Extension Study to Assess the Efficacy and Safety of Repeat Treatment With Rituximab (MabThera) in Participants With Active Rheumatoid Arthritis (RA)
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT02093026
Collaborator
Genentech, Inc. (Industry)
465
92
1
124
5.1
0
Study Details
Study Description
Brief Summary
This study will assess the long-term safety and efficacy of repeat treatment courses of rituximab, in combination with methotrexate in a disease-modifying anti-rheumatic drug (DMARD) inadequate responder population of participants who were previously randomized into studies WA16291 (NCT02693210) or WA17043/U2644g (NCT00074438). The study permits multiple re-treatments until the protocol-defined end-of-treatment date (31 December 2011). Participants will then enter a safety follow-up (SFU) period of at least 48 weeks. This will provide at least 7 years follow-up data on all participants initially randomized into WA16291 or WA17043/U2644g. Approximately 600 participants will potentially be eligible to enter this open label extension study from their respective feeder studies.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
465 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label Study of the Efficacy and Safety of Re-treatments With Rituximab (MabThera®/Rituxan®) in Patients With Active Rheumatoid Arthritis
Study Start Date
:
Aug 1, 2002
Actual Primary Completion Date
:
Dec 1, 2012
Actual Study Completion Date
:
Dec 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Rituximab Participants will receive rituximab 1 gram intravenously (IV) on Days 1 and 15 of each course of retreatment. In addition, participants will receive methotrexate 10-25 milligrams per week (mg/week) orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid greater than or equal to (>=) 5 mg/week or equivalent. Participants will receive retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment will be based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab will be continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever is sooner. |
Drug: Rituximab
Participants will receive rituximab 1 gram IV on Days 1 and 15 of each course of retreatment.
Other Names:
Drug: Methotrexate
Participants will receive methotrexate 10-25 mg/week orally or parenterally.
Drug: Methylprednisolone
Participants will receive methylprednisolone 100 mg IV 30 minutes prior to each rituximab infusion.
Drug: Folic Acid
Participants will receive folic acid >= 5 mg/week or equivalent.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With an American College of Rheumatology 20 (ACR20) Response After First Course [24 weeks after first course of rituximab (up to approximately 26 weeks)]
A participant had an ACR20 response if there was at least a 20 percent (%) improvement, ie, reduction from Baseline, in tender joint count (TJC) and swollen joint count (SJC) (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [visual analog scale (VAS): 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either C-reactive protein [CRP] or erythrocyte sedimentation rate [ESR]). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
- Percentage of Participants With ACR20 Response After Second Course [24 weeks after second course of rituximab (median duration of 90.9 weeks)]
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
- Percentage of Participants With ACR20 Response After Third Course [24 weeks after third course of rituximab (median duration of 162.9 weeks)]
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
- Percentage of Participants With ACR20 Response After Fourth Course [24 weeks after fourth course of rituximab (median duration of 232 weeks)]
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
- Percentage of Participants With ACR20 Response After Fifth Course [24 weeks after fifth course of rituximab (median duration of 297.3 weeks)]
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
- Percentage of Participants With ACR20 Response After Sixth Course [24 weeks after sixth course of rituximab (median duration of 354.4 weeks)]
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
- Percentage of Participants With ACR20 Response After Seventh Course [24 weeks after seventh course of rituximab (median duration of 406.7 weeks)]
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Secondary Outcome Measures
- Percentage of Participants With ACR50 and ACR70 Response [24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)]
A participant had an ACR50 and ACR70 response if there was at least a 50% or 70% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of disease activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (CRP or ESR). The ACR50 and ACR70 responses were compared to Baseline in the precursor studies WA16291 or WA17043.
- American College of Rheumatology Index of Improvement (ACRn) Response [24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)]
The ACRn is calculated for each participant by taking the lowest percentage improvement in (1) SJC or (2) TJC or (3) the median of the remaining 5 components of the ACR response (patient's assessment of disease activity; patient's global assessment of pain; physician's assessment of disease activity; participant's assessment of physical function; an acute phase reactant value [either CRP or ESR]). The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA. ACRn scores were calculated considering the original baseline in the precursor studies WA16291 or WA17043.
- Percentage of Participants With Low Disease Activity and Clinical Remission Based on DAS28-ESR [24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)]
DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (millimeters per hour [mm/hour]), and Patient's Global Assessment of Disease Activity (VAS: 0=no disease activity to 100=maximum disease activity). DAS28-ESR = 0.56*square root (sqrt)(TJC28) + 0.28*sqrt(SJC28) + 0.70*natural logarithm (ln) (ESR) + 0.014*Patient's Global Assessment of Disease Activity. Total score range: 0-10, higher score=more disease activity. DAS28-ESR <= 3.2 implied low disease activity (LDA) and DAS28-ESR <2.6 = clinical remission.
- Percentage of Participants With European League Against Rheumatism (EULAR) Response of 'Good' or 'Moderate' [24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)]
DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and Physician's Global Assessment of Disease Activity (VAS: 0=no disease activity to 100=maximum disease activity). DAS28-ESR = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*ln(ESR) + 0.014*Patient's Global Assessment of Disease Activity. The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline greater than (>) 1.2 with a DAS28 score less than or equal to (≤) 3.2; moderate responders had a change from baseline >1.2 with a DAS28 score >3.2 to less than or equal to (≤) 5.1 or a change from baseline >0.6 to ≤1.2 with a DAS28 score ≤5.1.
- Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at 24 Weeks Following Each Course [24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)]
The HAQ-DI is a questionnaire specific for rheumatoid arthritis and consists of 20 questions referring to 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Participants completed the questionnaire by answering the 20 questions on a scale of 0 (without difficulty) to 3 (unable to do). The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement.
- Change From Baseline in Total Rheumatoid Factors (RF) at 24 Weeks Following Each Course [24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)]
- Percentage of Participants Who Discontinued Treatment Due to Insufficient Response [First, second, third, fourth, fifth, sixth, and seventh course of rituximab (up to a median of approximately 2, 62, 124, 186, 248, 310, and 372 weeks, respectively)]
- Time Since Last Treatment Course [Baseline up to 10 years]
Time since last treatment course = The last day of the last dose of rituximab to date of last contact. Date of last contact is the last available date of efficacy, complete medication start date, laboratory, adverse event assessments, early withdrawal visit, date of last contact, or date of death.
