Phase 3
Completed N=519
A Study of RoActemra/Actemra and, if Initially Inadequately Responded to RoActemra/Actemra, Followed by MabThera/Rituxan in Patients With Rheumatoid Arthritis
Source: ClinicalTrials.gov NCT01332994 ↗Enrolled (actual)
519
Serious AEs
10.4%
Results posted
Sep 2015
Primary outcomePrimary: Percentage of Participants Achieving Remission at Week 16 According to DAS28 — 42.8 percentage of participants — p=0.1648
Summary
This open-label, multi-center, two-arm, uncontrolled and non-randomized study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in patients with rheumatoid arthritis. Patients will receive 8 mg/kg RoActemra/Actemra intravenously every 4 weeks for 12 weeks and - if adequately responded - for further 12 weeks. Patients, who show an inadequate clinical response after the first 12 weeks to RoActemra/Actemra, will receive 1 g MabThera/Rituxan (rituximab) intravenously at Week 16 and 18. The anticipated time of study treatment is 32 weeks.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Achieving Remission at Week 16 According to DAS28 |
42.8 | 0.1648 |
| SECONDARY Percentage of Participants Achieving Remission According to DAS28 at Weeks 4, 8, and 12 |
21.6; 40.1; 43.2 | — |
| SECONDARY Percentage of Participants Achieving Remission According to DAS28 at Weeks 16, 20, 24, and 28 Among Participants Treated With 8 Courses of Tocilizumab |
1.4; 41.3; 51.2; 55.9 | — |
| SECONDARY Percentage of Participants Achieving Remission According to DAS28 at Week 32 Among Participants Treated With 8 Courses of Tocilizumab |
54.9 | — |
| SECONDARY Percentage of Participants Achieving Remission According to DAS28 at Week 32 Among Nonresponding Participants Treated With Rituximab |
14.8 | — |
| SECONDARY Percentage of Participants Achieving Low Disease Activity Score (LDAS) According to DAS28 |
68.8 | — |
| SECONDARY Percentage of Participants Achieving LDAS According to DAS28 Among Among Nonresponding Participants Treated With Rituximab |
33.3 | — |
| SECONDARY Percentage of Participants Achieving a Clinically Relevant Reduction From Baseline in DAS28 at Week 16 |
86.1 | — |
| SECONDARY Percentage of Participants Achieving a Clinically Relevant Reduction From Baseline in DAS28 at Weeks 4, 8, and 12 |
74.6; 81.5; 83.4 | — |
| SECONDARY Percentage of Participants Achieving a Clinically Relevant Reduction in DAS28 From Week 16 to Week 32 Among Nonresponding Participants Treated With Rituximab |
37.0 | — |
| SECONDARY DAS28 Scores During and After Treatment |
5.7; 3.6; 3.0; 2.8; 2.6 | — |
| SECONDARY DAS28 Scores During and After Treatment Among Participants Treated With 8 Courses of Tocilizumab |
6.0; 4.0; 3.4; 3.3; 3.3; 2.8 | — |
| SECONDARY DAS28 Scores During and After Treatment Among Nonresponding Participants Treated With Rituximab |
5.7; 4.5; 4.2; 4.8; 5.1; 4.6 | — |
| SECONDARY DAS28 Scores During Safety Follow-Up Among Nonresponding Participants Treated With Rituximab |
3.9; 3.9; 4.1; 3.9 | — |
| SECONDARY Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16 |
36.0; 47.8; 16.2; 56.1; 30.6; 13.3 | — |
| SECONDARY Percentage of Participants Achieving a Response According to EULAR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab |
25.9; 29.6; 44.4 | — |
| SECONDARY Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab |
65.3; 30.0; 4.7; 68.1; 23.9; 8.0 | — |
| SECONDARY Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16 |
39.1; 15.0; 5.8; 61.1; 33.5; 15.2 | — |
| SECONDARY Percentage of Participants Achieving a Response According to ACR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab |
40.7; 33.3; 22.2 | — |
| SECONDARY Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab |
74.2; 45.1; 21.1; 72.8; 49.8; 21.6 | — |
| SECONDARY Change From Baseline in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) Scores at Weeks 4, 8, 12, and 16 |
-10.9; -16.5; -18.3; -19.4; -12.3; -17.9 | — |
| SECONDARY Change From Week 16 to 32 in CDAI and SDAI Scores Among Nonresponding Participants Treated With Rituximab |
-14.2; -14.0 | — |
| SECONDARY Change From Baseline in CDAI and SDAI Scores at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab |
-21.7; -22.8; -24.6; -24.0; -22.9; -24.3 | — |
| SECONDARY Change From Baseline in Hemoglobin at Weeks 4, 8, 12, and 16 |
4.9; 6.4; 6.9; 7.5 | — |
| SECONDARY Change From Baseline in CRP at Weeks 4, 8, 12, and 16 |
-1.4; -1.4; -1.4; -1.3 | — |
