6 and every 3 months through 36 months]

   Myasthenia Gravis (QMG) test. QMG total scores range from 0 to 39 for a given visit, with higher scores indicating more severe disease.

4. Subgroup Analyses of Time-weighted Average Alternate-day Prednisone Dose (mg) by Prednisone Use at Enrollment [baseline, month 3, 4, 6 and every 3 months through 36 months]

   Participants reported alternate-day prednisone dose (mg) intake from baseline through withdrawn or completed 3 years follow up. The prednisone dosages had been weighted over the days of reporting period.

5. Subgroup Analyses of Time-weighted Average Alternate-day Prednisone Dose (mg) by Sex [baseline, month 3, 4, 6 and every 3 months through 36 months]

   Participants reported alternate-day prednisone dose (mg) intake from baseline through withdrawn or completed 3 years follow up. The prednisone dosages had been weighted over the days of reporting period.

6. Subgroup Analyses of Time-weighted Average Average Alternate-day Prednisone Dose (mg) by Age at Disease Onset [baseline, month 3, 4, 6 and every 3 months through 36 months]

   Participants reported alternate-day prednisone dose (mg) intake from baseline through withdrawn or completed 3 years follow up. The prednisone dosages had been weighted over the days of reporting period.

7. Number of Serious Adverse Events [baseline to 3 years]

   Number of participant who experienced at least one serious adverse events over 3 years: Thymectomy plus prednisone n=25 (out of 66); Prednisone alone n=33 (out of 60)

8. Number of Patients With at Least One Serious Adverse Events [baseline to 3 years]

   Number of participant who experienced at least one serious adverse events over 3 years: Thymectomy plus prednisone n=25 (out of 66); Prednisone alone n=33 (out of 60)

9. Classification of Serious Adverse Events [baseline to 3 years]

10. Hospitalization for Exacerbation of Myasthenia Gravis [baseline to 2 years and baseline to 3 years]

11. Cumulative Number of Hospital Days [baseline to 3 years]

    Number who had hospitalization: Thymectomy plus prednisone n=15 (out of 66); Prednisone alone n=31 (out of 60)

12. Reason for Hospitalization According to Medical Dictionary for Regulatory Activities Term [baseline to 3 years]

    Number who had hospitalization: Thymectomy plus prednisone n=15 (out of 66); Prednisone alone n=31 (out of 60)

13. Time-weighted Average Prescribed Alternate Day Prednisone Dose (mg) [baseline-day 20, month 1,2, 3, 4, 6 and every 3 months through 36 months]

    Physicians reported prescribed alternate-day prednisone dose (mg) intake from baseline through withdrawn or completed 3 years follow up. The prescribed prednisone dosages had been weighted over the days of reporting period.

14. Penalized Time-weighted Average Alternative Day Prednisone Dose (mg; Method 1: Penalized Using Maximum Dose Before Azathioprine) [baseline, month 3, 4, 6 and every 3 months through 36 months]

    For each participant who took azathioprine, we penalized them by taking the maximum dose of prednisone before azathioprine was added. We then applied the same method to compute the time-weighted alternative day prednisone dose from baseline, month 3, 4, 6 and every 3 months through 36 months.

15. Penalized Time-weighted Average Alternative Day Prednisone Dose (mg; Method 2: Penalized Using Dose at Time of Starting Azathioprine) [baseline, month 1 , 2 , 3, 4, 6 and every 3 months through 36 months]

    For each participant who took azathioprine, we penalized them by taking the prednisone dose at the time azathioprine commenced. We then applied the same method to compute the time-weighted alternative day prednisone dose from baseline, month 3, 4, 6 and every 3 months through 36 months.

16. Time-Weighted Average MG Activity of Daily Living (MG-ADL) [baseline, month 4, 6 and every 3 months through 36 months]

    MG Activity of Daily Living total scores range from 0 to 24, with the lower scores indicating better daily living quality of life.

17. Time-Weighted Average MG Activity of Daily Living (MG-ADL) at Month 12, 24, and 36 [Month 12, 24, and 36]

    MG Activity of Daily Living total scores range from 0 to 24 by visit, with the lower scores indicating better daily living quality of life.

18. Azathioprine Use [baseline to 3 years]

19. Plasma Exchange Use [baseline to 3 years]

20. Intravenous Immunoglobulin Use [baseline to 3 years]

21. Minimal Manifestation (MM) Status at Month 12, 24 and 36 [Month 12, 24 and 36]

    Number of participants who were in minimal manifestation status at month 12, 24 and 36.

22. Cumulative Days in Hospital for Myasthenia Gravis Exacerbation [baseline to 2 years]

    Number of patients with MG exacerbation: Thymectomy plus prednisone=6 (out of 66); Prednisone alone=17 (out of 60)

23. Cumulative Days in Hospital for Myasthenia Gravis Exacerbation [baseline to 3 years]

    Number of patients with MG exacerbation: Thymectomy plus prednisone=6 (out of 66); Prednisone alone=22 (out of 60)

24. Short Form-36 Standardized Physical Component [Month 0, Month 12, Month 24 and Month 36]

    Range from 0 to 100, the higher the physical component value, the better the mental health.

25. Short Form-36 Standardized Mental Component [Month 0, Month 12, Month 24 and Month 36]

    Range from 0 to 100, the higher the mental component value, the better the mental health.

26. Treatment Associated Complications (TAC) [Month 0, 1, 2, 3, 4 then every 3 months through Month 36]

    Treatment associated complications measured complications occurred by myasthenia gravis patients. Report number of participant with at least one complications by each visit.

27. Treatment Associated Symptoms (TAS) [Month 0, 1, 2, 3, 4 then every 3 months through Month 36]

    Treatment associated symptoms measured myasthenia gravis symptoms such as back pain and/or bruises. Report number of participant with at least one treatment associated symptoms by each visit.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and female MG patients age greater than 18 and less than 65 years

• Onset of generalized MG within the last 5 years

• Positive serum anti-acetylcholine receptor binding antibodies (muscle acetylcholine receptors, AchRAb =/> 1.00 nmol/L. AchRAb levels of 0.50-0.99 nmol/L will be acceptable if there is another confirmatory test for MG, including single-fiber electromyography (EMG), repetitive nerve stimulation, or unequivocal edrophonium testing.)

• MGFA class II-IV at entry, using the MG Foundation of America (MGFA) classification, while receiving optimal anti-cholinesterase treatment with or without oral prednisone

Exclusion Criteria:

• Ocular MG without generalized weakness (MGFA Class I) or minimal weakness that would not require the use of corticosteroids

• Myasthenic weakness requiring intubation (MGFA Class IV) in the prior month

• Immunosuppressive therapy other than corticosteroids in the preceding year

• Medically unfit for thymectomy

• Chest CT evidence of thymoma.

• Pregnancy or lactation; contraindications to the use of corticosteroids, unless postmenopausal or surgically sterile. Women considering becoming pregnant during the period of the study are to be excluded.

• A serious concurrent medical, neurological or psychiatric condition that would interfere with thymectomy or subsequent clinical assessments

• Current alternate day dose of prednisone > than 1.5 mg/kg or 100 mg or the equivalent daily doses (> 0.75 mg/kg or 50 mg).

