Rheumatoid Arthritis
Conditions
Brief summary
This prospective observational study aims to evaluate safety, application and onset of effect of rituximab in clinical routine treatment of severe active rheumatoid arthritis during the first 6 months (in case of re-therapy: 12 months).
Interventions
DRUGRituximab
As prescribed by physician
Sponsors
Hoffmann-La Roche
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* No pretreatment with rituximab * Age 18 years or older * Patients with active, severe rheumatoid arthritis with prescription of rituximab according to German Summary of Product Characteristics (SmPC - Fachinformation) * Patients with signed informed consent * Female patients with secure contraception
Exclusion criteria
* Violation of Selection criteria: 1. Active severe infection 2. Severe heart failure (NYHA class IV) or severe, uncontrollable heart disease 3. Participation in an interventional study within the last 3 months before therapy start with rituximab 4. Pretreatment with rituximab 5. Age \<18 years 6. Known intolerability of monoclonal antibodies or chimeric monoclonal antibodies 7. Known pregnancy or breastfeeding * Data of patients without approval of data by the physician * Patients without informed consent * Double documentation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DAS28 Score | at baseline of each cycle and approximately 15 days, 6 weeks (only cycle 1), 12 weeks (3 months), 18 weeks (only cycle 1), and 24 weeks (6 months) after the start of the respective cycle | The DAS28 consists of swollen joint count (SJC) and tender joint count (TJC) measurements, the erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hr), and the Patient's Global Assessment of Disease Activity (participant-rated rheumatoid arthritis \[RA\] activity assessment) with transformed scores ranging 0 to 10; higher scores indicate greater affectation due to disease activity. |
| HAQ Disability Index (HAQ-DI) | at baseline of each cycle and approximately 15 days, 6 weeks (only cycle 1), 12 weeks (3 months), 18 weeks (only cycle 1), and 24 weeks (6 months) after the start of the respective cycle | The HAQ-DI score consists of questions referring to 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. For each of the categories, participants reported the amount of difficulty they had in performing 2 or 3 specific subcategory items. The standard disability score is calculated from the 8 categories by dividing the sum of the individual categories by the number of categories answered, yielding a score from 0 (without any difficulty) to 3 (unable to do). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | during Cycle 1, during Cycle 2, during the trial (within 12 months) | — |
| Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | 24 weeks after starting Cycle 1 | In the Main Analysis Set participants with only one treatment cycle, the HAQ score was categorized for 12 subgroups as Clinically relevant improvement of HAQ-Score ≥0.3, Other or no clinical relevant change of HAQ Score, or Clinically relevant worsening of HAQ Score ≥0.3. Subgroups are defined as Anti-Cyclic citrullinated peptide (CCP) and Rheumatoid factor (RF) negative (-), positive (+), or Non-specified (n.sp.) and Seropositive Non-specified (n.sp.), Seronegative, or Seropositive. |
| Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | 24 weeks after starting Cycle 2 | In the Subpopulation With Two Cycles, the HAQ score was categorized for 12 subgroups as Clinically relevant improvement of HAQ-Score ≥0.3, Other or no clinical relevant change of HAQ Score, or Clinically relevant worsening of HAQ Score ≥0.3. Subgroups are defined as Anti-Cyclic citrullinated peptide (CCP) and Rheumatoid factor (RF) negative (-), positive (+), or Non-specified (n.sp.) and Seropositive Non-specified (n.sp.), Seronegative, or Seropositive. |
Countries
Germany
Participant flow
Recruitment details
Data were recorded throughout Germany in 264 study centers.