Eligibility Criteria
Criteria
Ages Eligible for Study:
21 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
participants with active RA
-
completed 24 weeks of treatment in WA16291 or WA17043
-
eligible for re-treatment, based on clinical symptoms (Disease Activity Score in 28 joints >=2.6)
-
females of childbearing potential using reliable contraception
Exclusion Criteria:
-
participants who participated in rituximab studies WA16291 or WA17043 but withdrew into the safety follow-up phases of these trials
-
previous rituximab non-responders
-
current treatment with any other disease-modifying drug (apart from methotrexate), or any anti-tumor necrosis factor alfa, anti-interleukin-1, or other biologic therapies
-
participants with known active infection of any kind
-
evidence of any new or uncontrolled concomitant disease or development of any new contraindications which would preclude repeat treatment with rituximab
-
history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
-
female participants who are pregnant or breastfeeding
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Birmingham | Alabama | United States | 35294 | |
| 2 | Peoria | Arizona | United States | 85381 | |
| 3 | Little Rock | Arkansas | United States | 72205 | |
| 4 | La Jolla | California | United States | 92037 | |
| 5 | Long Beach | California | United States | 92813 | |
| 6 | Rancho Mirage | California | United States | 92270 | |
| 7 | San Diego | California | United States | 92108 | |
| 8 | Colorado Springs | Colorado | United States | 80920 | |
| 9 | Aventura | Florida | United States | 33180 | |
| 10 | Boca Raton | Florida | United States | 33486 | |
| 11 | Fort Lauderdale | Florida | United States | 33334 | |
| 12 | Largo | Florida | United States | 33773 | |
| 13 | South Miami | Florida | United States | 33143 | |
| 14 | Boise | Idaho | United States | 83702 | |
| 15 | Chicago | Illinois | United States | 60611 | |
| 16 | Chicago | Illinois | United States | 60637 | |
| 17 | Indianapolis | Indiana | United States | 46202-5149 | |
| 18 | Indianapolis | Indiana | United States | 46260 | |
| 19 | Boston | Massachusetts | United States | 02215 | |
| 20 | Minneapolis | Minnesota | United States | 55416 | |
| 21 | Saint Louis | Missouri | United States | 63141 | |
| 22 | Lebanon | New Hampshire | United States | 03756 | |
| 23 | Voorhees | New Jersey | United States | 08043 | |
| 24 | Great Neck | New York | United States | 11021 | |
| 25 | Plainview | New York | United States | 11803 | |
| 26 | Rochester | New York | United States | 14618 | |
| 27 | Smithtown | New York | United States | 11787 | |
| 28 | Greenville | North Carolina | United States | 27834 | |
| 29 | Winston Salem | North Carolina | United States | 27157 | |
| 30 | Beachwood | Ohio | United States | 44122 | |
| 31 | Dayton | Ohio | United States | 45402 | |
| 32 | Mayfield | Ohio | United States | 44143 | |
| 33 | Tulsa | Oklahoma | United States | 74104 | |
| 34 | Tulsa | Oklahoma | United States | 74135 | |
| 35 | Portland | Oregon | United States | 97239 | |
| 36 | Duncansville | Pennsylvania | United States | 16635 | |
| 37 | Dallas | Texas | United States | 75231 | |
| 38 | Houston | Texas | United States | 77074 | |
| 39 | Salt Lake City | Utah | United States | 84132 | |
| 40 | Seattle | Washington | United States | 98104 | |
| 41 | Glendale | Wisconsin | United States | 53217 | |
| 42 | Wausau | Wisconsin | United States | 54401 | |
| 43 | Maroochydore | Queensland | Australia | 4558 | |
| 44 | Melbourne | Victoria | Australia | 3168 | |
| 45 | Perth | Western Australia | Australia | 6979 | |
| 46 | Gent | Belgium | 9000 | ||
| 47 | Curtiba | PR | Brazil | 80030-110 | |
| 48 | Campinas | SP | Brazil | 13083-888 | |
| 49 | Sao Paulo | SP | Brazil | 04026-000 | |
| 50 | Calgary | Alberta | Canada | T2N 4Z6 | |
| 51 | Vancouver | British Columbia | Canada | V5Z 1L7 | |
| 52 | St John's | Newfoundland and Labrador | Canada | A1A 5E8 | |
| 53 | London | Ontario | Canada | N6A 4V2 | |
| 54 | Praha | Czech Republic | 128 50 | ||
| 55 | Heinola | Finland | 18120 | ||
| 56 | Helsinki | Finland | 00290 | ||
| 57 | Köln | Germany | 50924 | ||
| 58 | Leipzig | Germany | 04103 | ||
| 59 | Ratingen | Germany | 40882 | ||
| 60 | Regensburg | Germany | 93053 | ||
| 61 | Wuerzburg | Germany | 97080 | ||
| 62 | Haifa | Israel | 3109601 | ||
| 63 | Haifa | Israel | 3339419 | ||
| 64 | Modena | Emilia-Romagna | Italy | 41100 | |
| 65 | Udine | Friuli-Venezia Giulia | Italy | 33100 | |
| 66 | Genova | Liguria | Italy | 16132 | |
| 67 | Milano | Lombardia | Italy | 20157 | |
| 68 | Mexico City | Mexico | 06726 | ||
| 69 | Mexico City | Mexico | 10700 | ||
| 70 | Mexico | Mexico | 44620 | ||
| 71 | Monterrey | Mexico | 64460 | ||
| 72 | Auckland City | New Zealand | 0620 | ||
| 73 | Auckland | New Zealand | 2025 | ||
| 74 | Bialystok | Poland | 15-351 | ||
| 75 | Lublin | Poland | 20-022 | ||
| 76 | Poznan | Poland | 61-545 | ||
| 77 | Warszawa | Poland | 02-637 | ||
| 78 | Wroclaw | Poland | 50-556 | ||
| 79 | Merida | Badajoz | Spain | 06800 | |
| 80 | Santiago de Compostela | La Coruña | Spain | 15706 | |
| 81 | La Laguna | Tenerife | Spain | 38320 | |
| 82 | Madrid | Spain | 28006 | ||
| 83 | Madrid | Spain | 28007 | ||
| 84 | Madrid | Spain | 28046 | ||
| 85 | Sevilla | Spain | 41014 | ||
| 86 | Göteborg | Sweden | 413 45 | ||
| 87 | Stockholm | Sweden | 171 76 | ||
| 88 | Birmingham | United Kingdom | B29 6JD | ||
| 89 | Cambridge | United Kingdom | CB2 2QQ | ||
| 90 | Cannock | United Kingdom | WS11 5XY | ||
| 91 | Leeds | United Kingdom | LS7 4SA | ||
| 92 | Stoke-on-trent | United Kingdom | ST6 7AG |
Sponsors and Collaborators
- Hoffmann-La Roche
- Genentech, Inc.
