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

Rheumatoid Arthritis Clinical Trial

— ANTIBODY-RA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01981473
• Other study ID #: B1801364
• Secondary ID: ANTIBODY-RA
• Status: Completed
• Phase: Phase 4
• First received: November 5, 2013
• Last updated: December 8, 2015
• Start date: January 2014
• Est. completion date: December 2014

Study information

• Verified date: December 2015
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 605
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age 18 years or older.

2. Diagnosis of RA based on the 1987 American College of Rheumatology revised criteria

3. Current continuous treatment with either etanercept, adalimumab, or infliximab for a minimum of 6 months and maximum of 24 months.

Exclusion Criteria:

1. Treatment with biosimilar or investigational etanercept, adalimumab, or infliximab within past 6 months.

2. Treatment with any other investigational drugs within past 3 months or five half lives of the drug, whichever is longer.

3. Any medical condition that would interfere with rheumatoid arthritis evaluation or other study assessments (eg, fibromyalgia, lupus).

Study Design

Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Other:
• no intervention

• no intervention

• no intervention

Locations

Country	Name	City	State
Argentina	Hospital Británico de Buenos Aires	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Clínica Adventista Belgrano	Ciudad Autónoma de Buenos Aires / Buenos Aires	Ciudad Autónoma de Buenos Aires / Buenos Aires /Argentina.
Argentina	Sociedad Italiana de Beneficencia en Buenos Aires (Hospital Italiano de Buenos Aires)	Ciudad Autónoma de Buenos Aires / Buenos Aires	Buenos Aires / Argentina
Argentina	CIER, centro de investigaciones en enfermedades reumáticas (Razón social: ARIES MEDICA S.R.L.)	Ciudad de Buenos Aires / Buenos Aires	Ciudad de Buenos Aires, Buenos Aires, Argentina
Argentina	Sociedad Española de Beneficiencia y Mutualidad Hospital español de Mendoza	Godoy Cruz	Mendoza / Argentina
Argentina	DIM Clinica Privada	Ramos Mejía	Ramos Mejía / Buenos Aires / Argentina
Argentina	Instituto CAICI SRL.	Rosario	Santa Fe / Argentina
Argentina	Centro Integral de Reumatología S.R.L.	S.M. de Tucumán / Tucumán	S.M. de Tucumán / Tucumán / Argentina.
Argentina	Instituto de Asistencia Reumatológica Integral I.A.R.I	San Fernando	Buenos Aires / Argentina
Argentina	C.E.R - Centro Polivalente de Asistencia e Investigación Clínica propiedad de CER SAN JUAN S.R.L.	San Juan	San Juan / San Juan / Buenos Aires
Argentina	I.N.Ne.L S.R.L. (Instituto de Neurología y Neurorrehabilitación del Litoral S.R.L.)	Santa Fé	Santa Fé / Argentina
Australia	Southern Clinical Research Pty Ltd	Sandy Bay, Hobart	Tasmania
Bulgaria	MHAT Burgas	Burgas
Bulgaria	DCC Sveti Pantaleimon OOD	Pleven
Bulgaria	MHAT Kaspela EOOD	Plovdiv
Bulgaria	UMHAT "Sv.Ivan Rilski"	Sofia
Turkey	Cukurova Universitesi Tip Fakultesi Balcali Hastanesi	Adana
Turkey	Hacettepe Universitesi Tip Fakultesi Hastanesi	Ankara
Turkey	Ataturk Universitesi Yakutiye Egitim ve Arastirma Hastanesi	Erzurum
Turkey	Osmangazi Universitesi Tip Fakultesi Hastanesi	Eskisehir
United States	Austin Regional Clinic	Austin	Texas
United States	Rheumatology Associates of Baltimore	Baltimore	Maryland
United States	Advanced Arthritis Care Center	Brooklyn	New York
United States	Box Arthritis and Rheumatology	Charlotte	North Carolina
United States	Center for Arthritis and Rheumatic Diseases, P.C.	Chesapeake	Virginia
United States	Omega Research Consultants, LLC	Debary	Florida
United States	Phase III Clinical Research	Fall River	Massachusetts
United States	David S. Rosenberg, M.D	Florissant	Missouri
United States	Center for Rheumatology, Immunology, and Arthritis	Fort Lauderdale	Florida
United States	Florida Medical Research	Gainesville	Florida
United States	Northeast Georgia Diagnostic Clinic, LLC	Gainesville	Georgia
United States	Arizona Arthritis & Rheumatology	Glendale	Arizona
United States	Comprehensive Rheumatology Care	Hendersonville	Tennessee
United States	Elizabeth Marini Simpson	Hixon	Tennessee
United States	Mercy Clinic Hot Springs Communities	Hot Springs	Arkansas
United States	Accurate Clinical Research	Houston	Texas
United States	Clinical Research Institute of Houston	Houston	Texas
United States	Rheumatology Consultants of Delaware dba Delaware Arthritis	Lewes	Delaware
United States	Dr Melvin Albert Churchill Jr	Lincoln	Nebraska
United States	Arizona Arthritis & Rheumatology Associates, P. C.	Mesa	Arizona
United States	Prospect Medical Offices	Midland Park	New Jersey
United States	Low Country Rheumatology, PA	North Charleston	South Carolina
United States	Arizona Arthritis & Rheumatology	Phoenix	Arizona
United States	Arizona Arthritis and Rheumatology Research, PLLC	Phoenix	Arizona
United States	Prem C.Chatpar, M.D., LLC	Plainview	New York
United States	Sutter Institute for Medical Research	Sacramento	California
United States	Arthritis Care Center, