Drug Concentration, Immunogenicity, and Efficacy Study in Patients With Rheumatoid Arthritis Currently Treated With Etanercept, Adalimumab, or Infliximab

Study Overview
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Brief Summary
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The purpose of this study is to examine the relationship between anti-drug antibodies, serum drug concentrations, and clinical response for rheumatoid arthritis patients being treated with etanercept, adalimumab or infliximab.

Detailed Description
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cross-sectional Population will be selected through convenience sampling. Patients sequentially visiting the rheumatology clinic for routine care who are receiving etanercept, adalimumab, or infliximab for between 6 and 24 months will be evaluated for eligibility and interest in participation. A maximum of 200 patients per treatment will be enrolled.

Official Title
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Anti-tnf Inhibitor Antibody-mediated Blockade Of Drug Efficacy In Rheumatoid Arthritis (Antibody-ra)

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Other: no intervention
* Other: no intervention
* Other: no intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older. Diagnosis of RA based on the 1987 American College of Rheumatology revised criteria Current continuous treatment with either etanercept, adalimumab, or infliximab for a minimum of 6 months and maximum of 24 months. Exclusion Criteria: Treatment with biosimilar or investigational etanercept, adalimumab, or infliximab within past 6 months. Treatment with any other investigational drugs within past 3 months or five half lives of the drug, whichever is longer. Any medical condition that would interfere with rheumatoid arthritis evaluation or other study assessments (eg, fibromyalgia, lupus).

