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

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

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.

Study Overview

• Status: Terminated
• Conditions: Rheumatoid Arthritis (RA)
• Intervention / Treatment: Other: non-interventional study

Detailed Description

no sampling

• Study Type: Observational
• Enrollment (Actual): 79

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Universitetshospital Nord/Reumatologisk Afdelning
  • Aarhus C., Denmark, 8000
    • Aarhus Universitetshospital/Reumatologisk Afdelning U
  • Esbjerg, Denmark, 6700
    • Sydvestjysk Sygehus / Reumatologisk Afdeling
  • Frederiksberg, Denmark, 2000
    • Frederiksberg Hospital / Reumatologisk Afdeling
  • Hellerup, Denmark, 2900
    • Gentofte Hospital, Medicinsk afd. C
  • Hillerod, Denmark, 3400
    • Hillerod Hospital/Reumatologisk Afdeling
  • Holbaek, Denmark, 4300
    • Holbaek Sygehus
  • Kolding, Denmark, 6000
    • Reumatologisk afd
  • Odense C, Denmark, 5000
    • Odense Universitets Hospital/Reumatologisk Afdeling C
  • Randers NØ, Denmark, 8930
    • Regionshospitalet Randers / Reumatologisk Klinik
  • Svendborg, Denmark, 5700
    • Svendborg Sygehus / Medicinsk Afdeling M
  • Vejle, Denmark, 7100
    • Vejle Sygehus / Medicinsk Afdeling
  • Viborg, Denmark, 8800
    • Hospitalsenheden Viborg Reumatologisk Ambulatorium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

patients with Rheumatoid Arthritis (RA)

Description

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 Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Etanercept	Other: non-interventional study; Study with 4 arms/groups with 36 patients per group. In total 144 patients.
adalimumab	Other: non-interventional study; Study with 4 arms/groups with 36 patients per group. In total 144 patients.
infliximab	Other: non-interventional study; Study with 4 arms/groups with 36 patients per group. In total 144 patients.
Certolizumab	Other: non-interventional study; Study with 4 arms/groups with 36 patients per group. In total 144 patients.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: September 12, 2012
• First Submitted That Met QC Criteria: September 21, 2012
• First Posted (Estimate): September 24, 2012

Study Record Updates

• Last Update Posted (Estimate): December 29, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: B1801347