Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Conditions
Keywords
rituximab, maintenance, remission
Brief summary
The purpose of this study is to determine the best management strategy to maintain remission in patients with ANCA vasculitis who have been treated with rituximab induced B cell depletion for at least two years. This study will compare intermittent B Cell depletion upon B cell return or intermittent B cell depletion upon serologic relapse.
Detailed description
Anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis is a systemic autoimmune disease characterized by small vessel inflammation caused by pathogenic autoantibodies directed against proteinase 3 (PR3) or myeloperoxidase (MPO). Immunosuppressive therapy can result in remission; however, many patients relapse, which results in additional injury. Rituximab, a humanized murine monoclonal antibody directed against CD20 located on the surface of B-lymphocytes (B cells), is effective in depleting B cells. The RAVE and RITUXVAS trials have shown efficacy of rituximab with steroids for induction of remission in ANCA vasculitis, similar to cyclophosphamide and steroids. Rituximab is now FDA-approved for induction of remission therapy in ANCA vasculitis. The utility of anti-B-cell therapy for early induction of remission in ANCA vasculitis is not surprising given that ANCA are pathogenic in vitro and in vivo. It is clear that remission in many patients is not sustained with a single induction course of rituximab, and relapses often occur after B cell re-population suggesting that scheduled, serial dosing of rituximab could result in sustained remissions. Despite yielding promising outcomes, rituximab is also associated with a number of adverse events including infectious complications and late onset of neutropenia5, 15. Furthermore, the complications of continuous B cell depletion for extended durations are unknown. One of the major goals in the field is to utilize prolonged B cell depletion only in the subpopulation of patients where the risk of disease relapse outweighs the risk of treatment-related adverse events. A rise in ANCA titers and reconstitution of B cells are promising biomarkers of impending disease relapse following treatment with rituximab4-6 A prospective and longitudinal clinical trial is needed to determine the ideal treatment strategy for long-term maintenance of remission. We propose to compare intermittent rituximab dosing based on B cell return and a serologic ANCA flare The study design is an open-label, single center, randomized and two-arm controlled trial to evaluate the optimal maintenance of remission strategy that provides the best relapse-free survival in patients with ANCA vasculitis as determined by relapse-free remission at 18, 24 and 36 months from enrollment. The investigators are looking to enroll and randomize 200 subjects with ANCA vasculitis on rituximab-induced continuous B cell depletion for a minimum of two years to one of two arms as follows: 1. Intermittent B cell depletion with rituximab re-dosing upon B cell return: Subjects will not receive their regularly-scheduled every-six-month dose of rituximab and will instead receive rituximab 1000 mg IV x 1 dose (spaced 2-3 weeks apart) once peripheral B cells return ( ≥ 10 B cells/mm3). This cycle will then re-start. Subjects will be seen in clinic every three months. Patients will continue to be dosed with rituximab each time the B cell count rises to 10 cells/mm3. In the unique scenario that the B cells are detectable, but less than the threshold of 10 cells/mm3, subjects will be asked to return in 6 weeks for repeat B cell testing. 2. Hold continuous dosing with rituximab with re-dosing upon a significant ANCA titer increase: For MPO, a significant increase will be defined as a 5-fold rise in ANCA titer and a level greater than 4 times the cutoff value for the assay. For PR3, a significant rise will be defined as a 4-fold rise in ANCA titer to a level at least twofold above the cutoff for the assay. Subjects will not receive regularly scheduled every six-month doses of rituximab and will instead be seen in clinic to have their ANCA titer monitored every three months. Subjects who sustain a significant increase in ANCA titer will receive rituximab 1000mg IV x 2 doses, \ 2-3 weeks apart. If the ANCA titer remains two-fold above baseline and above a specified threshold (the cutoff value of the assay for PR3 and 4 times the cutoff value for MPO) , subjects will continue to receive rituximab 1000mg IV every 6 months for a maximum of 2 doses, at which time a new baseline ANCA titer will be established and the cycle will re-start.
Interventions
DRUGRituximab
re-dosing dependent on interventional arm parameter.