Investigators
- Study Chair: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02093026
Other Study ID Numbers:
- WA16855
- U2653g
First Posted:
Mar 20, 2014
Last Update Posted:
Mar 13, 2017
Last Verified:
Jan 1, 2017
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This study included participants who had previously participated in studies WA16291 (NCT02693210) or WA17043 (NCT00074438). |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Rituximab |
|---|---|
| Arm/Group Description | Participants received rituximab 1 gram intravenously (IV) on Days 1 and 15 of each course of retreatment. In addition, participants received methotrexate 10-25 milligrams per week (mg/week) orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid greater than or equal to (>=) 5 mg/week or equivalent. Participants received retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment was based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab was continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever occurred earlier. |
| Period Title: Overall Study | |
| STARTED | 465 |
| COMPLETED | 272 |
| NOT COMPLETED | 193 |
Baseline Characteristics
| Arm/Group Title | Rituximab |
|---|---|
| Arm/Group Description | Participants received rituximab 1 gram IV on Days 1 and 15 of each course of retreatment. In addition, participants received methotrexate 10-25 mg/week orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid >=5 mg/week or equivalent. Participants received retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment was based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab was continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever occurred earlier. |
| Overall Participants | 465 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
51
(12.01)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
364
78.3%
|
| Male |
101
21.7%
|
Outcome Measures
| Title | Percentage of Participants With an American College of Rheumatology 20 (ACR20) Response After First Course |
|---|---|
| Description | A participant had an ACR20 response if there was at least a 20 percent (%) improvement, ie, reduction from Baseline, in tender joint count (TJC) and swollen joint count (SJC) (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [visual analog scale (VAS): 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either C-reactive protein [CRP] or erythrocyte sedimentation rate [ESR]). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043. |
| Time Frame | 24 weeks after first course of rituximab (up to approximately 26 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat (ITT) Population included all participants who received any part of an infusion of study medication under Study WA16855. Here, number of participants analyzed = participants who were evaluable for this outcome. |
| Arm/Group Title | Rituximab |
|---|---|
| Arm/Group Description | Participants received rituximab 1 gram IV on Days 1 and 15 of each course of retreatment. In addition, participants received methotrexate 10-25 mg/week orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid >=5 mg/week or equivalent. Participants received retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment was based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab was continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever occurred earlier. |
| Measure Participants | 447 |
| Number [percentage of participants] |
67.1
14.4%
|
| Title | Percentage of Participants With ACR20 Response After Second Course |
|---|---|
| Description | A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043. |
| Time Frame | 24 weeks after second course of rituximab (median duration of 90.9 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Here, number of participants analyzed = participants who were evaluable for this outcome. |
| Arm/Group Title | Rituximab |
|---|---|
| Arm/Group Description | Participants received rituximab 1 gram IV on Days 1 and 15 of each course of retreatment. In addition, participants received methotrexate 10-25 mg/week orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid >=5 mg/week or equivalent. Participants received retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment was based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab was continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever occurred earlier. |
| Measure Participants | 384 |
| Number [percentage of participants] |
70.8
15.2%
|
| Title | Percentage of Participants With ACR20 Response After Third Course |
|---|---|
| Description | A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043. |
| Time Frame | 24 weeks after third course of rituximab (median duration of 162.9 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Here, number of participants analyzed = participants who were evaluable for this outcome. |
| Arm/Group Title | Rituximab |
|---|---|
| Arm/Group Description | Participants received rituximab 1 gram IV on Days 1 and 15 of each course of retreatment. In addition, participants received methotrexate 10-25 mg/week orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid >=5 mg/week or equivalent. Participants received retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment was based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab was continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever occurred earlier. |
| Measure Participants | 310 |
| Number [percentage of participants] |
73.2
15.7%
|
| Title | Percentage of Participants With ACR20 Response After Fourth Course |
|---|---|
| Description | A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043. |
| Time Frame | 24 weeks after fourth course of rituximab (median duration of 232 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Here, number of participants analyzed = participants who were evaluable for this outcome. |
| Arm/Group Title | Rituximab |
|---|---|
| Arm/Group Description | Participants received rituximab 1 gram IV on Days 1 and 15 of each course of retreatment. In addition, participants received methotrexate 10-25 mg/week orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid >=5 mg/week or equivalent. Participants received retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment was based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab was continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever occurred earlier. |
| Measure Participants | 245 |
| Number [percentage of participants] |
75.1
16.2%
|
| Title | Percentage of Participants With ACR20 Response After Fifth Course |
|---|---|
| Description | A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043. |
| Time Frame | 24 weeks after fifth course of rituximab (median duration of 297.3 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Here, number of participants analyzed = participants who were evaluable for this outcome. |
| Arm/Group Title | Rituximab |
|---|---|
| Arm/Group Description | Participants received rituximab 1 gram IV on Days 1 and 15 of each course of retreatment. In addition, participants received methotrexate 10-25 mg/week orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid >=5 mg/week or equivalent. Participants received retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment was based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab was continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever occurred earlier. |
| Measure Participants | 175 |
| Number [percentage of participants] |
69.7
15%
|
| Title | Percentage of Participants With ACR20 Response After Sixth Course |
|---|---|
| Description | A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043. |
| Time Frame | 24 weeks after sixth course of rituximab (median duration of 354.4 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Here, number of participants analyzed = participants who were evaluable for this outcome. |
| Arm/Group Title | Rituximab |
|---|---|
| Arm/Group Description | Participants received rituximab 1 gram IV on Days 1 and 15 of each course of retreatment. In addition, participants received methotrexate 10-25 mg/week orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid >=5 mg/week or equivalent. Participants received retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment was based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab was continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever occurred earlier. |
| Measure Participants | 110 |
| Number [percentage of participants] |
68.2
14.7%
|
| Title | Percentage of Participants With ACR20 Response After Seventh Course |
|---|---|
| Description | A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043. |
| Time Frame | 24 weeks after seventh course of rituximab (median duration of 406.7 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Here, number of participants analyzed = participants who were evaluable for this outcome. |
| Arm/Group Title | Rituximab |
|---|---|
| Arm/Group Description | Participants received rituximab 1 gram IV on Days 1 and 15 of each course of retreatment. In addition, participants received methotrexate 10-25 mg/week orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid >=5 mg/week or equivalent. Participants received retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment was based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab was continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever occurred earlier. |
| Measure Participants | 74 |
| Number [percentage of participants] |
59.5
12.8%
|
| Title | Percentage of Participants With ACR50 and ACR70 Response |
|---|---|
| Description | A participant had an ACR50 and ACR70 response if there was at least a 50% or 70% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of disease activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (CRP or ESR). The ACR50 and ACR70 responses were compared to Baseline in the precursor studies WA16291 or WA17043. |
| Time Frame | 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Here, number of participants analyzed = participants who were evaluable for this outcome. Number analyzed = participants who were evaluable for specified category. |
| Arm/Group Title | Rituximab |
|---|---|
| Arm/Group Description | Participants received rituximab 1 gram IV on Days 1 and 15 of each course of retreatment. In addition, participants received methotrexate 10-25 mg/week orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid >=5 mg/week or equivalent. Participants received retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment was based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab was continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever occurred earlier. |
| Measure Participants | 447 |
| ACR50: 24 weeks after first course |
39.4
8.5%
|
| ACR50: 24 weeks after second course |
41.9
9%
|
| ACR50: 24 weeks after third course |
44.8
9.6%
|
| ACR50: 24 weeks after fourth course |
46.9
10.1%
|
| ACR50: 24 weeks after fifth course |
40.0
8.6%
|
| ACR50: 24 weeks after sixth course |
40.0
8.6%
|
| ACR50: 24 weeks after seventh course |
36.5
7.8%
|
| ACR70: 24 weeks after first course |
16.3
3.5%
|
| ACR70: 24 weeks after second course |
21.6
4.6%
|
| ACR70: 24 weeks after third course |
20.0
4.3%
|
| ACR70: 24 weeks after fourth course |
20.0
4.3%
|
| ACR70: 24 weeks after fifth course |
18.9
4.1%
|
| ACR70: 24 weeks after sixth course |
20.9
4.5%
|
| ACR70: 24 weeks after seventh course |
18.9
4.1%
|
| Title | American College of Rheumatology Index of Improvement (ACRn) Response |
|---|---|
| Description | The ACRn is calculated for each participant by taking the lowest percentage improvement in (1) SJC or (2) TJC or (3) the median of the remaining 5 components of the ACR response (patient's assessment of disease activity; patient's global assessment of pain; physician's assessment of disease activity; participant's assessment of physical function; an acute phase reactant value [either CRP or ESR]). The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA. ACRn scores were calculated considering the original baseline in the precursor studies WA16291 or WA17043. |
| Time Frame | 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Here, number of participants analyzed = participants who were evaluable for this outcome. Number analyzed = participants who were evaluable for specified category. |
| Arm/Group Title | Rituximab |
|---|---|
| Arm/Group Description | Participants received rituximab 1 gram IV on Days 1 and 15 of each course of retreatment. In addition, participants received methotrexate 10-25 mg/week orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid >=5 mg/week or equivalent. Participants received retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment was based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab was continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever occurred earlier. |
| Measure Participants | 447 |
| 24 weeks after first course |
31.07
(50.188)
|
| 24 weeks after second course |
34.15
(58.769)
|
| 24 weeks after third course |
36.93
(44.912)
|
| 24 weeks after fourth course |
39.59
(39.393)
|
| 24 weeks after fifth course |
33.76
(48.309)
|
| 24 weeks after sixth course |
29.74
(57.197)
|
| 24 weeks after seventh course |
24.87
(51.336)
|
| Title | Percentage of Participants With Low Disease Activity and Clinical Remission Based on DAS28-ESR |
|---|---|
| Description | DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (millimeters per hour [mm/hour]), and Patient's Global Assessment of Disease Activity (VAS: 0=no disease activity to 100=maximum disease activity). DAS28-ESR = 0.56*square root (sqrt)(TJC28) + 0.28*sqrt(SJC28) + 0.70*natural logarithm (ln) (ESR) + 0.014*Patient's Global Assessment of Disease Activity. Total score range: 0-10, higher score=more disease activity. DAS28-ESR <= 3.2 implied low disease activity (LDA) and DAS28-ESR <2.6 = clinical remission. |
