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An Observational Study of MabThera/Rituxan (Rituximab) and Alternative TNF-Inhibitors in Patients With Rheumatoid Arthritis and an Inadequate Response to a Single Previous TNF-Inhibitor

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ClinicalTrials.gov Identifier: NCT01557348
Recruitment Status : Completed
First Posted : March 19, 2012
Results First Posted : January 24, 2017
Last Update Posted : January 24, 2017
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Observational
Study Design Observational Model: Cohort;   Time Perspective: Prospective
Condition Rheumatoid Arthritis
Enrollment 1239
Recruitment Details This observational study was conducted in 11 countries from 02 June 2009 to 19 March 2012.
Pre-assignment Details Of 1239 enrolled participants, 9 had no information on second biologic treatment/reasons for discontinuing prior tumor necrosis factor inhibitor (TNFi), 1111 had one previous TNFi,119 had more than one previous TNFi. Of 1111 participants, 728 were considered for primary effectiveness analysis (405 in Rituximab arm and 323 in Alternative TNFi arm).
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy. Eligible participants received alternative TNFi treatment as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Period Title: Overall Study
Started 604 507
Safety Population 604 507
Completed 524 417
Not Completed 80 90
Reason Not Completed
Adverse Event             6             16
Infusion reaction event             5             5
Death             7             4
Insufficient Therapeutic Response             13             28
Withdrawal by Subject             5             4
Lost to Follow-up             26             22
Administrative             18             11
Arm/Group Title Rituximab Alternative TNFi Total
Hide Arm/Group Description Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy. Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy. Total of all reporting groups
Overall Number of Baseline Participants 405 323 728
Hide Baseline Analysis Population Description
The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at baseline (day of change in biologic therapy [<=Day 1]), had only one previous biologic therapy, and contributed for 24-week disease activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) for primary analysis.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 405 participants 323 participants 728 participants
56.5  (12.61) 54.7  (13.26) 55.7  (12.93)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 405 participants 323 participants 728 participants
Female
310
  76.5%
259
  80.2%
569
  78.2%
Male
95
  23.5%
64
  19.8%
159
  21.8%
1.Primary Outcome
Title Least Squares Mean Change From Baseline in Disease Activity Score (3 Variables)-Erythrocyte Sedimentation Rate at Month 6
Hide Description The DAS28-3 (ESR) is a measure of disease activity in rheumatoid arthritis. It is calculated from the number of swollen joint count (SJC) and tender joint count (TJC) using the 28 joints count, and ESR (millimeters per hour [mm/hr]). Total score ranges from 0 to 9.4, where higher score indicated more disease activity. Decrease in score indicated improvement in disease activity.
Time Frame Baseline (Day of change in biologic therapy [<=Day 1]) and Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis.
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description:
Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Overall Number of Participants Analyzed 405 323
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-1.5  (0.22) -1.1  (0.23)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0068
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
2.Secondary Outcome
Title Least Squares Mean Change From Baseline in Disease Activity Score (3 Variables)-Erythrocyte Sedimentation Rate at Month12
Hide Description The DAS28-3 (ESR) is a measure of disease activity in rheumatoid arthritis. It is calculated from the number of swollen joint count (SJC) and tender joint count (TJC) using the 28 joints count, and ESR (millimeters per hour [mm/hr]). Total score ranges from 0 to 9.4, where higher score indicated more disease activity. Decrease in score indicated improvement in disease activity.
Time Frame Baseline (Day of change in biologic therapy [<=Day 1]) and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis.
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description:
Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Overall Number of Participants Analyzed 332 266
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-1.5  (0.27) -1.2  (0.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0588
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
3.Secondary Outcome
Title Least Squares Mean Change From Baseline in TJC at Months 6 and 12
Hide Description The TJC is the most specific clinical method to quantify abnormalities in participants with rheumatoid arthritis (RA). A total of 28 joints were assessed for tenderness. Decrease in score indicated an improvement in disease activity.
Time Frame Baseline, Month 6, and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points were analyzed and are denoted as ‘n’.
