Granulomatosis With Polyangiitis, Microscopic Polyangiitis
Conditions
Brief summary
This prospective observational study will evaluate the long-term safety of MabThera/Rituxan (rituximab) in participants with granulomatosis with polyangiitis (Wegener's) or microscopic polyangiitis. Data will be collected for a maximum of 4 years from participants initiated on MabThera/Rituxan therapy by their physician according to prescribing information.
Interventions
DRUGRituximab
Participants received rituximab at the discretion of their treating physicians.
Sponsors
Genentech, Inc.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult participants, \>/= 18 years of age * Granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), according to Chapel Hill Consensus Conference Definitions for MPA and American College of Rheumatology (ACR) Criteria for the Classification of GPA * Disease severity requiring rituximab treatment per the investigator's assessment
Exclusion criteria
* Prior use of rituximab (except if received within 4 weeks of screening) * Known hypersensitivity to rituximab, to any component of the product, or to murine proteins * Pregnant or breastfeeding women * Diagnosis of Churg-Strauss syndrome
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate of Serious Infections | From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years) | A serious infection was defined as an infection that was a serious adverse event (SAE) or a non-SAE infection that required treatment with intravenous antimicrobials. A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate of Serious Cardiac Adverse Events | From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years) | A serious cardiac adverse event was defined as a SAE that was coded to the Medical Dictionary for Regulatory Activities (MedDRA) cardiac system organ class. A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years. |
| Percentage of Participants With Any Serious Adverse Events During or Within 24 Hours After Any Rituximab Infusion | From the start of an infusion up to 24 hours following infusion completion (Up to 4.32 years) | A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. |
| Incidence Rate of Serious Vascular Adverse Events | From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years) | A serious vascular adverse event was defined as a SAE coded to the MedDRA vascular system organ class. A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years. |
| Incidence Rate of Malignancy, Excluding Non-melanoma Skin Cancer | From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years) | Malignancies were clinical findings of cancer and excluded non-melanoma skin cancer. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years. |
| Percentage of Participants With a Serious Infusion-related Reaction | From the start of an infusion up to 24 hours following infusion completion (Up to 4.32 years) | A serious infusion-related reaction was defined as a SAE during or within 24 hours after any rituximab infusion and considered infusion related by the Principal Investigator. A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. |
| Incidence Rate of Adverse Events With Fatal Outcomes | From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years) | Incidence rate is defined as events per 100 patient years. |
| Incidence Rate of Serious Adverse Events in Participants Who Received Re-treatment With MabThera/Rituximab | From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years) | A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years. |
| Incidence Rate of Serious Infections in Participants Who Received Re-treatment With MabThera/Rituximab | From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years) | A serious infection was defined as an infection that was a serious adverse event (SAE) or a non-SAE infection that required treatment with intravenous antimicrobials. A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years. |
| Incidence Rate of Serious Adverse Events | From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years) | A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years. |
Countries
United States
Participant flow
Recruitment details
A total of 100 participants were enrolled in 15 investigational sites in United States. 3 participants out of 100 enrolled participants were not included in the analysis population as that site became unresponsive.
Participants by arm
| Arm | Count |
|---|---|
| Rituximab Participants with GPA (Wegener's granulomatosis) or MPA who received rituximab as per investigator's discretion were followed for a maximum of 4.32 years. | 97 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 9 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Reason not specified | 3 |
| Overall Study | Withdrawal by Subject | 8 |
Baseline characteristics
| Characteristic | Rituximab |
|---|---|
| Age, Continuous | 56.3 years STANDARD_DEVIATION 16.5 |
| Sex: Female, Male Female | 57 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 9 / 97 |
| other Total, other adverse events | 5 / 97 |
| serious Total, serious adverse events | 38 / 97 |
Outcome results
Primary
Incidence Rate of Serious Infections
A serious infection was defined as an infection that was a serious adverse event (SAE) or a non-SAE infection that required treatment with intravenous antimicrobials. A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years.