| Time Frame | 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Here, number of participants analyzed = participants who were evaluable for this outcome. Number analyzed = participants who were evaluable for specified category. |
| Arm/Group Title | Rituximab |
|---|---|
| Arm/Group Description | Participants received rituximab 1 gram IV on Days 1 and 15 of each course of retreatment. In addition, participants received methotrexate 10-25 mg/week orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid >=5 mg/week or equivalent. Participants received retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment was based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab was continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever occurred earlier. |
| Measure Participants | 441 |
| LDA: 24 weeks after first course |
24.3
5.2%
|
| LDA: 24 weeks after second course |
30.1
6.5%
|
| LDA: 24 weeks after third course |
29.3
6.3%
|
| LDA: 24 weeks after fourth course |
28.0
6%
|
| LDA: 24 weeks after fifth course |
23.8
5.1%
|
| LDA: 24 weeks after sixth course |
27.3
5.9%
|
| LDA: 24 weeks after seventh course |
24.7
5.3%
|
| Remission: 24 weeks after first course |
11.3
2.4%
|
| Remission: 24 weeks after second course |
16.8
3.6%
|
| Remission: 24 weeks after third course |
17.1
3.7%
|
| Remission: 24 weeks after fourth course |
15.7
3.4%
|
| Remission: 24 weeks after fifth course |
15.7
3.4%
|
| Remission: 24 weeks after sixth course |
17.3
3.7%
|
| Remission: 24 weeks after seventh course |
13.7
2.9%
|
| Title | Percentage of Participants With European League Against Rheumatism (EULAR) Response of 'Good' or 'Moderate' |
|---|---|
| Description | DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and Physician's Global Assessment of Disease Activity (VAS: 0=no disease activity to 100=maximum disease activity). DAS28-ESR = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*ln(ESR) + 0.014*Patient's Global Assessment of Disease Activity. The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline greater than (>) 1.2 with a DAS28 score less than or equal to (≤) 3.2; moderate responders had a change from baseline >1.2 with a DAS28 score >3.2 to less than or equal to (≤) 5.1 or a change from baseline >0.6 to ≤1.2 with a DAS28 score ≤5.1. |
| Time Frame | 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Here, number of participants analyzed = participants who were evaluable for this outcome. Number analyzed = participants who were evaluable for specified category. |
| Arm/Group Title | Rituximab |
|---|---|
| Arm/Group Description | Participants received rituximab 1 gram IV on Days 1 and 15 of each course of retreatment. In addition, participants received methotrexate 10-25 mg/week orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid >=5 mg/week or equivalent. Participants received retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment was based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab was continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever occurred earlier. |
| Measure Participants | 436 |
| Moderate: 24 weeks after first course |
57.8
12.4%
|
| Moderate: 24 weeks after second course |
58.5
12.6%
|
| Moderate: 24 weeks after third course |
59.5
12.8%
|
| Moderate: 24 weeks after fourth course |
60.9
13.1%
|
| Moderate: 24 weeks after fifth course |
62.1
13.4%
|
| Moderate: 24 weeks after sixth course |
57.0
12.3%
|
| Moderate: 24 weeks after seventh course |
60.0
12.9%
|
| Good: 24 weeks after first course |
24.3
5.2%
|
| Good: 24 weeks after second course |
30.4
6.5%
|
| Good: 24 weeks after third course |
29.1
6.3%
|
| Good: 24 weeks after fourth course |
27.9
6%
|
| Good: 24 weeks after fifth course |
24.3
5.2%
|
| Good: 24 weeks after sixth course |
27.1
5.8%
|
| Good: 24 weeks after seventh course |
25.7
5.5%
|
| Title | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at 24 Weeks Following Each Course |
|---|---|
| Description | The HAQ-DI is a questionnaire specific for rheumatoid arthritis and consists of 20 questions referring to 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Participants completed the questionnaire by answering the 20 questions on a scale of 0 (without difficulty) to 3 (unable to do). The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement. |
| Time Frame | 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Here, number of participants analyzed = participants who were evaluable for this outcome. Number analyzed = participants who were evaluable for specified category. |
| Arm/Group Title | Rituximab |
|---|---|
| Arm/Group Description | Participants received rituximab 1 gram IV on Days 1 and 15 of each course of retreatment. In addition, participants received methotrexate 10-25 mg/week orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid >=5 mg/week or equivalent. Participants received retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment was based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab was continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever occurred earlier. |
| Measure Participants | 447 |
| 24 weeks after first course |
-0.51
(0.555)
|
| 24 weeks after second course |
-0.48
(0.556)
|
| 24 weeks after third course |
-0.43
(0.532)
|
| 24 weeks after fourth course |
-0.47
(0.529)
|
| 24 weeks after fifth course |
-0.44
(0.541)
|
| 24 weeks after sixth course |
-0.38
(0.600)
|
| 24 weeks after seventh course |
-0.37
(0.576)
|
| Title | Change From Baseline in Total Rheumatoid Factors (RF) at 24 Weeks Following Each Course |
|---|---|
| Description | |
| Time Frame | 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The data for this outcome measure was not analyzed as this outcome was removed per changes in the planned analysis. Per changes in the planned analysis, only key efficacy parameters were analyzed as the long-term efficacy of rituximab is well established. |
| Arm/Group Title | Rituximab |
|---|---|
| Arm/Group Description | Participants received rituximab 1 gram IV on Days 1 and 15 of each course of retreatment. In addition, participants received methotrexate 10-25 mg/week orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid >=5 mg/week or equivalent. Participants received retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment was based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab was continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever occurred earlier. |
| Measure Participants | 0 |
| Title | Percentage of Participants Who Discontinued Treatment Due to Insufficient Response |
|---|---|
| Description | |
| Time Frame | First, second, third, fourth, fifth, sixth, and seventh course of rituximab (up to a median of approximately 2, 62, 124, 186, 248, 310, and 372 weeks, respectively) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. Number analyzed = participants who were evaluable for specified category. |
| Arm/Group Title | Rituximab |
|---|---|
