Rheumatoid Arthritis (RA)
Conditions
Brief summary
The rationale for this study is to further explore if development of antibodies against TNF-α blocking agents is associated with reduced clinical effect/worsened clinical outcome. An important aspect of the study is to carry out an exploratory analysis of the immunogenicity of the 4 recommended TNF-α blockers in the treatment of RA in Denmark, using the same cell-based assay.
Detailed description
no sampling
Interventions
OTHERnon-interventional study
Study with 4 arms/groups with 36 patients per group. In total 144 patients.
Sponsors
Pfizer
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject fulfils criteria for Rheumatoid Arthritis (RA) according to ACR or EULAR criteria. * Subjects who are planned to start treatment with ADA, ETA, CER or IFX * Subjects taking a minimum weekly dose of 7.5 mg of methotrexate
Exclusion criteria
* Patients with compliance problems * Patients who have difficulties in reading and understanding local language * Patients with Juvenile Idiopathic Arthritis (JIA) * Azathioprine or cyclophosphamide treatment within 6 months before entering into the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Anti-drug Antibodies Formation Levels 6 Months After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab | Month 6 | Anti-drug antibodies to Adalimumab, Certolizumab, Etanercept and Infliximab were to be measured in serum samples using a validated commercially available cell-based reporter-gene assay. |
| Number of Participants With Presence of Active Drugs in Serum 6 Months After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab | Month 6 | Presence of active drugs in serum 6 months after treatment with Adalimumab, Certolizumab, Etanercept and Infliximab were to be measured in serum samples using a validated commercially available cell-based reporter-gene assay. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between Formation of Antibodies to Adalimumab, Certolizumab, Etanercept or Infliximab 6 Months After Initiation of Treatment and Disease Activity Score 28 (DAS28) 12 Months After Initiation of Treatment | Month 6, 12 | Association between formation of antibodies to Adalimumab, Certolizumab, Etanercept, Infliximab and DAS28 was to be analyzed using Pearson and Spearman correlations across and within each of the four treatment groups. DAS28-4 was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joint count, C-reactive protein (CRP) in milligram per liter (mg/L) and participant global assessment (PGA) of disease activity (participant rated arthritis activity assessment with total score ranging from 0 \[good condition\] to 10 \[worst condition\]; higher score indicates worse condition). DAS28-4 total score range: 0 (no disease activity) to 9.4 (maximum disease activity), higher score indicates more disease activity. |
| Correlation Between Formation of Antibodies to Adalimumab, Certolizumab, Etanercept or Infliximab 6 Months After Initiation of Treatment and Health Assessment Questionnaire (HAQ) 12 Months After Initiation of Treatment | Month 6, 12 | Association between formation of antibodies to Adalimumab, Certolizumab, Etanercept, Infliximab and HAQ scores was to be analyzed using Pearson and Spearman correlations across and within each of the four treatment groups. HAQ was a self-reported, valid assessment of functional disability in rheumatoid arthritis based on ability of participants to perform daily activities. HAQ total score range: 0 (normal functioning) to 3 (worst functioning), where higher score indicates worse functioning. |
| Correlation Between Formation of Antibodies to Adalimumab, Certolizumab, Etanercept or Infliximab 6 Months After Initiation of Treatment and Cessation of Therapy Between Month 6 and 12 Visits | Month 6, 12 | Association between formation of antibodies to Adalimumab, Certolizumab, Etanercept and Infliximab and cessation of therapy was to be analyzed. Cessation of therapy between month 6 and month 12 was the time to withdrawal from study due to either adverse events or lack of effect between the 6 month visit and the 12 month visit. |
| Number of Participants With Anti-drug Antibodies Levels 3 and 12 Months After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab | Month 3, 12 | Anti-drug antibodies to Adalimumab, Certolizumab, Etanercept and Infliximab were to be measured in serum samples using a validated commercially available cell-based reporter-gene assay. |
| Correlation Between the Formation of Anti-drug Antibodies to Adalimumab, Certolizumab, Etanercept or Infliximab and Concomitant Methotrexate Treatment | Month 12 | Association between formation of anti-drug antibodies to Adalimumab, Certolizumab, Etanercept and Infliximab and concomitant Methotrexate treatment (weekly dose of 7.5 milligram) was to be analyzed. |
