Trial Outcomes & Findings for A Study of Mycophenolate Mofetil (CellCept) in Management of Patients With Lupus Nephritis. (NCT NCT00377637)

Last Updated: 2011-12-06

Results Overview

Treatment response was adjudicated by a blinded clinical endpoints committee (CEC) and defined as: a) Decrease in proteinuria, defined as a decrease in the urine protein to creatinine ratio (UPCr) to \<3 in subjects with baseline proteinuria ≥3 UPCr or a decrease in the UPCr by ≥50% in subjects with proteinuria \<3 UPCr at Baseline, and b) Stabilization of serum creatinine or improvement. UPCr were derived from the 24 hour urine collection. Patients who did not show a treatment response at Week 24 or who withdrew earlier than Week 24 were considered non-responders.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

370 participants

Primary outcome timeframe

24 weeks

Results posted on

2011-12-06

Participant Flow

The induction phase was a prospective, randomized, open-label, active controlled, parallel group, international multicenter, 2-arm comparison study of MMF versus IVC in inducing a response in patients with Lupus nephritis. Responders in the induction phase were re-randomized into a double-blind, double-dummy, active controlled Maintenance Phase.

Participant milestones

Participant milestones
Measure	Induction Phase: Cyclophosphamide Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Induction Phase: Mycophenolate Mofetil Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.	Maintenance Phase: Mycophenolate Mofetil Participants who responded to Induction Phase treatment received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase.	Maintenance Phase: Azathioprine Participants who responded to Induction Phase treatment received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase.
Induction Phase STARTED	185	185	0	0
Induction Phase Safety Population	180	184	0	0
Induction Phase COMPLETED	156	150	0	0
Induction Phase NOT COMPLETED	29	35	0	0
Maintenance Phase STARTED	0	0	116	111
Maintenance Phase COMPLETED	0	0	73	54
Maintenance Phase NOT COMPLETED	0	0	43	57

Reasons for withdrawal

Reasons for withdrawal
Measure	Induction Phase: Cyclophosphamide Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Induction Phase: Mycophenolate Mofetil Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.	Maintenance Phase: Mycophenolate Mofetil Participants who responded to Induction Phase treatment received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase.	Maintenance Phase: Azathioprine Participants who responded to Induction Phase treatment received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase.
Induction Phase Adverse Event	12	21	0	0
Induction Phase Deterioration/serum creatinine	2	0	0	0
Induction Phase Dose reduction of MMF < 2 g/day for 14 d	0	1	0	0
Induction Phase Lost to Follow-up	2	1	0	0
Induction Phase Death	1	3	0	0
Induction Phase Withdrawal by Subject	5	6	0	0
Induction Phase Physician Decision	3	1	0	0
Induction Phase Sponsor decision	1	2	0	0
Induction Phase Non-Compliance	1	0	0	0
Induction Phase Reason for withdrawal is not noted	2	0	0	0
Maintenance Phase Adverse Event	0	0	29	43
Maintenance Phase Physician Decision	0	0	5	4
Maintenance Phase Lost to Follow-up	0	0	3	1
Maintenance Phase Withdrawal by Subject	0	0	3	3
Maintenance Phase Sponsor decision	0	0	2	3
Maintenance Phase Non-compliance	0	0	1	1
Maintenance Phase Study medication stopped > 14 days	0	0	0	1
Maintenance Phase Death	0	0	0	1