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description:
Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Overall Number of Participants Analyzed 338 255
Least Squares Mean (Standard Error)
Unit of Measure: tender joints
Month 6 (n= 338, 255) -5.7  (1.20) -4.5  (1.24)
Month 12 (n= 281, 216) -4.7  (1.29) -3.7  (1.36)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments Comparison of least squares mean change from Baseline in TJC at Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1126
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments Comparison of least squares mean change from Baseline in TJC at Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2342
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
4.Secondary Outcome
Title Least Squares Mean Change From Baseline in SJC at Months 6 and 12
Hide Description The SJC is the most specific clinical method to quantify abnormalities in participants with RA. A total of 28 joints were assessed for swelling. Decrease in the score indicated improvement in disease activity.
Time Frame Baseline, Month 6, and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points were analyzed and are denoted as ‘n’.
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description:
Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Overall Number of Participants Analyzed 339 256
Least Squares Mean (Standard Error)
Unit of Measure: swollen joints
Month 6 (n= 339, 256) -3.3  (0.93) -2.8  (0.97)
Month 12 (n= 283, 215) -2.7  (0.99) -2.4  (1.04)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments Comparison of least squares mean change from Baseline in SJC at Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4168
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments Comparison of least squares mean change from Baseline in SJC at Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5867
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
5.Secondary Outcome
Title Least Squares Mean Change From Baseline in C-reactive Protein at Months 6 and 12
Hide Description C-reactive protein (CRP) is an inflammation marker. Normal range is from 0-10 milligram/Liter. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement in disease activity.
Time Frame Baseline, Month 6, and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points were analyzed and are denoted as ‘n’.
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description:
Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Overall Number of Participants Analyzed 278 227
Least Squares Mean (Standard Error)
Unit of Measure: milligram/Liter
Month 6 (n= 278, 227) -29.1  (7.95) -29.9  (8.43)
Month 12 (n=251, 199) -11.6  (8.47) -15.3  (8.91)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments Comparison of least squares mean change from Baseline in CRP at Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8758
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments Comparison of least squares mean change from Baseline in CRP at Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4849
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
6.Secondary Outcome
Title Least Squares Mean Change From Baseline in ESR at Months 6 and 12
Hide Description The ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells sediment in a period of one hour. Normal range is 0-30 mm/hr. A reduction in the level of ESR is considered as an improvement in disease activity.
Time Frame Baseline, Month 6, and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points were analyzed and are denoted as ‘n’.
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description:
Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Overall Number of Participants Analyzed 343 250
Least Squares Mean (Standard Error)
Unit of Measure: mm/hr
Month 6 (n= 343, 250) -13.2  (3.91) -7.0  (4.22)
Month 12 (n=297, 215) -11.6  (4.58) -8.6  (4.90)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments Comparison of least squares mean change from Baseline in ESR at Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0086
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments Comparison of least squares mean change from Baseline in ESR at Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2918
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
7.Secondary Outcome
Title Least Squares Mean Change From Baseline in Physician Global Assessment of Disease at Months 6 and 12
Hide Description Physician global assessment of disease was measured on a 0 to 100 millimeter (mm) visual analog scale (VAS), with 0 mm = no disease activity and 100 mm = highest possible disease activity. Higher scores indicate worsening of disease.
Time Frame Baseline, Month 6, and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points were analyzed and are denoted as ‘n’.
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description:
Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Overall Number of Participants Analyzed 203 169
Least Squares Mean (Standard Error)
Unit of Measure: mm
Month 6 (n= 203, 169) -21.0  (6.13) -14.8  (6.65)
Month 12 (n= 169, 144) -21.8  (6.69) -14.3  (7.30)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments Comparison of least squares mean change from Baseline in Physician Global Assessment of Disease at Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0764
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments Comparison of least squares mean change from Baseline in Physician Global Assessment of Disease at Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0587
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
8.Secondary Outcome
Title Least Squares Mean Change From Baseline in Patient Global Assessment of Disease at Months 6 and 12
Hide Description Patient Global Assessment of Disease was measured on a 0 to 100 mm VAS, with 0 mm = no disease activity and 100 mm = highest possible disease activity. Higher scores indicate worsening of disease.
Time Frame Baseline, Month 6, and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points were analyzed and are denoted as ‘n’.
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description:
Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Overall Number of Participants Analyzed 288 219
Least Squares Mean (Standard Error)
Unit of Measure: mm
Month 6 (n= 288, 219) -17.0  (5.48) -10.2  (5.77)
Month 12 (n= 242, 189) -19.7  (5.85) -17.1  (6.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments Comparison of least squares mean change from Baseline in Patient Global Assessment of Disease at Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0443
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments Comparison of least squares mean change from Baseline in Patient Global Assessment of Disease at Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4802
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
9.Secondary Outcome
Title Least Squares Mean Change From Baseline in Participant’s VAS Pain Score at Months 6 and 12
Hide Description Participants were asked to assess their pain intensity (severity of pain) on a 100-millimeter (mm) VAS with the left edge (0 mm) defined as “no pain” and the right edge (100 mm) defined as “severest pain”. Higher scores indicate worsening of disease.
Time Frame Baseline, Month 6, and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points were analyzed and are denoted as ‘n’.
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description:
Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Overall Number of Participants Analyzed 236 197
Least Squares Mean (Standard Error)
Unit of Measure: mm
Month 6 (n= 236, 197) -15.7  (6.48) -10.8  (7.02)
Month 12 (n=194, 171) -19.0  (6.58) -10.0  (7.10)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments Comparison of least squares mean change from Baseline in Participant's Visual Analogue Scale Pain Score at Months 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2026
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments Comparison of least squares mean change from Baseline in Participant's Visual Analogue Scale Pain Score at Months 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0295
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
10.Secondary Outcome
Title Least Squares Mean Change From Baseline in Health Assessment Questionnaire-Disability Index at Months 6 and 12
Hide Description Health Assessment Questionnaire-Disability Index (HAQ-DI) is participant reported assessment of ability to perform tasks in 8 categories of daily living activities as dress/groom, arise, eat, walk, reach, grip, hygiene, and common activities over past week. Each item was scored on a 4-point scale from 0 to 3, where 0=no difficulty, 1=some difficulty, 2=much difficulty, and 3=unable to do. Overall score was computed as the sum of domain scores divided by the number of domains answered. Total possible score range was 0-3, where 0 = least difficulty and 3 = extreme difficulty.
Time Frame Baseline, Month 6, and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points were analyzed and are denoted as ‘n’.
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description:
Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Overall Number of Participants Analyzed 164 131
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Month 6 (n= 164, 131) -0.6  (0.18) -0.5  (0.19)
Month 12 (n=142, 112) -0.3  (0.20) -0.2  (0.22)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments Comparison of least squares mean change from Baseline in HAQ-DI at Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3370
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments Comparison of least squares mean change from Baseline in HAQ-DI at Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1515
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
11.Secondary Outcome
Title Least Squares Mean Change From Baseline in Duration of Morning Stiffness at Months 6 and 12
Hide Description Duration of morning stiffness is defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness in minutes. Participants with available data at the time of assessment were included in the analysis.
Time Frame Baseline, Month 6, and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at Baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points were analyzed and are denoted as ‘n’.
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description:
Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Overall Number of Participants Analyzed 233 180
Least Squares Mean (Standard Error)
Unit of Measure: minutes
Month 6 (n= 233, 180) -19.0  (25.38) -4.3  (27.37)
Month 12 (n=206, 156) -16.7  (25.81) -1.4  (28.19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments Comparison of least squares mean change from Baseline in duration of morning stiffness at month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3253
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Alternative TNFi
Comments Comparison of least squares mean change from Baseline in duration of morning stiffness at month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3535
Comments LsMean and p-value are based on an ANCOVA model adjusted for significant factors leading to selection of new biologic therapy and unbalanced baseline covariates.
Method ANCOVA
Comments [Not Specified]
12.Secondary Outcome
Title Percentage of Participants Who Remained on Their Second Biologic Therapy at Months 6 and 12 After Start of Second Biologic Therapy
Hide Description Percentage of participants who remained on their second biologic therapy at 6 and 12 months after start of second biologic therapy were reported.
Time Frame Month 6 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis population included all enrolled participants with only one previous TNFi whose second biologic therapy (i.e,Treatment Group) and reason for changing biologic therapy was known.
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description:
Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Overall Number of Participants Analyzed 604 507
Measure Type: Number
Unit of Measure: Percentage of participants
NA [1]  NA [2] 
[1]

The data recorded on the eCRF was insufficient to determine this outcome measure.

The data recorded on the eCRF was insufficient for us to be able to determine this measure.

[2]
The data recorded on the eCRF was insufficient to determine this outcome measure.
13.Secondary Outcome
Title Reasons for Stopping the Second Biologic Therapy and Subsequent Therapy Choice
Hide Description [Not Specified]
Time Frame Up to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis population included all enrolled participants with only one previous TNFi whose second biologic therapy (ie,Treatment Group) and reason for changing biologic therapy was known.