• Participation in another experimental clinical trial

• History of alcohol or drug abuse within the 2 years prior to randomization.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham, Department of Neurology, Sparks Center, Suite 350, 1720 7th Avenue South	Birmingham	Alabama	United States	35233
2	Data Coordination Center: University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
3	Barrow Neurological Institute, Saint Joseph's Hospital and Medical Center, 350 W Thomas Rd	Phoenix	Arizona	United States	85016
4	University of Southern California, Doheny Institute, 1450 San Pablo St	Los Angeles	California	United States	90033
5	University of California Irvine, 101 The City Drive S, Bldg. 22 C, Route 13	Orange	California	United States	92868
6	California Pacific Medical Center, Castro St & Duboce Ave	San Francisco	California	United States	94114
7	University of Florida Jacksonville, Tower I, 8th Floor, 580 W. 8th ST.	Jacksonville	Florida	United States	32209
8	University of Miami, 1120 NW 14th Street, Suite 1300	Miami	Florida	United States	33136
9	Emory University, 201 Dowman Dr	Atlanta	Georgia	United States	30322
10	Augusta University, 1120 15th St	Augusta	Georgia	United States	30912
11	Indiana University, Dept of Neurology, Regenstrief Health Center, 6th floor, 1050 Walnut St, Indiana University Medical Center	Indianapolis	Indiana	United States	46202-2859
12	The University of Kansas Medical Center, 3901 Rainbow Blvd.	Kansas City	Kansas	United States	66160
13	Brigham and Women's Hospital, 75 Francis Street, 5th Floor Tower	Boston	Massachusetts	United States	02115-6110
14	Wayne State University School of Medicine, 4201 St Antoine, 8D UHC	Detroit	Michigan	United States	48201
15	William Beaumont Hospital, 3601 W. Thirteen Mile Road, Royal Oak	Royal Oak	Michigan	United States	48073
16	University of Minnesota, Department of Neurology, MMC 295, 420 Delaware St. S.E.,	Minneapolis	Minnesota	United States	55455
17	Mayo Clinic Rochester, 200 First St. SW	Rochester	Minnesota	United States	55905
18	St. Louis University, One North Grand St. Louis	St. Louis	Missouri	United States	63103-2097
19	Robert Wood Johnson University,	New Brunswick	New Jersey	United States	08901
20	Mount Sinai Hospital,1 Gustave L. Levy Pl	New York	New York	United States	10029
21	University of Rochester, 601 Elmwood Ave	Rochester	New York	United States	14642
22	Duke University, 200 Trent Dr	Durham	North Carolina	United States	27710
23	Case Western Reserve University, University Hospitals of Cleveland, 1100 Euclid Avenue	Cleveland	Ohio	United States	44106
24	The Ohio State University Wexmer Medical Center, Rm 461 Means Hall, The Ohio State University Medical Center,1654 Upham Dr.	Columbus	Ohio	United States	43210
25	University of Texas Southwestern Medical Center, 5232 Harry Hines Blvd,	Dallas	Texas	United States	75390-8897
26	University of Texas Medical Branch, 301 University Blvd	Galveston	Texas	United States	77555-0539
27	Nerve and Muscle Center of Texas, 6624 Fannin St # 1670	Houston	Texas	United States	77030
28	University of Texas Health Science Center, Mail code 7883, 7703 Floyd Curl Drive	San Antonio	Texas	United States	78229-3900
29	University of Vermont College of Medicine, Given Bldg C225, 89 Beaumont Avenue	Burlington	Vermont	United States	05405
30	University of Virginia, 1215 Lee St	Charlottesville	Virginia	United States	22908
31	University of Washington, 1410 NE Campus Pkwy	Seattle	Washington	United States	98195
32	West Virginia University, Dept of Neurology, WVU Eye Institute, Neurology Suite, 1 Stadium Drive,	Morgantown	West Virginia	United States	26506
33	Medical College of Wisconsin, 8701 Watertown Plank Road	Milwaukee	Wisconsin	United States	53226
34	University of Buenis, Centro de Asistencia Docencia e Investigacion en Miastenia (CADIMI) Av. Forest 1146 - Ciudad Autonoma de Buenos Aires	Buenos Aires		Argentina
35	University of Sydney, Royal Prince Alfred Hospital and The University of Sydney	Sydney		Australia
36	University of Melbourne, Melbourne, The Royal Melbourne Hospital, Dept of Neurology, Royal Melbourne Hospital	Victoria		Australia	3050
37	Hospital de Base do Distrito Federal	Brasilia		Brazil	CEP 71640 255
38	Universidade Federal do Parana	Curitiba		Brazil	80060-900
39	Federal University of Rio De Janeiro	Rio De Janeiro		Brazil	CEP 20520-053
40	University of Calgary, Heritage Medical Research Clinic Room 1132 3330 Hospital Dr NW	Calgary	Alberta	Canada	T2N 2T9
41	University of British Columbia	Vancouver	British Columbia	Canada	V6T 2B5
42	University of Ottawa, The Ottawa Hospital General Campus, Division of Neurology, 501 Smyth Rd. Box 601	Ottawa	Ontario	Canada	K1H 8L6
43	McGill University Health Center	Montreal	Quebec	Canada	H3G 1A4
44	Hospital Del Salvador, Departamento de Ciencias Neurológicas, Universidad de Chile, Salvador 95 Of 416, Providencia	Santiago		Chile
45	University of Heidelberg, Seminarstraße 2	Mannheim	Baden-Württemberg	Germany	69117
46	University of Regensburg, Dept. of Neurology, Universitätsstr. 84, D	Regensburg	Bavaria	Germany	93043
47	University of Düsseldorf	Düsseldorf	North Rhine-Westphalia	Germany	D-40225
48	Johannes-Gutenberg University, Klinikum der Johannes Gutenberg-Universität, Klinik und Poliklinik für Neurologie, Langenbeckstr	Mainz	Rhineland-Palatinate	Germany	55101
49	University of Münster, Schlossplatz 2	Münster		Germany	48149
50	University of Tübingen	Tübingen		Germany	72076
51	National Neurological Institute "Carlo Besta", Myopathology and Immunology Unit, Dept of Neurology IV, Natl. Neurolog Inst. "C. Besta", Via Celoria, 11,	Milan		Italy	20133
52	University of Rome "Sapienza"	Rome		Italy	00189
53	Catholic University, Universita Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, e	Rome		Italy
54	University of Torino	Torino		Italy
55	Kanazawa University, Department of Neurology, Kanazawa University Hospital, 13-1 Takaramachi	Kanazawa	Ishikawa	Japan	920-8641
56	Nagasaki University, First Department of Internal Medicine,Graduate School of Biomedical Sciences,1-7-1,Sakamoto	Nagasaki	Kyushu	Japan	852-8501
57	Instituto Nacional de la Nutrición	Mexico		Mexico	14000
58	Leiden University	Leiden		Netherlands
59	Medical University of Warsaw	Warsaw	Województwo	Poland	02 097
60	Institute of Tuberculosis and Lung Disease	Warsaw	Województwo	Poland
61	Porto University, Serviço de Neurologia,Hospital Geral de Santo António, Largo Prof Abel Salazar	Porto		Portugal	4099-001
62	University of Cape Town, Division of Neurology E8-74, Groote Schuur Hospital,Observatory	Cape Town		South Africa
63	H. Sant Pau, Universitat Autònoma de Barcelona, Neurology Department, Hospital Sta Creu i Sant Pau, C/Mas Casanovas no 90 4o pis 4o modul.	Barcelona		Spain	08025
64	Fu-Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist	New Taipei		Taiwan	24205
65	Ramathibodi Hospital, Mahidol University	Bangkok		Thailand	10400
66	Queen Elizabeth University Hospital, Glasgow	Glasgow		United Kingdom	G51 4TF
67	Walton Centre for Neurology and Neurosurgery, Liverpool Heart and Chest Hospital, Liverpool. The Walton Centre for Neurology and Neurosurgery, Lower Lane, Fazakerley	Liverpool		United Kingdom	L9 7LJ
68	University of Manchester, Oxford Road	Manchester		United Kingdom	M13 9PL
69	University of Oxford, Dept of Clinical Neurology, University of Oxford, Radcliffe Infirmary	Oxford		United Kingdom	OX2 6HE
70	University of Sheffield, Western Bank	Sheffield		United Kingdom	S10 2TN

Sponsors and Collaborators

• University of Alabama at Birmingham
• National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Gary Cutter, PhD, University of Alabama at Birmingham School of Public Health, Department of Biostatistics
• Principal Investigator: Gil Wolfe, MD, University of Buffalo, Jacobs School of Medicine and Biomedical Sciences
• Principal Investigator: Henry Kaminski, MD, George Washington University School of Medicine and Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gary Cutter, PhD, Principle Investigator, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT00294658
• Other Study ID Numbers: R01NS050733; 1U01NS042685-01A2; CRC
• First Posted: Feb 22, 2006
• Last Update Posted: May 23, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Gary Cutter, PhD, Principle Investigator, University of Alabama at Birmingham: myasthenia gravis; thymectomy; prednisone; corticosteroid; extended transsternal thymectomy; ETTX; MG; thymus; thymoma
• Additional relevant MeSH terms: Myasthenia Gravis; Muscle Weakness; Prednisone; Prednisolone

Study Results

Participant Flow

Recruitment Details	The first enrollment of two patients started with July 26, 2006 and the last patient was recruited on November 28, 2012. Of the 126 randomized patients, 96 were from centers outside the US and 30 were from US centers.
Pre-assignment Detail	After informed consent signed, 66 patients were randomized to extended transsternal thymectomy with prednisone treatment and 60 patients were assigned to take prednisone without surgery. Within the 126 subject that started, 15 dropped out before 3 year follow-up.