| Arm/Group Description | Participants received rituximab 1 gram IV on Days 1 and 15 of each course of retreatment. In addition, participants received methotrexate 10-25 mg/week orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid >=5 mg/week or equivalent. Participants received retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment was based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab was continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever occurred earlier. |
| Measure Participants | 465 |
| First course |
1.1
0.2%
|
| Second course |
2.3
0.5%
|
| Third course |
2.0
0.4%
|
| Fourth course |
2.0
0.4%
|
| Fifth course |
0.8
0.2%
|
| Sixth course |
0.0
0%
|
| Seventh course |
0.6
0.1%
|
| Title | Time Since Last Treatment Course |
|---|---|
| Description | Time since last treatment course = The last day of the last dose of rituximab to date of last contact. Date of last contact is the last available date of efficacy, complete medication start date, laboratory, adverse event assessments, early withdrawal visit, date of last contact, or date of death. |
| Time Frame | Baseline up to 10 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Here, number of participants analyzed = participants who entered into safety follow-up. |
| Arm/Group Title | Rituximab |
|---|---|
| Arm/Group Description | Participants received rituximab 1 gram IV on Days 1 and 15 of each course of retreatment. In addition, participants received methotrexate 10-25 mg/week orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid >=5 mg/week or equivalent. Participants received retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment was based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab was continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever occurred earlier. |
| Measure Participants | 31 |
| Mean (Standard Deviation) [years] |
4.21
(2.234)
|
Adverse Events
| Time Frame | Baseline up to approximately 11 years | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The rituximab treatment group includes all data beginning with the first treatment with rituximab (either in Study WA17043 or Study WA16291 or Study WA16855). Participants who received placebo are included in the rituximab treatment group from the time they received their first course of rituximab. | |||
| Arm/Group Title | Rituximab | Placebo | ||
| Arm/Group Description | Participants received rituximab 1 gram IV on Days 1 and 15 of each course of retreatment. In addition, participants received methotrexate 10-25 mg/week orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid >=5 mg/week or equivalent. Participants received retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment was based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab was continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever occurred earlier. | Data for participants who received placebo in Study WA17043 or WA16291 are included in this reporting group for data collected until they received their first dose of rituximab in this study (Study WA16855). Data from these participants collected after the first dose of rituximab are included in the rituximab reporting group. | ||
All Cause Mortality |
||||
| Rituximab | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Rituximab | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 230/465 (49.5%) | 12/127 (9.4%) | ||
| Blood and lymphatic system disorders | ||||
| Neutropenia | 3/465 (0.6%) | 0/127 (0%) | ||
| Anaemia | 1/465 (0.2%) | 0/127 (0%) | ||
| Anaemia macrocytic | 1/465 (0.2%) | 0/127 (0%) | ||
| Anaemia megaloblastic | 1/465 (0.2%) | 0/127 (0%) | ||
| Febrile neutropenia | 1/465 (0.2%) | 0/127 (0%) | ||
| Iron deficiency anaemia | 1/465 (0.2%) | 0/127 (0%) | ||
| Microcytic anaemia | 1/465 (0.2%) | 0/127 (0%) | ||
| Pancytopenia | 1/465 (0.2%) | 0/127 (0%) | ||
| Cardiac disorders | ||||
| Myocardial infarction | 9/465 (1.9%) | 0/127 (0%) | ||
| Coronary artery disease | 5/465 (1.1%) | 0/127 (0%) | ||
| Myocardial ischaemia | 4/465 (0.9%) | 0/127 (0%) | ||
| Atrial fibrillation | 3/465 (0.6%) | 0/127 (0%) | ||
| Cardiac failure congestive | 3/465 (0.6%) | 0/127 (0%) | ||
| Angina pectoris | 2/465 (0.4%) | 0/127 (0%) | ||
| Cardiac arrest | 2/465 (0.4%) | 0/127 (0%) | ||
| Pericarditis | 2/465 (0.4%) | 0/127 (0%) | ||
| Acute coronary syndrome | 1/465 (0.2%) | 0/127 (0%) | ||
| Acute myocardial infaction | 1/465 (0.2%) | 0/127 (0%) | ||
| Angina unstable | 1/465 (0.2%) | 0/127 (0%) | ||
| Aortic valve incompetence | 1/465 (0.2%) | 0/127 (0%) | ||
| Arrhythmia | 1/465 (0.2%) | 0/127 (0%) | ||
| Atrial flutter | 1/465 (0.2%) | 0/127 (0%) | ||
| Cardiac failure | 1/465 (0.2%) | 0/127 (0%) | ||
| Cardiac failure chronic | 1/465 (0.2%) | 0/127 (0%) | ||
| Heart valve incompetence | 1/465 (0.2%) | 0/127 (0%) | ||
| Myocarditis | 1/465 (0.2%) | 0/127 (0%) | ||
| Stress cardiomyopathy | 1/465 (0.2%) | 0/127 (0%) | ||
| Ventricular extrasystoles | 1/465 (0.2%) | 0/127 (0%) | ||
| Congenital, familial and genetic disorders | ||||
| Cerebrovascular arteriovenous malformation | 1/465 (0.2%) | 0/127 (0%) | ||
| Mesonephric duct cyst | 1/465 (0.2%) | 0/127 (0%) | ||
| Ear and labyrinth disorders | ||||
| Vertigo | 1/465 (0.2%) | 0/127 (0%) | ||
| Vertigo positional | 1/465 (0.2%) | 0/127 (0%) | ||
| Endocrine disorders | ||||
| Basedow's disease | 0/465 (0%) | 1/127 (0.8%) | ||
| Goitre | 1/465 (0.2%) | 0/127 (0%) | ||
| Eye disorders | ||||
| Cataract | 1/465 (0.2%) | 0/127 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal hernia obstructive | 1/465 (0.2%) | 0/127 (0%) | ||
| Colitis ischaemic | 1/465 (0.2%) | 0/127 (0%) | ||
| Colitis ulcerative | 1/465 (0.2%) | 0/127 (0%) | ||
| Constipation | 1/465 (0.2%) | 0/127 (0%) | ||
| Diarrhoea | 1/465 (0.2%) | 0/127 (0%) | ||
| Duodenal ulcer | 1/465 (0.2%) | 0/127 (0%) | ||
| Duodenal ulcer haemorrhage | 1/465 (0.2%) | 0/127 (0%) | ||
| Enterocutaneous fistula | 1/465 (0.2%) | 0/127 (0%) | ||
| Gastritis | 1/465 (0.2%) | 0/127 (0%) | ||
| Gastrointestinal haemorrhage | 1/465 (0.2%) | 0/127 (0%) | ||
| Ileus | 1/465 (0.2%) | 0/127 (0%) | ||
| Inguinal hernia | 1/465 (0.2%) | 0/127 (0%) | ||
| Intestinal obstruction | 1/465 (0.2%) | 0/127 (0%) | ||
| Large intestine perforation | 1/465 (0.2%) | 0/127 (0%) | ||
| Melaena | 1/465 (0.2%) | 0/127 (0%) | ||
| Pancreatitis acute | 1/465 (0.2%) | 0/127 (0%) | ||
| Umbilical hernia obstructive | 1/465 (0.2%) | 0/127 (0%) | ||
| Upper gastrointestinal haemorrhage | 1/465 (0.2%) | 0/127 (0%) | ||
| Vomiting | 1/465 (0.2%) | 0/127 (0%) | ||
| General disorders | ||||
| Device dislocation | 6/465 (1.3%) | 0/127 (0%) | ||
| Chest pain | 4/465 (0.9%) | 0/127 (0%) | ||
| Infusion related reaction | 2/465 (0.4%) | 0/127 (0%) | ||
| Catheter site haemorrhage | 0/465 (0%) | 1/127 (0.8%) | ||
| Death | 1/465 (0.2%) | 0/127 (0%) | ||
| Device failure | 1/465 (0.2%) | 0/127 (0%) | ||
| Drug interaction | 1/465 (0.2%) | 0/127 (0%) | ||
| Pyrexia | 1/465 (0.2%) | 0/127 (0%) | ||
| Systemic inflammatory response syndrome | 1/465 (0.2%) | 0/127 (0%) | ||
| Hepatobiliary disorders | ||||
| Cholelithiasis | 3/465 (0.6%) | 1/127 (0.8%) | ||
