Rituximab Vasculitis Maintenance Study (RITAZAREM)

• ClinicalTrials.gov Identifier: NCT01697267
• Recruitment Status: Completed
• First Posted: October 2, 2012
• Results First Posted: March 18, 2022
• Last Update Posted: March 18, 2022
• Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Collaborators: Arthritis Research UK; Roche Pharma AG; Genentech, Inc.; University of Pennsylvania
• Information provided by (Responsible Party): David Jayne, Cambridge University Hospitals NHS Foundation Trust

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Microscopic Polyangiitis; Wegener Granulomatosis
• Interventions: Biological: Rituximab; Drug: Azathioprine
• Enrollment: 188

Participant Flow

Recruitment Details
Pre-assignment Details	Of 188 enrolled participants, 170 met the criteria for randomisation and were randomised for treatment.

Arm/Group Title	Rituximab Maintenance	Azathioprine Maintenance
Arm/Group Description	Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.	Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Period Title: Overall Study
Started	85	85
Month 24	78	78
Completed	71	70
Not Completed	14	15
Reason Not Completed
Death	3	1
Withdrawal by Subject	5	5
Adverse Event	2	1
Lost to Follow-up	2	4
Physician Decision	2	4

Baseline Characteristics

Arm/Group Title		Rituximab Maintenance	Azathioprine Maintenance	Total
Arm/Group Description		Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.	Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.	Total of all reporting groups
Overall Number of Baseline Participants		85	85	170
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	85 participants	85 participants	170 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	54 63.5%	51 60.0%	105 61.8%
	>=65 years	31 36.5%	34 40.0%	65 38.2%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	85 participants	85 participants	170 participants
		57.1 (15.1)	58.6 (13.9)	57.8 (14.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	85 participants	85 participants	170 participants
	Female	42 49.4%	44 51.8%	86 50.6%
	Male	43 50.6%	41 48.2%	84 49.4%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	85 participants	85 participants	170 participants
White		78 91.8%	77 90.6%	155 91.2%
Black		0 0.0%	0 0.0%	0 0.0%
Asian		5 5.9%	5 5.9%	10 5.9%
Hispanic		2 2.4%	1 1.2%	3 1.8%
Other		0 0.0%	2 2.4%	2 1.2%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	85 participants	85 participants	170 participants
Canada		13 15.3%	11 12.9%	24 14.1%
Sweden		3 3.5%	2 2.4%	5 2.9%
United States		26 30.6%	22 25.9%	48 28.2%
Czechia		0 0.0%	1 1.2%	1 0.6%
Japan		2 2.4%	2 2.4%	4 2.4%
United Kingdom		36 42.4%	42 49.4%	78 45.9%
Australia		5 5.9%	5 5.9%	10 5.9%
ANCA type [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	85 participants	85 participants	170 participants
	anti-PR3	61 71.8%	62 72.9%	123 72.4%
	anti-MPO	24 28.2%	23 27.1%	47 27.6%
		[1] Measure Description: Anti-neutrophil cytoplasm antibodies (ANCA) are autoantibodies that target a type of human white blood cell called neutrophils, which are important in health for fighting infection partly through the release of toxic substances that destroy bacteria. In ANCA-associated vasculitis, ANCA specifically bind to two proteins that are normally found in the fluid within the neutrophil (cytoplasm). The two proteins are called proteinase 3 (PR3) and myeloperoxidase (MPO) which can be measured by ELISA (Enzyme-Linked Immunosorbant Assay).
Prednisone Induction Regimen [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	85 participants	85 participants	170 participants
	1A (starting dose 1mg/kg/day)	24 28.2%	24 28.2%	48 28.2%
	1B (starting dose 0.5mg/kg/day)	61 71.8%	61 71.8%	122 71.8%
		[1] Measure Description: Patients will be stratified at the time of randomisation according to selected prednisone induction regimen: 1A higher dose induction regimen or 1B lower dose induction regimen to take into consideration variability in disease severity and local GC prescribing.
Relapse type [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	85 participants	85 participants	170 participants
	Severe	52 61.2%	54 63.5%	106 62.4%
	Non-severe	33 38.8%	31 36.5%	64 37.6%
		[1] Measure Description: Major relapse (severe): The development of a new or recurrent major disease activity item using the BVAS/WG assessment tool Minor relapse (non-severe): Any increase in disease activity that does not meet the definition of Major Relapse