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy had been performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen had been taken every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Period Title: Overall Study
STARTED	66	60
COMPLETED	60	51
NOT COMPLETED	6	9

Baseline Characteristics

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone	Total
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.	Total of all reporting groups
Overall Participants	66	60	126
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	32	33	32
Sex: Female, Male (Count of Participants)
Female	50 75.8%	39 65%	89 70.6%
Male	16 24.2%	21 35%	37 29.4%
Race/Ethnicity, Customized (participants) [Number]
Asian	6 9.1%	4 6.7%	10 7.9%
Black	7 10.6%	6 10%	13 10.3%
Hispanic	17 25.8%	17 28.3%	34 27%
Non-Hispanic	31 47%	30 50%	61 48.4%
Other	5 7.6%	3 5%	8 6.3%
Region of Enrollment (participants) [Number]
Argentina	10 15.2%	11 18.3%	21 16.7%
United States	16 24.2%	14 23.3%	30 23.8%
Japan	1 1.5%	1 1.7%	2 1.6%
United Kingdom	2 3%	2 3.3%	4 3.2%
Thailand	3 4.5%	2 3.3%	5 4%
Canada	9 13.6%	9 15%	18 14.3%
Netherlands	1 1.5%	0 0%	1 0.8%
Brazil	3 4.5%	2 3.3%	5 4%
Poland	1 1.5%	1 1.7%	2 1.6%
Italy	6 9.1%	4 6.7%	10 7.9%
Mexico	1 1.5%	0 0%	1 0.8%
South Africa	4 6.1%	4 6.7%	8 6.3%
Australia	2 3%	2 3.3%	4 3.2%
Chile	5 7.6%	5 8.3%	10 7.9%
Germany	2 3%	3 5%	5 4%
Therapy at enrollment - Pyridostigimine (participants) [Number]
Yes	60 90.9%	56 93.3%	116 92.1%
No	5 7.6%	1 1.7%	6 4.8%
Missing	1 1.5%	3 5%	4 3.2%
Therapy at enrollment - Glucocorticoid (participants) [Number]
Yes	49 74.2%	47 78.3%	96 76.2%
No	16 24.2%	10 16.7%	26 20.6%
Missing	1 1.5%	3 5%	4 3.2%
Previous therapy - Intravenous immue globulin (participants) [Number]
Yes	12 18.2%	13 21.7%	25 19.8%
No	53 80.3%	44 73.3%	97 77%
Missing	1 1.5%	3 5%	4 3.2%
Previous therapy - Plasma exchange (participants) [Number]
Yes	9 13.6%	7 11.7%	16 12.7%
No	56 84.8%	50 83.3%	106 84.1%
Missing	1 1.5%	3 5%	4 3.2%
MGFA class (participants) [Number]
IIa	25 37.9%	25 41.7%	50 39.7%
IIb	18 27.3%	14 23.3%	32 25.4%
III	21 31.8%	20 33.3%	41 32.5%
IV	2 3%	1 1.7%	3 2.4%
Duration of disease (years) [Median (Full Range) ]
Median (Full Range) [years]	1.08	1.14	1.11
QMG score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	11.40 (5.12)	12.35 (4.90)	11.84 (5.02)
Prednisone use at baseline (participants) [Number]
Yes	49 74.2%	47 78.3%	96 76.2%
No	16 24.2%	10 16.7%	26 20.6%
Missing	1 1.5%	3 5%	4 3.2%
Prednisone Dosage at baseline (mg) (mg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg]	43.43 (28.92)	42.49 (23.52)	42.97 (26.28)

Outcome Measures

1. Primary Outcome

Title	Time-weighted Average Quantitative Myasthenia Gravis Weakness Score Over 3 Years
Description	Myasthenia Gravis (QMG) test. QMG total scores range from 0 to 39 for a given visit, with higher scores indicating more severe disease. The time weighted average is a calculation that provides an integrated measure of the outcome over the time of followup. The denominator that was used to compute the time-weighted average for the Quantitative Myasthenia Gravis (QMG) score and the prednisone dose was the number of days from randomization to the last visit. Computations used the trapezoidal method where in the QMG score is multiplied by the number of days at this level from one visit to the next and added up over the entire followup experience and divided by the total number of days from randomization.
Time Frame	baseline, month 3, 4, 6 and every 3 months through 36 months

Outcome Measure Data

Analysis Population Description

Four participants in each group did not provide the information to enable calculation of the time-weighted Quantitative Myasthenia Gravis Weakness Score over 3 years.

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	62	56
Mean (Standard Deviation) [units on a scale]	6.15 (4.09)	8.99 (4.93)

2. Primary Outcome

Title	Time-weighted Average Alternate-day Prednisone Dose (mg) Measured Over 3 Years
Description	Participants reported alternate-day prednisone dose (mg) intake from baseline through withdrawn or completed 3 years follow up. The prednisone dosages had been weighted over the days of reporting period.
Time Frame	baseline, month 1 , 2 , 3, 4, 6 and every 3 months through 36 months

Outcome Measure Data

Analysis Population Description

Five participants in Thymectomy plus prednisone and 4 in Prednisone alone group did not provide the information to enable calculation of the time-weighted average alternate-day prednisone dose (mg) over 3 years.

