Rheumatoid Arthritis
Conditions
Brief summary
This study involves review and analysis of disease activity in patients with rheumatoid arthritis who where treated with either conventional DMARDs (Disease Modifying Antirheumatic Drugs) or Biologics and have two existing, consecutive radiographs (x-ray images) of hand and feet taken as part of routine treatment monitoring within a time interval of 12 to 36 months.
Interventions
DRUGDMARDs or Biologics
Sponsors
Pfizer
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Secure diagnosis of rheumatoid arthritis * Older than 18 years * Two consecutive plain radiographs of the hands and feet with a time interval of 12 to 36 months are available. The radiographs are recorded 2003 or later and are in accordance with a defined X-ray protocol.
Exclusion criteria
\- Patients who receive Anakinra, Rituximab or Abatacept
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Joint Status Assessed by Radiographic (Roentgen) Progression | Baseline (Day 0) up to 48 months | Radiographic progression assessed using Ratingen score with range of 0 = normal joint; 1 = one or more erosions, \<20% of the joint surface are destroyed; 2 = 21% to 40% of the joint surface are destroyed; 3 = 41% to 60% of joint surface are destroyed; 4 = 61% to 80% of the joint surface are destroyed; 5 = \>80% of the joint surface are destroyed. Total possible score based on 38 joints was 0 to 190; higher scores indicated greater joint destruction. Annualized change in Ratingen score calculated as (total change in Ratingen score / time period between radiograph 1 and 2 \[months\])\*12 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Without Erosions | Baseline (Day 0) up to 48 months | Radiographic assessment of no erosions using Ratingen scoring categorized as score of 0=normal joint. |
| Change From Baseline in Disease Activity Score Based on 28 Joints (DAS 28) | Baseline (Day 0) up to 48 months | DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2 = low disease activity, DAS28 \>3.2 to 5.1 = moderate to high disease activity. |
| Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Baseline (Day 0) up to 48 months | Erythrocyte Sedimentation Rate measured as millimeters per hour (mm/h). |
| Number of Participants Without Radiographic Progression | Baseline (Day 0) up to 48 months | An increase of 4 or more points in the Ratingen score was necessary to detect a difference in radiographic progression. Ratingen score range 0 = normal joint to 5 = \>80% of the joint surface are destroyed. Total possible score based on 38 joints was 0 to 190; higher scores indicated greater joint destruction. A decrease of 4 (smallest detectable difference) or more points in total Ratingen score was considered a decrease in erosive damage. |
| Number of Participants With Change From Baseline in Rheumatoid Factor (RF) | Baseline (Day 0) up to 48 months | Rheumatoid Factor measured as a titer and categorized as negative (\<1:16 ratio) or positive. A ratio \>1:16 indicates a higher level of RF. |
| Number of Participants With Laboratory Result for Cyclic Citrullinated Peptide-autoantibody-test (CCP) | Baseline (Day 0) up to 48 months | Cyclic citrullinated peptide-autoantibody-test measured as Enzyme-linked immunosorbent assay (ELISA units or EU) and categorized as negative (\<20 EU) or positive (≥20 up to \>60 EU). |
| Change From Baseline in C-reactive Protein (CRP) | Baseline (Day 0) up to 48 months | C-reactive protein measured as milligrams per liter (mg/l) |
Countries
Denmark
Participant flow
Recruitment details
A total of 160 participants were screened and 156 entered this non-randomized retrospective evaluation of conventional systemic therapies and biologics in participants with rheumatoid arthritis in routine practice.
Pre-assignment details
Participants had been treated according to authorized dosages for disease-modifying anti-rheumatic drug (DMARDs) and biologics in Germany. No investigational product had been provided.
Participants by arm
| Arm | Count |
|---|---|
| DMARDS Participants had received disease-modifying basic Rheumatoid Arthritis (RA) therapy with a conventional anti-rheumatic drug (DMARDS) such as methotrexate, leflunomide, or a combination of these. | 92 |
| Biologics Participants had received disease-modifying basic Rheumatoid Arthritis (RA) therapy with a tumor necrosis factor (TNF)-alpha-blocker such as etanercept (Enbrel®), infliximab (Remicade®) or adalimumab (Humira®) - may be administered in combination with a conventional DMARD. | 64 |
| Total | 156 |
Baseline characteristics
| Characteristic | DMARDS | Biologics | Total |
|---|---|---|---|
| Age, Customized | 61.6 years STANDARD_DEVIATION 12.6 | 58.9 years STANDARD_DEVIATION 13.1 | 60.5 years STANDARD_DEVIATION 12.8 |
| Sex: Female, Male Female | 63 Participants | 50 Participants | 113 Participants |
| Sex: Female, Male Male | 29 Participants | 14 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 92 | 0 / 65 |
| serious Total, serious adverse events | 0 / 92 | 0 / 65 |
Outcome results
Primary
Change From Baseline in Joint Status Assessed by Radiographic (Roentgen) Progression
Radiographic progression assessed using Ratingen score with range of 0 = normal joint; 1 = one or more erosions, \<20% of the joint surface are destroyed; 2 = 21% to 40% of the joint surface are destroyed; 3 = 41% to 60% of joint surface are destroyed; 4 = 61% to 80% of the joint surface are destroyed; 5 = \>80% of the joint surface are destroyed. Total possible score based on 38 joints was 0 to 190; higher scores indicated greater joint destruction. Annualized change in Ratingen score calculated as (total change in Ratingen score / time period between radiograph 1 and 2 \[months\])\*12 months.