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 82 Years
Healthy volunteers
No
Inclusion criteria
1. All patients must be able and willing to give written informed consent and comply with the requirements of the study protocol. 2. Diagnosis: ANCA vasculitis as defined by a positive MPO- and/or PR3-ANCA test together with clinical features characteristic of ANCA-positive diseases as detailed in the 2012 Chapel Hill Consensus Conference Definitions(18). 3. eGFR ≥ 73 cc/min/1.73m2 4. Age: 18-82 years old 5. Treated with rituximab-induced continuous B cell depletion at regularly scheduled interval with a goal of undetectable B cells for at least 24 months 6. In sustained remission (defined by a modified BVAS-WG=0 AND a prednisone dose of ≤ 7.5 mg) for at least 12 months. 7. Undetectable (\<10mm3) B cells (quantified by CD20+ number) on day 0 8. Urine Hcg negative for women of child bearing potential and not planning to become pregnant for at least 12 months from enrollment and at least 12 months after any study related rituximab dose 9. Judged to be otherwise healthy by the Investigator, based on medical history and physical examination (no known active disease process for which life expectancy is less than 36 months)
Exclusion criteria
1. Secondary Disease: disease suspected to be induced by levamisole-adulterated cocaine 2. All transplanted patients 3. Treatment: additional immunosuppressive agents other than rituximab and/or total daily prednisone dose ≥ 7.5 milligrams 4. Hypogammaglobulinemia: IgG level \< 300 mg/dL 5. Terminal cancer or other primary illness with life expectancy of less than 36 months 6. Active anti-GBM disease and other known autoimmune disease for which the need for additional immunosuppression is likely 7. Pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Disease Relapse(s) as Defined by a Birmingham Vasculitis Activity Score for Wegner's Granulomatosis (BVAS/WG) ≥ 2 | Median follow-up period of 4.1 years (IQR, 2.5 - 5.0) | Relapses recording period was from 6/1/2016 to 12/31/2021. The outcome was reported as the number of participants with disease relapse who had either positive ANCA titers specific for myeloperoxidase (MPO-ANCA) or proteinase 3 (PR3-ANCA). The Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG ) is a form with 34 predefined items grouped into 9 organ systems. The items are clinical features observed in patients with active ANCA vasculitis. Each item has a specified weight of either 3 or 1, depending on whether it reflects major or minor disease activity. The total BVAS/WG score is the weighted sum of individual manifestations that are present and believed to be due to active ANCA vasculitis. Higher scores reflect more active disease. BVAS/WG scores range from 0 to 64. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite of Disease Relapse (Defined a BVAS/WG ≥ 2) and Serious Adverse Events | Median follow-up period of 4.1 years (IQR, 2.5 - 5.0) | Number of disease relapse added with the number of SAE in each group |
| Number of Patients With Hypogammaglobulinemia | Median follow-up period of 4.1 years (IQR, 2.5 - 5.0) | Hypogammaglobulinemia defined as an IgG \< 250mg/dL |
| Patient Survival | 5.5 years | number of deaths throughout the study. |
| Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Assessed throughout the study period, every 6 months unless such time point was not reached or was missed by the patient. Median follow-up period is of 4.1 years (IQR, 2.5 - 5.0) | The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 is a measure of health status and is commonly used in health economics as a variable in the quality-adjusted life year calculation to determine the cost-effectiveness of a health treatment. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. |
| Number of Patients Affected by Serious Adverse Events | Median follow-up period of 4.1 years (IQR, 2.5 - 5.0) | Number of patients with serious adverse events (SAEs), including all episodes of late onset neutropenia (LON). SAE are defined in the Serious adverse event section. Serious adverse events were reported over the entire study period (5.5 years) |
| Organ Damage as Assessed by the Vasculitis Damage Index (VDI). | 3 years starting at inclusion | The Vasculitis Damage Index (VDI) is a validated formal assessment tool in ANCA-associated vasculitis clinical trials. The VDI distinguishes vasculitis-induced chronic damage from active inflammation or persistent disease. Each item represents a disease manifestation and is given a score (of 1) if present for at least 3 months. Neither the cause of damage (vasculitis vs treatment) nor an ongoing activity are taken into consideration. The VDI includes 64 items categorized into 11 groups (by organ system) and the scored items are summed to give a total score ranging from 0 to 64. A higher score means more accrued damage. |