| Disease Activity Score Based on 28-Joints Count (DAS28) After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Month 3, 6 and 12 | Month 3, 6, 12 | DAS28-4 was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joint count, C-reactive protein (CRP) in milligram per liter (mg/L) and participant global assessment (PGA) of disease activity (participant rated arthritis activity assessment with total score ranging from 0 \[good condition\] to 10 \[worst condition\]; higher score indicates worse condition). DAS28-4 total score range: 0 (no disease activity) to 9.4 (maximum disease activity), higher score indicates more disease activity. DAS28-4 (CRP) less than or equal to (\<=) 3.2 implied low disease activity and greater than (\>) 3.2 to 5.1 implied moderate to high disease activity. |
| Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12 | Baseline, Month 3, 6, 12 | HAQ was a self-reported, valid assessment of functional disability in rheumatoid arthritis based on ability of participants to perform daily activities. HAQ total score range: 0 (normal functioning) to 3 (worst functioning), where higher score indicates worse functioning. |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adalimumab Participants with rheumatoid arthritis (RA) who received adalimumab as per summary of product characteristics (SmPC) during daily clinical practice, were observed prospectively for 12 months. | 8 |
| Etanercept Participants with RA who received etanercept as per SmPC during daily clinical practice, were observed prospectively for 12 months. | 26 |
| Certolizumab Participants with RA who received certolizumab as per SmPC during daily clinical practice, were observed prospectively for 12 months. | 36 |
| Infliximab Participants with RA who received infliximab as per SmPC during daily clinical practice, were observed prospectively for 12 months. | 9 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 5 | 1 | 1 |
| Overall Study | Lack of Efficacy | 2 | 3 | 7 | 0 |
| Overall Study | Other | 0 | 0 | 2 | 0 |
| Overall Study | Premature Termination | 1 | 6 | 0 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Adalimumab | Etanercept | Certolizumab | Infliximab | Total |
|---|---|---|---|---|---|
| Age, Continuous | 51 years STANDARD_DEVIATION 6 | 57 years STANDARD_DEVIATION 13 | 56 years STANDARD_DEVIATION 14 | 51 years STANDARD_DEVIATION 11 | 55 years STANDARD_DEVIATION 13 |
| Gender Female | 4 Participants | 21 Participants | 23 Participants | 6 Participants | 54 Participants |
| Gender Male | 4 Participants | 5 Participants | 13 Participants | 3 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 8 | 13 / 26 | 6 / 36 | 6 / 9 |
| serious Total, serious adverse events | 1 / 8 | 2 / 26 | 2 / 36 | 0 / 9 |
Outcome results
Primary
Number of Participants With Anti-drug Antibodies Formation Levels 6 Months After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab
Anti-drug antibodies to Adalimumab, Certolizumab, Etanercept and Infliximab were to be measured in serum samples using a validated commercially available cell-based reporter-gene assay.
Time frame: Month 6
Population: Data was not collected since this outcome measure was not analyzed due to premature termination of the study.
Primary
Number of Participants With Presence of Active Drugs in Serum 6 Months After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab
Presence of active drugs in serum 6 months after treatment with Adalimumab, Certolizumab, Etanercept and Infliximab were to be measured in serum samples using a validated commercially available cell-based reporter-gene assay.
Time frame: Month 6
Population: Data was not collected since this outcome measure was not analyzed due to premature termination of the study.
Secondary
Correlation Between Formation of Antibodies to Adalimumab, Certolizumab, Etanercept or Infliximab 6 Months After Initiation of Treatment and Cessation of Therapy Between Month 6 and 12 Visits
Association between formation of antibodies to Adalimumab, Certolizumab, Etanercept and Infliximab and cessation of therapy was to be analyzed. Cessation of therapy between month 6 and month 12 was the time to withdrawal from study due to either adverse events or lack of effect between the 6 month visit and the 12 month visit.
Time frame: Month 6, 12
Population: Data was not collected since this outcome measure was not analyzed due to premature termination of the study.
Secondary
Correlation Between Formation of Antibodies to Adalimumab, Certolizumab, Etanercept or Infliximab 6 Months After Initiation of Treatment and Disease Activity Score 28 (DAS28) 12 Months After Initiation of Treatment
Association between formation of antibodies to Adalimumab, Certolizumab, Etanercept, Infliximab and DAS28 was to be analyzed using Pearson and Spearman correlations across and within each of the four treatment groups. DAS28-4 was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joint count, C-reactive protein (CRP) in milligram per liter (mg/L) and participant global assessment (PGA) of disease activity (participant rated arthritis activity assessment with total score ranging from 0 \[good condition\] to 10 \[worst condition\]; higher score indicates worse condition). DAS28-4 total score range: 0 (no disease activity) to 9.4 (maximum disease activity), higher score indicates more disease activity.