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	61	56
Mean (Standard Deviation) [mg]	32 (23)	54 (29)

3. Secondary Outcome

Title	Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Prednisone Use at Enrollment
Description	Myasthenia Gravis (QMG) test. QMG total scores range from 0 to 39 for a given visit, with higher scores indicating more severe disease.
Time Frame	baseline, month 3, 4, 6 and every 3 months through 36 months

Outcome Measure Data

Analysis Population Description

Four participants in Thymectomy plus prednisone and 5 in Prednisone alone group did not provide information to enable the calculation of Time-weighted average Quantitative Myasthenia Gravis Score by prednisone use at enrollment over 3 years.

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	62	55
Not prednisone naïve	6.30 (3.89)	9.10 (5.06)
Prednisone naïve	5.66 (4.79)	8.84 (4.60)

4. Secondary Outcome

Title	Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Sex
Description	Myasthenia Gravis (QMG) test. QMG total scores range from 0 to 39 for a given visit, with higher scores indicating more severe disease.
Time Frame	baseline, month 3, 4, 6 and every 3 months through 36 months

Outcome Measure Data

Analysis Population Description

Four participants in each group did not provide the information to enable calculation of the time-weighted Quantitative Myasthenia Gravis Weakness Score over 3 years.

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	62	56
Female	6.47 (4.13)	9.73 (5.16)
Male	5.23 (3.95)	7.45 (4.11)

5. Secondary Outcome

Title	Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Age at Disease Onset
Description	Myasthenia Gravis (QMG) test. QMG total scores range from 0 to 39 for a given visit, with higher scores indicating more severe disease.
Time Frame	baseline, month 3, 4, 6 and every 3 months through 36 months

Outcome Measure Data

Analysis Population Description

Four participants in each group did not provide the information to enable calculation of the time-weighted average Quantitative Myasthenia Gravis Weakness Score over 3 years. Another 2 participants in Thymectomy plus prednisone and 4 in Prednisone alone group did not provide the age at disease onset information.

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	60	52
Age (years) at Disease Onset < 40	6.50 (4.41)	9.60 (5.32)
Age (years) at Disease Onset ≥ 40	5.33 (2.79)	7.85 (3.50)

6. Secondary Outcome

Title	Subgroup Analyses of Time-weighted Average Alternate-day Prednisone Dose (mg) by Prednisone Use at Enrollment
Description	Participants reported alternate-day prednisone dose (mg) intake from baseline through withdrawn or completed 3 years follow up. The prednisone dosages had been weighted over the days of reporting period.
Time Frame	baseline, month 3, 4, 6 and every 3 months through 36 months

Outcome Measure Data

Analysis Population Description

Five participants in Thymectomy plus prednisone and 4 in Prednisone alone group did not provide the information to enable calculation of time-weighted average alternate-day prednisone dose (mg) over 3 years. Another 1 in Prednisone alone group did not provide prednisone use at enrollment information.

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	61	55
Not prednisone naïve	35 (25)	56 (31)
Prednisone naïve	25 (17)	45 (22)

7. Secondary Outcome

Title	Subgroup Analyses of Time-weighted Average Alternate-day Prednisone Dose (mg) by Sex
Description	Participants reported alternate-day prednisone dose (mg) intake from baseline through withdrawn or completed 3 years follow up. The prednisone dosages had been weighted over the days of reporting period.
Time Frame	baseline, month 3, 4, 6 and every 3 months through 36 months

Outcome Measure Data

Analysis Population Description

Five participants in Thymectomy plus prednisone and 4 in Prednisone alone group did not provide the information to enable calculation of the time-weighted average alternate-day prednisone dose (mg) over 3 years.

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	61	56
Female	33 (25)	54 (27)
Male	31 (18)	55 (34)

8. Secondary Outcome

Title	Subgroup Analyses of Time-weighted Average Average Alternate-day Prednisone Dose (mg) by Age at Disease Onset
Description	Participants reported alternate-day prednisone dose (mg) intake from baseline through withdrawn or completed 3 years follow up. The prednisone dosages had been weighted over the days of reporting period.
Time Frame	baseline, month 3, 4, 6 and every 3 months through 36 months

Outcome Measure Data

Analysis Population Description

Five participants in Thymectomy plus prednisone and 4 in Prednisone alone group did not provide the information to enable calculation of the time-weighted average alternate-day prednisone dose (mg) over 3 years. Another 2 in Thymectomy plus prednisone group and 4 in Prednisone alone group did not provide age at disease onset information.

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	59	52
Age (Years) at Disease Onset < 40	35 (25)	55 (30)
Age (Years) at Disease Onset ≥ 40	27 (18)	49 (29)

9. Secondary Outcome

Title	Number of Serious Adverse Events
Description	Number of participant who experienced at least one serious adverse events over 3 years: Thymectomy plus prednisone n=25 (out of 66); Prednisone alone n=33 (out of 60)
Time Frame	baseline to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	25	33
Number [events]	48	93

10. Secondary Outcome

Title	Number of Patients With at Least One Serious Adverse Events
Description	Number of participant who experienced at least one serious adverse events over 3 years: Thymectomy plus prednisone n=25 (out of 66); Prednisone alone n=33 (out of 60)
Time Frame	baseline to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	66	60
Number [participants]	25 37.9%	33 55%

11. Secondary Outcome

Title	Classification of Serious Adverse Events
Time Frame	baseline to 3 years

Outcome Measure Data

Analysis Population Description

One participant might had experienced more than one serious adverse event.

