Trial Outcomes & Findings for Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy (NCT NCT00294658)

Last Updated: 2017-05-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

126 participants

Primary outcome timeframe

baseline, month 3, 4, 6 and every 3 months through 36 months

Results posted on

2017-05-23

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Thymectomy Plus Prednisone Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy had been performed as soon as possible after randomization.	Prednisone Alone 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.
Overall Study STARTED	66	60
Overall Study COMPLETED	60	51
Overall Study NOT COMPLETED	6	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Thymectomy Plus Prednisone Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy had been performed as soon as possible after randomization.	Prednisone Alone 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.
Overall Study Death	0	1
Overall Study Lost to Follow-up	4	0
Overall Study Physician Decision	1	2
Overall Study Pregnancy	0	1
Overall Study Withdrawal by Subject	0	4
Overall Study Found to have invasive thymoma	1	0
Overall Study Patient and family were not satisfied	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Thymectomy Plus Prednisone n=66 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=60 Participants 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 n=126 Participants Total of all reporting groups
Age, Continuous	32 years n=99 Participants	33 years n=107 Participants	32 years n=206 Participants
Sex: Female, Male Female	50 Participants n=99 Participants	39 Participants n=107 Participants	89 Participants n=206 Participants
Sex: Female, Male Male	16 Participants n=99 Participants	21 Participants n=107 Participants	37 Participants n=206 Participants
Race/Ethnicity, Customized Asian	6 participants n=99 Participants	4 participants n=107 Participants	10 participants n=206 Participants
Race/Ethnicity, Customized Black	7 participants n=99 Participants	6 participants n=107 Participants	13 participants n=206 Participants
Race/Ethnicity, Customized Hispanic	17 participants n=99 Participants	17 participants n=107 Participants	34 participants n=206 Participants
Race/Ethnicity, Customized Non-Hispanic	31 participants n=99 Participants	30 participants n=107 Participants	61 participants n=206 Participants
Race/Ethnicity, Customized Other	5 participants n=99 Participants	3 participants n=107 Participants	8 participants n=206 Participants
Region of Enrollment Argentina	10 participants n=99 Participants	11 participants n=107 Participants	21 participants n=206 Participants
Region of Enrollment United States	16 participants n=99 Participants	14 participants n=107 Participants	30 participants n=206 Participants
Region of Enrollment Japan	1 participants n=99 Participants	1 participants n=107 Participants	2 participants n=206 Participants
Region of Enrollment United Kingdom	2 participants n=99 Participants	2 participants n=107 Participants	4 participants n=206 Participants
Region of Enrollment Thailand	3 participants n=99 Participants	2 participants n=107 Participants	5 participants n=206 Participants
Region of Enrollment Canada	9 participants n=99 Participants	9 participants n=107 Participants	18 participants n=206 Participants
Region of Enrollment Netherlands	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants
Region of Enrollment Brazil	3 participants n=99 Participants	2 participants n=107 Participants	5 participants n=206 Participants
Region of Enrollment Poland	1 participants n=99 Participants	1 participants n=107 Participants	2 participants n=206 Participants
Region of Enrollment Italy	6 participants n=99 Participants	4 participants n=107 Participants	10 participants n=206 Participants