Baseline Characteristics

A Study of Mycophenolate Mofetil (CellCept) in Management of Patients With Lupus Nephritis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Induction Phase: Cyclophosphamide n=185 Participants Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Induction Phase: Mycophenolate Mofetil n=185 Participants Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.	Maintenance Phase: Mycophenolate Mofetil n=116 Participants Participants who responded to Induction Phase treatment received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase.	Maintenance Phase: Azathioprine n=111 Participants Participants who responded to Induction Phase treatment received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase.	Total n=597 Participants Total of all reporting groups
Age, Customized Induction Phase	31.3 years STANDARD_DEVIATION 10.25 • n=5 Participants	32.4 years STANDARD_DEVIATION 11.7 • n=7 Participants	NA years STANDARD_DEVIATION NA • n=5 Participants	NA years STANDARD_DEVIATION NA • n=4 Participants	31.9 years STANDARD_DEVIATION 10.72 • n=21 Participants
Age, Customized Maintenance Phase	NA years STANDARD_DEVIATION NA • n=5 Participants	NA years STANDARD_DEVIATION NA • n=7 Participants	31.8 years STANDARD_DEVIATION 10.59 • n=5 Participants	31.0 years STANDARD_DEVIATION 10.77 • n=4 Participants	31.4 years STANDARD_DEVIATION 10.65 • n=21 Participants
Sex/Gender, Customized Induction Phase - Female	156 Participants n=5 Participants	157 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	313 Participants n=21 Participants
Sex/Gender, Customized Induction Phase - Male	29 Participants n=5 Participants	28 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	57 Participants n=21 Participants
Sex/Gender, Customized Maintenance Phase - Female	0 Participants n=5 Participants	0 Participants n=7 Participants	99 Participants n=5 Participants	96 Participants n=4 Participants	195 Participants n=21 Participants
Sex/Gender, Customized Maintenance Phase - Male	0 Participants n=5 Participants	0 Participants n=7 Participants	17 Participants n=5 Participants	15 Participants n=4 Participants	32 Participants n=21 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: Analysis population was intent to treat which comprised all subjects who were randomized into the study and had at least one post-baseline efficacy assessment.

Outcome measures

Outcome measures
Measure	Intravenous Cyclophosphamide n=185 Participants Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Mycophenolate Mofetil n=185 Participants Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Induction Phase: Number of Patients Showing Treatment Response Responder	98 participants	104 participants
Induction Phase: Number of Patients Showing Treatment Response Non-responder	87 participants	81 participants

PRIMARY outcome

Timeframe: From the start of the Maintenance Phase to Month 36

Population: Intent to treat analysis population which consisted of all subjects who were randomized to the maintenance phase of the study and had at least 1 maintenance efficacy assessment.

Treatment Failure was adjudicated by a clinical endpoints committee and was defined as the time to the earliest occurrence of any one of the following: death, end stage renal disease, sustained doubling of serum creatinine, renal flare, or a requirement for rescue therapy for exacerbation or deterioration of Lupus nephritis. Kaplan-Meier survival curves were estimated from the observed time to treatment failure for each patient. The data presented are the percentage of participants who were treatment-failure free at each time interval as estimated by Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Intravenous Cyclophosphamide n=116 Participants Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Mycophenolate Mofetil n=111 Participants Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval Month 3 to Month 6	93.7 Percentage of participants	89.3 Percentage of participants
Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval Month 6 to Month 9	89.9 Percentage of participants	86.2 Percentage of participants
Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval Month 9 to Month 12	86.0 Percentage of participants	83.0 Percentage of participants
Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval Month 21 to Month 24	83.9 Percentage of participants	68.3 Percentage of participants
Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval Month 24 to Month 27	82.8 Percentage of participants	67.1 Percentage of participants
Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval Month 27 to Month 30	82.8 Percentage of participants	65.9 Percentage of participants
Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval Month 30 to Month 33	81.7 Percentage of participants	63.4 Percentage of participants
Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval Start of Maintenance Phase to Month 3	98.2 Percentage of participants	97.2 Percentage of participants
Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval Month 33 to Month 36	81.7 Percentage of participants	58.6 Percentage of participants
Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval Month 12 to Month 15	86.0 Percentage of participants	77.5 Percentage of participants
Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval Month 15 to Month 18	84.9 Percentage of participants	74.1 Percentage of participants
Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval Month 18 to Month 21	84.9 Percentage of participants	70.7 Percentage of participants

SECONDARY outcome

Timeframe: 24 weeks

Population: Analysis population was intent to treat.

Number of participants achieving complete remission as defined by return to normal serum creatinine, proteinuria ≤500 mg/24 hours and an inactive urinary sediment (absence of red blood cells, white blood cells or cellular or granular casts) after 24 weeks.

Outcome measures

Outcome measures
Measure	Intravenous Cyclophosphamide n=185 Participants Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Mycophenolate Mofetil n=185 Participants Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Induction Phase: Number of Participants Achieving Complete Remission Complete Remission - Yes	15 participants	16 participants
Induction Phase: Number of Participants Achieving Complete Remission Complete Remission - No	170 participants	169 participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis population was intent to treat. The analysis included only those patients for whom data was available at both time points, as indicated by "n".