| Number of Major Relapses Defined as a BVAS/WG ≥ 3 | Median follow-up period of 4.1 years (IQR, 2.5 - 5.0) | The Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG ) is a form with 34 predefined items grouped into 9 organ systems. The items are clinical features observed in patients with active ANCA vasculitis. Each item has a specified weight of either 3 or 1, depending on whether it reflects major or minor disease activity. The total BVAS/WG score is the weighted sum of individual manifestations that are present and believed to be due to active ANCA vasculitis. Higher scores reflect more active disease. BVAS/WG scores range from 0 to 64. |
| Number of Infections | Median follow-up period of 4.1 years (IQR, 2.5 - 5.0) | Number of infections mild and severe, whether they were treated or not with antibiotics |
| Mean Number of Rituximab Infusions Per Subject | Median follow-up period of 4.1 years (IQR, 2.5 - 5.0) | The rituximab utilization was measured in how many times a subject received Rituximab throughout the study which was then averaged for all subjects in each treatment arm, including those who did not receive any infusion. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| B Cell Reconstitution Subjects will not receive their regularly-scheduled every-six-month dose of rituximab (1000mg IV) and will instead receive rituximab 1000 mg IV x 1 dose only once peripheral B cells return ( ≥ 10 B cells/mm3). This cycle will then re-start. Subjects will be seen in clinic every three months. Patients will continue to be dosed with rituximab (1 dose of 1000mg IV) each time the B cell count rises to 10 cells/mm3. In the unique scenario that the B cells are detectable, but less than the threshold of 10 cells/mm3, subjects will be asked to return in 6 weeks for repeat B cell testing.
Rituximab: re-dosing dependent on interventional arm parameter. | 58 |
| Serologic ANCA Flare Subjects will not receive regularly scheduled every six-month doses of rituximab (1000mg IV) and will instead be seen in clinic for ANCA titer monitoring every 3 months. Re-dosing will occur upon a significant ANCA titer increase. For MPO, a significant rise will be defined as a 5-fold rise in ANCA titer and a level greater than 4 times the cutoff value for the assay. For PR3, a significant rise will be defined as a 4-fold rise in ANCA titer to a level at least twofold above the cutoff for the assay. Subjects who sustain a significant increase in ANCA titer will receive rituximab 1000mg IV x 2 doses, spaced \
2-3 weeks apart. If the ANCA titer remains two-fold above baseline and above a specified threshold (the cutoff value of the assay for PR3 and 4 times the cutoff value for MPO) , subjects will continue to receive rituximab 1000mg IV every 6 months for a maximum of 2 doses, at which time a new baseline ANCA titer will be established and the cycle will re-start. In this arm, rituximab administration is not contingent upon B cell levels but on significant ANCA titer rise as described above. Baseline ANCA titer will be recalculated to an average of the two highest of the last four values if all four are less than the original baseline. Patients in the ANCA arm will move to once yearly CD20 testing after CD20 levels return to normal levels (\>90 cells/uL). | 57 |
| Total | 115 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 |
| Overall Study | Cancer | 1 | 0 |
| Overall Study | Major relapse with ILD, BVAS-WG ≥ 3 | 2 | 3 |
| Overall Study | Major relapse without ILD, BVAS-WG ≥ 3 | 2 | 4 |
| Overall Study | Minor relapse, BVAS-WG = 2 | 1 | 7 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Requiring glucocorticoids | 0 | 3 |
| Overall Study | Serious Adverse Event, Related, infection, COVID-19, with death | 2 | 0 |
| Overall Study | Serious Adverse Event, Related, infection, COVID-19, without death | 4 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 7 |
Baseline characteristics
| Characteristic | Serologic ANCA Flare | Total | B Cell Reconstitution |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 23 Participants | 45 Participants | 22 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants | 70 Participants | 36 Participants |
| Age, Continuous | 62 years STANDARD_DEVIATION 12 | 61 years STANDARD_DEVIATION 11 | 61 years STANDARD_DEVIATION 10 |
| ANCA serotype Anti-MPO | 26 Participants | 53 Participants | 27 Participants |
| ANCA serotype Anti-PR3 | 31 Participants | 62 Participants | 31 Participants |
| BVAS/WG at entry | 0 units on a scale STANDARD_DEVIATION 0 | 0 units on a scale STANDARD_DEVIATION 0 | 0 units on a scale STANDARD_DEVIATION 0 |
| Clinical manifestations at diagnosis HD dependent | 0 Participants | 0 Participants | 0 Participants |
| Clinical manifestations at diagnosis ILD | 1 Participants | 3 Participants | 2 Participants |
| Clinical manifestations at diagnosis Otitis | 17 Participants | 34 Participants | 17 Participants |
| Clinical manifestations at diagnosis Pulmonary Hemorrhage | 13 Participants | 19 Participants | 6 Participants |
| Clinical manifestations at diagnosis Rapidly Progressive Glomerulonephritis (RPGN) | 15 Participants | 35 Participants | 20 Participants |
| Clinical manifestations at diagnosis Renal involvement (including RPGN, required Hemodialysis and HD dependent) | 30 Participants | 61 Participants | 31 Participants |
| Clinical manifestations at diagnosis Required Hemodialysis | 1 Participants | 2 Participants | 1 Participants |
| Clinical manifestations at diagnosis Scleritis | 13 Participants | 31 Participants | 18 Participants |
| Clinical manifestations at diagnosis Sinusitis | 26 Participants | 56 Participants | 30 Participants |
| Clinical manifestations at diagnosis Tracheal Stenosis | 2 Participants | 4 Participants | 2 Participants |
| Continuous Rituximab prior to entry Less than 3 years at entry | 28 Participants | 57 Participants | 29 Participants |
| Continuous Rituximab prior to entry More than 3 years at entry | 29 Participants | 58 Participants | 29 Participants |
| Creatinine at entry | 1.09 mg/dL | 1.08 mg/dL | 1.04 mg/dL |
| Disease status Newly diagnosed | 40 Participants | 82 Participants | 42 Participants |
| Disease status Previous relapse | 17 Participants | 33 Participants | 16 Participants |
| eGFR at entry | 60 cc/min/1.73m^2 | 60 cc/min/1.73m^2 | 60 cc/min/1.73m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants | 114 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Ig levels at entry IgG | 750 mg/dL | 710 mg/dL | 699 mg/dL |
| Ig levels at entry IgM | 31 mg/dL | 29 mg/dL | 23 mg/dL |
| Induction Regimen- Plasma Exchange | 9 Participants | 21 Participants | 12 Participants |
| Induction Regimen- Rituximab and Cyclophosphamide Cyclophosphamide | 12 Participants | 22 Participants | 10 Participants |
| Induction Regimen- Rituximab and Cyclophosphamide Cyclophosphamide and Rituximab | 32 Participants | 64 Participants | 32 Participants |
| Induction Regimen- Rituximab and Cyclophosphamide Rituximab | 13 Participants | 29 Participants | 16 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 53 Participants | 108 Participants | 55 Participants |
| Region of Enrollment United States | 57 participants | 115 participants | 58 participants |
| Sex: Female, Male Female | 26 Participants | 56 Participants | 30 Participants |
| Sex: Female, Male Male | 31 Participants | 59 Participants | 28 Participants |
| VDI at entry | 1 units on a scale STANDARD_DEVIATION 1 | 1 units on a scale STANDARD_DEVIATION 1 | 1 units on a scale STANDARD_DEVIATION 1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 58 | 0 / 57 |
| other Total, other adverse events | 46 / 58 | 44 / 57 |
| serious Total, serious adverse events | 15 / 58 | 14 / 57 |
Outcome results
Primary
Number of Patients With Disease Relapse(s) as Defined by a Birmingham Vasculitis Activity Score for Wegner's Granulomatosis (BVAS/WG) ≥ 2
Relapses recording period was from 6/1/2016 to 12/31/2021. The outcome was reported as the number of participants with disease relapse who had either positive ANCA titers specific for myeloperoxidase (MPO-ANCA) or proteinase 3 (PR3-ANCA). The Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG ) is a form with 34 predefined items grouped into 9 organ systems. The items are clinical features observed in patients with active ANCA vasculitis. Each item has a specified weight of either 3 or 1, depending on whether it reflects major or minor disease activity. The total BVAS/WG score is the weighted sum of individual manifestations that are present and believed to be due to active ANCA vasculitis. Higher scores reflect more active disease. BVAS/WG scores range from 0 to 64.