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description:
Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Eligible participants received alternative TNFi treatment as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Overall Number of Participants Analyzed 604 507
Measure Type: Number
Unit of Measure: Number of participants
NA [1]  NA [1] 
[1]
Data was not actually collected as per the eCRF
14.Secondary Outcome
Title Number of Participants With Any Adverse Events, Any Serious Adverse Event, Adverse Events Leading to Withdrawal, and Death
Hide Description An Adverse event is defined as any unfavorable and unintended medical occurrence/sign (including an abnormal laboratory finding), symptom or disease in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A serious adverse event is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is medically significant or requires intervention to prevent one or other of the outcomes listed above.
Time Frame Up to 12 Months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis population included all enrolled participants with only one previous TNFi whose second biologic therapy and reason for changing biologic therapy was known.
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description:
Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Overall Number of Participants Analyzed 604 507
Measure Type: Number
Unit of Measure: participants
Any AE 291 241
Any SAE 82 56
AE leading to withdrawal 17 39
Death 7 4
15.Secondary Outcome
Title Number of Participants With Reasons for Discontinuation of the First TNFi Therapy
Hide Description The reasons for discontinuation of first TNFi therapy included inefficacy, intolerance and other reasons. The other reasons included complete remission and participants' non-compliance.
Time Frame Day 1 (Study entry visit)
Hide Outcome Measure Data
Hide Analysis Population Description
The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis.
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description:
Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Overall Number of Participants Analyzed 405 323
Measure Type: Number
Unit of Measure: participants
Inefficacy 311 236
Intolerance 89 79
Other reasons 5 8
16.Secondary Outcome
Title Number of Participants With Previous TNFi Therapy
Hide Description The previous TNFi therapy included adalimumab, etanercept, infliximab, and others (certolizumab, and golimumab). Number of participants with previous TNFi therapy history was reported.
Time Frame Day 1 (Study entry visit)
Hide Outcome Measure Data
Hide Analysis Population Description
The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points are denoted as ‘n’.
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description:
Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Overall Number of Participants Analyzed 405 323
Measure Type: Number
Unit of Measure: participants
Adalimumab (Humira) 131 116
Etanercept (Enbrel) 176 162
Infliximab (Remicade) 95 42
Certolizumab pegol (Cimzia) 3 0
Golimumab (Simponi) 0 3
17.Secondary Outcome
Title Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy
Hide Description The previous disease-modifying anti-rheumatic drugs therapy included auranofin, aurothioglucose, aurotioprol, azathioprine, chloroquine, ciclosporin, gold, hydroxychloroquine, infliximab, leflunomide, methotrexate, methotrexate sodium, minocycline, penicillamine, sodium aurothiomalate, sodium aurotiosulfate, sulfasalazine, and tiopronin. Number of participants with previous disease-modifying anti-rheumatic drugs therapy was reported.
Time Frame Day 1 (Study entry visit)
Hide Outcome Measure Data
Hide Analysis Population Description
The primary effectiveness population included all participants who received at least one dose of a second biologic therapy at baseline, had only one previous biologic therapy, and contributed to 24-week DAS28-ESR primary endpoint analysis. Participants with available data at specified time points are denoted as ‘n’.
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description:
Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Overall Number of Participants Analyzed 405 323
Measure Type: Number
Unit of Measure: participants
Auranofin 5 6
Aurothioglucose 0 1
Aurotioprol 4 4
Azathioprine 20 9
Chloroquine 27 11
Ciclosporin 25 27
Gold 27 20
Hydroxychloroquine 96 99
Infliximab 1 0
Leflunomide 144 126
Methotrexate 199 180
Methotrexate sodium 3 1
Minocycline 0 3
Penicillamine 7 5
Sodium aurothiomalate 17 4
Sodium aurotiosulfate 0 1
Sulfasalazine 107 86
Tiopronin 0 1
18.Secondary Outcome
Title Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi
Hide Description The factors included participant characteristics and the reasons that led to the selection of second biologic therapy following an insufficient response or intolerance to a single previous TNFi. The participant characteristics included participant's option for treatment and option for follow-up. The other reasons included RA disease (rheumatoid factor [RF] and cyclic citrullinated peptide [CCP] status), primary failure, and new treatment characteristics (rapidity of action, route of administration, frequency of administration, low infectious risk, and no lymphoma risk). Participants were included in more than one of these factors.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis population included all enrolled participants with only one previous TNFi whose second biologic therapy and reason for changing biologic therapy was known.