Region of Enrollment Mexico	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants
Region of Enrollment South Africa	4 participants n=99 Participants	4 participants n=107 Participants	8 participants n=206 Participants
Region of Enrollment Australia	2 participants n=99 Participants	2 participants n=107 Participants	4 participants n=206 Participants
Region of Enrollment Chile	5 participants n=99 Participants	5 participants n=107 Participants	10 participants n=206 Participants
Region of Enrollment Germany	2 participants n=99 Participants	3 participants n=107 Participants	5 participants n=206 Participants
Therapy at enrollment - Pyridostigimine Yes	60 participants n=99 Participants	56 participants n=107 Participants	116 participants n=206 Participants
Therapy at enrollment - Pyridostigimine No	5 participants n=99 Participants	1 participants n=107 Participants	6 participants n=206 Participants
Therapy at enrollment - Pyridostigimine Missing	1 participants n=99 Participants	3 participants n=107 Participants	4 participants n=206 Participants
Therapy at enrollment - Glucocorticoid Yes	49 participants n=99 Participants	47 participants n=107 Participants	96 participants n=206 Participants
Therapy at enrollment - Glucocorticoid No	16 participants n=99 Participants	10 participants n=107 Participants	26 participants n=206 Participants
Therapy at enrollment - Glucocorticoid Missing	1 participants n=99 Participants	3 participants n=107 Participants	4 participants n=206 Participants
Previous therapy - Intravenous immue globulin Yes	12 participants n=99 Participants	13 participants n=107 Participants	25 participants n=206 Participants
Previous therapy - Intravenous immue globulin No	53 participants n=99 Participants	44 participants n=107 Participants	97 participants n=206 Participants
Previous therapy - Intravenous immue globulin Missing	1 participants n=99 Participants	3 participants n=107 Participants	4 participants n=206 Participants
Previous therapy - Plasma exchange Yes	9 participants n=99 Participants	7 participants n=107 Participants	16 participants n=206 Participants
Previous therapy - Plasma exchange No	56 participants n=99 Participants	50 participants n=107 Participants	106 participants n=206 Participants
Previous therapy - Plasma exchange Missing	1 participants n=99 Participants	3 participants n=107 Participants	4 participants n=206 Participants
MGFA class IIa	25 participants n=99 Participants	25 participants n=107 Participants	50 participants n=206 Participants
MGFA class IIb	18 participants n=99 Participants	14 participants n=107 Participants	32 participants n=206 Participants
MGFA class III	21 participants n=99 Participants	20 participants n=107 Participants	41 participants n=206 Participants
MGFA class IV	2 participants n=99 Participants	1 participants n=107 Participants	3 participants n=206 Participants
Duration of disease	1.08 years n=99 Participants	1.14 years n=107 Participants	1.11 years n=206 Participants
QMG score	11.40 units on a scale STANDARD_DEVIATION 5.12 • n=99 Participants	12.35 units on a scale STANDARD_DEVIATION 4.90 • n=107 Participants	11.84 units on a scale STANDARD_DEVIATION 5.02 • n=206 Participants
Prednisone use at baseline Yes	49 participants n=99 Participants	47 participants n=107 Participants	96 participants n=206 Participants
Prednisone use at baseline No	16 participants n=99 Participants	10 participants n=107 Participants	26 participants n=206 Participants
Prednisone use at baseline Missing	1 participants n=99 Participants	3 participants n=107 Participants	4 participants n=206 Participants
Prednisone Dosage at baseline (mg)	43.43 mg STANDARD_DEVIATION 28.92 • n=99 Participants	42.49 mg STANDARD_DEVIATION 23.52 • n=107 Participants	42.97 mg STANDARD_DEVIATION 26.28 • n=206 Participants

PRIMARY outcome

Timeframe: baseline, month 3, 4, 6 and every 3 months through 36 months

Population: 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.

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=62 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=56 Participants 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.
Time-weighted Average Quantitative Myasthenia Gravis Weakness Score Over 3 Years	6.15 units on a scale Standard Deviation 4.09	8.99 units on a scale Standard Deviation 4.93

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=61 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=56 Participants 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.
Time-weighted Average Alternate-day Prednisone Dose (mg) Measured Over 3 Years	32 mg Standard Deviation 23	54 mg Standard Deviation 29

SECONDARY outcome

Timeframe: baseline, month 3, 4, 6 and every 3 months through 36 months

Population: 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.

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

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=62 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=55 Participants 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.
Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Prednisone Use at Enrollment Not prednisone naïve	6.30 units on a scale Standard Deviation 3.89	9.10 units on a scale Standard Deviation 5.06
Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Prednisone Use at Enrollment Prednisone naïve	5.66 units on a scale Standard Deviation 4.79	8.84 units on a scale Standard Deviation 4.60

SECONDARY outcome

Timeframe: baseline, month 3, 4, 6 and every 3 months through 36 months

Population: 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.

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

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=62 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=56 Participants 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.
Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Sex Female	6.47 units on a scale Standard Deviation 4.13	9.73 units on a scale Standard Deviation 5.16
Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Sex Male	5.23 units on a scale Standard Deviation 3.95	7.45 units on a scale Standard Deviation 4.11

SECONDARY outcome

Timeframe: baseline, month 3, 4, 6 and every 3 months through 36 months

Population: 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.

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

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=60 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=52 Participants 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.
Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Age at Disease Onset Age (years) at Disease Onset < 40	6.50 units on a scale Standard Deviation 4.41	9.60 units on a scale Standard Deviation 5.32
Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Age at Disease Onset Age (years) at Disease Onset ≥ 40	5.33 units on a scale Standard Deviation 2.79	7.85 units on a scale Standard Deviation 3.50

SECONDARY outcome

Timeframe: baseline, month 3, 4, 6 and every 3 months through 36 months

Population: 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.

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=61 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=55 Participants 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.
Subgroup Analyses of Time-weighted Average Alternate-day Prednisone Dose (mg) by Prednisone Use at Enrollment Not prednisone naïve	35 mg Standard Deviation 25	56 mg Standard Deviation 31
Subgroup Analyses of Time-weighted Average Alternate-day Prednisone Dose (mg) by Prednisone Use at Enrollment Prednisone naïve	25 mg Standard Deviation 17	45 mg Standard Deviation 22

SECONDARY outcome

Timeframe: baseline, month 3, 4, 6 and every 3 months through 36 months

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=61 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=56 Participants 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.
Subgroup Analyses of Time-weighted Average Alternate-day Prednisone Dose (mg) by Sex Female	33 mg Standard Deviation 25	54 mg Standard Deviation 27
Subgroup Analyses of Time-weighted Average Alternate-day Prednisone Dose (mg) by Sex Male	31 mg Standard Deviation 18	55 mg Standard Deviation 34

SECONDARY outcome

Timeframe: baseline, month 3, 4, 6 and every 3 months through 36 months

Population: 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.

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=59 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=52 Participants 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.
Subgroup Analyses of Time-weighted Average Average Alternate-day Prednisone Dose (mg) by Age at Disease Onset Age (Years) at Disease Onset < 40	35 mg Standard Deviation 25	55 mg Standard Deviation 30
Subgroup Analyses of Time-weighted Average Average Alternate-day Prednisone Dose (mg) by Age at Disease Onset Age (Years) at Disease Onset ≥ 40	27 mg Standard Deviation 18	49 mg Standard Deviation 29

SECONDARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=25 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=33 Participants 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.
Number of Serious Adverse Events	48 events	93 events

SECONDARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=66 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=60 Participants 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.
Number of Patients With at Least One Serious Adverse Events	25 participants	33 participants

SECONDARY outcome

Timeframe: baseline to 3 years

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

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=25 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=33 Participants 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.
Classification of Serious Adverse Events Life-threatening	1 participants	7 participants
Classification of Serious Adverse Events Disability or incapacity	8 participants	2 participants
Classification of Serious Adverse Events Medical or surgical intervention	9 participants	5 participants
Classification of Serious Adverse Events Death	0 participants	1 participants
Classification of Serious Adverse Events Complication due to thytmectomy	1 participants	0 participants
Classification of Serious Adverse Events Hospitalization	15 participants	31 participants

SECONDARY outcome

Timeframe: baseline to 2 years and baseline to 3 years

Population: Number of participants who had hospitalized over 2 and 3 years

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=15 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=31 Participants 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.
Hospitalization for Exacerbation of Myasthenia Gravis Months 0-24	6 participants	17 participants
Hospitalization for Exacerbation of Myasthenia Gravis Months 0-36	6 participants	22 participants

SECONDARY outcome

Timeframe: baseline to 3 years

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

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=15 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=31 Participants 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.
Cumulative Number of Hospital Days	8.4 days Standard Deviation 8.6	19.2 days Standard Deviation 24.5