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	25	33
Life-threatening	1 1.5%	7 11.7%
Disability or incapacity	8 12.1%	2 3.3%
Medical or surgical intervention	9 13.6%	5 8.3%
Death	0 0%	1 1.7%
Complication due to thytmectomy	1 1.5%	0 0%
Hospitalization	15 22.7%	31 51.7%

12. Secondary Outcome

Title	Hospitalization for Exacerbation of Myasthenia Gravis
Time Frame	baseline to 2 years and baseline to 3 years

Outcome Measure Data

Analysis Population Description

Number of participants who had hospitalized over 2 and 3 years

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	15	31
Months 0-24	6 9.1%	17 28.3%
Months 0-36	6 9.1%	22 36.7%

13. Secondary Outcome

Title	Cumulative Number of Hospital Days
Description	Number who had hospitalization: Thymectomy plus prednisone n=15 (out of 66); Prednisone alone n=31 (out of 60)
Time Frame	baseline to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	15	31
Mean (Standard Deviation) [days]	8.4 (8.6)	19.2 (24.5)

14. Secondary Outcome

Title	Reason for Hospitalization According to Medical Dictionary for Regulatory Activities Term
Description	Number who had hospitalization: Thymectomy plus prednisone n=15 (out of 66); Prednisone alone n=31 (out of 60)
Time Frame	baseline to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	15	31
Gastrointestinal disorder	2	2
Hepatobiliary disorder	0	1
Infection or infestation	4	7
Injury, poisoning, or procedure complication	2	0
Metabolism or nutrition disorder	1	0
Nervous system disorder	8	22
Respiratory, thoracic, or mediastinal disorder	1	2
Surgical or medical procedure	0	7
Vascular disorder	0	1

15. Secondary Outcome

Title	Time-weighted Average Prescribed Alternate Day Prednisone Dose (mg)
Description	Physicians reported prescribed alternate-day prednisone dose (mg) intake from baseline through withdrawn or completed 3 years follow up. The prescribed prednisone dosages had been weighted over the days of reporting period.
Time Frame	baseline-day 20, month 1,2, 3, 4, 6 and every 3 months through 36 months

Outcome Measure Data

Analysis Population Description

Four participants in each group did not provide the information to enable calculation of the time-weighted average prescribed alternate-day prednisone dose (mg) over 3 years.

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	62	56
Mean (Standard Deviation) [mg]	34.3 (22.7)	55.6 (29.4)

16. Secondary Outcome

Title	Penalized Time-weighted Average Alternative Day Prednisone Dose (mg; Method 1: Penalized Using Maximum Dose Before Azathioprine)
Description	For each participant who took azathioprine, we penalized them by taking the maximum dose of prednisone before azathioprine was added. We then applied the same method to compute the time-weighted alternative day prednisone dose from baseline, month 3, 4, 6 and every 3 months through 36 months.
Time Frame	baseline, month 3, 4, 6 and every 3 months through 36 months

Outcome Measure Data

Analysis Population Description

Five participants in Thymectomy plus prednisone and 4 in Prednisone alone group did not provide the information to enable calculation of the penalized time-weighted average alternate-day prednisone dose (mg) over 3 years.

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	61	56
Mean (Standard Deviation) [mg]	34.4 (28.2)	64.4 (40.8)

17. Secondary Outcome

Title	Penalized Time-weighted Average Alternative Day Prednisone Dose (mg; Method 2: Penalized Using Dose at Time of Starting Azathioprine)
Description	For each participant who took azathioprine, we penalized them by taking the prednisone dose at the time azathioprine commenced. We then applied the same method to compute the time-weighted alternative day prednisone dose from baseline, month 3, 4, 6 and every 3 months through 36 months.
Time Frame	baseline, month 1 , 2 , 3, 4, 6 and every 3 months through 36 months

Outcome Measure Data

Analysis Population Description

Five participants in Thymectomy plus prednisone and 4 in Prednisone alone group did not provide the information to enable calculation of the penalized time-weighted average alternate-day prednisone dose (mg) over 3 years.

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	61	56
Mean (Standard Deviation) [mg]	33.3 (27.2)	57.9 (36.9)

18. Secondary Outcome

Title	Time-Weighted Average MG Activity of Daily Living (MG-ADL)
Description	MG Activity of Daily Living total scores range from 0 to 24, with the lower scores indicating better daily living quality of life.
Time Frame	baseline, month 4, 6 and every 3 months through 36 months

Outcome Measure Data

Analysis Population Description

Five participants in each group did not provide the information to enable calculation of the time-weighted average MG activity of daily life over 3 years.

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	61	55
Mean (Standard Deviation) [units on a scale]	2.24 (2.09)	3.41 (2.58)

19. Secondary Outcome

Title	Time-Weighted Average MG Activity of Daily Living (MG-ADL) at Month 12, 24, and 36
Description	MG Activity of Daily Living total scores range from 0 to 24 by visit, with the lower scores indicating better daily living quality of life.
Time Frame	Month 12, 24, and 36

Outcome Measure Data

Analysis Population Description

Participants were in and out at month 12, 24 and 36 visit.

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	66	60
Month 12	1.92 (2.73)	3.33 (3.40)
Month 24	2.02 (2.78)	3.11 (2.93)
Month 36	2.14 (2.92)	2.69 (2.80)

20. Secondary Outcome

Title	Azathioprine Use
Time Frame	baseline to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	65	58
Number [participants]	11 16.7%	28 46.7%

21. Secondary Outcome

Title	Plasma Exchange Use
Time Frame	baseline to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	65	58
Number [participants]	10 15.2%	9 15%

22. Secondary Outcome

Title	Intravenous Immunoglobulin Use
Time Frame	baseline to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	65	58
Number [participants]	11 16.7%	23 38.3%

23. Secondary Outcome

Title	Minimal Manifestation (MM) Status at Month 12, 24 and 36
Description	Number of participants who were in minimal manifestation status at month 12, 24 and 36.
Time Frame	Month 12, 24 and 36