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description:
Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Overall Number of Participants Analyzed 604 507
Measure Type: Number
Unit of Measure: participants
RA Disease (RF and CCP Status) 344 216
Primary failure 256 135
Rapidity of action 82 203
Route of administration 123 289
Frequency of administration 303 174
Low infectious risk 172 62
No lymphoma risk 120 17
Participant's option for treatment 272 278
Participant's option for follow-up 91 89
Time Frame Up to 12 months
Adverse Event Reporting Description All serious adverse events (SAEs) and non-serious adverse events (AEs) were reported for the safety population which included all participants who received a second biologic therapy at baseline and had one and only one previous biologic therapy.
 
Arm/Group Title Rituximab Alternative TNFi
Hide Arm/Group Description Eligible participants received rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy. Eligible participants received alternative TNFi as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
All-Cause Mortality
Rituximab Alternative TNFi
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Rituximab Alternative TNFi
Affected / at Risk (%) Affected / at Risk (%)
Total   82/604 (13.58%)   56/507 (11.05%) 
Blood and lymphatic system disorders     
Neutropenia  1  2/604 (0.33%)  1/507 (0.20%) 
Anaemia  1  1/604 (0.17%)  1/507 (0.20%) 
Cardiac disorders     
Acute myocardial infarction  1  2/604 (0.33%)  1/507 (0.20%) 
Angina unstable  1  2/604 (0.33%)  0/507 (0.00%) 
Myocardial infarction  1  1/604 (0.17%)  1/507 (0.20%) 
Angina pectoris  1  0/604 (0.00%)  1/507 (0.20%) 
Atrial tachycardia  1  0/604 (0.00%)  1/507 (0.20%) 
Cardiac arrest  1  1/604 (0.17%)  0/507 (0.00%) 
Cardiac failure congestive  1  1/604 (0.17%)  0/507 (0.00%) 
Coronary artery disease  1  1/604 (0.17%)  0/507 (0.00%) 
Hypertensive heart disease  1  1/604 (0.17%)  0/507 (0.00%) 
Left ventricular failure  1  0/604 (0.00%)  1/507 (0.20%) 
Myopericarditis  1  1/604 (0.17%)  0/507 (0.00%) 
Pericarditis  1  1/604 (0.17%)  0/507 (0.00%) 
Pericarditis constrictive  1  1/604 (0.17%)  0/507 (0.00%) 
Supraventricular tachycardia  1  1/604 (0.17%)  0/507 (0.00%) 
Tachycardia  1  0/604 (0.00%)  1/507 (0.20%) 
Gastrointestinal disorders     
Abdominal pain  1  1/604 (0.17%)  2/507 (0.39%) 
Abdominal pain lower  1  1/604 (0.17%)  0/507 (0.00%) 
Abdominal pain upper  1  1/604 (0.17%)  0/507 (0.00%) 
Ascites  1  1/604 (0.17%)  0/507 (0.00%) 
Duodenal ulcer  1  1/604 (0.17%)  0/507 (0.00%) 
Gastritis  1  1/604 (0.17%)  0/507 (0.00%) 
Gastrointestinal disorder  1  0/604 (0.00%)  1/507 (0.20%) 
Intestinal ischaemia  1  0/604 (0.00%)  1/507 (0.20%) 
Large intestine perforation  1  1/604 (0.17%)  0/507 (0.00%) 
Pancreatitis acute  1  0/604 (0.00%)  1/507 (0.20%) 
Peptic ulcer perforation  1  0/604 (0.00%)  1/507 (0.20%) 
Periodontal disease  1  1/604 (0.17%)  0/507 (0.00%) 
Sigmoiditis  1  1/604 (0.17%)  0/507 (0.00%) 
General disorders     
Chest pain  1  2/604 (0.33%)  1/507 (0.20%) 
Device dislocation  1  1/604 (0.17%)  2/507 (0.39%) 