Participants by arm
| Arm | Count |
|---|---|
| Main Analysis Set Participants who received at least one cycle of rituximab | 1,653 |
| Total | 1,653 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Participants Who Received One Cycle | Change of therapy | 6 |
| Participants Who Received One Cycle | Death | 5 |
| Participants Who Received One Cycle | Lack of Efficacy | 18 |
| Participants Who Received One Cycle | Lack of tolerability | 14 |
| Participants Who Received One Cycle | Patient requirement | 20 |
| Participants Who Received One Cycle | Severe concomitant disease | 2 |
| Subpopulation Who Received Two Cycles | Lack of Efficacy | 3 |
| Subpopulation Who Received Two Cycles | Lack of Tolerability | 4 |
| Subpopulation Who Received Two Cycles | Patient Requirement | 7 |
| Subpopulation Who Received Two Cycles | Remission | 1 |
Baseline characteristics
| Characteristic | Main Analysis Set |
|---|---|
| Age, Continuous | 60.0 years |
| Sex: Female, Male Female | 1199 Participants |
| Sex: Female, Male Male | 454 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 1,653 | 0 / 820 | 0 / 1,653 |
| serious Total, serious adverse events | 144 / 1,653 | 47 / 820 | 180 / 1,653 |
Outcome results
Primary
DAS28 Score
The DAS28 consists of swollen joint count (SJC) and tender joint count (TJC) measurements, the erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hr), and the Patient's Global Assessment of Disease Activity (participant-rated rheumatoid arthritis \[RA\] activity assessment) with transformed scores ranging 0 to 10; higher scores indicate greater affectation due to disease activity.
Time frame: at baseline of each cycle and approximately 15 days, 6 weeks (only cycle 1), 12 weeks (3 months), 18 weeks (only cycle 1), and 24 weeks (6 months) after the start of the respective cycle
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Analysis Set | DAS28 Score | Baseline (n=1396,150,1186) | 5.3 units on a scale | Standard Deviation 1.4 |
| Main Analysis Set | DAS28 Score | 15 days (n=1133,120,957) | 4.8 units on a scale | Standard Deviation 1.4 |
| Main Analysis Set | DAS28 Score | 6 weeks (n=778,73,670) | 4.4 units on a scale | Standard Deviation 1.4 |
| Main Analysis Set | DAS28 Score | 12 weeks (n=785,75,666) | 4.0 units on a scale | Standard Deviation 1.3 |
| Main Analysis Set | DAS28 Score | 18 weeks (n=601,57,520) | 3.8 units on a scale | Standard Deviation 1.3 |
| Main Analysis Set | DAS28 Score | 24 weeks (n=641,60,553) | 3.8 units on a scale | Standard Deviation 1.4 |
| Main Analysis Set | DAS28 Score | Start 2nd cycle (n=588,47,517) | 4.1 units on a scale | Standard Deviation 1.4 |
| Main Analysis Set | DAS28 Score | 15 days (n=525,43,460) | 3.9 units on a scale | Standard Deviation 1.4 |
| Main Analysis Set | DAS28 Score | 3 months (n=451,37,393) | 3.5 units on a scale | Standard Deviation 1.3 |
| Main Analysis Set | DAS28 Score | 6 months (n=491,34,438) | 3.5 units on a scale | Standard Deviation 1.4 |
| Seronegative Participants | DAS28 Score | 3 months (n=451,37,393) | 3.7 units on a scale | Standard Deviation 1.5 |
| Seronegative Participants | DAS28 Score | Baseline (n=1396,150,1186) | 5.0 units on a scale | Standard Deviation 1.4 |
| Seronegative Participants | DAS28 Score | 24 weeks (n=641,60,553) | 4.1 units on a scale | Standard Deviation 1.3 |
| Seronegative Participants | DAS28 Score | 18 weeks (n=601,57,520) | 4.1 units on a scale | Standard Deviation 1.4 |
| Seronegative Participants | DAS28 Score | 15 days (n=1133,120,957) | 4.6 units on a scale | Standard Deviation 1.4 |