Outcome Measures

1. Primary Outcome

Title	Relapse-free Survival
Description	The primary efficacy outcome measure of the trial is relapse-free survival, where a relapse is either major or minor. The primary analysis will be a Cox regression model adjusted for the stratification factors (ANCA type, relapse severity and prednisone induction regimen) for the difference in the distribution of relapse-free survival between the rituximab arm and the azathioprine (control) arm (two-sided at α-level of 5%).
Time Frame	Any patients who have not relapsed at up to a maximum of 4 years will be censored.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab Maintenance	Azathioprine Maintenance
Arm/Group Description:	Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.	Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Overall Number of Participants Analyzed	85	85
Measure Type: Number; Unit of Measure: participants
Total number of patients with a relapse	38	60
Total number of patients with a relapse during treatment	13	32
Total number of patients with a relapse post treatment	25	28

2. Secondary Outcome

Title	Number of Participants in Remission at 24 and 48 Months
Description	Proportion of patients who maintain remission at 24 and 48 months
Time Frame	24 and 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab Maintenance	Azathioprine Maintenance
Arm/Group Description:	Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.	Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Overall Number of Participants Analyzed	85	85
Measure Type: Count of Participants; Unit of Measure: Participants
Month 24	73 85.9%	70 82.4%
Month 48	54 63.5%	44 51.8%

3. Secondary Outcome

Title	Combined Damage Assessment Score (Disease Related Damage Assessment)
Description	Cumulative accrual of damage as measured by the combined damage assessment score (CDA). Each persistent or new occurrence of damage is given a score of 1. The cumulative accrual of damage is obtained by summing across the different types of damage to get an overall score (max score = 64).
Time Frame	data in Rows represent the change from randomization (month 4) to months 12, 24, 36, and 48.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab Maintenance	Azathioprine Maintenance
Arm/Group Description:	Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.	Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Overall Number of Participants Analyzed	85	85
Mean (Standard Deviation); Unit of Measure: score on a scale
Randomisation to month 12	0.275 (0.656)	0.337 (0.610)
Randomisation to month 24	0.571 (0.909)	0.533 (0.777)
Randomisation to month 36	0.676 (0.995)	0.899 (1.352)
Randomisation to month 48	1.09 (1.18)	1.38 (1.65)

4. Secondary Outcome

Title	Cumulative GC Exposure
Description	Cumulative glucocorticoid (GC) exposure during the trial. The trial had a common close out date when the final patient reached month 36 in the trial. Patients were followed until month 48 or the common close out date, whichever happened sooner. Therefore, follow up varied between 36 and 48 months. Cumulative glucocorticoid exposure is presented as a dose in mg for during the treatment period (up to month 24) and across the whole trial (until month 48 or common close out when the final patient reached month 36).
Time Frame	Up to 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab Maintenance	Azathioprine Maintenance
Arm/Group Description:	Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.	Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Overall Number of Participants Analyzed	85	85
Mean (Standard Deviation); Unit of Measure: mg
Overall (randomisation to end of trial)	3717 (3318)	4780 (3387)
Maintenance treatment period (randomisation to month 24)	2184 (1100)	2426 (1324)

5. Secondary Outcome

Title	Severe Adverse Event Rate
Description	Severe adverse event (SAE) rate
Time Frame	Up to 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab Maintenance	Azathioprine Maintenance
Arm/Group Description:	Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.	Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Overall Number of Participants Analyzed	85	85
Measure Type: Count of Participants; Unit of Measure: Participants
	37 43.5%	48 56.5%

6. Secondary Outcome

Title	Infection Rates
Description	Infection (treated with intravenous or oral antibiotics) rates
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab Maintenance	Azathioprine Maintenance
Arm/Group Description:	Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.	Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Overall Number of Participants Analyzed	85	85
Measure Type: Count of Participants; Unit of Measure: Participants
	54 63.5%	62 72.9%

7. Secondary Outcome

Title	Health-related Quality of Life Using the SF-36 Physical Composite
Description	The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab Maintenance	Azathioprine Maintenance
Arm/Group Description:	Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.	Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Overall Number of Participants Analyzed	83	81
Mean (Standard Deviation); Unit of Measure: score on a scale
	36.7 (15.4)	36.1 (14.1)

8. Secondary Outcome

Title	Health-related Quality of Life Using the SF-36 Mental Composite
Description	The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab Maintenance	Azathioprine Maintenance
Arm/Group Description:	Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.	Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Overall Number of Participants Analyzed	83	81
Mean (Standard Deviation); Unit of Measure: score on a scale
	51.8 (11.3)	51.0 (11.4)