Outcome measures

Outcome measures
Measure	Intravenous Cyclophosphamide n=185 Participants Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Mycophenolate Mofetil n=185 Participants Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Induction Phase: Change From Baseline to Week 24 in Serum Creatinine Baseline [n= 184, 185]	92.7 µmol/L Standard Deviation 56.88	108.6 µmol/L Standard Deviation 97.21
Induction Phase: Change From Baseline to Week 24 in Serum Creatinine Week 24 [n= 155, 151]	83.5 µmol/L Standard Deviation 56.26	77.6 µmol/L Standard Deviation 35.08
Induction Phase: Change From Baseline to Week 24 in Serum Creatinine Change from Baseline to Week 24 [n= 154, 151]	-5.1 µmol/L Standard Deviation 45.96	-18.9 µmol/L Standard Deviation 59.03

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis population was intent to treat. The analysis included only those patients for whom data was available at both time points, as indicated by "n".

24-hour urine protein was measured at Baseline and Week 24.

Outcome measures

Outcome measures
Measure	Intravenous Cyclophosphamide n=185 Participants Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Mycophenolate Mofetil n=185 Participants Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Induction Phase: Change From Baseline to Week 24 in 24-hour Urine Protein Change from Baseline to Week 24 [n= 146, 142]	-2513.7 mg/day Standard Deviation 3223.68	-2510.6 mg/day Standard Deviation 3132.69
Induction Phase: Change From Baseline to Week 24 in 24-hour Urine Protein Baseline [n=180, 180]	4451.4 mg/day Standard Deviation 3506.59	4208.9 mg/day Standard Deviation 3347.34
Induction Phase: Change From Baseline to Week 24 in 24-hour Urine Protein Week 24 [n= 150, 144]	1831.6 mg/day Standard Deviation 2413.84	1599.0 mg/day Standard Deviation 2165.80

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis population was intent to treat. The analysis included only those patients for whom data was available at both time points, as indicated by "n".

Outcome measures

Outcome measures
Measure	Intravenous Cyclophosphamide n=185 Participants Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Mycophenolate Mofetil n=185 Participants Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Induction Phase: Change From Baseline to Week 24 in Serum Albumin Baseline [n=184, 185]	28.6 g/L Standard Deviation 6.98	30.5 g/L Standard Deviation 6.90
Induction Phase: Change From Baseline to Week 24 in Serum Albumin Week 24 [n=155, 151]	38.3 g/L Standard Deviation 6.16	38.4 g/L Standard Deviation 5.50
Induction Phase: Change From Baseline to Week 24 in Serum Albumin Change from Baseline to Week 24 [n=154, 151]	9.0 g/L Standard Deviation 6.77	7.5 g/L Standard Deviation 6.25

SECONDARY outcome

Timeframe: Baseline, 24 weeks

Population: Analysis population was intent to treat. The endpoint was defined using the last observation carried forward approach. If no post-Baseline value was available, endpoint was considered missing.

BILAG indices provide a scoring system for the assessment of lupus disease activity in terms of the need for steroid treatment in 8 organs/systems. Eighty-six items were scored resulting in a classification of A (severe activity), B (moderate activity), C (mild activity), D (no current activity) and E (no activity ever observed) for each organ system. The BILAG individual system summaries were calculated by a program supplied by ADS-Limathon (Sheffield, UK). The score at baseline was compared to the score at the 24 week endpoint for each treatment group, reported here for the renal system.