Time frame: Baseline (Day 0) up to 48 months
Population: Evaluable population: all participants who had provided two evaluable, consecutive radiographs of the hands and forefeet, taken at intervals of 12 to 48 months. Since the time period between the first and second radiograph could range between 12 to 48 months, changes in Ratingen score were to be normalized to 1 year.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DMARDS | Change From Baseline in Joint Status Assessed by Radiographic (Roentgen) Progression | Baseline Ratingen score - first radiograph | 6.9 scores on a scale | Standard Deviation 10.7 |
| DMARDS | Change From Baseline in Joint Status Assessed by Radiographic (Roentgen) Progression | Change at second radiograph | 0.0 scores on a scale | Standard Deviation 3 |
| DMARDS | Change From Baseline in Joint Status Assessed by Radiographic (Roentgen) Progression | Annualized change in Ratingen score | -0.1 scores on a scale | Standard Deviation 1.4 |
| Biologics | Change From Baseline in Joint Status Assessed by Radiographic (Roentgen) Progression | Baseline Ratingen score - first radiograph | 24.3 scores on a scale | Standard Deviation 30.7 |
| Biologics | Change From Baseline in Joint Status Assessed by Radiographic (Roentgen) Progression | Change at second radiograph | 0.3 scores on a scale | Standard Deviation 6.3 |
| Biologics | Change From Baseline in Joint Status Assessed by Radiographic (Roentgen) Progression | Annualized change in Ratingen score | 0.0 scores on a scale | Standard Deviation 3.3 |
Secondary
Change From Baseline in C-reactive Protein (CRP)
C-reactive protein measured as milligrams per liter (mg/l)
Time frame: Baseline (Day 0) up to 48 months
Population: Evaluable population; (n)=number of participants with analyzable data at observation for DMARDS and Biologics, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DMARDS | Change From Baseline in C-reactive Protein (CRP) | Baseline CRP- first radiograph (n=90, 64) | 12.9 mg/l | Standard Deviation 20.2 |
| DMARDS | Change From Baseline in C-reactive Protein (CRP) | Change at second radiograph (n=89, 64) | -5.4 mg/l | Standard Deviation 22.6 |
| Biologics | Change From Baseline in C-reactive Protein (CRP) | Baseline CRP- first radiograph (n=90, 64) | 12.9 mg/l | Standard Deviation 20.6 |
| Biologics | Change From Baseline in C-reactive Protein (CRP) | Change at second radiograph (n=89, 64) | -4.3 mg/l | Standard Deviation 21.5 |
Secondary
Change From Baseline in Disease Activity Score Based on 28 Joints (DAS 28)
DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2 = low disease activity, DAS28 \>3.2 to 5.1 = moderate to high disease activity.
Time frame: Baseline (Day 0) up to 48 months
Population: Evaluable population; (n)=number of participants with analyzable data at observation for DMARDS and Biologics, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DMARDS | Change From Baseline in Disease Activity Score Based on 28 Joints (DAS 28) | Baseline DAS 28 - first radiograph (n=85, 61) | 4.0 scores on a scale | Standard Deviation 1.7 |
| DMARDS | Change From Baseline in Disease Activity Score Based on 28 Joints (DAS 28) | Change at second radiograph (n=83, 58) | -0.8 scores on a scale | Standard Deviation 1.6 |
| Biologics | Change From Baseline in Disease Activity Score Based on 28 Joints (DAS 28) | Baseline DAS 28 - first radiograph (n=85, 61) | 4.0 scores on a scale | Standard Deviation 1.7 |
| Biologics | Change From Baseline in Disease Activity Score Based on 28 Joints (DAS 28) | Change at second radiograph (n=83, 58) | -0.7 scores on a scale | Standard Deviation 1.5 |
Secondary
Change From Baseline in Erythrocyte Sedimentation Rate (ESR)
Erythrocyte Sedimentation Rate measured as millimeters per hour (mm/h).