| Seronegative Participants | DAS28 Score | 6 months (n=491,34,438) | 3.9 units on a scale | Standard Deviation 1.6 |
| Seronegative Participants | DAS28 Score | 15 days (n=525,43,460) | 4.0 units on a scale | Standard Deviation 1.5 |
| Seronegative Participants | DAS28 Score | 6 weeks (n=778,73,670) | 4.3 units on a scale | Standard Deviation 1.4 |
| Seronegative Participants | DAS28 Score | Start 2nd cycle (n=588,47,517) | 4.2 units on a scale | Standard Deviation 1.5 |
| Seronegative Participants | DAS28 Score | 12 weeks (n=785,75,666) | 4.0 units on a scale | Standard Deviation 1.3 |
| Seropositive Participants | DAS28 Score | 15 days (n=525,43,460) | 3.8 units on a scale | Standard Deviation 1.4 |
| Seropositive Participants | DAS28 Score | 12 weeks (n=785,75,666) | 4.0 units on a scale | Standard Deviation 1.3 |
| Seropositive Participants | DAS28 Score | 18 weeks (n=601,57,520) | 3.8 units on a scale | Standard Deviation 1.3 |
| Seropositive Participants | DAS28 Score | 24 weeks (n=641,60,553) | 3.8 units on a scale | Standard Deviation 1.4 |
| Seropositive Participants | DAS28 Score | 3 months (n=451,37,393) | 3.5 units on a scale | Standard Deviation 1.3 |
| Seropositive Participants | DAS28 Score | Start 2nd cycle (n=588,47,517) | 4.1 units on a scale | Standard Deviation 1.4 |
| Seropositive Participants | DAS28 Score | Baseline (n=1396,150,1186) | 5.4 units on a scale | Standard Deviation 1.4 |
| Seropositive Participants | DAS28 Score | 6 months (n=491,34,438) | 3.5 units on a scale | Standard Deviation 1.3 |
| Seropositive Participants | DAS28 Score | 15 days (n=1133,120,957) | 4.9 units on a scale | Standard Deviation 1.4 |
| Seropositive Participants | DAS28 Score | 6 weeks (n=778,73,670) | 4.4 units on a scale | Standard Deviation 1.4 |
Primary
HAQ Disability Index (HAQ-DI)
The HAQ-DI score consists of questions referring to 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. For each of the categories, participants reported the amount of difficulty they had in performing 2 or 3 specific subcategory items. The standard disability score is calculated from the 8 categories by dividing the sum of the individual categories by the number of categories answered, yielding a score from 0 (without any difficulty) to 3 (unable to do).
Time frame: at baseline of each cycle and approximately 15 days, 6 weeks (only cycle 1), 12 weeks (3 months), 18 weeks (only cycle 1), and 24 weeks (6 months) after the start of the respective cycle
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Analysis Set | HAQ Disability Index (HAQ-DI) | 15 days (n=706,67,610) | 1.2 units on a scale | Standard Deviation 0.7 |
| Main Analysis Set | HAQ Disability Index (HAQ-DI) | Baseline (n=1579,174,1326) | 1.5 units on a scale | Standard Deviation 0.7 |
| Main Analysis Set | HAQ Disability Index (HAQ-DI) | 12 weeks (n=1015,116,848) | 1.2 units on a scale | Standard Deviation 0.7 |
| Main Analysis Set | HAQ Disability Index (HAQ-DI) | 6 months (n=626,56,546) | 1.2 units on a scale | Standard Deviation 0.7 |
| Main Analysis Set | HAQ Disability Index (HAQ-DI) | 3 months (n=594,59,508) | 1.1 units on a scale | Standard Deviation 0.7 |
| Main Analysis Set | HAQ Disability Index (HAQ-DI) | 24 weeks (n=810,90,681) | 1.2 units on a scale | Standard Deviation 0.7 |
| Main Analysis Set | HAQ Disability Index (HAQ-DI) | 6 weeks (n=983,0,0) | 1.3 units on a scale | Standard Deviation 0.7 |