Outcome measures

Outcome measures
Measure	Intravenous Cyclophosphamide n=181 Participants Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Mycophenolate Mofetil n=181 Participants Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score Shift from Baseline=A to 24 Week Endpoint=B	34.8 Percentage of participants	39.2 Percentage of participants
Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score Shift from Baseline=A to 24 Week Endpoint=C	24.9 Percentage of participants	33.1 Percentage of participants
Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score Shift from Baseline=A to 24 Week Endpoint=D	9.4 Percentage of participants	5.5 Percentage of participants
Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score Shift from Baseline=B to 24 Week Endpoint=A	0.0 Percentage of participants	0.0 Percentage of participants
Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score Shift from Baseline=B to 24 Week Endpoint=B	1.1 Percentage of participants	1.7 Percentage of participants
Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score Shift from Baseline=B to 24 Week Endpoint=C	1.7 Percentage of participants	2.2 Percentage of participants
Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score Shift from Baseline=A to 24 Week Endpoint=A	27.1 Percentage of participants	17.1 Percentage of participants
Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score Shift from Baseline=B to 24 Week Endpoint=D	0.0 Percentage of participants	1.1 Percentage of participants
Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score Shift from Baseline=C to 24 Week Endpoint=A	0.0 Percentage of participants	0.0 Percentage of participants
Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score Shift from Baseline=C to 24 Week Endpoint=B	0.6 Percentage of participants	0.0 Percentage of participants
Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score Shift from Baseline=C to 24 Week Endpoint=C	0.0 Percentage of participants	0.0 Percentage of participants
Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score Shift from Baseline=C to 24 Week Endpoint=D	0.0 Percentage of participants	0.0 Percentage of participants
Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score Shift from Baseline=D to 24 Week Endpoint=A	0.0 Percentage of participants	0.0 Percentage of participants
Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score Shift from Baseline=D to 24 Week Endpoint=B	0.0 Percentage of participants	0.0 Percentage of participants
Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score Shift from Baseline=D to 24 Week Endpoint=C	0.6 Percentage of participants	0.0 Percentage of participants
Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score Shift from Baseline=D to 24 Week Endpoint=D	0.0 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: This analysis population is intention to treat. The analysis included only those patients for whom data was available at both time points, as indicated by "n".

The SF-36 is a 36 item quality of life questionnaire. The short-form version has eleven questions that permit the participant to rate how they feel that particular day. The SF-36 consists of eight scaled scores and two component scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 score with the higher scores indicating better quality of life.

Outcome measures

Outcome measures
Measure	Intravenous Cyclophosphamide n=185 Participants Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Mycophenolate Mofetil n=185 Participants Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores Bodily Pain Score [n=141, 137]	16.8 Scores on a scale Standard Deviation 25.85	13.4 Scores on a scale Standard Deviation 24.57
Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores General Health Score [n=139, 137]	11.5 Scores on a scale Standard Deviation 20.90	9.1 Scores on a scale Standard Deviation 19.49
Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores Mental Health Score [n=141, 137]	9.8 Scores on a scale Standard Deviation 19.47	9.3 Scores on a scale Standard Deviation 18.96
Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores Physical functioning Score [n=141, 137]	9.3 Scores on a scale Standard Deviation 24.63	11.6 Scores on a scale Standard Deviation 23.12
Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores Role-Emotional Score [n=141, 137]	18.4 Scores on a scale Standard Deviation 46.71	23.4 Scores on a scale Standard Deviation 44.90
Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores Role-Physical Score [n=141, 137]	34.0 Scores on a scale Standard Deviation 47.65	28.6 Scores on a scale Standard Deviation 48.18
Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores Social Function Score [n=141, 137]	18.2 Scores on a scale Standard Deviation 29.26	17.7 Scores on a scale Standard Deviation 28.06
Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores Vitality Score [n=141, 137]	11.6 Scores on a scale Standard Deviation 20.68	14.2 Scores on a scale Standard Deviation 23.30
Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores Physical Component Summary [n=139, 137]	6.4 Scores on a scale Standard Deviation 8.74	5.2 Scores on a scale Standard Deviation 8.60
Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores Mental Component Summary [n=139, 137]	5.7 Scores on a scale Standard Deviation 11.39	6.7 Scores on a scale Standard Deviation 11.45

SECONDARY outcome

Timeframe: From the start of the Maintenance Phase to Month 36

Population: Maintenance Phase intent to treat population.

Treatment Failure was adjudicated by a clinical endpoints committee (CEC) and was defined as the time to the earliest occurrence of any one of the following: death, end stage renal disease, sustained doubling of serum creatinine, renal flare, or a requirement for rescue therapy for exacerbation or deterioration of Lupus nephritis (LN).

Outcome measures

Outcome measures
Measure	Intravenous Cyclophosphamide n=116 Participants Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Mycophenolate Mofetil n=111 Participants Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Deaths	0 Deaths	1 Deaths

SECONDARY outcome

Timeframe: From the start of the Maintenance Phase to Month 36

Population: Maintenance Phase intent to treat population. The analysis includes all event data, regardless of whether or not the event was the earliest Clinical Endpoints Committee-adjudicated reason for treatment failure.

Time to treatment failure, adjudicated by the Clinical Endpoints Committee (CEC), was defined as any 1 the following: death, ESRD, sustained doubling of serum creatinine, renal flare (proteinuric or nephritic), or requirement for rescue therapy to treat deterioration or exacerbation of Lupus nephritis. ESRD is defined as progression to chronic hemodialysis or renal transplant.