Time frame: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| B Cell Reconstitution | Number of Patients With Disease Relapse(s) as Defined by a Birmingham Vasculitis Activity Score for Wegner's Granulomatosis (BVAS/WG) ≥ 2 | PR3 | 1 Participants |
| B Cell Reconstitution | Number of Patients With Disease Relapse(s) as Defined by a Birmingham Vasculitis Activity Score for Wegner's Granulomatosis (BVAS/WG) ≥ 2 | MPO | 4 Participants |
| Serologic ANCA Flare | Number of Patients With Disease Relapse(s) as Defined by a Birmingham Vasculitis Activity Score for Wegner's Granulomatosis (BVAS/WG) ≥ 2 | PR3 | 7 Participants |
| Serologic ANCA Flare | Number of Patients With Disease Relapse(s) as Defined by a Birmingham Vasculitis Activity Score for Wegner's Granulomatosis (BVAS/WG) ≥ 2 | MPO | 7 Participants |
Comparison: The difference between the two treatment strategies was assessed using the log-rank test. P values of 0.05 were considered significant. Both rows were included and combined in the statistical analysis (ANCA-PR3 and ANCA-MPO) to assess the difference in treatment strategies.~Null hypothesis: No difference in the ANCA and B-cell arm in the probability of relapses.p-value: 0.04595% CI: [0.15, 0.9]Log Rank
Secondary
Composite of Disease Relapse (Defined a BVAS/WG ≥ 2) and Serious Adverse Events
Number of disease relapse added with the number of SAE in each group
Time frame: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| B Cell Reconstitution | Composite of Disease Relapse (Defined a BVAS/WG ≥ 2) and Serious Adverse Events | 27 Number of events |
| Serologic ANCA Flare | Composite of Disease Relapse (Defined a BVAS/WG ≥ 2) and Serious Adverse Events | 36 Number of events |
Secondary
Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores
The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 is a measure of health status and is commonly used in health economics as a variable in the quality-adjusted life year calculation to determine the cost-effectiveness of a health treatment. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time frame: Assessed throughout the study period, every 6 months unless such time point was not reached or was missed by the patient. Median follow-up period is of 4.1 years (IQR, 2.5 - 5.0)
Population: We collected data using the SF-36 on the quality of life due to its importance in the long-term treatment of ANCA vasculitis. Questionnaires were given to patients every 6 months throughout the study period. Some participants do not have scores at certain time points due to either a missed visit or not being enrolled anymore in the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 30 months | 85 score on a scale | Standard Deviation 17 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/fatigue at 6 months | 65 score on a scale | Standard Deviation 15 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 30 months | 74 score on a scale | Standard Deviation 38 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 12 months | 92 score on a scale | Standard Deviation 18 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 30 months | 87 score on a scale | Standard Deviation 27 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/fatigue at 36 months | 58 score on a scale | Standard Deviation 17 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/fatigue at 30 months | 64 score on a scale | Standard Deviation 16 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 12 months | 81 score on a scale | Standard Deviation 19 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 30 months | 81 score on a scale | Standard Deviation 12 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 6 months | 79 score on a scale | Standard Deviation 23 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 30 months | 90 score on a scale | Standard Deviation 19 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 12 months | 66 score on a scale | Standard Deviation 17 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 30 months | 86 score on a scale | Standard Deviation 17 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 36 months | 76 score on a scale | Standard Deviation 19 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 30 months | 60 score on a scale | Standard Deviation 14 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 18 months | 83 score on a scale | Standard Deviation 19 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 42 months | 76 score on a scale | Standard Deviation 25 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 6 months | 79 score on a scale | Standard Deviation 34 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 42 months | 58 score on a scale | Standard Deviation 49 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 18 months | 70 score on a scale | Standard Deviation 41 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 42 months | 67 score on a scale | Standard Deviation 47 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 36 months | 83 score on a scale | Standard Deviation 25 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/fatigue at 42 months | 60 score on a scale | Standard Deviation 19 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 18 months | 88 score on a scale | Standard Deviation 29 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 42 months | 77 score on a scale | Standard Deviation 18 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 6 months | 66 score on a scale | Standard Deviation 15 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 42 months | 85 score on a scale | Standard Deviation 15 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/fatigue at 18 months | 69 score on a scale | Standard Deviation 14 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 42 months | 83 score on a scale | Standard Deviation 16 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 36 months | 69 score on a scale | Standard Deviation 23 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 42 months | 59 score on a scale | Standard Deviation 13 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 18 months | 85 score on a scale | Standard Deviation 9 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 48 months | 65 score on a scale | Standard Deviation 29 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 6 months | 83 score on a scale | Standard Deviation 12 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 48 months | 67 score on a scale | Standard Deviation 52 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 18 months | 96 score on a scale | Standard Deviation 9 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 