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

Terminated
Conditions
Rheumatoid Arthritis (RA)
Interventions
Other: non-interventional study
Registration Number
NCT01691014
Lead Sponsor
Pfizer
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

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
79
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
infliximabnon-interventional study-
adalimumabnon-interventional study-
Certolizumabnon-interventional study-
Etanerceptnon-interventional study-
Primary Outcome Measures
NameTimeMethod
Number of Participants With Anti-drug Antibodies Formation Levels 6 Months After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or InfliximabMonth 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 InfliximabMonth 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 Outcome Measures
NameTimeMethod
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 TreatmentMonth 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 TreatmentMonth 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.

Disease Activity Score Based on 28-Joints Count (DAS28) After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Month 3, 6 and 12Month 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.

Number of Participants With Anti-drug Antibodies Levels 3 and 12 Months After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or InfliximabMonth 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 TreatmentMonth 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.

Health Assessment Questionnaire (HAQ) Score After Initiation of Treatment With Adalimumab, Certolizumab, Etanercept or Infliximab at Baseline, Month 3, 6 and 12Baseline, 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.

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 VisitsMonth 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.

Trial Locations

Locations (13)

Gentofte Hospital, Medicinsk afd. C

🇩🇰

Hellerup, Denmark

Hillerod Hospital/Reumatologisk Afdeling

🇩🇰

Hillerod, Denmark

Odense Universitets Hospital/Reumatologisk Afdeling C

🇩🇰

Odense C, Denmark

Regionshospitalet Randers / Reumatologisk Klinik

🇩🇰

Randers NØ, Denmark

Vejle Sygehus / Medicinsk Afdeling

🇩🇰

Vejle, Denmark

Sydvestjysk Sygehus / Reumatologisk Afdeling

🇩🇰

Esbjerg, Denmark

Aalborg Universitetshospital Nord/Reumatologisk Afdelning

🇩🇰

Aalborg, Denmark

Aarhus Universitetshospital/Reumatologisk Afdelning U

🇩🇰

Aarhus C., Denmark

Frederiksberg Hospital / Reumatologisk Afdeling

🇩🇰

Frederiksberg, Denmark

Holbaek Sygehus

🇩🇰

Holbaek, Denmark

Reumatologisk afd

🇩🇰

Kolding, Denmark

Svendborg Sygehus / Medicinsk Afdeling M

🇩🇰

Svendborg, Denmark

Hospitalsenheden Viborg Reumatologisk Ambulatorium

🇩🇰

Viborg, Denmark

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