| Main Analysis Set | HAQ Disability Index (HAQ-DI) | 18 weeks (n=784,0,0) | 1.2 units on a scale | Standard Deviation 0.7 |
| Main Analysis Set | HAQ Disability Index (HAQ-DI) | Start 2nd cycle (n=768,68,669) | 1.2 units on a scale | Standard Deviation 0.7 |
| Main Analysis Set | HAQ Disability Index (HAQ-DI) | 15 days (n=1514,169,1270) | 1.4 units on a scale | Standard Deviation 0.7 |
| Seronegative Participants | HAQ Disability Index (HAQ-DI) | Start 2nd cycle (n=768,68,669) | 1.4 units on a scale | Standard Deviation 0.8 |
| Seronegative Participants | HAQ Disability Index (HAQ-DI) | 15 days (n=706,67,610) | 1.2 units on a scale | Standard Deviation 0.7 |
| Seronegative Participants | HAQ Disability Index (HAQ-DI) | 15 days (n=1514,169,1270) | 1.4 units on a scale | Standard Deviation 0.8 |
| Seronegative Participants | HAQ Disability Index (HAQ-DI) | 3 months (n=594,59,508) | 1.3 units on a scale | Standard Deviation 0.7 |
| Seronegative Participants | HAQ Disability Index (HAQ-DI) | 6 months (n=626,56,546) | 1.3 units on a scale | Standard Deviation 0.8 |
| Seronegative Participants | HAQ Disability Index (HAQ-DI) | 6 weeks (n=983,0,0) | NA units on a scale | — |
| Seronegative Participants | HAQ Disability Index (HAQ-DI) | Baseline (n=1579,174,1326) | 1.5 units on a scale | Standard Deviation 0.7 |
| Seronegative Participants | HAQ Disability Index (HAQ-DI) | 12 weeks (n=1015,116,848) | 1.3 units on a scale | Standard Deviation 0.8 |
| Seronegative Participants | HAQ Disability Index (HAQ-DI) | 18 weeks (n=784,0,0) | NA units on a scale | — |
| Seronegative Participants | HAQ Disability Index (HAQ-DI) | 24 weeks (n=810,90,681) | 1.3 units on a scale | Standard Deviation 0.8 |
| Seropositive Participants | HAQ Disability Index (HAQ-DI) | 6 months (n=626,56,546) | 1.1 units on a scale | Standard Deviation 0.7 |
| Seropositive Participants | HAQ Disability Index (HAQ-DI) | 18 weeks (n=784,0,0) | NA units on a scale | — |
| Seropositive Participants | HAQ Disability Index (HAQ-DI) | Baseline (n=1579,174,1326) | 1.5 units on a scale | Standard Deviation 0.7 |
| Seropositive Participants | HAQ Disability Index (HAQ-DI) | 15 days (n=1514,169,1270) | 1.4 units on a scale | Standard Deviation 0.7 |
| Seropositive Participants | HAQ Disability Index (HAQ-DI) | 6 weeks (n=983,0,0) | NA units on a scale | — |
| Seropositive Participants | HAQ Disability Index (HAQ-DI) | 24 weeks (n=810,90,681) | 1.2 units on a scale | Standard Deviation 0.7 |
| Seropositive Participants | HAQ Disability Index (HAQ-DI) | Start 2nd cycle (n=768,68,669) | 1.2 units on a scale | Standard Deviation 0.7 |
| Seropositive Participants | HAQ Disability Index (HAQ-DI) | 15 days (n=706,67,610) | 1.2 units on a scale | Standard Deviation 0.7 |
| Seropositive Participants | HAQ Disability Index (HAQ-DI) | 3 months (n=594,59,508) | 1.1 units on a scale | Standard Deviation 0.7 |
| Seropositive Participants | HAQ Disability Index (HAQ-DI) | 12 weeks (n=1015,116,848) | 1.2 units on a scale | Standard Deviation 0.7 |
Secondary
Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized)
In the Main Analysis Set participants with only one treatment cycle, the HAQ score was categorized for 12 subgroups as Clinically relevant improvement of HAQ-Score ≥0.3, Other or no clinical relevant change of HAQ Score, or Clinically relevant worsening of HAQ Score ≥0.3. Subgroups are defined as Anti-Cyclic citrullinated peptide (CCP) and Rheumatoid factor (RF) negative (-), positive (+), or Non-specified (n.sp.) and Seropositive Non-specified (n.sp.), Seronegative, or Seropositive.