Time frame: From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years)
Population: The safety population included all participants who received any active dose of rituximab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Incidence Rate of Serious Infections | 7.11 events per 100 patient year |
Secondary
Incidence Rate of Adverse Events With Fatal Outcomes
Incidence rate is defined as events per 100 patient years.
Time frame: From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years)
Population: The safety population included all participants who received any active dose of rituximab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Incidence Rate of Adverse Events With Fatal Outcomes | 2.67 events per 100 patient year |
Secondary
Incidence Rate of Malignancy, Excluding Non-melanoma Skin Cancer
Malignancies were clinical findings of cancer and excluded non-melanoma skin cancer. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years.
Time frame: From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years)
Population: The safety population included all participants who received any active dose of rituximab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Incidence Rate of Malignancy, Excluding Non-melanoma Skin Cancer | 0.89 events per 100 patient year |
Secondary
Incidence Rate of Serious Adverse Events
A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years.
Time frame: From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years)
Population: The safety population included all participants who received any active dose of rituximab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Incidence Rate of Serious Adverse Events | 27.84 events per 100 patient year |
Secondary
Incidence Rate of Serious Adverse Events in Participants Who Received Re-treatment With MabThera/Rituximab
A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years.
Time frame: From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years)
Population: The re-treated safety population was a subset of the safety population and included all participants who received more than one course of rituximab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Incidence Rate of Serious Adverse Events in Participants Who Received Re-treatment With MabThera/Rituximab | 23.90 events per 100 patient year |
Secondary
Incidence Rate of Serious Cardiac Adverse Events
A serious cardiac adverse event was defined as a SAE that was coded to the Medical Dictionary for Regulatory Activities (MedDRA) cardiac system organ class. A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years.
Time frame: From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years)
Population: The safety population included all participants who received any active dose of rituximab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Incidence Rate of Serious Cardiac Adverse Events | 5.03 events per 100 patient year |
Secondary
Incidence Rate of Serious Infections in Participants Who Received Re-treatment With MabThera/Rituximab
A serious infection was defined as an infection that was a serious adverse event (SAE) or a non-SAE infection that required treatment with intravenous antimicrobials. A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years.
Time frame: From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years)
Population: The re-treated safety population was a subset of the safety population and included all participants who received more than one course of rituximab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Incidence Rate of Serious Infections in Participants Who Received Re-treatment With MabThera/Rituximab | 6.07 events per 100 patient year |
Secondary
Incidence Rate of Serious Vascular Adverse Events
A serious vascular adverse event was defined as a SAE coded to the MedDRA vascular system organ class. A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above. Multiple events reported in the same participant were counted multiple times in the calculation of incidence. Incidence rate is defined as events per 100 patient years.
Time frame: From first dose until participant withdrawal or the date of last participant, last visit (up to 4.32 years)
Population: The safety population included all participants who received any active dose of rituximab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Incidence Rate of Serious Vascular Adverse Events | 2.37 events per 100 patient year |
Secondary
Percentage of Participants With Any Serious Adverse Events During or Within 24 Hours After Any Rituximab Infusion
A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above.
Time frame: From the start of an infusion up to 24 hours following infusion completion (Up to 4.32 years)
Population: The safety population included all participants who received any active dose of rituximab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Percentage of Participants With Any Serious Adverse Events During or Within 24 Hours After Any Rituximab Infusion | 0 percentage of participants |
Secondary
Percentage of Participants With a Serious Infusion-related Reaction
A serious infusion-related reaction was defined as a SAE during or within 24 hours after any rituximab infusion and considered infusion related by the Principal Investigator. A SAE was defined as any adverse event that fulfilled at least one of the following criteria: •Was fatal (results in death) •Was life-threatening •Required in-patient hospitalization or prolongation of existing hospitalization •Resulted in persistent or significant disability/incapacity •Was a congenital anomaly/birth defect •Was medically significant or required intervention to prevent one or other of the outcomes listed above.
Time frame: From the start of an infusion up to 24 hours following infusion completion (Up to 4.32 years)
Population: The safety population included all participants who received any active dose of rituximab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Percentage of Participants With a Serious Infusion-related Reaction | 0 percentage of participants |