General physical health deterioration  1  1/604 (0.17%)  1/507 (0.20%) 
Pain  1  0/604 (0.00%)  1/507 (0.20%) 
Hepatobiliary disorders     
Cholecystitis  1  2/604 (0.33%)  0/507 (0.00%) 
Cholelithiasis  1  0/604 (0.00%)  1/507 (0.20%) 
Infections and infestations     
Pneumonia  1  4/604 (0.66%)  1/507 (0.20%) 
Urinary tract infection  1  4/604 (0.66%)  0/507 (0.00%) 
Lower respiratory tract infection  1  3/604 (0.50%)  0/507 (0.00%) 
Abscess limb  1  2/604 (0.33%)  0/507 (0.00%) 
Sepsis  1  2/604 (0.33%)  0/507 (0.00%) 
Arthritis bacterial  1  1/604 (0.17%)  0/507 (0.00%) 
Bronchitis  1  0/604 (0.00%)  1/507 (0.20%) 
Cellulitis  1  1/604 (0.17%)  0/507 (0.00%) 
Device related infection  1  0/604 (0.00%)  1/507 (0.20%) 
Diverticulitis  1  0/604 (0.00%)  1/507 (0.20%) 
Gastroenteritis  1  1/604 (0.17%)  0/507 (0.00%) 
Gastroenteritis viral  1  0/604 (0.00%)  1/507 (0.20%) 
Genital infection female  1  1/604 (0.17%)  0/507 (0.00%) 
Lower respiratory tract infection viral  1  0/604 (0.00%)  1/507 (0.20%) 
Lung infection  1  1/604 (0.17%)  0/507 (0.00%) 
Meningitis aseptic  1  1/604 (0.17%)  0/507 (0.00%) 
Pelvic abscess  1  1/604 (0.17%)  0/507 (0.00%) 
Pyelonephritis  1  0/604 (0.00%)  1/507 (0.20%) 
Septic Shock  1  0/604 (0.00%)  1/507 (0.20%) 
Skin infection  1  0/604 (0.00%)  1/507 (0.20%) 
Subcutaneous abscess  1  1/604 (0.17%)  0/507 (0.00%) 
Tooth abscess  1  1/604 (0.17%)  0/507 (0.00%) 
Injury, poisoning and procedural complications     
Head injury  1  1/604 (0.17%)  0/507 (0.00%) 
Hip fracture  1  1/604 (0.17%)  0/507 (0.00%) 
Joint dislocation  1  0/604 (0.00%)  1/507 (0.20%) 
Thoracic vertebral fracture  1  1/604 (0.17%)  0/507 (0.00%) 
Metabolism and nutrition disorders     
Gout  1  0/604 (0.00%)  1/507 (0.20%) 
Hyponatraemia  1  0/604 (0.00%)  1/507 (0.20%) 
Hypovolaemia  1  0/604 (0.00%)  1/507 (0.20%) 
Musculoskeletal and connective tissue disorders     
Rheumatoid arthritis  1  8/604 (1.32%)  8/507 (1.58%) 
Osteoarthritis  1  3/604 (0.50%)  5/507 (0.99%) 
Arthralgia  1  1/604 (0.17%)  3/507 (0.59%) 
Arthritis  1  1/604 (0.17%)  2/507 (0.39%) 
Foot deformity  1  1/604 (0.17%)  1/507 (0.20%) 
Rotator cuff syndrome  1  2/604 (0.33%)  0/507 (0.00%) 
Back pain  1  1/604 (0.17%)  0/507 (0.00%) 
Joint range of motion decreased  1  0/604 (0.00%)  1/507 (0.20%) 
Joint stiffness  1  0/604 (0.00%)  1/507 (0.20%) 
Joint swelling  1  1/604 (0.17%)  0/507 (0.00%) 
Musculoskeletal pain  1  1/604 (0.17%)  0/507 (0.00%) 
Osteonecrosis of jaw  1  1/604 (0.17%)  0/507 (0.00%) 
Osteoporosis  1  0/604 (0.00%)  1/507 (0.20%) 
Synovitis  1  1/604 (0.17%)  0/507 (0.00%) 
Tendon disorder  1  1/604 (0.17%)  0/507 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  2/604 (0.33%)  0/507 (0.00%) 
Squamous cell carcinoma of skin  1  0/604 (0.00%)  2/507 (0.39%) 
Laryngeal cancer recurrent  1  1/604 (0.17%)  0/507 (0.00%) 
Lung adenocarcinoma  1  0/604 (0.00%)  1/507 (0.20%) 
Lung neoplasm  1  0/604 (0.00%)  1/507 (0.20%) 
Lymphoma  1  0/604 (0.00%)  1/507 (0.20%) 
Non-Hodgkin's lymphoma  1  0/604 (0.00%)  1/507 (0.20%) 
Prostate cancer metastatic  1  1/604 (0.17%)  0/507 (0.00%) 