Time frame: 24 weeks after starting Cycle 1
Population: Main Analysis Set with HAQ Score
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Main Analysis Set | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 1+6+8: seronegative (n=75) | 19 participants |
| Main Analysis Set | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 5: Anti-CCP n.sp./RF+ (n=109) | 46 participants |
| Main Analysis Set | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 10: Anti-CCP and RF n.sp. (n=36) | 12 participants |
| Main Analysis Set | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 2: Anti-CCP-/RF+ (n=19) | 2 participants |
| Main Analysis Set | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 6: Anti-CCP n.sp./RF- (n=29) | 9 participants |
| Main Analysis Set | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 4: Anti-CCP+/RF+ (n=375) | 146 participants |
| Main Analysis Set | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 9: Seropositive n.sp. (n=17) | 6 participants |
| Main Analysis Set | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 7: Anti-CCP+/RF n.sp. (n=19) | 8 participants |
| Main Analysis Set | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 1: Anti-CCP-/RF- (n=44) | 10 participants |
| Main Analysis Set | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 2+3+4+5+7+9: seropositive (n=584) | 222 participants |
| Main Analysis Set | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 8: Anti-CCP-/RF n.sp. (n=2) | 0 participants |
| Main Analysis Set | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 3: Anti-CCP+/RF- (n=45) | 14 participants |
| Seronegative Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 8: Anti-CCP-/RF n.sp. (n=2) | 1 participants |
| Seronegative Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 9: Seropositive n.sp. (n=17) | 9 participants |
| Seronegative Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 3: Anti-CCP+/RF- (n=45) | 29 participants |
| Seronegative Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 10: Anti-CCP and RF n.sp. (n=36) | 20 participants |
| Seronegative Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 1+6+8: seronegative (n=75) | 42 participants |
| Seronegative Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 2+3+4+5+7+9: seropositive (n=584) | 304 participants |
| Seronegative Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 1: Anti-CCP-/RF- (n=44) | 28 participants |
| Seronegative Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 4: Anti-CCP+/RF+ (n=375) | 185 participants |
| Seronegative Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 5: Anti-CCP n.sp./RF+ (n=109) | 57 participants |
| Seronegative Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 6: Anti-CCP n.sp./RF- (n=29) | 13 participants |
| Seronegative Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 2: Anti-CCP-/RF+ (n=19) | 17 participants |
| Seronegative Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 7: Anti-CCP+/RF n.sp. (n=19) | 7 participants |
| Seropositive Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 2+3+4+5+7+9: seropositive (n=584) | 58 participants |
| Seropositive Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 1: Anti-CCP-/RF- (n=44) | 6 participants |
| Seropositive Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 2: Anti-CCP-/RF+ (n=19) | 0 participants |
| Seropositive Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 3: Anti-CCP+/RF- (n=45) | 2 participants |
| Seropositive Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 4: Anti-CCP+/RF+ (n=375) | 44 participants |
| Seropositive Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 5: Anti-CCP n.sp./RF+ (n=109) | 6 participants |
| Seropositive Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 6: Anti-CCP n.sp./RF- (n=29) | 7 participants |
| Seropositive Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 7: Anti-CCP+/RF n.sp. (n=19) | 4 participants |
| Seropositive Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 8: Anti-CCP-/RF n.sp. (n=2) | 1 participants |
| Seropositive Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 9: Seropositive n.sp. (n=17) | 2 participants |
| Seropositive Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 10: Anti-CCP and RF n.sp. (n=36) | 4 participants |
| Seropositive Participants | Number of Participants Who Received Only One Treatment Cycle With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 1+6+8: seronegative (n=75) | 14 participants |
Secondary
Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized)
In the Subpopulation With Two Cycles, the HAQ score was categorized for 12 subgroups as Clinically relevant improvement of HAQ-Score ≥0.3, Other or no clinical relevant change of HAQ Score, or Clinically relevant worsening of HAQ Score ≥0.3. Subgroups are defined as Anti-Cyclic citrullinated peptide (CCP) and Rheumatoid factor (RF) negative (-), positive (+), or Non-specified (n.sp.) and Seropositive Non-specified (n.sp.), Seronegative, or Seropositive.