48 months | 67 score on a scale | Standard Deviation 52 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 36 months | 60 score on a scale | Standard Deviation 20 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/fatigue at 48 months | 52 score on a scale | Standard Deviation 21 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 18 months | 84 score on a scale | Standard Deviation 18 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 48 months | 73 score on a scale | Standard Deviation 29 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 36 months | 74 score on a scale | Standard Deviation 27 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 48 months | 65 score on a scale | Standard Deviation 41 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 18 months | 68 score on a scale | Standard Deviation 17 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 48 months | 70 score on a scale | Standard Deviation 32 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 12 months | 79 score on a scale | Standard Deviation 24 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 48 months | 61 score on a scale | Standard Deviation 22 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 24 months | 83 score on a scale | Standard Deviation 24 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 54 months | 88 score on a scale | Standard Deviation 14 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 54 months | 50 score on a scale | Standard Deviation 58 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 54 months | 67 score on a scale | Standard Deviation 38 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/fatigue at 54 months | 67 score on a scale | Standard Deviation 19 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 54 months | 84 score on a scale | Standard Deviation 5 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 54 months | 84 score on a scale | Standard Deviation 19 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 54 months | 81 score on a scale | Standard Deviation 26 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 54 months | 59 score on a scale | Standard Deviation 6 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 60 months | 72 score on a scale | Standard Deviation 25 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 6 months | 66 score on a scale | Standard Deviation 40 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 60 months | 33 score on a scale | Standard Deviation 58 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 24 months | 71 score on a scale | Standard Deviation 40 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 60 months | 100 score on a scale | Standard Deviation 0 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 12 months | 61 score on a scale | Standard Deviation 43 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/fatigue at 60 months | 48 score on a scale | Standard Deviation 24 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 24 months | 84 score on a scale | Standard Deviation 33 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 60 months | 82 score on a scale | Standard Deviation 10 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 36 months | 50 score on a scale | Standard Deviation 47 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 60 months | 63 score on a scale | Standard Deviation 38 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/fatigue at 24 months | 68 score on a scale | Standard Deviation 15 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 60 months | 53 score on a scale | Standard Deviation 13 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 12 months | 82 score on a scale | Standard Deviation 34 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 60 months | 58 score on a scale | Standard Deviation 32 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 6 months | 84 score on a scale | Standard Deviation 19 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 24 months | 82 score on a scale | Standard Deviation 15 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 6 months | 89 score on a scale | Standard Deviation 19 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 24 months | 91 score on a scale | Standard Deviation 20 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/ fatigue at 12 months | 65 score on a scale | Standard Deviation 20 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 24 months | 81 score on a scale | Standard Deviation 22 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 36 months | 65 score on a scale | Standard Deviation 46 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 24 months | 69 score on a scale | Standard Deviation 15 |
| B Cell Reconstitution | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 12 months | 86 score on a scale | Standard Deviation 11 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 60 months | 70 score on a scale | Standard Deviation 23 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 6 months | 82 score on a scale | Standard Deviation 23 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 6 months | 65 score on a scale | Standard Deviation 45 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 6 months | 75 score on a scale | Standard Deviation 41 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/fatigue at 6 months | 67 score on a scale | Standard Deviation 23 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 6 months | 81 score on a scale | Standard Deviation 16 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 6 months | 88 score on a scale | Standard Deviation 21 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 6 months | 82 score on a scale | Standard Deviation 20 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 6 months | 63 score on a scale | Standard Deviation 20 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 36 months | 88 score on a scale | Standard Deviation 19 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 36 months | 79 score on a scale | Standard Deviation 36 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 36 months | 82 score on a scale | Standard Deviation 27 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/fatigue at 36 months | 73 score on a scale | Standard Deviation 17 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 36 months | 84 score on a scale | Standard Deviation 10 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 36 months | 95 score on a scale | Standard Deviation 13 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 36 months | 87 score on a scale | Standard Deviation 16 