| SECONDARY Change From Baseline in ESR at Weeks 4, 8, 12, and 16 |
-25.2; -26.6; -26.3; -27.5 | — |
| SECONDARY Change in Hemoglobin From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab |
-2.0 | — |
| SECONDARY Change in CRP From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab |
0.7 | — |
| SECONDARY Change in ESR From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab |
11.5 | — |
| SECONDARY Change From Baseline in Hemoglobin at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab |
5.5; 6.6; 6.9; 8.3 | — |
| SECONDARY Change From Baseline in CRP at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab |
-1.3; -1.4; -1.3; -1.3 | — |
| SECONDARY Change From Baseline in ESR at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab |
-28.6; -29.4; -29.4; -28.6 | — |
| SECONDARY Percentage of Participants Withdrawing From the Study for Insufficient Therapeutic Response |
0.2 | — |
| SECONDARY Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants With Early Remission |
61.1; 1.4; 58.1; 56.4; 46.5; 11.1 | — |
| SECONDARY Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants Treated With 8 Courses of Tocilizumab |
57.1; 1.3; 55.5; 63.2; 49.7; 11.6 | — |
| SECONDARY Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Nonresponding Participants Treated With Rituximab |
65.9; 1.6; 61.9; 45.1; 41.5; 9.1 | — |
| SECONDARY Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Week 16 Among Participants With Early Remission |
-0.02258; -0.00949; -0.01920; -0.03148; 0.03221; 0.05419 | 0.7559 |
| SECONDARY Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab |
0.00007; -0.06529; 0.02334; 0.03478; -0.01889; -0.04161 | 0.9993 |
| SECONDARY Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab |
0.09611; 0.08571; 0.00870; -0.60000; -0.15217; -0.04004 | 0.6551 |
| SECONDARY Mean Number of Work Days Missed Per Week |
1.03; 0.39; 0.14; 0.32 | — |
| SECONDARY Quality of Life as Assessed Using Short Form 36 (SF-36) |
49.6; 64.1; 12.9; 29.9; 31.3; 55.3 | — |
| SECONDARY Change From Baseline in Quality of Life as Assessed Using SF-36 at Week 16 |
14.3; 17.0; 23.9; 10.4; 13.9; 12.0 | — |
| SECONDARY Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Participants Treated With 8 Courses of Tocilizumab |
3.6; 2.0; 3.2; 2.6; 2.7; -0.3 | — |
| SECONDARY Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Nonresponding Participants Treated With Rituximab |
2.5; -1.0; 10.6; 5.2; 1.0; -3.1 | — |
| SECONDARY Quality of Life as Assessed Using HAQ-DI |
1.24; 0.75 | — |
| SECONDARY Change From Baseline in Quality of Life as Assessed Using HAQ-DI at Week 16 |
-0.48 | — |
| SECONDARY Change From Week 16 to 32 in Quality of Life as Assessed Using HAQ-DI Among Participants Treated With 8 Courses of Tocilizumab |
-0.06 | — |
| SECONDARY Change From Week 16 to 32 in Quality of Life as Assessed Using HAQ-DI Among Nonresponding Participants Treated With Rituximab |
-0.10 | — |
| SECONDARY Percentage of Participants Achieving a Response According to HAQ-DI Criteria |
61.1 | — |
| SECONDARY Quality of Life as Assessed Using Functional Assessment of Chronic Illness Therapy (FACIT) |
66.2; 80.8; 71.1; 82.6; 103.8; 121.9 | — |
| SECONDARY Change From Baseline in Quality of Life as Assessed Using FACIT at Week 16 |
14.2; 10.8; 17.5; 6.6 | — |
| SECONDARY Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Participants Treated With 8 Courses of Tocilizumab |
1.7; 1.1; 2.0; 0.8 | — |
| SECONDARY Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Nonresponding Participants Treated With Rituximab |
2.9; 3.0; 4.4; 1.4 | — |
Eligibility Criteria
Inclusion Criteria
- Adult patients >/=18 years of age
- Body weight 3.2
- Inadequate clinical response to a stable dose of traditional Disease-Modifying Anti-Rheumatic Drugs (DMARD)
- Have received permitted DMARDs, one or more; current DMARD therapy must have been at stable dose for at least 4 weeks prior to baseline
Exclusion Criteria
- Prior treatment with TNF-inhibitors or other biologic DMARD
- Major surgery (including joint surgery) within eight weeks prior to baseline or planned major surgery within the study duration
- Functional class IV (American College of Rheumatology classification)
- Rheumatic autoimmune disease other than rheumatoid arthritis
- History of or current inflammatory joint disease other than rheumatoid arthritis
Data sourced from ClinicalTrials.gov (NCT01332994). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.