Outcome Measure Data

Analysis Population Description

Number analyzed: Thymectomy plus prednisone: n=61 (Month 12), 59 (Month 24) , and 58 (Month 36); Prednisone alone n=54 (Month 12), 53 (Month 24), and 51 (Month 36)

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	66	60
Month 12	41 62.1%	20 33.3%
Month 24	39 59.1%	20 33.3%
Month 36	39 59.1%	24 40%

24. Secondary Outcome

Title	Cumulative Days in Hospital for Myasthenia Gravis Exacerbation
Description	Number of patients with MG exacerbation: Thymectomy plus prednisone=6 (out of 66); Prednisone alone=17 (out of 60)
Time Frame	baseline to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	6	17
Mean (Standard Deviation) [days]	5.5 (2.9)	26.4 (28.9)

25. Secondary Outcome

Title	Cumulative Days in Hospital for Myasthenia Gravis Exacerbation
Description	Number of patients with MG exacerbation: Thymectomy plus prednisone=6 (out of 66); Prednisone alone=22 (out of 60)
Time Frame	baseline to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	6	22
Mean (Standard Deviation) [days]	8.7 (7.7)	22.5 (27.1)

26. Secondary Outcome

Title	Short Form-36 Standardized Physical Component
Description	Range from 0 to 100, the higher the physical component value, the better the mental health.
Time Frame	Month 0, Month 12, Month 24 and Month 36

Outcome Measure Data

Analysis Population Description

Participants were in and out by visit.

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	66	60
Month 0	41.4	37.9
Month 12	48.4	44.4
Month 24	50.3	43.0
Month 36	48.2	44.2

27. Secondary Outcome

Title	Short Form-36 Standardized Mental Component
Description	Range from 0 to 100, the higher the mental component value, the better the mental health.
Time Frame	Month 0, Month 12, Month 24 and Month 36

Outcome Measure Data

Analysis Population Description

Participants were in and out by visit.

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	66	60
Month 0	49.1	46.2
Month 12	39.1	41.7
Month 24	49.9	46.7
Month 36	51.7	48.2

28. Secondary Outcome

Title	Treatment Associated Complications (TAC)
Description	Treatment associated complications measured complications occurred by myasthenia gravis patients. Report number of participant with at least one complications by each visit.
Time Frame	Month 0, 1, 2, 3, 4 then every 3 months through Month 36

Outcome Measure Data

Analysis Population Description

Participants were in and out by each visit.

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	66	60
Month 0	22 33.3%	17 28.3%
Month 1	15 22.7%	15 25%
Month 2	22 33.3%	20 33.3%
Month 3	21 31.8%	16 26.7%
Month 4	23 34.8%	23 38.3%
Month 6	21 31.8%	22 36.7%
Month 9	37 56.1%	26 43.3%
Month 12	35 53%	28 46.7%
Month 15	29 43.9%	24 40%
Month 18	28 42.4%	24 40%
Month 21	22 33.3%	20 33.3%
Mpnth 24	28 42.4%	23 38.3%
Mpnth 27	25 37.9%	17 28.3%
Month 30	23 34.8%	19 31.7%
Month 33	24 36.4%	23 38.3%
Month 36	23 34.8%	23 38.3%

29. Secondary Outcome

Title	Treatment Associated Symptoms (TAS)
Description	Treatment associated symptoms measured myasthenia gravis symptoms such as back pain and/or bruises. Report number of participant with at least one treatment associated symptoms by each visit.
Time Frame	Month 0, 1, 2, 3, 4 then every 3 months through Month 36

Outcome Measure Data

Analysis Population Description

Patients were in and out by visit

Arm/Group Title	Thymectomy Plus Prednisone	Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Measure Participants	66	60
Month 0	63 95.5%	53 88.3%
Month 1	55 83.3%	52 86.7%
Month 2	61 92.4%	53 88.3%
Month 3	60 90.9%	54 90%
Month 4	59 89.4%	54 90%
Month 6	60 90.9%	53 88.3%
Month 9	59 89.4%	50 83.3%
Month 12	56 84.8%	52 86.7%
Month 15	56 84.8%	51 85%
Month 18	52 78.8%	51 85%
Month 21	52 78.8%	50 83.3%
Mpnth 24	52 78.8%	51 85%
Mpnth 27	50 75.8%	50 83.3%
Month 30	49 74.2%	50 83.3%
Month 33	51 77.3%	48 80%
Month 36	49 74.2%	47 78.3%