9. Secondary Outcome

Title	Health-related Quality of Life Using the SF-36 Physical Composite
Description	The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab Maintenance	Azathioprine Maintenance
Arm/Group Description:	Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.	Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Overall Number of Participants Analyzed	80	80
Mean (Standard Deviation); Unit of Measure: score on a scale
	38.2 (15.2)	34.6 (15.0)

10. Secondary Outcome

Title	Health-related Quality of Life Using the SF-36 Mental Composite
Description	The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab Maintenance	Azathioprine Maintenance
Arm/Group Description:	Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.	Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Overall Number of Participants Analyzed	80	80
Mean (Standard Deviation); Unit of Measure: score on a scale
	50.8 (12.4)	51.9 (11.6)

11. Secondary Outcome

Title	Health-related Quality of Life Using the SF-36 Physical Composite
Description	The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab Maintenance	Azathioprine Maintenance
Arm/Group Description:	Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.	Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Overall Number of Participants Analyzed	77	70
Mean (Standard Deviation); Unit of Measure: score on a scale
	36.7 (15.8)	35.6 (14.5)

12. Secondary Outcome

Title	Health-related Quality of Life Using the SF-36 Mental Composite
Description	The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab Maintenance	Azathioprine Maintenance
Arm/Group Description:	Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.	Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Overall Number of Participants Analyzed	77	70
Mean (Standard Deviation); Unit of Measure: score on a scale
	51.9 (11.9)	53.5 (10.7)

13. Secondary Outcome

Title	Health-related Quality of Life Using the SF-36 Physical Composite
Description	The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab Maintenance	Azathioprine Maintenance
Arm/Group Description:	Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.	Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Overall Number of Participants Analyzed	74	69
Mean (Standard Deviation); Unit of Measure: score on a scale
	34.6 (15.9)	33.8 (15.6)

14. Secondary Outcome

Title	Health-related Quality of Life Using the SF-36 Mental Composite
Description	The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab Maintenance	Azathioprine Maintenance
Arm/Group Description:	Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.	Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Overall Number of Participants Analyzed	74	69
Mean (Standard Deviation); Unit of Measure: score on a scale
	52.3 (12.5)	51.8 (10.8)

15. Secondary Outcome

Title	Health-related Quality of Life Using the SF-36 Physical Composite
Description	The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time Frame	48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab Maintenance	Azathioprine Maintenance
Arm/Group Description:	Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.	Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Overall Number of Participants Analyzed	55	51
Mean (Standard Deviation); Unit of Measure: score on a scale
	35.8 (14.9)	35.0 (16.3)

16. Secondary Outcome

Title	Health-related Quality of Life Using the SF-36 Mental Composite
Description	The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time Frame	48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab Maintenance	Azathioprine Maintenance
Arm/Group Description:	Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.	Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Overall Number of Participants Analyzed	55	51
Mean (Standard Deviation); Unit of Measure: score on a scale
	50.9 (13.0)	53.9 (9.8)