Outcome measures

Outcome measures
Measure	Intravenous Cyclophosphamide n=116 Participants Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Mycophenolate Mofetil n=111 Participants Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With End-stage Renal Disease (ESRD)	0 participants	3 participants

SECONDARY outcome

Timeframe: From the start of the Maintenance Phase to Month 36

Sustained doubling of serum creatinine concentration is defined as the first serum creatinine value that is twice the mean of the lowest 2 values from screening to end of induction, as confirmed by a second serum creatinine value obtained at least 4 weeks after the initial doubling.

Outcome measures

Outcome measures
Measure	Intravenous Cyclophosphamide n=116 Participants Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Mycophenolate Mofetil n=111 Participants Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With Sustained Doubling of Serum Creatinine	1 participants	5 participants

SECONDARY outcome

Timeframe: From the start of the Maintenance Phase to Month 36

A proteinuric flare is defined as a doubling of the urine protein:creatinine ratio, and proteinuria ≥1 g/24 h in patients with urine protein ≤0.5 g/24 h at the end of the induction phase, or proteinuria ≥2 g/24 h if urine protein was \>0.5 g/24 h at the end of the induction phase. A nephritic flare is defined as a 25% increase in serum creatinine accompanied by 1 or more of the following: (a) simultaneous doubling of the proteinuria reaching a minimum of 2 g/24 h (b) new/increased hematuria or (c) the appearance of cellular casts. All flares were adjudicated by a clinical endpoints committee.

Outcome measures

Outcome measures
Measure	Intravenous Cyclophosphamide n=116 Participants Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Mycophenolate Mofetil n=111 Participants Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval Month 15 to Month 18	86.8 Percentage of participants	79.2 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval Month 21 to Month 24	86.8 Percentage of participants	75.5 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval Month 24 to Month 27	86.8 Percentage of participants	74.2 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval Month 30 to Month 33	85.6 Percentage of participants	72.9 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval Start of Maintenance Phase to Month 3	98.2 Percentage of participants	97.2 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval Month 3 to Month 6	94.6 Percentage of participants	90.3 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval Month 6 to Month 9	90.8 Percentage of participants	87.2 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval Month 9 to Month 12	87.8 Percentage of participants	85.0 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval Month 12 to Month 15	87.8 Percentage of participants	82.8 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval Month 18 to Month 21	86.8 Percentage of participants	78.0 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval Month 27 to Month 30	86.8 Percentage of participants	74.2 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval Month 33 to Month 36	85.6 Percentage of participants	70.1 Percentage of participants

SECONDARY outcome

Timeframe: From the start of the Maintenance Phase to Month 36

The primary efficacy parameter was the time to treatment failure, adjudicated by the Clinical Endpoints Committee (CEC), defined as any of the following: death, end stage renal disease, sustained doubling of serum creatinine, renal flare, or requirement for rescue therapy to treat deterioration or exacerbation of Lupus nephritis. Kaplan-Meier survival curves were estimated from the observed time to rescue treatment for each patient. The data presented are the percentage of participants who were rescue treatment free at each time interval as estimated by Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Intravenous Cyclophosphamide n=116 Participants Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Mycophenolate Mofetil n=111 Participants Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy Month 3 to Month 6	98.2 Percentage of participants	95.1 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy Month 9 to Month 12	94.2 Percentage of participants	91.9 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy Month 12 to Month 15	94.2 Percentage of participants	88.4 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy Month 18 to Month 21	93.1 Percentage of participants	83.1 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy Month 21 to Month 24	91.9 Percentage of participants	83.1 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy Month 24 to Month 27	90.8 Percentage of participants	81.7 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy Month 30 to Month 33	90.8 Percentage of participants	78.8 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy Month 33 to Month 36	90.8 Percentage of participants	75.9 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy Start of Maintenance Phase to Month 3	100 Percentage of participants	99.1 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy Month 6 to Month 9	97.2 Percentage of participants	93.0 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy Month 15 to Month 18	94.2 Percentage of participants	87.1 Percentage of participants
Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy Month 27 to Month 30	90.8 Percentage of participants	80.3 Percentage of participants

SECONDARY outcome

Timeframe: From the start of the Maintenance Phase to Month 36

Population: Maintenance Phase intent to treat population.