SECONDARY outcome

Timeframe: baseline to 3 years

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

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=15 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=31 Participants 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.
Reason for Hospitalization According to Medical Dictionary for Regulatory Activities Term Nervous system disorder	8 events	22 events
Reason for Hospitalization According to Medical Dictionary for Regulatory Activities Term Gastrointestinal disorder	2 events	2 events
Reason for Hospitalization According to Medical Dictionary for Regulatory Activities Term Hepatobiliary disorder	0 events	1 events
Reason for Hospitalization According to Medical Dictionary for Regulatory Activities Term Infection or infestation	4 events	7 events
Reason for Hospitalization According to Medical Dictionary for Regulatory Activities Term Injury, poisoning, or procedure complication	2 events	0 events
Reason for Hospitalization According to Medical Dictionary for Regulatory Activities Term Metabolism or nutrition disorder	1 events	0 events
Reason for Hospitalization According to Medical Dictionary for Regulatory Activities Term Respiratory, thoracic, or mediastinal disorder	1 events	2 events
Reason for Hospitalization According to Medical Dictionary for Regulatory Activities Term Surgical or medical procedure	0 events	7 events
Reason for Hospitalization According to Medical Dictionary for Regulatory Activities Term Vascular disorder	0 events	1 events

SECONDARY outcome

Timeframe: baseline-day 20, month 1,2, 3, 4, 6 and every 3 months through 36 months

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=62 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=56 Participants 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.
Time-weighted Average Prescribed Alternate Day Prednisone Dose (mg)	34.3 mg Standard Deviation 22.7	55.6 mg Standard Deviation 29.4

SECONDARY outcome

Timeframe: baseline, month 3, 4, 6 and every 3 months through 36 months

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=61 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=56 Participants 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.
Penalized Time-weighted Average Alternative Day Prednisone Dose (mg; Method 1: Penalized Using Maximum Dose Before Azathioprine)	34.4 mg Standard Deviation 28.2	64.4 mg Standard Deviation 40.8

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=61 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=56 Participants 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.
Penalized Time-weighted Average Alternative Day Prednisone Dose (mg; Method 2: Penalized Using Dose at Time of Starting Azathioprine)	33.3 mg Standard Deviation 27.2	57.9 mg Standard Deviation 36.9

SECONDARY outcome

Timeframe: baseline, month 4, 6 and every 3 months through 36 months

Population: 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.

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

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=61 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=55 Participants 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.
Time-Weighted Average MG Activity of Daily Living (MG-ADL)	2.24 units on a scale Standard Deviation 2.09	3.41 units on a scale Standard Deviation 2.58

SECONDARY outcome

Timeframe: Month 12, 24, and 36

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

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.

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=66 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=60 Participants 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.
Time-Weighted Average MG Activity of Daily Living (MG-ADL) at Month 12, 24, and 36 Month 12	1.92 units on a scale Standard Deviation 2.73	3.33 units on a scale Standard Deviation 3.40
Time-Weighted Average MG Activity of Daily Living (MG-ADL) at Month 12, 24, and 36 Month 24	2.02 units on a scale Standard Deviation 2.78	3.11 units on a scale Standard Deviation 2.93
Time-Weighted Average MG Activity of Daily Living (MG-ADL) at Month 12, 24, and 36 Month 36	2.14 units on a scale Standard Deviation 2.92	2.69 units on a scale Standard Deviation 2.80

SECONDARY outcome

Timeframe: baseline to 3 years

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=65 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=58 Participants 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.
Azathioprine Use	11 participants	28 participants

SECONDARY outcome

Timeframe: baseline to 3 years

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=65 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=58 Participants 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.
Plasma Exchange Use	10 participants	9 participants

SECONDARY outcome

Timeframe: baseline to 3 years

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=65 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=58 Participants 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.
Intravenous Immunoglobulin Use	11 participants	23 participants

SECONDARY outcome

Timeframe: Month 12, 24 and 36

Population: 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)

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

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=66 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=60 Participants 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.
Minimal Manifestation (MM) Status at Month 12, 24 and 36 Month 12	41 participants	20 participants
Minimal Manifestation (MM) Status at Month 12, 24 and 36 Month 24	39 participants	20 participants
Minimal Manifestation (MM) Status at Month 12, 24 and 36 Month 36	39 participants	24 participants