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 36 months | 70 score on a scale | Standard Deviation 20 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 12 months | 82 score on a scale | Standard Deviation 23 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 12 months | 63 score on a scale | Standard Deviation 43 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 12 months | 68 score on a scale | Standard Deviation 42 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/ fatigue at 12 months | 65 score on a scale | Standard Deviation 22 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 12 months | 81 score on a scale | Standard Deviation 14 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 12 months | 86 score on a scale | Standard Deviation 22 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 12 months | 80 score on a scale | Standard Deviation 21 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 12 months | 63 score on a scale | Standard Deviation 21 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 18 months | 82 score on a scale | Standard Deviation 25 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 18 months | 62 score on a scale | Standard Deviation 44 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 18 months | 74 score on a scale | Standard Deviation 42 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/fatigue at 18 months | 68 score on a scale | Standard Deviation 17 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 18 months | 81 score on a scale | Standard Deviation 13 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 18 months | 92 score on a scale | Standard Deviation 16 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 18 months | 82 score on a scale | Standard Deviation 19 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 18 months | 67 score on a scale | Standard Deviation 18 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 24 months | 88 score on a scale | Standard Deviation 15 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 24 months | 71 score on a scale | Standard Deviation 42 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 24 months | 80 score on a scale | Standard Deviation 38 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/fatigue at 24 months | 76 score on a scale | Standard Deviation 13 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 24 months | 85 score on a scale | Standard Deviation 12 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 24 months | 94 score on a scale | Standard Deviation 14 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 24 months | 82 score on a scale | Standard Deviation 15 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 24 months | 70 score on a scale | Standard Deviation 16 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 30 months | 88 score on a scale | Standard Deviation 17 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 30 months | 72 score on a scale | Standard Deviation 40 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 30 months | 80 score on a scale | Standard Deviation 39 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/fatigue at 30 months | 72 score on a scale | Standard Deviation 19 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 30 months | 84 score on a scale | Standard Deviation 14 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 30 months | 94 score on a scale | Standard Deviation 12 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 30 months | 83 score on a scale | Standard Deviation 18 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 30 months | 70 score on a scale | Standard Deviation 16 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 42 months | 82 score on a scale | Standard Deviation 24 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 42 months | 60 score on a scale | Standard Deviation 40 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 42 months | 76 score on a scale | Standard Deviation 37 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/fatigue at 42 months | 70 score on a scale | Standard Deviation 24 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 42 months | 85 score on a scale | Standard Deviation 12 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 42 months | 87 score on a scale | Standard Deviation 24 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 42 months | 82 score on a scale | Standard Deviation 21 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 42 months | 63 score on a scale | Standard Deviation 22 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 48 months | 95 score on a scale | Standard Deviation 0 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 48 months | 100 score on a scale | Standard Deviation 0 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 48 months | 100 score on a scale | Standard Deviation 0 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/fatigue at 48 months | 75 score on a scale | Standard Deviation 0 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 48 months | 85 score on a scale | Standard Deviation 0 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 48 months | 100 score on a scale | Standard Deviation 0 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 48 months | 80 score on a scale | Standard Deviation 0 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | General health at 48 months | 75 score on a scale | Standard Deviation 0 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Physical functioning at 60 months | 92 score on a scale | Standard Deviation 3 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/physical at 60 months | 100 score on a scale | Standard Deviation 0 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Role functioning/emotional at 60 months | 89 score on a scale | Standard Deviation 19 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Energy/fatigue at 60 months | 71 score on a scale | Standard Deviation 14 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Emotional well-being at 60 months | 83 score on a scale | Standard Deviation 6 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Social functioning at 60 months | 92 score on a scale | Standard Deviation 14 |
| Serologic ANCA Flare | Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores | Pain at 60 months | 83 score on a scale | Standard Deviation 13 |
Secondary
Mean Number of Rituximab Infusions Per Subject
The rituximab utilization was measured in how many times a subject received Rituximab throughout the study which was then averaged for all subjects in each treatment arm, including those who did not receive any infusion.