A major extra-renal flare is defined as a British Isles Lupus Assessment Group (BILAG) Score category A in one extrarenal organ or three organs with concurrent category B scores. BILAG indices provide a scoring system for the assessment of lupus disease activity in terms of the need for steroid treatment in 8 organs/systems. Eighty-six items were scored resulting in a classification of A (severe activity), B (moderate activity), C (mild activity), D (no current activity) and E (no activity ever observed) for each organ system.

Outcome measures

Outcome measures
Measure	Intravenous Cyclophosphamide n=116 Participants Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Mycophenolate Mofetil n=111 Participants Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.
Maintenance Phase: Participants With Major Extra-renal Flare	7 participants	6 participants

Adverse Events

Induction Phase: Cyclophosphamide

Serious events: 41 serious events

Other events: 171 other events

Deaths: 0 deaths

Induction Phase: Mycophenolate Mofetil

Serious events: 51 serious events

Other events: 177 other events

Deaths: 0 deaths

Maintenance Phase: Mycophenolate Mofetil

Serious events: 27 serious events

Other events: 113 other events

Deaths: 0 deaths

Maintenance Phase: Azathioprine

Serious events: 37 serious events

Other events: 108 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Induction Phase: Cyclophosphamide n=180 participants at risk Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Induction Phase: Mycophenolate Mofetil n=184 participants at risk Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.	Maintenance Phase: Mycophenolate Mofetil n=115 participants at risk Participants who responded to Induction Phase treatment received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase.	Maintenance Phase: Azathioprine n=111 participants at risk Participants who responded to Induction Phase treatment received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase.
Vascular disorders Subclavian vein thrombosis	0.56% 1/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Osteomyelitis	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.87% 1/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Wound infection	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.87% 1/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Influenza	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.87% 1/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Pneumonia	1.7% 3/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	2.7% 5/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	1.7% 2/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.90% 1/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Bronchitis	0.56% 1/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Bronchopneumonia	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Lung infection	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Lobar pneumonia	0.56% 1/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Herpes zoster	1.1% 2/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	2.7% 5/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.87% 1/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.90% 1/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Herpes simplex	0.56% 1/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Septic shock	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	1.1% 2/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Acinetobacter bacteraemia	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Meningitis tuberculous	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Pulmonary tuberculosis	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Tuberculosis gastrointestinal	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Urosepsis	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.87% 1/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Gastroenteritis	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.87% 1/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Retroperitoneal abscess	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Gastrointestinal infection	0.56% 1/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Skin infection	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Subcutaneous abscess	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.87% 1/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Fungaemia	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Respiratory tract infection	1.1% 2/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Infection	0.56% 1/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Meningitis streptococcal	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Viral infection	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Gastroenteritis viral	0.56% 1/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Cellulitis	1.1% 2/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.90% 1/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Meningitis bacterial	0.56% 1/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Subacute endocarditis	0.56% 1/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Tonsillitis	0.56% 1/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.90% 1/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Upper respiratory tract infection	2.2% 4/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Gastrointestinal disorders Diarrhoea	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	1.6% 3/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.87% 1/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Gastrointestinal disorders Vomiting	0.56% 1/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	1.1% 2/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Gastrointestinal disorders Dyspepsia	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Gastrointestinal disorders Abdominal pain	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.90% 1/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.54% 1/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Gastrointestinal disorders Abdominal distension	0.56% 1/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Gastrointestinal disorders Gingivitis	0.56% 1/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.

