Formation of Antibodies and Subsequent Prediction of Clinical Response in Patients With Rheumatoid Arthritis Treated With Four TNF Blocking Agents

Study Overview
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Brief Summary
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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
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no sampling

Official Title
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Formation Of Antibodies And Subsequent Prediction Of Clinical Response In Patients With Rheumatoid Arthritis Treated With Four Tnf Blocking Agents

Conditions
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Rheumatoid Arthritis (RA)

Intervention / Treatment
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* Other: non-interventional study
* Other: non-interventional study
* Other: non-interventional study
* Other: non-interventional study


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| adalimumab<br> | Other: non-interventional study<br>* Study with 4 arms/groups with 36 patients per group. In total 144 patients.<br>|
| Etanercept<br> | Other: non-interventional study<br>* Study with 4 arms/groups with 36 patients per group. In total 144 patients.<br>|
| infliximab<br> | Other: non-interventional study<br>* Study with 4 arms/groups with 36 patients per group. In total 144 patients.<br>|
| Certolizumab<br> | Other: non-interventional study<br>* Study with 4 arms/groups with 36 patients per group. In total 144 patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Month 6 | 
| 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. | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Month 6, 12 | 
| 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. | Month 6, 12 | 
| 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. | Month 6, 12 | 
| 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. | Month 3, 12 | 
| 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. | Month 12 | 
| 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. | Month 3, 6, 12 | 
| 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. | Baseline, Month 3, 6, 12 |