Adverse Events

Time Frame	Adverse events were collected for up to 48 months or until the last patient recruited reached Month 36.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Rituximab Maintenance		Azathioprine Maintenance
Arm/Group Description	Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.		Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
All-Cause Mortality
	Rituximab Maintenance		Azathioprine Maintenance
	Affected / at Risk (%)		Affected / at Risk (%)
Total	3/85 (3.53%)		1/85 (1.18%)
Serious Adverse Events
	Rituximab Maintenance		Azathioprine Maintenance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/85 (22.35%)		31/85 (36.47%)
Blood and lymphatic system disorders
Iron deficiency anaemia † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Neutropenia † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Cardiac disorders
Atrial fibrillation † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Atrioventricular block complete † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Cardiac failure congestive † 1	2/85 (2.35%)	2	0/85 (0.00%)	0
Cardiomyopathy † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Coronary artery disease † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Myocardial infarction † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Eye disorders
Periorbital oedema † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	2/85 (2.35%)	2	0/85 (0.00%)	0
Oesophageal spasm † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Oesophagitis † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Pancreatitis † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Small intestinal obstruction † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Enterovesical fistula † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
General disorders
Chest pain † 1	2/85 (2.35%)	2	0/85 (0.00%)	0
Pyrexia † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Perforated ulcer † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Stenosis † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Hepatobiliary disorders
Cholecystitis † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Cholecystitis acute † 1	1/85 (1.18%)	1	1/85 (1.18%)	1
Cholelithiasis † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Immune system disorders
Drug hypersensitivity † 1	0/85 (0.00%)	0	2/85 (2.35%)	2
Pulmonary vasculitis † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Vasculitis † 1	4/85 (4.71%)	13	9/85 (10.59%)	13
Infections and infestations
Appendicitis † 1	2/85 (2.35%)	2	1/85 (1.18%)	1
Bronchitis † 1	1/85 (1.18%)	1	2/85 (2.35%)	2
Cellulitis † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Dacryocystitis † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Diverticulitis † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Gastroenteritis viral † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Influenza † 1	2/85 (2.35%)	2	3/85 (3.53%)	3
Lower respiratory tract infection † 1	0/85 (0.00%)	0	2/85 (2.35%)	2
Peritonitis † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Pneumonia † 1	5/85 (5.88%)	5	3/85 (3.53%)	3
Pneumonia klebsiella † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Pneumonia viral † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Sepsis † 1	2/85 (2.35%)	2	0/85 (0.00%)	0
Sinusitis † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Urinary tract infection † 1	1/85 (1.18%)	1	2/85 (2.35%)	2
Escherichia urinary tract infection † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Periorbital abscess † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Infective exacerbation of chronic obstructive airways disease † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Respiratory tract infection † 1	1/85 (1.18%)	1	3/85 (3.53%)	3
Metapneumovirus infection † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Oral herpes † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Injury, poisoning and procedural complications
Accident † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Fall † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Subdural haematoma † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Post procedural complication † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Intra-abdominal haemorrhage † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Vascular access complication † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Investigations
Medical observation † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Transaminases increased † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Metabolism and nutrition disorders
Dehydration † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Hyperglycaemia † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Hyperkalaemia † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Metabolic acidosis † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Musculoskeletal and connective tissue disorders
Myasthenia gravis † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Osteoarthritis † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Intervertebral disc protrusion † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Myasthenia gravis crisis † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Pubis fracture † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder papilloma † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Lung adenocarcinoma † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Pancreatic carcinoma metastatic † 1	1/85 (1.18%)	1	1/85 (1.18%)	1
Sarcoma of skin † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Squamous cell carcinoma † 1	1/85 (1.18%)	1	1/85 (1.18%)	1
Colon neoplasm 1 † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Anal squamous cell carcinoma † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Nervous system disorders
Haemorrhagic stroke † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Sleep apnoea syndrome † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Subdural haemorrhage † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Psychiatric disorders
Conversion disorder † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Renal and urinary disorders
Nephrolithiasis † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Proteinuria † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Renal impairment † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Acute kidney injury † 1	0/85 (0.00%)	0	4/85 (4.71%)	4
Respiratory, thoracic and mediastinal disorders
Bronchospasm † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Chronic obstructive pulmonary disease † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Dyspnoea † 1	0/85 (0.00%)	0	2/85 (2.35%)	2
Laryngeal stenosis † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Pneumonitis † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Pneumothorax † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Stridor † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Pneumomediastinum † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Surgical and medical procedures