| Cholecystitis | 2/465 (0.4%) | 0/127 (0%) | ||
| Bile duct stone | 1/465 (0.2%) | 0/127 (0%) | ||
| Biliary colic | 1/465 (0.2%) | 0/127 (0%) | ||
| Fatty liver alcoholic | 1/465 (0.2%) | 0/127 (0%) | ||
| Hepatotoxicity | 1/465 (0.2%) | 0/127 (0%) | ||
| Immune system disorders | ||||
| Drug hypersensitivity | 1/465 (0.2%) | 0/127 (0%) | ||
| Infections and infestations | ||||
| Pneumonia | 13/465 (2.8%) | 1/127 (0.8%) | ||
| Urinary tract infection | 7/465 (1.5%) | 0/127 (0%) | ||
| Lower respiratory tract infection | 6/465 (1.3%) | 0/127 (0%) | ||
| Cellulitis | 5/465 (1.1%) | 0/127 (0%) | ||
| Bronchopneumonia | 4/465 (0.9%) | 0/127 (0%) | ||
| Gastroenteritis | 4/465 (0.9%) | 0/127 (0%) | ||
| Respiratory tract infection | 3/465 (0.6%) | 1/127 (0.8%) | ||
| Bronchitis | 3/465 (0.6%) | 0/127 (0%) | ||
| Urosepsis | 3/465 (0.6%) | 0/127 (0%) | ||
| Appendicitis | 2/465 (0.4%) | 0/127 (0%) | ||
| Arthritis bacterial | 2/465 (0.4%) | 0/127 (0%) | ||
| Diverticulitis | 2/465 (0.4%) | 0/127 (0%) | ||
| Herpes simplex | 2/465 (0.4%) | 0/127 (0%) | ||
| Pseudomembranous colitis | 2/465 (0.4%) | 0/127 (0%) | ||
| Pyelonephritis | 2/465 (0.4%) | 0/127 (0%) | ||
| Pyelonephritis acute | 2/465 (0.4%) | 0/127 (0%) | ||
| Septic shock | 2/465 (0.4%) | 0/127 (0%) | ||
| Abscess bacterial | 0/465 (0%) | 1/127 (0.8%) | ||
| Appendicitis perforated | 1/465 (0.2%) | 0/127 (0%) | ||
| Arthritis infective | 1/465 (0.2%) | 0/127 (0%) | ||
| Atypical pneumonia | 1/465 (0.2%) | 0/127 (0%) | ||
| Bursitis infective | 1/465 (0.2%) | 0/127 (0%) | ||
| Clostridium difficile colitis | 1/465 (0.2%) | 0/127 (0%) | ||
| Clostridium difficile infection | 1/465 (0.2%) | 0/127 (0%) | ||
| Clostridium difficile sepsis | 1/465 (0.2%) | 0/127 (0%) | ||
| Empyema | 1/465 (0.2%) | 0/127 (0%) | ||
| Epiglottitis | 1/465 (0.2%) | 0/127 (0%) | ||
| Gastroenteritis escherichia coli | 1/465 (0.2%) | 0/127 (0%) | ||
| Gastroenteritis salmonella | 1/465 (0.2%) | 0/127 (0%) | ||
| Herpes zoster | 1/465 (0.2%) | 0/127 (0%) | ||
| Infection | 1/465 (0.2%) | 0/127 (0%) | ||
| Kidney infection | 1/465 (0.2%) | 0/127 (0%) | ||
| Laryngitis | 1/465 (0.2%) | 0/127 (0%) | ||
| Lobar pneumonia | 1/465 (0.2%) | 0/127 (0%) | ||
| Localised infection | 1/465 (0.2%) | 0/127 (0%) | ||
| Otitis media | 1/465 (0.2%) | 0/127 (0%) | ||
| Pharyngitis | 1/465 (0.2%) | 0/127 (0%) | ||
| Pharyngotonsillitis | 1/465 (0.2%) | 0/127 (0%) | ||
| Postopeative wound infection | 1/465 (0.2%) | 0/127 (0%) | ||
| Sepsis | 1/465 (0.2%) | 0/127 (0%) | ||
| Sinusitis | 1/465 (0.2%) | 0/127 (0%) | ||
| Staphylococcal skin infection | 1/465 (0.2%) | 0/127 (0%) | ||
| Upper respiratory tract infection | 1/465 (0.2%) | 0/127 (0%) | ||
| Urinary tract infection styphlococcal | 1/465 (0.2%) | 0/127 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Fall | 19/465 (4.1%) | 0/127 (0%) | ||
| Tendon rupture | 4/465 (0.9%) | 0/127 (0%) | ||
| Accident | 3/465 (0.6%) | 0/127 (0%) | ||
| Femoral neck fracture | 3/465 (0.6%) | 0/127 (0%) | ||
| Road traffic accident | 3/465 (0.6%) | 0/127 (0%) | ||
| Femure fracture | 2/465 (0.4%) | 0/127 (0%) | ||
| Hip fracture | 2/465 (0.4%) | 0/127 (0%) | ||
| Alcohol poisoning | 1/465 (0.2%) | 0/127 (0%) | ||
| Chest injury | 1/465 (0.2%) | 0/127 (0%) | ||
| Eye injury | 1/465 (0.2%) | 0/127 (0%) | ||
| Gastroenteritis radiation | 1/465 (0.2%) | 0/127 (0%) | ||
| Incisional hernia | 1/465 (0.2%) | 0/127 (0%) | ||
| Lower limb fracture | 1/465 (0.2%) | 0/127 (0%) | ||
| Lumbar vertebral fracture | 1/465 (0.2%) | 0/127 (0%) | ||
| Muscle strain | 1/465 (0.2%) | 0/127 (0%) | ||
| Periprosthetic fracture | 1/465 (0.2%) | 0/127 (0%) | ||
| Post procedural complication | 1/465 (0.2%) | 0/127 (0%) | ||
| Radius fracture | 0/465 (0%) | 1/127 (0.8%) | ||
| Spinal fracture | 1/465 (0.2%) | 0/127 (0%) | ||
| Toxicity to various agents | 1/465 (0.2%) | 0/127 (0%) | ||
| Wound | 1/465 (0.2%) | 0/127 (0%) | ||
| Procedural complication | 1/465 (0.2%) | 0/127 (0%) | ||
| Investigations | ||||
| Weight decreased | 0/465 (0%) | 1/127 (0.8%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 1/465 (0.2%) | 0/127 (0%) | ||
| Diabetes mellitus | 1/465 (0.2%) | 0/127 (0%) | ||
| Electrolyte imbalance | 1/465 (0.2%) | 0/127 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Rheumatoid arthritis | 19/465 (4.1%) | 1/127 (0.8%) | ||
| Osteoarthritis | 12/465 (2.6%) | 0/127 (0%) | ||
| Joint destruction | 6/465 (1.3%) | 0/127 (0%) | ||
| Arthralgia | 3/465 (0.6%) | 0/127 (0%) | ||
| Arthritis | 3/465 (0.6%) | 0/127 (0%) | ||
| Spinal osteoarthritis | 3/465 (0.6%) | 0/127 (0%) | ||
| Back pain | 1/465 (0.2%) | 1/127 (0.8%) | ||
| Intervertebral disc protrusion | 2/465 (0.4%) | 0/127 (0%) | ||
| Osteonecrosis | 2/465 (0.4%) | 0/127 (0%) | ||
| Pathological fracture | 2/465 (0.4%) | 0/127 (0%) | ||
| Spinal disorder | 2/465 (0.4%) | 0/127 (0%) | ||
| Synovitis | 2/465 (0.4%) | 0/127 (0%) | ||
| Arthropathy | 1/465 (0.2%) | 0/127 (0%) | ||
| Chondropathy | 1/465 (0.2%) | 0/127 (0%) | ||
| Connective tissue disorder | 1/465 (0.2%) | 0/127 (0%) | ||
| Costochondritis | 1/465 (0.2%) | 0/127 (0%) | ||
| Foot deformity | 1/465 (0.2%) | 0/127 (0%) | ||
| Intervertebral disc degenration | 1/465 (0.2%) | 0/127 (0%) | ||
| Joint effusion | 1/465 (0.2%) | 0/127 (0%) | ||
| Joint swelling | 1/465 (0.2%) | 0/127 (0%) | ||
| Osteopenia | 1/465 (0.2%) | 0/127 (0%) | ||
| Rotator cuff syndrome | 1/465 (0.2%) | 0/127 (0%) | ||
| Still's disease adult onset | 1/465 (0.2%) | 0/127 (0%) | ||
| Tenosynovitis | 1/465 (0.2%) | 0/127 (0%) | ||
| Osteoporotic fracture | 1/465 (0.2%) | 0/127 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Breast cancer | 4/465 (0.9%) | 0/127 (0%) | ||
| Prostrate cancer | 3/465 (0.6%) | 0/127 (0%) | ||
| Uterine Leiomyoma | 2/465 (0.4%) | 1/127 (0.8%) | ||
| Bladder cancer | 2/465 (0.4%) | 0/127 (0%) | ||
| Colon cancer | 2/465 (0.4%) | 0/127 (0%) | ||
| Lung neoplasm malignant | 2/465 (0.4%) | 0/127 (0%) | ||
| Malignant melanoma in situ | 2/465 (0.4%) | 0/127 (0%) | ||
| Abdominal neoplasm | 1/465 (0.2%) | 0/127 (0%) | ||
| Adenocarcinoma | 1/465 (0.2%) | 0/127 (0%) | ||
| Adrenal neoplasm | 1/465 (0.2%) | 0/127 (0%) | ||
| Basal cell carcinoma | 1/465 (0.2%) | 0/127 (0%) | ||
| Bladder neoplasm | 1/465 (0.2%) | 0/127 (0%) | ||
| Endometrial cancer stage I | 1/465 (0.2%) | 0/127 (0%) | ||
| Hodgkin's disease | 1/465 (0.2%) | 0/127 (0%) | ||
| Malignant melanoma | 1/465 (0.2%) | 0/127 (0%) | ||
| Papillary thyroid cancer | 1/465 (0.2%) | 0/127 (0%) | ||
| Phaeochromocytoma | 1/465 (0.2%) | 0/127 (0%) | ||
| Prostate cancer metastatic | 1/465 (0.2%) | 0/127 (0%) | ||
| Renal oncocytoma | 1/465 (0.2%) | 0/127 (0%) | ||
| Salivary gland adenoma | 1/465 (0.2%) | 0/127 (0%) | ||
| Salivary gland cancer | 1/465 (0.2%) | 0/127 (0%) | ||
| Squamous cell carcinoma | 1/465 (0.2%) | 0/127 (0%) | ||
| Thyroid cancer | 1/465 (0.2%) | 0/127 (0%) | ||
| Transitional cell carcinoma | 1/465 (0.2%) | 0/127 (0%) | ||
| Nervous system disorders | ||||
| Syncope | 4/465 (0.9%) | 0/127 (0%) | ||