Renal cell carcinoma  1  0/604 (0.00%)  1/507 (0.20%) 
Renal neoplasm  1  0/604 (0.00%)  1/507 (0.20%) 
Nervous system disorders     
Sciatica  1  1/604 (0.17%)  1/507 (0.20%) 
Cerebrovascular accident  1  0/604 (0.00%)  1/507 (0.20%) 
Headache  1  0/604 (0.00%)  1/507 (0.20%) 
Quadriparesis  1  1/604 (0.17%)  0/507 (0.00%) 
Spinal cord compression  1  1/604 (0.17%)  0/507 (0.00%) 
Syncope  1  1/604 (0.17%)  0/507 (0.00%) 
Pregnancy, puerperium and perinatal conditions     
Pregnancy  1  2/604 (0.33%)  1/507 (0.20%) 
Psychiatric disorders     
Depression  1  0/604 (0.00%)  2/507 (0.39%) 
Completed suicide  1  0/604 (0.00%)  1/507 (0.20%) 
Renal and urinary disorders     
Nephrolithiasis  1  1/604 (0.17%)  0/507 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  2/604 (0.33%)  0/507 (0.00%) 
Asthma  1  1/604 (0.17%)  0/507 (0.00%) 
Chronic obstructive pulmonary disease  1  1/604 (0.17%)  0/507 (0.00%) 
Interstitial lung disease  1  1/604 (0.17%)  0/507 (0.00%) 
Lung disorder  1  0/604 (0.00%)  1/507 (0.20%) 
Pneumothorax  1  1/604 (0.17%)  0/507 (0.00%) 
Pulmonary embolism  1  1/604 (0.17%)  0/507 (0.00%) 
Pulmonary fibrosis  1  1/604 (0.17%)  0/507 (0.00%) 
Sleep apnoea syndrome  1  0/604 (0.00%)  1/507 (0.20%) 
Skin and subcutaneous tissue disorders     
Leukocytoclastic vasculitis  1  0/604 (0.00%)  1/507 (0.20%) 
Pruritus  1  1/604 (0.17%)  0/507 (0.00%) 
Swelling face  1  0/604 (0.00%)  1/507 (0.20%) 
Surgical and medical procedures     
Hip arthroplasty  1  2/604 (0.33%)  0/507 (0.00%) 
Abdominal hernia repair  1  1/604 (0.17%)  0/507 (0.00%) 
Hospitalisation  1  1/604 (0.17%)  0/507 (0.00%) 
Joint fluid drainage  1  1/604 (0.17%)  0/507 (0.00%) 
Urethral meatotomy  1  1/604 (0.17%)  0/507 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  0/604 (0.00%)  1/507 (0.20%) 
Hypotension  1  0/604 (0.00%)  1/507 (0.20%) 
Intermittent claudication  1  0/604 (0.00%)  1/507 (0.20%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Rituximab Alternative TNFi
Affected / at Risk (%) Affected / at Risk (%)
Total   79/604 (13.08%)   79/507 (15.58%) 
Gastrointestinal disorders     
Diarrhoea  1  5/604 (0.83%)  12/507 (2.37%) 
Nausea  1  12/604 (1.99%)  13/507 (2.56%) 
Infections and infestations     
Lower respiratory tract infection  1  14/604 (2.32%)  10/507 (1.97%) 
Urinary tract infection  1  25/604 (4.14%)  16/507 (3.16%) 
Nervous system disorders     
Headache  1  15/604 (2.48%)  15/507 (2.96%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  10/604 (1.66%)  14/507 (2.76%) 
Skin and subcutaneous tissue disorders     
Rash  1  8/604 (1.32%)  15/507 (2.96%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor’s intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Roche Trial Information Hotline
Organization: F. Hoffmann-La Roche AG
Phone: +41 61 6878333
EMail: global.trial_information@roche.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01557348     History of Changes
Other Study ID Numbers: MA22401
First Submitted: March 13, 2012
First Posted: March 19, 2012
Results First Submitted: November 28, 2016
Results First Posted: January 24, 2017
Last Update Posted: January 24, 2017