Aortic valve replacement † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Bunion operation † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Cholecystectomy † 1	1/85 (1.18%)	1	1/85 (1.18%)	1
Colostomy closure † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Dacryocystorhinostomy † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Hip arthroplasty † 1	2/85 (2.35%)	2	3/85 (3.53%)	3
Knee arthroplasty † 1	2/85 (2.35%)	2	1/85 (1.18%)	1
Lung lobectomy † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Renal transplant † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Spinal decompression † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Renal and pancreas transplant † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Sigmoidectomy † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Cardiac ablation † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Infusion † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Colporrhaphy † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Thyroidectomy † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Joint resurfacing surgery † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Vascular anastomosis † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Vascular disorders
Epistaxis † 1	0/85 (0.00%)	0	2/85 (2.35%)	2
Haemoptysis † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Orthostatic hypotension † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Pulmonary embolism † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Vascular injury † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Vascular pseudoaneurysm † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Haemorrhage † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
1 Term from vocabulary, MedDRA (19.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Rituximab Maintenance		Azathioprine Maintenance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/85 (49.41%)		43/85 (50.59%)
General disorders
Malaise † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Hepatobiliary disorders
Cholecystitis † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Infections and infestations
Bacterial dacryocystitis † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Bacterial infection † 1	2/85 (2.35%)	2	0/85 (0.00%)	0
Beta haemolytic streptococcal infection † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Bronchitis haemophilus † 1	2/85 (2.35%)	2	0/85 (0.00%)	0
Cellulitis † 1	3/85 (3.53%)	3	5/85 (5.88%)	5
Cellulitis orbital † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Citrobacter infection † 1	1/85 (1.18%)	1	1/85 (1.18%)	1
Cystitis escherichia † 1	1/85 (1.18%)	1	2/85 (2.35%)	2
Cystitis klebsiella † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Enterococcal infection † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Escherichia urinary tract infection † 1	3/85 (3.53%)	3	2/85 (2.35%)	2
Haemophilus infection † 1	2/85 (2.35%)	2	4/85 (4.71%)	4
Klebsiella infection † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Pneumonia haemophilus † 1	1/85 (1.18%)	1	1/85 (1.18%)	1
Pneumonia klebsiella † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Pneumonia pneumococca † 1	2/85 (2.35%)	2	0/85 (0.00%)	0
Pneumonia pseudomonal † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Proteus infection † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Pseudomonas bronchitis † 1	2/85 (2.35%)	2	1/85 (1.18%)	1
Pseudomonas infection † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Staphylococcal impetigo † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Staphylococcal infection † 1	3/85 (3.53%)	3	2/85 (2.35%)	2
Tonsillitis bacterial † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Urinary tract infection enterococcal † 1	2/85 (2.35%)	2	1/85 (1.18%)	1
Body tinea † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Candida infection † 1	1/85 (1.18%)	1	1/85 (1.18%)	1
Oesophageal candidiasis † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Oral candidiasis † 1	2/85 (2.35%)	2	1/85 (1.18%)	1
Tinea infection † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Tinea pedis † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Vulvovaginal candidiasis † 1	1/85 (1.18%)	1	2/85 (2.35%)	2
Vulvovaginal mycotic infection † 1	2/85 (2.35%)	2	0/85 (0.00%)	0
Bronchitis † 1	2/85 (2.35%)	2	0/85 (0.00%)	0
Conjunctivitis † 1	2/85 (2.35%)	2	2/85 (2.35%)	2
Cystitis † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Diverticulitis † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Ear infection † 1	5/85 (5.88%)	5	4/85 (4.71%)	4
Eye infection † 1	0/85 (0.00%)	0	2/85 (2.35%)	2
Gastrointestinal infection † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Infection † 1	1/85 (1.18%)	1	2/85 (2.35%)	2
Lower respiratory tract infection † 1	2/85 (2.35%)	2	7/85 (8.24%)	7
Lung infection † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Mastoiditis † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Otitis media † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Paronychia † 1	2/85 (2.35%)	2	0/85 (0.00%)	0
Pharyngitis † 1	2/85 (2.35%)	2	2/85 (2.35%)	2
Pneumonia † 1	3/85 (3.53%)	3	1/85 (1.18%)	1
Prostate infection † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Respiratory tract infection † 1	19/85 (22.35%)	19	31/85 (36.47%)	31
Root canal infection † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Sinusitis † 1	15/85 (17.65%)	15	10/85 (11.76%)	10
Skin infection † 1	5/85 (5.88%)	5	4/85 (4.71%)	4
Systemic infection † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Tonsillitis † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Tooth abscess † 1	1/85 (1.18%)	1	2/85 (2.35%)	2
Tooth infection † 1	3/85 (3.53%)	3	0/85 (0.00%)	0
Upper respiratory tract infection † 1	17/85 (20.00%)	17	17/85 (20.00%)	17
Urinary tract infection † 1	9/85 (10.59%)	9	7/85 (8.24%)	7
Herpes simplex † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Herpes zoster † 1	1/85 (1.18%)	1	1/85 (1.18%)	1
Oral herpes † 1	0/85 (0.00%)	0	2/85 (2.35%)	2
Respiratory tract infection viral † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Varicella zoster virus infection † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Viral infection † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Investigations
Streptococcus test positive † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
Skin and subcutaneous tissue disorders
Eczema † 1	1/85 (1.18%)	1	0/85 (0.00%)	0
Rosacea † 1	0/85 (0.00%)	0	1/85 (1.18%)	1
1 Term from vocabulary, MedDRA (19.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Prof David Jayne
• Organization: Cambridge University Hospitals NHS Foundation Trust
• Phone: 01223 748062
• EMail: dj106@cam.ac.uk