Time frame: Month 6, 12
Population: Data was not collected since this outcome measure was not analyzed due to premature termination of the study.
Secondary
Correlation Between Formation of Antibodies to Adalimumab, Certolizumab, Etanercept or Infliximab 6 Months After Initiation of Treatment and Health Assessment Questionnaire (HAQ) 12 Months After Initiation of Treatment
Association between formation of antibodies to Adalimumab, Certolizumab, Etanercept, Infliximab and HAQ scores was to be analyzed using Pearson and Spearman correlations across and within each of the four treatment groups. HAQ was a self-reported, valid assessment of functional disability in rheumatoid arthritis based on ability of participants to perform daily activities. HAQ total score range: 0 (normal functioning) to 3 (worst functioning), where higher score indicates worse functioning.
Time frame: Month 6, 12
Population: Data was not collected since this outcome measure was not analyzed due to premature termination of the study.
Secondary
Correlation Between the Formation of Anti-drug Antibodies to Adalimumab, Certolizumab, Etanercept or Infliximab and Concomitant Methotrexate Treatment
Association between formation of anti-drug antibodies to Adalimumab, Certolizumab, Etanercept and Infliximab and concomitant Methotrexate treatment (weekly dose of 7.5 milligram) was to be analyzed.
Time frame: Month 12
Population: Data was not collected since this outcome measure was not analyzed due to premature termination of the study.
Secondary
Disease Activity Score Based on 28-Joints Count (DAS28) After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Month 3, 6 and 12
DAS28-4 was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joint count, C-reactive protein (CRP) in milligram per liter (mg/L) and participant global assessment (PGA) of disease activity (participant rated arthritis activity assessment with total score ranging from 0 \[good condition\] to 10 \[worst condition\]; higher score indicates worse condition). DAS28-4 total score range: 0 (no disease activity) to 9.4 (maximum disease activity), higher score indicates more disease activity. DAS28-4 (CRP) less than or equal to (\<=) 3.2 implied low disease activity and greater than (\>) 3.2 to 5.1 implied moderate to high disease activity.
Time frame: Month 3, 6, 12
Population: EAS included all participants that provided at least 1 post-baseline assessment. Here,n signifies number of participants evaluable at the specified time points for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adalimumab | Disease Activity Score Based on 28-Joints Count (DAS28) After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Month 3, 6 and 12 | Month 12 (n= 5, 11, 25, 4) | 2.6 units on a scale | Standard Deviation 0.8 |
| Adalimumab | Disease Activity Score Based on 28-Joints Count (DAS28) After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Month 3, 6 and 12 | Month 6 (n= 6, 18, 26, 6) | 2.7 units on a scale | Standard Deviation 1.6 |
| Adalimumab | Disease Activity Score Based on 28-Joints Count (DAS28) After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Month 3, 6 and 12 | Month 3 (n= 7, 23, 34, 8) | 3.2 units on a scale | Standard Deviation 1 |
| Etanercept | Disease Activity Score Based on 28-Joints Count (DAS28) After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Month 3, 6 and 12 | Month 6 (n= 6, 18, 26, 6) | 2.2 units on a scale | Standard Deviation 1.1 |
| Etanercept | Disease Activity Score Based on 28-Joints Count (DAS28) After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Month 3, 6 and 12 | Month 12 (n= 5, 11, 25, 4) | 2.4 units on a scale | Standard Deviation 0.8 |
| Etanercept | Disease Activity Score Based on 28-Joints Count (DAS28) After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Month 3, 6 and 12 | Month 3 (n= 7, 23, 34, 8) | 3.0 units on a scale | Standard Deviation 1.1 |
| Certolizumab | Disease Activity Score Based on 28-Joints Count (DAS28) After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Month 3, 6 and 12 | Month 6 (n= 6, 18, 26, 6) | 2.4 units on a scale | Standard Deviation 1.3 |
| Certolizumab | Disease Activity Score Based on 28-Joints Count (DAS28) After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Month 3, 6 and 12 | Month 3 (n= 7, 23, 34, 8) | 3.0 units on a scale | Standard Deviation 1.4 |
| Certolizumab | Disease Activity Score Based on 28-Joints Count (DAS28) After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Month 3, 6 and 12 | Month 12 (n= 5, 11, 25, 4) | 2.5 units on a scale | Standard Deviation 1.1 |
| Infliximab | Disease Activity Score Based on 28-Joints Count (DAS28) After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Month 3, 6 and 12 | Month 12 (n= 5, 11, 25, 4) | 2.7 units on a scale | Standard Deviation 0.6 |
| Infliximab | Disease Activity Score Based on 28-Joints Count (DAS28) After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Month 3, 6 and 12 | Month 6 (n= 6, 18, 26, 6) | 1.8 units on a scale | Standard Deviation 1 |
| Infliximab | Disease Activity Score Based on 28-Joints Count (DAS28) After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Month 3, 6 and 12 | Month 3 (n= 7, 23, 34, 8) | 3.0 units on a scale | Standard Deviation 2 |
Comparison: DAS28: Month 3: Continuous variables were compared between treatment groups using one way analysis of variance (ANOVA).p-value: 0.99Fisher Exact
Comparison: DAS28: Month 6: Continuous variables were compared between treatment groups using one way ANOVA.p-value: 0.586Fisher Exact
Comparison: DAS28: Month 12: Continuous variables were compared between treatment groups using one way ANOVA.p-value: 0.98Fisher Exact
Secondary
Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12
HAQ was a self-reported, valid assessment of functional disability in rheumatoid arthritis based on ability of participants to perform daily activities. HAQ total score range: 0 (normal functioning) to 3 (worst functioning), where higher score indicates worse functioning.