Other adverse events
Measure	Induction Phase: Cyclophosphamide n=180 participants at risk Participants received monthly intravenous infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.	Induction Phase: Mycophenolate Mofetil n=184 participants at risk Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24-weeks of the Induction Phase.	Maintenance Phase: Mycophenolate Mofetil n=115 participants at risk Participants who responded to Induction Phase treatment received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase.	Maintenance Phase: Azathioprine n=111 participants at risk Participants who responded to Induction Phase treatment received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase.
Vascular disorders Hypertension	13.9% 25/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	14.1% 26/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	7.0% 8/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	6.3% 7/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Investigations White blood cell count decreased	8.9% 16/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	2.7% 5/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Nasopharyngitis	16.1% 29/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	13.6% 25/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	13.0% 15/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	11.7% 13/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Upper respiratory tract infection	15.6% 28/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	9.2% 17/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	35.7% 41/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	32.4% 36/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Herpes zoster	3.3% 6/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	7.6% 14/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	6.1% 7/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	5.4% 6/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Urinary tract infection	9.4% 17/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	10.3% 19/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	17.4% 20/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	24.3% 27/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Gastrointestinal disorders Diarrhoea	12.8% 23/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	28.3% 52/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	19.1% 22/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	18.0% 20/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Gastrointestinal disorders Nausea	45.6% 82/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	14.7% 27/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	17.4% 20/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	18.9% 21/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Gastrointestinal disorders Vomiting	37.8% 68/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	13.6% 25/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	12.2% 14/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	16.2% 18/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Gastrointestinal disorders Abdominal pain	7.2% 13/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	10.3% 19/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	9.6% 11/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	12.6% 14/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Gastrointestinal disorders Abdominal pain upper	10.0% 18/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	8.2% 15/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	11.3% 13/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	9.9% 11/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Gastrointestinal disorders Constipation	5.0% 9/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	6.5% 12/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Gastrointestinal disorders Dyspepsia	2.8% 5/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	5.4% 10/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	2.6% 3/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	6.3% 7/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
General disorders Oedema peripheral	16.7% 30/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	19.0% 35/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	7.0% 8/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	6.3% 7/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
General disorders Oedema	9.4% 17/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	6.0% 11/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
General disorders Fatigue	10.0% 18/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	9.8% 18/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	14.8% 17/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	18.0% 20/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
General disorders Asthenia	8.3% 15/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	4.9% 9/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	5.2% 6/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	5.4% 6/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
General disorders Chest pain	5.6% 10/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	4.3% 8/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
General disorders Pyrexia	16.7% 30/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	6.5% 12/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Skin and subcutaneous tissue disorders Alopecia	35.6% 64/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	10.9% 20/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	10.4% 12/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	9.9% 11/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Skin and subcutaneous tissue disorders Rash	11.7% 21/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	10.3% 19/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	13.0% 15/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	12.6% 14/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Skin and subcutaneous tissue disorders Acne	5.0% 9/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	4.9% 9/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Skin and subcutaneous tissue disorders Erythema	5.6% 10/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	2.7% 5/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Musculoskeletal and connective tissue disorders Arthralgia	23.9% 43/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	15.8% 29/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	25.2% 29/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	28.8% 32/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Musculoskeletal and connective tissue disorders Back pain	8.9% 16/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	10.3% 19/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	11.3% 13/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	11.7% 13/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Musculoskeletal and connective tissue disorders Pain in extremity	5.0% 9/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	3.3% 6/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	8.7% 10/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	8.1% 9/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Musculoskeletal and connective tissue disorders Arthritis	5.6% 10/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	2.2% 4/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	7.0% 8/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	9.9% 11/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Nervous system disorders Headache	26.1% 47/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	20.7% 38/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	21.7% 25/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	24.3% 27/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Nervous system disorders Dizziness	5.6% 10/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	4.3% 8/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	4.3% 5/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	9.0% 10/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Respiratory, thoracic and mediastinal disorders Cough	8.9% 16/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	13.0% 24/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	13.9% 16/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	12.6% 14/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.3% 6/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	5.4% 10/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	3.5% 4/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	5.4% 6/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Metabolism and nutrition disorders Hypokalaemia	1.7% 3/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	7.1% 13/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	5.2% 6/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.90% 1/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Blood and lymphatic system disorders Anaemia	6.7% 12/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	12.5% 23/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	11.3% 13/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	15.3% 17/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Blood and lymphatic system disorders Leukopenia	21.1% 38/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	6.0% 11/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	22.6% 26/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	36.0% 40/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Blood and lymphatic system disorders Neutropenia	6.7% 12/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	1.6% 3/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Psychiatric disorders Insomnia	6.1% 11/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	5.4% 10/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	9.6% 11/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	2.7% 3/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Cardiac disorders Palpitations	3.3% 6/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	6.0% 11/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Cardiac disorders Tachycardia	3.3% 6/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	5.4% 10/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Endocrine disorders Cushingoid	6.1% 11/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	4.9% 9/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.
Infections and infestations Sinusitis	0.00% 0/180 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	0.00% 0/184 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	8.7% 10/115 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.	3.6% 4/111 • AEs were monitored from the time of informed consent throughout the course of the study (up to 42 months). The induction and maintenance phases were analyzed separately. All safety analyses are based on the safety population.