Publications:

Watts RA, Suppiah R, Merkel PA, Luqmani R. Systemic vasculitis--is it time to reclassify? Rheumatology (Oxford). 2011 Apr;50(4):643-5. doi: 10.1093/rheumatology/keq229. Epub 2010 Jul 20. No abstract available.

Falk RJ, Jennette JC. ANCA disease: where is this field heading? J Am Soc Nephrol. 2010 May;21(5):745-52. doi: 10.1681/ASN.2009121238. Epub 2010 Apr 15.

Watts RA, Scott DG. Epidemiology of the vasculitides. Curr Opin Rheumatol. 2003 Jan;15(1):11-6. doi: 10.1097/00002281-200301000-00003.

Booth AD, Almond MK, Burns A, Ellis P, Gaskin G, Neild GH, Plaisance M, Pusey CD, Jayne DR; Pan-Thames Renal Research Group. Outcome of ANCA-associated renal vasculitis: a 5-year retrospective study. Am J Kidney Dis. 2003 Apr;41(4):776-84. doi: 10.1016/s0272-6386(03)00025-8.

Jayne D, Rasmussen N, Andrassy K, Bacon P, Tervaert JW, Dadoniene J, Ekstrand A, Gaskin G, Gregorini G, de Groot K, Gross W, Hagen EC, Mirapeix E, Pettersson E, Siegert C, Sinico A, Tesar V, Westman K, Pusey C; European Vasculitis Study Group. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med. 2003 Jul 3;349(1):36-44. doi: 10.1056/NEJMoa020286.

de Groot K, Harper L, Jayne DR, Flores Suarez LF, Gregorini G, Gross WL, Luqmani R, Pusey CD, Rasmussen N, Sinico RA, Tesar V, Vanhille P, Westman K, Savage CO; EUVAS (European Vasculitis Study Group). Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med. 2009 May 19;150(10):670-80. doi: 10.7326/0003-4819-150-10-200905190-00004.

De Groot K, Rasmussen N, Bacon PA, Tervaert JW, Feighery C, Gregorini G, Gross WL, Luqmani R, Jayne DR. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2005 Aug;52(8):2461-9. doi: 10.1002/art.21142.

Wegener's Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med. 2005 Jan 27;352(4):351-61. doi: 10.1056/NEJMoa041884.

Seo P, Min YI, Holbrook JT, Hoffman GS, Merkel PA, Spiera R, Davis JC, Ytterberg SR, St Clair EW, McCune WJ, Specks U, Allen NB, Luqmani RA, Stone JH; WGET Research Group. Damage caused by Wegener's granulomatosis and its treatment: prospective data from the Wegener's Granulomatosis Etanercept Trial (WGET). Arthritis Rheum. 2005 Jul;52(7):2168-78. doi: 10.1002/art.21117.

Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, Newman RA, Hanna N, Anderson DR. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994 Jan 15;83(2):435-45.

Jones RB, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA, Savage CO, Segelmark M, Tesar V, van Paassen P, Walsh D, Walsh M, Westman K, Jayne DR; European Vasculitis Study Group. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010 Jul 15;363(3):211-20. doi: 10.1056/NEJMoa0909169.

Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Turkiewicz A, Tchao NK, Webber L, Ding L, Sejismundo LP, Mieras K, Weitzenkamp D, Ikle D, Seyfert-Margolis V, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh KA, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Specks U; RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010 Jul 15;363(3):221-32. doi: 10.1056/NEJMoa0909905.

Jones RB, Ferraro AJ, Chaudhry AN, Brogan P, Salama AD, Smith KG, Savage CO, Jayne DR. A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2009 Jul;60(7):2156-68. doi: 10.1002/art.24637.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gopaluni S, Smith RM, Lewin M, McAlear CA, Mynard K, Jones RB, Specks U, Merkel PA, Jayne DR; RITAZAREM Investigators. Rituximab versus azathioprine as therapy for maintenance of remission for anti-neutrophil cytoplasm antibody-associated vasculitis (RITAZAREM): study protocol for a randomized controlled trial. Trials. 2017 Mar 7;18(1):112. doi: 10.1186/s13063-017-1857-z.

• Responsible Party: David Jayne, Cambridge University Hospitals NHS Foundation Trust
• ClinicalTrials.gov Identifier: NCT01697267
• Other Study ID Numbers: RITAZAREM; 2012-001102-14 ( EudraCT Number )
• First Submitted: August 31, 2012
• First Posted: October 2, 2012
• Results First Submitted: March 17, 2021
• Results First Posted: March 18, 2022
• Last Update Posted: March 18, 2022