SECONDARY outcome

Timeframe: baseline to 2 years

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

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=6 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=17 Participants 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.
Cumulative Days in Hospital for Myasthenia Gravis Exacerbation	5.5 days Standard Deviation 2.9	26.4 days Standard Deviation 28.9

SECONDARY outcome

Timeframe: baseline to 3 years

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

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=6 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=22 Participants 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.
Cumulative Days in Hospital for Myasthenia Gravis Exacerbation	8.7 days Standard Deviation 7.7	22.5 days Standard Deviation 27.1

SECONDARY outcome

Timeframe: Month 0, Month 12, Month 24 and Month 36

Population: Participants were in and out by visit.

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

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=66 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=60 Participants 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.
Short Form-36 Standardized Physical Component Month 0	41.4 units on a scale Interval 18.2 to 60.0	37.9 units on a scale Interval 13.5 to 64.3
Short Form-36 Standardized Physical Component Month 12	48.4 units on a scale Interval 11.5 to 64.4	44.4 units on a scale Interval 21.2 to 58.8
Short Form-36 Standardized Physical Component Month 24	50.3 units on a scale Interval 11.2 to 60.5	43.0 units on a scale Interval 25.3 to 59.6
Short Form-36 Standardized Physical Component Month 36	48.2 units on a scale Interval 9.8 to 61.8	44.2 units on a scale Interval 20.4 to 58.9

SECONDARY outcome

Timeframe: Month 0, Month 12, Month 24 and Month 36

Population: Participants were in and out by visit.

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

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=66 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=60 Participants 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.
Short Form-36 Standardized Mental Component Month 0	49.1 units on a scale Interval 14.6 to 65.3	46.2 units on a scale Interval 22.4 to 70.7
Short Form-36 Standardized Mental Component Month 12	39.1 units on a scale Interval 17.6 to 66.7	41.7 units on a scale Interval 7.6 to 64.4
Short Form-36 Standardized Mental Component Month 24	49.9 units on a scale Interval 14.4 to 62.3	46.7 units on a scale Interval 21.3 to 69.1
Short Form-36 Standardized Mental Component Month 36	51.7 units on a scale Interval 29.9 to 65.1	48.2 units on a scale Interval 24.1 to 69.2

SECONDARY outcome

Timeframe: Month 0, 1, 2, 3, 4 then every 3 months through Month 36

Population: Participants were in and out by each visit.

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

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=66 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=60 Participants 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.
Treatment Associated Complications (TAC) Month 0	22 Participants	17 Participants
Treatment Associated Complications (TAC) Month 1	15 Participants	15 Participants
Treatment Associated Complications (TAC) Month 2	22 Participants	20 Participants
Treatment Associated Complications (TAC) Month 3	21 Participants	16 Participants
Treatment Associated Complications (TAC) Month 4	23 Participants	23 Participants
Treatment Associated Complications (TAC) Month 6	21 Participants	22 Participants
Treatment Associated Complications (TAC) Month 9	37 Participants	26 Participants
Treatment Associated Complications (TAC) Month 12	35 Participants	28 Participants
Treatment Associated Complications (TAC) Month 15	29 Participants	24 Participants
Treatment Associated Complications (TAC) Month 18	28 Participants	24 Participants
Treatment Associated Complications (TAC) Month 21	22 Participants	20 Participants
Treatment Associated Complications (TAC) Mpnth 24	28 Participants	23 Participants
Treatment Associated Complications (TAC) Mpnth 27	25 Participants	17 Participants
Treatment Associated Complications (TAC) Month 30	23 Participants	19 Participants
Treatment Associated Complications (TAC) Month 33	24 Participants	23 Participants
Treatment Associated Complications (TAC) Month 36	23 Participants	23 Participants

SECONDARY outcome

Timeframe: Month 0, 1, 2, 3, 4 then every 3 months through Month 36

Population: Patients were in and out by visit

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.