Time frame: Baseline (Day 0) up to 48 months
Population: Evaluable population; (n)=number of participants with analyzable data at observation for DMARDS and Biologics, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DMARDS | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Baseline ESR - first radiograph (n=91, 63) | 23.8 mm/h | Standard Deviation 21.1 |
| DMARDS | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Change at second radiograph (n=90, 63) | -3.2 mm/h | Standard Deviation 21.8 |
| Biologics | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Baseline ESR - first radiograph (n=91, 63) | 22.3 mm/h | Standard Deviation 20.5 |
| Biologics | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Change at second radiograph (n=90, 63) | 0.3 mm/h | Standard Deviation 19.7 |
Secondary
Number of Participants With Change From Baseline in Rheumatoid Factor (RF)
Rheumatoid Factor measured as a titer and categorized as negative (\<1:16 ratio) or positive. A ratio \>1:16 indicates a higher level of RF.
Time frame: Baseline (Day 0) up to 48 months
Population: Evaluable population; (n)=number of participants with analyzable data at observation for Positive or Negative status for DMARDS and Biologics, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DMARDS | Number of Participants With Change From Baseline in Rheumatoid Factor (RF) | Baseline Positive RF- first radiograph (n=89, 62) | 52 participants |
| DMARDS | Number of Participants With Change From Baseline in Rheumatoid Factor (RF) | Baseline Negative RF- first radiograph | 37 participants |
| DMARDS | Number of Participants With Change From Baseline in Rheumatoid Factor (RF) | Positive RF at second radiograph (n=85, 61) | 47 participants |
| DMARDS | Number of Participants With Change From Baseline in Rheumatoid Factor (RF) | Negative RF at second radiograph | 38 participants |
| Biologics | Number of Participants With Change From Baseline in Rheumatoid Factor (RF) | Negative RF at second radiograph | 12 participants |
| Biologics | Number of Participants With Change From Baseline in Rheumatoid Factor (RF) | Baseline Positive RF- first radiograph (n=89, 62) | 46 participants |
| Biologics | Number of Participants With Change From Baseline in Rheumatoid Factor (RF) | Positive RF at second radiograph (n=85, 61) | 49 participants |
| Biologics | Number of Participants With Change From Baseline in Rheumatoid Factor (RF) | Baseline Negative RF- first radiograph | 16 participants |
Secondary
Number of Participants With Laboratory Result for Cyclic Citrullinated Peptide-autoantibody-test (CCP)
Cyclic citrullinated peptide-autoantibody-test measured as Enzyme-linked immunosorbent assay (ELISA units or EU) and categorized as negative (\<20 EU) or positive (≥20 up to \>60 EU).
Time frame: Baseline (Day 0) up to 48 months
Population: Evaluable population; N=number of participants with evaluable data for CCP. CCP value as a laboratory diagnostic marker was collected within the complete timeframe and was documented only once; calculation for change in value not applicable.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DMARDS | Number of Participants With Laboratory Result for Cyclic Citrullinated Peptide-autoantibody-test (CCP) | Positive CCP | 50 participants |
| DMARDS | Number of Participants With Laboratory Result for Cyclic Citrullinated Peptide-autoantibody-test (CCP) | Negative CCP | 35 participants |
| Biologics | Number of Participants With Laboratory Result for Cyclic Citrullinated Peptide-autoantibody-test (CCP) | Positive CCP | 53 participants |
| Biologics | Number of Participants With Laboratory Result for Cyclic Citrullinated Peptide-autoantibody-test (CCP) | Negative CCP | 11 participants |
Secondary
Number of Participants Without Erosions
Radiographic assessment of no erosions using Ratingen scoring categorized as score of 0=normal joint.
Time frame: Baseline (Day 0) up to 48 months
Population: Evaluable population. Ratingen scores were calculated based on radiographic assessment, but score of 0 (no erosions) was not reported separately; data not summarized.
Secondary
Number of Participants Without Radiographic Progression
An increase of 4 or more points in the Ratingen score was necessary to detect a difference in radiographic progression. Ratingen score range 0 = normal joint to 5 = \>80% of the joint surface are destroyed. Total possible score based on 38 joints was 0 to 190; higher scores indicated greater joint destruction. A decrease of 4 (smallest detectable difference) or more points in total Ratingen score was considered a decrease in erosive damage.
Time frame: Baseline (Day 0) up to 48 months
Population: Evaluable population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DMARDS | Number of Participants Without Radiographic Progression | 89 participants |
| Biologics | Number of Participants Without Radiographic Progression | 59 participants |