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 |
| --- | --- |
| etanercept<br>Participants currently receiving etanercept treatment in a clinical setting for a minimum of 6 months and maximum of 24 months prior to study assessment visit. | Other: no intervention<br> <br> * Other names: Enbrel;|
| adalimumab<br>Participants currently receiving adalimumab treatment in a clinical setting for a minimum of 6 months and maximum of 24 months prior to study assessment visit. | Other: no intervention<br> <br> * Other names: Humira;|
| infliximab<br>Participants currently receiving infliximab treatment in a clinical setting for a minimum of 6 months and maximum of 24 months prior to study assessment visit. | Other: no intervention<br> <br> * Other names: Remicade;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Positive for Antidrug Antibodies Among Those Treated With Etanercept Versus Those Treated With Monoclonal Antibodies (Adalimumab or Infliximab). | Percentage of participants positive for antidrug antibodies among those treated with etanercept versus those treated with monoclonal antibodies (adalimumab or infliximab) was determined. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Low Disease Activity (LDA) (DAS28 ESR Score ≤ 3.2) Among Those Who Are Antidrug Antibody Positive Versus Negative (All Patients Receiving Etanercept, Adalimumab, or Infliximab Combined). | Percentage of participants with Low Disease Activity (LDA) (Disease Activity Score based on a 28-joint count [DAS28] Erythrocyte sedimentation rate [ESR] score ≤3.2) among those who are antidrug antibody positive versus negative (all participants receiving etanercept, adalimumab, or infliximab combined). | 1 day | 
| Serum Trough Drug Concentrations for Etanercept, Adalimumab, and Infliximab Compared Between Participants Who Are Antidrug Antibody Positive Versus Negative. | Serum trough drug concentrations for etanercept, adalimumab, and infliximab compared between participants who are antidrug antibody positive versus negative. Units of measurement for Serum trough drug concentration is µg/mL. | 1 day | 
| Percentage of Participants Positive for Antidrug Antibodies Among Those Treated With Etanercept, Adalimumab, or Infliximab. | Percentage of participants positive for antidrug antibodies among those treated with etanercept, adalimumab, or infliximab were determined. | 1 Day | 
| The Clinical Disease Activity Index (CDAI) Total Scores for Etanercept, Adalimumab, or Infliximab Compared Between Participants Who Are Antidrug Antibody Positive Versus Negative. | The CDAI total scores for etanercept, adalimumab, or infliximab compared between participants who are antidrug antibody positive versus negative. CDAI = Disease activity score (DAS) 28 prorated Swollen Joint Count (0-28) + DAS 28 prorated Tender Joint Count (0-28) + Physician's Global Assessment (0-10) + Subject's Global Assessment (0-10). The total score range is 0-76. Score interpretation: Remission ≤ 2.8; Low Disease Activity CDAI > 2.8 and ≤ 10; Moderate Disease Activity CDAI > 10 and ≤ 22; High Disease Activity CDAI > 22. | 1 Day | 
| The Simplified Disease Activity Index (SDAI) Total Scores for Etanercept, Adalimumab, or Infliximab Compared Between Participants Who Are Antidrug Antibody Positive Versus Negative. | The SDAI Total Scores for etanercept, adalimumab, or infliximab compared between participants who are antidrug antibody positive versus negative. SDAI = DAS 28 prorated Swollen Joint Count (0-28) + DAS 28 prorated Tender Joint Count (0-28) + Physician's Global Assessment (0-10) + Subject's Global Assessment (0-10) + C-reactive protein (CRP) (in mg/dL). The total score range is 0-86. Score interpretation: Remission SDAI ≤ 3.3; Low Disease Activity SDAI > 3.3 and ≤ 11; Moderate Disease Activity SDAI > 11 and ≤ 26; High Disease Activity SDAI > 26. | 1 day | 
| Disease Activity Score Based on a 28-joint Count (DAS28), Calculated With Erythrocyte Sedimentation Rate for Etanercept, Adalimumab, or Infliximab Compared Between Participants Who Are Antidrug Antibody Positive Versus Negative. | The DAS28 assessment is a derived measurement with differential weight given to each component. DAS28 will be calculated twice, utilizing first ESR, and then CRP as the acute phase reactant: 1) DAS28-ESR = 0.56 sqrt (28 painful/tender joint count) + 0.28 sqrt (28 swollen joint count) + 0.70 (ln ESR) + 0.014 GH, where GH=subject general health VAS (0-100 mm). 2) DAS28-4 CRP = 0.56 sqrt (28 painful/tender joint count) + 0.28 sqrt (28 swollen count) + 0.36 (ln CRP+1) + 0.014 GH + 0.96, where GH=subject general health VAS (0- 100 mm), higher scores were indicative of a worse outcome. The specific components of the DAS28 assessment that were used in this study are: Tender/Painful Joint Count (28), Swollen Joint Count (28), ESR/CRP, and Subject's General Health VAS assessment. | 1 day | 
| Disease Activity Score, 28 Joint Count, Calculated With C-reactive Protein (DAS28-CRP) for Etanercept, Adalimumab, or Infliximab Compared Between Participants Who Are Antidrug Antibody Positive Versus Negative. | The DAS28 assessment is a derived measurement with differential weight given to each component. DAS28 will be calculated twice, utilizing first ESR, and then CRP as the acute phase reactant: 1) DAS28-ESR = 0.56 sqrt (28 painful/tender joint count) + 0.28 sqrt (28 swollen joint count) + 0.70 (ln ESR) + 0.014 GH, where GH=subject general health VAS (0 100 mm). 2) DAS28-4 CRP = 0.56 sqrt (28 painful/tender joint count) + 0.28 sqrt (28 swollen count) + 0.36 (ln CRP+1) + 0.014 GH + 0.96, where GH=subject general health VAS (0-100 mm), higher scores were indicative of a worse outcome. The specific components of the DAS28 assessment that were used in this study are: Tender/Painful Joint Count (28), Swollen Joint Count (28), ESR/CRP, and Subject's General Health VAS assessment. | 1 day | 
| Health Assessment Questionnaire-Disability Index (HAQ DI) Scores for for Etanercept, Adalimumab, or Infliximab Compared Between Participants Who Are Antidrug Antibody Positive Versus Negative. | The HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consists of 2-3 items. For each question in the questionnaire, the level of difficulty is scored from 0 to 3 with 0 representing no difficulty, 1 as some difficulty, 2 as much difficulty, and 3 as unable to do. Any activity that requires assistance from another individual or requires the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status. The total score range for the HAQ-DI scale, minimum score was 0 (best), maximum score was 3 (worst). | 1 day | 
| Percentage of HAQ DI (<=0.5) Scores for Etanercept, Adalimumab, or Infliximab Compared Between Participants Who Are Antidrug Antibody Positive Versus Negative. | HAQ DI (<=0.5) scores for etanercept, adalimumab, or infliximab compared between participants who are antidrug antibody positive versus negative. | 1 day | 
| Correlation of Antidrug Antibody Titers With Efficacy Measures. | Correlation of antidrug antibody titers with efficacy measures analysed using Spearman correlation coefficient. | 1 day | 
| Correlation of Antidrug Antibody Titers With Trough Drug Concentration. | Correlation of antidrug antibody titers with trough drug concentration analysed using Spearman correlation coefficient. | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rheumatoid arthritis, etanercept, adalimumab, infliximab, anti-drug antibody, immunogenicity, drug concentration