Adverse Events

Time Frame	Adverse events were reported from baseline to 3 years
Adverse Event Reporting Description	There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone
Arm/Group Title	Thymectomy Plus Prednisone		Prednisone Alone
Arm/Group Description	Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.		Drug: prednisone alone protocol prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
All Cause Mortality
	Thymectomy Plus Prednisone		Prednisone Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Thymectomy Plus Prednisone		Prednisone Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/66 (37.9%)		33/60 (55%)
Blood and lymphatic system disorders
Pancytopenia	1/66 (1.5%)	1	0/60 (0%)	0
Ear and labyrinth disorders
Deafness	1/66 (1.5%)	1	0/60 (0%)	0
Gastrointestinal disorders
Abdominal hernia	1/66 (1.5%)	1	0/60 (0%)	0
Dyspepsia	0/66 (0%)	0	1/60 (1.7%)	1
Umbilical hernia	1/66 (1.5%)	1	0/60 (0%)	0
Vomiting	1/66 (1.5%)	1	1/60 (1.7%)	1
General disorders
Cardiac death	0/66 (0%)	0	1/60 (1.7%)	1
Hepatobiliary disorders
Bile duct stone	0/66 (0%)	0	1/60 (1.7%)	1
Cholelithiasis	1/66 (1.5%)	1	0/60 (0%)	0
Infections and infestations
Appendicitis	1/66 (1.5%)	1	0/60 (0%)	0
Bronchitis bacterial	1/66 (1.5%)	1	3/60 (5%)	4
Device related sepsis	1/66 (1.5%)	1	0/60 (0%)	0
Diverticulitis	0/66 (0%)	0	1/60 (1.7%)	4
Gastroenteritis	0/66 (0%)	0	1/60 (1.7%)	1
Incision site cellulitis	2/66 (3%)	2	0/60 (0%)	0
Pneumonia bacterial	1/66 (1.5%)	2	3/60 (5%)	3
Pyelonephritis	1/66 (1.5%)	1	0/60 (0%)	0
Pyelonephritis acute	1/66 (1.5%)	1	0/60 (0%)	0
Septic shock	1/66 (1.5%)	1	0/60 (0%)	0
Upper respiratory tract infection bacterial	0/66 (0%)	0	1/60 (1.7%)	1
Urinary tract infection	0/66 (0%)	0	1/60 (1.7%)	1
Viral upper respiratory tract infection	1/66 (1.5%)	1	0/60 (0%)	0
Injury, poisoning and procedural complications
Fibula fracture	1/66 (1.5%)	1	0/60 (0%)	0
Forearm fracture	1/66 (1.5%)	1	0/60 (0%)	0
Incisional hernia	1/66 (1.5%)	1	0/60 (0%)	0
Meniscus lesion	1/66 (1.5%)	1	0/60 (0%)	0
Muscle injury	1/66 (1.5%)	1	0/60 (0%)	0
Rib fracture	1/66 (1.5%)	1	0/60 (0%)	0
Tibia fracture	1/66 (1.5%)	1	0/60 (0%)	0
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	1/66 (1.5%)	2	0/60 (0%)	0
Musculoskeletal and connective tissue disorders
Osteonecrosis	0/66 (0%)	0	1/60 (1.7%)	1
Osteopenia	0/66 (0%)	0	1/60 (1.7%)	1
Osteoporotic fracture	1/66 (1.5%)	1	0/60 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/66 (0%)	0	1/60 (1.7%)	1
Nervous system disorders
Myasthenia gravis	6/66 (9.1%)	7	22/60 (36.7%)	43
Myasthenia gravis crisis	4/66 (6.1%)	6	10/60 (16.7%)	13
Phrenic nerve paralysis	1/66 (1.5%)	1	0/60 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/66 (0%)	0	1/60 (1.7%)	1
Pregnancy	0/66 (0%)	0	1/60 (1.7%)	1
Renal and urinary disorders
Renal failure	1/66 (1.5%)	1	0/60 (0%)	0
Renal impairment	0/66 (0%)	0	1/60 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Diaphragm muscle weakness	1/66 (1.5%)	1	0/60 (0%)	0
Dyspnoea	0/66 (0%)	0	1/60 (1.7%)	1
Hypoxia	1/66 (1.5%)	1	0/60 (0%)	0
Pleural effusion	1/66 (1.5%)	1	0/60 (0%)	0
Pleurisy	1/66 (1.5%)	1	0/60 (0%)	0
Pneumothorax	0/66 (0%)	0	1/60 (1.7%)	1
Pulmonary embolism	0/66 (0%)	0	1/60 (1.7%)	1
Sleep apnoea syndrome	1/66 (1.5%)	1	0/60 (0%)	0
Surgical and medical procedures
Eye operation	0/66 (0%)	0	1/60 (1.7%)	1
Supportive care	0/66 (0%)	0	1/60 (1.7%)	1
Thoracotomy	0/66 (0%)	0	1/60 (1.7%)	1
Thymectomy	0/66 (0%)	0	7/60 (11.7%)	7
Thyroidectomy	1/66 (1.5%)	1	0/60 (0%)	0
Vascular disorders
Hypertensive crisis	0/66 (0%)	0	1/60 (1.7%)	1
Other (Not Including Serious) Adverse Events
	Thymectomy Plus Prednisone		Prednisone Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	55/66 (83.3%)		48/60 (80%)
Eye disorders
Cataract	4/66 (6.1%)	14	7/60 (11.7%)	20
Glaucoma	5/66 (7.6%)	22	1/60 (1.7%)	1
Infections and infestations
Herpes zoster	5/66 (7.6%)	6	4/60 (6.7%)	8
Injury, poisoning and procedural complications
Tendon rupture	2/66 (3%)	2	3/60 (5%)	3
Investigations
Liver function test abnormal	2/66 (3%)	2	3/60 (5%)	3
Metabolism and nutrition disorders
Abnormal weight gain	32/66 (48.5%)	184	31/60 (51.7%)	141
Diabetes mellitus	6/66 (9.1%)	41	9/60 (15%)	44
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	15/66 (22.7%)	43	4/60 (6.7%)	9
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin cancer	1/66 (1.5%)	1	3/60 (5%)	3
Psychiatric disorders
Mental disorder	4/66 (6.1%)	4	5/60 (8.3%)	8
Sleep disorder	25/66 (37.9%)	86	22/60 (36.7%)	67
Skin and subcutaneous tissue disorders
Rash	21/66 (31.8%)	58	24/60 (40%)	48
Scab	11/66 (16.7%)	44	2/60 (3.3%)	2
Vascular disorders
Hypertension	16/66 (24.2%)	53	16/60 (26.7%)	55

Limitations/Caveats

Potential weakness of this trial include the single-blinded and pill count methodology.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.