Outcome measures

Outcome measures
Measure	Thymectomy Plus Prednisone n=66 Participants Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=60 Participants 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.
Treatment Associated Symptoms (TAS) Month 0	63 Participants	53 Participants
Treatment Associated Symptoms (TAS) Month 1	55 Participants	52 Participants
Treatment Associated Symptoms (TAS) Month 2	61 Participants	53 Participants
Treatment Associated Symptoms (TAS) Month 3	60 Participants	54 Participants
Treatment Associated Symptoms (TAS) Month 4	59 Participants	54 Participants
Treatment Associated Symptoms (TAS) Month 6	60 Participants	53 Participants
Treatment Associated Symptoms (TAS) Month 9	59 Participants	50 Participants
Treatment Associated Symptoms (TAS) Month 12	56 Participants	52 Participants
Treatment Associated Symptoms (TAS) Month 15	56 Participants	51 Participants
Treatment Associated Symptoms (TAS) Month 18	52 Participants	51 Participants
Treatment Associated Symptoms (TAS) Month 21	52 Participants	50 Participants
Treatment Associated Symptoms (TAS) Mpnth 24	52 Participants	51 Participants
Treatment Associated Symptoms (TAS) Mpnth 27	50 Participants	50 Participants
Treatment Associated Symptoms (TAS) Month 30	49 Participants	50 Participants
Treatment Associated Symptoms (TAS) Month 33	51 Participants	48 Participants
Treatment Associated Symptoms (TAS) Month 36	49 Participants	47 Participants

Adverse Events

Thymectomy Plus Prednisone

Serious events: 25 serious events

Other events: 55 other events

Deaths: 0 deaths

Prednisone Alone

Serious events: 33 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Thymectomy Plus Prednisone n=66 participants at risk Procedure: Extended Transsternal Thymectomy plus prednisone treatment thymectomy: The thymectomy will be performed as soon as possible after randomization.	Prednisone Alone n=60 participants at risk 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.
Eye disorders Cataract	6.1% 4/66 • Number of events 14 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone	11.7% 7/60 • Number of events 20 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone
Eye disorders Glaucoma	7.6% 5/66 • Number of events 22 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone	1.7% 1/60 • Number of events 1 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone
Infections and infestations Herpes zoster	7.6% 5/66 • Number of events 6 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone	6.7% 4/60 • Number of events 8 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone
Injury, poisoning and procedural complications Tendon rupture	3.0% 2/66 • Number of events 2 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone	5.0% 3/60 • Number of events 3 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone
Investigations Liver function test abnormal	3.0% 2/66 • Number of events 2 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone	5.0% 3/60 • Number of events 3 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone
Metabolism and nutrition disorders Abnormal weight gain	48.5% 32/66 • Number of events 184 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone	51.7% 31/60 • Number of events 141 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone
Metabolism and nutrition disorders Diabetes mellitus	9.1% 6/66 • Number of events 41 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone	15.0% 9/60 • Number of events 44 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	22.7% 15/66 • Number of events 43 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone	6.7% 4/60 • Number of events 9 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin cancer	1.5% 1/66 • Number of events 1 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone	5.0% 3/60 • Number of events 3 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone
Psychiatric disorders Mental disorder	6.1% 4/66 • Number of events 4 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone	8.3% 5/60 • Number of events 8 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone
Psychiatric disorders Sleep disorder	37.9% 25/66 • Number of events 86 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone	36.7% 22/60 • Number of events 67 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone
Skin and subcutaneous tissue disorders Rash	31.8% 21/66 • Number of events 58 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone	40.0% 24/60 • Number of events 48 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone
Skin and subcutaneous tissue disorders Scab	16.7% 11/66 • Number of events 44 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone	3.3% 2/60 • Number of events 2 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone
Vascular disorders Hypertension	24.2% 16/66 • Number of events 53 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone	26.7% 16/60 • Number of events 55 • Adverse events were reported from baseline to 3 years There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone

Additional Information

Dr. Gary Cutter, Professor

University of Alabama at Birmingham

Phone: 205-975-5048

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60