Time frame: 24 weeks after starting Cycle 2
Population: Subpopulation With Two Cycles with HAQ Score
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Main Analysis Set | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 3: Anti-CCP+/RF- (n=36) | 8 participants |
| Main Analysis Set | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 10: Anti-CCP and RF n.sp. (n=22) | 6 participants |
| Main Analysis Set | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 1+6+8: seronegative (n=52) | 11 participants |
| Main Analysis Set | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 4: Anti-CCP+/RF+ (n=314) | 147 participants |
| Main Analysis Set | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 2+3+4+5+7+9: seropositive (n=485) | 216 participants |
| Main Analysis Set | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 5: Anti-CCP n.sp./RF+ (n=100) | 42 participants |
| Main Analysis Set | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 1: Anti-CCP-/RF- (n=33) | 7 participants |
| Main Analysis Set | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 6: Anti-CCP n.sp./RF- (n=17) | 3 participants |
| Main Analysis Set | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 2: Anti-CCP-/RF+ (n=11) | 4 participants |
| Main Analysis Set | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 7: Anti-CCP+/RF n.sp. (n=14) | 10 participants |
| Main Analysis Set | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 8: Anti-CCP-/RF n.sp. (n=2) | 1 participants |
| Main Analysis Set | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 9: Seropositive n.sp. (n=10) | 5 participants |
| Seronegative Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 2: Anti-CCP-/RF+ (n=11) | 6 participants |
| Seronegative Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 9: Seropositive n.sp. (n=10) | 4 participants |
| Seronegative Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 3: Anti-CCP+/RF- (n=36) | 18 participants |
| Seronegative Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 5: Anti-CCP n.sp./RF+ (n=100) | 44 participants |
| Seronegative Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 10: Anti-CCP and RF n.sp. (n=22) | 14 participants |
| Seronegative Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 1: Anti-CCP-/RF- (n=33) | 17 participants |
| Seronegative Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 8: Anti-CCP-/RF n.sp. (n=2) | 1 participants |
| Seronegative Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 1+6+8: seronegative (n=52) | 24 participants |
| Seronegative Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 7: Anti-CCP+/RF n.sp. (n=14) | 3 participants |
| Seronegative Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 6: Anti-CCP n.sp./RF- (n=17) | 6 participants |
| Seronegative Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 2+3+4+5+7+9: seropositive (n=485) | 205 participants |
| Seronegative Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 4: Anti-CCP+/RF+ (n=314) | 130 participants |
| Seropositive Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 2+3+4+5+7+9: seropositive (n=485) | 64 participants |
| Seropositive Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 4: Anti-CCP+/RF+ (n=314) | 37 participants |
| Seropositive Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 1: Anti-CCP-/RF- (n=33) | 9 participants |
| Seropositive Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 3: Anti-CCP+/RF- (n=36) | 10 participants |
| Seropositive Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 5: Anti-CCP n.sp./RF+ (n=100) | 14 participants |
| Seropositive Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 6: Anti-CCP n.sp./RF- (n=17) | 8 participants |
| Seropositive Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 7: Anti-CCP+/RF n.sp. (n=14) | 1 participants |
| Seropositive Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 8: Anti-CCP-/RF n.sp. (n=2) | 0 participants |
| Seropositive Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 9: Seropositive n.sp. (n=10) | 1 participants |
| Seropositive Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 10: Anti-CCP and RF n.sp. (n=22) | 2 participants |
| Seropositive Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 1+6+8: seronegative (n=52) | 17 participants |
| Seropositive Participants | Number of Participants Who Received Two Cycles With Clinically Relevant Changes in HAQ-Score at Last Visit During Therapy Compared to Baseline (Categorized) | Subgroup 2: Anti-CCP-/RF+ (n=11) | 1 participants |
Secondary
Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE)
Time frame: during Cycle 1, during Cycle 2, during the trial (within 12 months)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Main Analysis Set | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any TEAE | 28.5 percentage of participants |
| Main Analysis Set | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any related serious TEAE | 2.5 percentage of participants |
| Main Analysis Set | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any related TEAE | 6.1 percentage of participants |
| Main Analysis Set | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any severe TEAE | 5.5 percentage of participants |
| Main Analysis Set | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any TEAE leading to death | 0.5 percentage of participants |
| Main Analysis Set | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any TEAE leading to discontinuation | 1.9 percentage of participants |
| Main Analysis Set | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any serious TEAE | 8.7 percentage of participants |
| Seronegative Participants | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any related TEAE | 6.2 percentage of participants |
| Seronegative Participants | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any severe TEAE | 4.3 percentage of participants |
| Seronegative Participants | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any TEAE | 21.1 percentage of participants |
| Seronegative Participants | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any serious TEAE | 5.7 percentage of participants |
| Seronegative Participants | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any related serious TEAE | 1.3 percentage of participants |
| Seronegative Participants | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any TEAE leading to discontinuation | 1.3 percentage of participants |
| Seronegative Participants | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any TEAE leading to death | 0.2 percentage of participants |
| Seropositive Participants | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any related serious TEAE | 3.0 percentage of participants |
| Seropositive Participants | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any TEAE | 34.8 percentage of participants |
| Seropositive Participants | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any TEAE leading to death | 0.6 percentage of participants |
| Seropositive Participants | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any TEAE leading to discontinuation | 2.6 percentage of participants |
| Seropositive Participants | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any related TEAE | 8.5 percentage of participants |
| Seropositive Participants | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any serious TEAE | 10.9 percentage of participants |
| Seropositive Participants | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) | Any severe TEAE | 7.0 percentage of participants |