Time frame: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| B Cell Reconstitution | Mean Number of Rituximab Infusions Per Subject | 3.6 Infusions per subject | Standard Deviation 2.4 |
| Serologic ANCA Flare | Mean Number of Rituximab Infusions Per Subject | 0.5 Infusions per subject | Standard Deviation 1.5 |
Comparison: Null hypothesis: no difference in the mean number of infusions per patient in each arm.p-value: <1t-test, 2 sided
Secondary
Number of Infections
Number of infections mild and severe, whether they were treated or not with antibiotics
Time frame: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| B Cell Reconstitution | Number of Infections | Serious Adverse Events- Infections | 12 number of events |
| B Cell Reconstitution | Number of Infections | Adverse Events- Infections | 72 number of events |
| Serologic ANCA Flare | Number of Infections | Serious Adverse Events- Infections | 6 number of events |
| Serologic ANCA Flare | Number of Infections | Adverse Events- Infections | 59 number of events |
Secondary
Number of Major Relapses Defined as a BVAS/WG ≥ 3
The Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG ) is a form with 34 predefined items grouped into 9 organ systems. The items are clinical features observed in patients with active ANCA vasculitis. Each item has a specified weight of either 3 or 1, depending on whether it reflects major or minor disease activity. The total BVAS/WG score is the weighted sum of individual manifestations that are present and believed to be due to active ANCA vasculitis. Higher scores reflect more active disease. BVAS/WG scores range from 0 to 64.
Time frame: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| B Cell Reconstitution | Number of Major Relapses Defined as a BVAS/WG ≥ 3 | 4 number of events |
| Serologic ANCA Flare | Number of Major Relapses Defined as a BVAS/WG ≥ 3 | 7 number of events |
Comparison: The difference between the two treatment strategies was assessed using the log-rank test. P values of 0.05 were considered significant.~Null hypothesis: No difference in the ANCA and B-cell arm in the probability of relapsesp-value: 0.4295% CI: [0.5, 5.36]Log Rank
Secondary
Number of Patients Affected by Serious Adverse Events
Number of patients with serious adverse events (SAEs), including all episodes of late onset neutropenia (LON). SAE are defined in the Serious adverse event section. Serious adverse events were reported over the entire study period (5.5 years)
Time frame: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| B Cell Reconstitution | Number of Patients Affected by Serious Adverse Events | 15 Participants |
| Serologic ANCA Flare | Number of Patients Affected by Serious Adverse Events | 14 Participants |
Comparison: Null hypothesis: No difference in the proportion of patients with SAEs in each armp-value: 0.87Chi-squared
Secondary
Number of Patients With Hypogammaglobulinemia
Hypogammaglobulinemia defined as an IgG \< 250mg/dL
Time frame: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| B Cell Reconstitution | Number of Patients With Hypogammaglobulinemia | 1 Participants |
| Serologic ANCA Flare | Number of Patients With Hypogammaglobulinemia | 0 Participants |
Secondary
Organ Damage as Assessed by the Vasculitis Damage Index (VDI).
The Vasculitis Damage Index (VDI) is a validated formal assessment tool in ANCA-associated vasculitis clinical trials. The VDI distinguishes vasculitis-induced chronic damage from active inflammation or persistent disease. Each item represents a disease manifestation and is given a score (of 1) if present for at least 3 months. Neither the cause of damage (vasculitis vs treatment) nor an ongoing activity are taken into consideration. The VDI includes 64 items categorized into 11 groups (by organ system) and the scored items are summed to give a total score ranging from 0 to 64. A higher score means more accrued damage.
Time frame: 3 years starting at inclusion
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B Cell Reconstitution | Organ Damage as Assessed by the Vasculitis Damage Index (VDI). | VDI at inclusion | 1.27 score on a scale | Standard Deviation 1.24 |
| B Cell Reconstitution | Organ Damage as Assessed by the Vasculitis Damage Index (VDI). | VDI at 3 years | 1.42 score on a scale | Standard Deviation 1.11 |
| Serologic ANCA Flare | Organ Damage as Assessed by the Vasculitis Damage Index (VDI). | VDI at inclusion | 1.07 score on a scale | Standard Deviation 1.11 |
| Serologic ANCA Flare | Organ Damage as Assessed by the Vasculitis Damage Index (VDI). | VDI at 3 years | 1.08 score on a scale | Standard Deviation 1.16 |
Comparison: Null hypothesis: there is no difference in the mean change from baseline Vasculitis Damage Index between each arm. A t-test was used.p-value: 0.1795% CI: [-0.34, -0.06]t-test, 2 sided
Secondary
Patient Survival
number of deaths throughout the study.
Time frame: 5.5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| B Cell Reconstitution | Patient Survival | 2 number of deaths |
| Serologic ANCA Flare | Patient Survival | 0 number of deaths |