Time frame: Baseline, Month 3, 6, 12
Population: EAS included all participants that provided at least 1 post-baseline assessment. Here, n signifies number of participants evaluable for this outcome measure at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adalimumab | Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12 | Baseline (n= 8, 26, 36, 9) | 1.1 units on a scale | Standard Deviation 0.6 |
| Adalimumab | Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12 | Month 3 (n= 7, 23, 34, 8) | 0.8 units on a scale | Standard Deviation 0.6 |
| Adalimumab | Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12 | Month 6 (n= 6, 18, 26, 6) | 0.8 units on a scale | Standard Deviation 0.2 |
| Adalimumab | Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12 | Month 12 (n= 5, 11, 25, 4) | 0.7 units on a scale | Standard Deviation 0.4 |
| Etanercept | Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12 | Month 3 (n= 7, 23, 34, 8) | 0.9 units on a scale | Standard Deviation 0.7 |
| Etanercept | Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12 | Month 6 (n= 6, 18, 26, 6) | 0.6 units on a scale | Standard Deviation 0.6 |
| Etanercept | Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12 | Month 12 (n= 5, 11, 25, 4) | 1.0 units on a scale | Standard Deviation 0.8 |
| Etanercept | Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12 | Baseline (n= 8, 26, 36, 9) | 1.2 units on a scale | Standard Deviation 0.6 |
| Certolizumab | Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12 | Month 6 (n= 6, 18, 26, 6) | 0.7 units on a scale | Standard Deviation 0.6 |
| Certolizumab | Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12 | Month 3 (n= 7, 23, 34, 8) | 0.8 units on a scale | Standard Deviation 0.7 |
| Certolizumab | Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12 | Month 12 (n= 5, 11, 25, 4) | 0.6 units on a scale | Standard Deviation 0.6 |
| Certolizumab | Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12 | Baseline (n= 8, 26, 36, 9) | 1.2 units on a scale | Standard Deviation 0.7 |
| Infliximab | Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12 | Month 12 (n= 5, 11, 25, 4) | 0.8 units on a scale | Standard Deviation 0.7 |
| Infliximab | Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12 | Month 3 (n= 7, 23, 34, 8) | 1.2 units on a scale | Standard Deviation 0.8 |
| Infliximab | Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12 | Baseline (n= 8, 26, 36, 9) | 1.1 units on a scale | Standard Deviation 0.5 |
| Infliximab | Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12 | Month 6 (n= 6, 18, 26, 6) | 0.8 units on a scale | Standard Deviation 0.7 |
Comparison: HAQ: Baseline: Continuous variables were compared between treatment groups using one way ANOVA.p-value: 0.945Fisher Exact
Comparison: HAQ: Month 3: Continuous variables were compared between treatment groups using one way ANOVA.p-value: 0.458Fisher Exact
Comparison: HAQ: Month 6: Continuous variables were compared between treatment groups using one way ANOVA.p-value: 0.896Fisher Exact
Comparison: HAQ: Month 12: Continuous variables were compared between treatment groups using one way ANOVA.p-value: 0.39Fisher Exact
Secondary
Number of Participants With Anti-drug Antibodies Levels 3 and 12 Months After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab
Anti-drug antibodies to Adalimumab, Certolizumab, Etanercept and Infliximab were to be measured in serum samples using a validated commercially available cell-based reporter-gene assay.
Time frame: Month 3, 12
Population: Data was not collected since this outcome measure was not analyzed due to premature termination of the study.