| Cerebrovascular accident | 2/465 (0.4%) | 0/127 (0%) | ||
| Headache | 2/465 (0.4%) | 0/127 (0%) | ||
| Cerebral circulatory failure | 1/465 (0.2%) | 0/127 (0%) | ||
| Cerebral infarction | 1/465 (0.2%) | 0/127 (0%) | ||
| Cervical myelopathy | 1/465 (0.2%) | 0/127 (0%) | ||
| Cervicobrachial syndrome | 1/465 (0.2%) | 0/127 (0%) | ||
| Ischaemic stroke | 1/465 (0.2%) | 0/127 (0%) | ||
| Neuropathy peripheral | 1/465 (0.2%) | 0/127 (0%) | ||
| Presyncope | 1/465 (0.2%) | 0/127 (0%) | ||
| Serotonin syndrome | 1/465 (0.2%) | 0/127 (0%) | ||
| Pregnancy, puerperium and perinatal conditions | ||||
| Pregnancy | 4/465 (0.9%) | 1/127 (0.8%) | ||
| Abortion spontaneous | 3/465 (0.6%) | 0/127 (0%) | ||
| Abortion missed | 2/465 (0.4%) | 0/127 (0%) | ||
| Foetal death | 1/465 (0.2%) | 0/127 (0%) | ||
| Psychiatric disorders | ||||
| Psychotic disorder | 2/465 (0.4%) | 0/127 (0%) | ||
| Suicidal ideation | 2/465 (0.4%) | 0/127 (0%) | ||
| Anxiety | 1/465 (0.2%) | 0/127 (0%) | ||
| Depression | 1/465 (0.2%) | 0/127 (0%) | ||
| Suicide attempt | 1/465 (0.2%) | 0/127 (0%) | ||
| Renal and urinary disorders | ||||
| Bladder disorder | 1/465 (0.2%) | 0/127 (0%) | ||
| Bladder prolapse | 1/465 (0.2%) | 0/127 (0%) | ||
| Focal segmental glomerulosclerosis | 1/465 (0.2%) | 0/127 (0%) | ||
| Renal failure acute | 1/465 (0.2%) | 0/127 (0%) | ||
| Renal failure chronic | 1/465 (0.2%) | 0/127 (0%) | ||
| Renal impairment | 1/465 (0.2%) | 0/127 (0%) | ||
| Stag horn calculus | 1/465 (0.2%) | 0/127 (0%) | ||
| Urethral caruncle | 1/465 (0.2%) | 0/127 (0%) | ||
| Reproductive system and breast disorders | ||||
| Metrorrhagia | 3/465 (0.6%) | 0/127 (0%) | ||
| Ovarian cyst | 2/465 (0.4%) | 0/127 (0%) | ||
| Cervical dysplasia | 1/465 (0.2%) | 0/127 (0%) | ||
| Cystocele | 1/465 (0.2%) | 0/127 (0%) | ||
| Endometrial hyperplasia | 1/465 (0.2%) | 0/127 (0%) | ||
| Ovulation pain | 1/465 (0.2%) | 0/127 (0%) | ||
| Prostatomegaly | 1/465 (0.2%) | 0/127 (0%) | ||
| Uterine cervical erosion | 1/465 (0.2%) | 0/127 (0%) | ||
| Uterine polyp | 1/465 (0.2%) | 0/127 (0%) | ||
| Uterine prolapse | 1/465 (0.2%) | 0/127 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Pulmonary embolism | 4/465 (0.9%) | 0/127 (0%) | ||
| Chronic obstructive pulmonary disease | 3/465 (0.6%) | 0/127 (0%) | ||
| Pneumonitis | 2/465 (0.4%) | 0/127 (0%) | ||
| Respiratory failure | 2/465 (0.4%) | 0/127 (0%) | ||
| Acute respiratory failure | 1/465 (0.2%) | 0/127 (0%) | ||
| Asthma | 1/465 (0.2%) | 0/127 (0%) | ||
| Bronchial hyperreactivity | 1/465 (0.2%) | 0/127 (0%) | ||
| Bronchiectasis | 1/465 (0.2%) | 0/127 (0%) | ||
| Bronchitis chronic | 1/465 (0.2%) | 0/127 (0%) | ||
| Interstitial lung disease | 1/465 (0.2%) | 0/127 (0%) | ||
| Pleuritic pain | 1/465 (0.2%) | 0/127 (0%) | ||
| Pulmonary artery thrombosis | 1/465 (0.2%) | 0/127 (0%) | ||
| Pulmonary infarction | 1/465 (0.2%) | 0/127 (0%) | ||
| Pulmonary mass | 1/465 (0.2%) | 0/127 (0%) | ||
| Pulmonary oedema | 1/465 (0.2%) | 0/127 (0%) | ||
| Rheumatoid lung | 1/465 (0.2%) | 0/127 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Psoriasis | 1/465 (0.2%) | 0/127 (0%) | ||
| Skin lesion | 1/465 (0.2%) | 0/127 (0%) | ||
| Skin ulcer | 1/465 (0.2%) | 0/127 (0%) | ||
| Surgical and medical procedures | ||||
| Abortion induced | 1/465 (0.2%) | 0/127 (0%) | ||
| Limb operation | 1/465 (0.2%) | 0/127 (0%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 3/465 (0.6%) | 0/127 (0%) | ||
| Venous thrombosis limb | 2/465 (0.4%) | 0/127 (0%) | ||
| Angiopathy | 1/465 (0.2%) | 0/127 (0%) | ||
| Aortic stenosis | 1/465 (0.2%) | 0/127 (0%) | ||
| Hypertension | 1/465 (0.2%) | 0/127 (0%) | ||
| Rheumatoid vasculitis | 1/465 (0.2%) | 0/127 (0%) | ||
| Thromboangiitis obliterans | 1/465 (0.2%) | 0/127 (0%) | ||
| Vasculitis | 1/465 (0.2%) | 0/127 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Rituximab | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 422/465 (90.8%) | 93/127 (73.2%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 39/465 (8.4%) | 0/127 (0%) | ||
| Ear and labyrinth disorders | ||||
| Vertigo | 27/465 (5.8%) | 1/127 (0.8%) | ||
| Eye disorders | ||||
| Cataract | 29/465 (6.2%) | 0/127 (0%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 85/465 (18.3%) | 9/127 (7.1%) | ||
| Nausea | 62/465 (13.3%) | 8/127 (6.3%) | ||
| Dyspepsia | 54/465 (11.6%) | 2/127 (1.6%) | ||
| Abdominal pain uppper | 28/465 (6%) | 2/127 (1.6%) | ||
| Abdominal pain | 26/465 (5.6%) | 2/127 (1.6%) | ||
| Vomiting | 25/465 (5.4%) | 3/127 (2.4%) | ||
| General disorders | ||||
| Infusion related reaction | 203/465 (43.7%) | 25/127 (19.7%) | ||
| Oedema peripheral | 45/465 (9.7%) | 7/127 (5.5%) | ||
| Fatigue | 38/465 (8.2%) | 8/127 (6.3%) | ||
| Infections and infestations | ||||
| Upper respiratory tract infection | 153/465 (32.9%) | 7/127 (5.5%) | ||
| Nasopharyngitis | 145/465 (31.2%) | 13/127 (10.2%) | ||
| Bronchitis | 108/465 (23.2%) | 6/127 (4.7%) | ||
| Urinary tract infection | 102/465 (21.9%) | 9/127 (7.1%) | ||
| Influenza | 56/465 (12%) | 3/127 (2.4%) | ||
| Sinusitis | 51/465 (11%) | 1/127 (0.8%) | ||
| Pharyngitis | 34/465 (7.3%) | 5/127 (3.9%) | ||
| Gastroenteritis | 31/465 (6.7%) | 1/127 (0.8%) | ||
| Lower respiratory tract infection | 28/465 (6%) | 2/127 (1.6%) | ||
| Herpes zoster | 26/465 (5.6%) | 1/127 (0.8%) | ||
| Injury, poisoning and procedural complications | ||||
| Fall | 64/465 (13.8%) | 0/127 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Hypercholesterolaemia | 37/465 (8%) | 3/127 (2.4%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Rheumatoid arthritis | 236/465 (50.8%) | 54/127 (42.5%) | ||
| Back pain | 84/465 (18.1%) | 7/127 (5.5%) | ||
| Arthralgia | 58/465 (12.5%) | 3/127 (2.4%) | ||
| Osteoarthritis | 40/465 (8.6%) | 1/127 (0.8%) | ||
| Musculoskeletal pain | 32/465 (6.9%) | 1/127 (0.8%) | ||
| Bursitis | 29/465 (6.2%) | 1/127 (0.8%) | ||
| Osteoporosis | 27/465 (5.8%) | 3/127 (2.4%) | ||
| Pain in extremity | 26/465 (5.6%) | 0/127 (0%) | ||
| Nervous system disorders | ||||
| Headache | 82/465 (17.6%) | 9/127 (7.1%) | ||
| Dizziness | 32/465 (6.9%) | 2/127 (1.6%) | ||
| Psychiatric disorders | ||||
| Depression | 41/465 (8.8%) | 0/127 (0%) | ||
| Insomnia | 29/465 (6.2%) | 3/127 (2.4%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 49/465 (10.5%) | 5/127 (3.9%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 43/465 (9.2%) | 4/127 (3.1%) | ||
| Vascular disorders | ||||
| Hypertension | 93/465 (20%) | 6/127 (4.7%) | ||
Limitations/Caveats
The interpretation of the efficacy data over time should take into consideration that only the response of participants who continued in the study and received further courses of rituximab was captured.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann-La Roche |
| Phone | 800-821-8590 |
| genentech@druginfo.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02093026
Other Study ID Numbers:
- WA16855
- U2653g
First Posted:
Mar 20, 2014
Last Update Posted:
Mar 13, 2017
Last Verified:
Jan 1, 2017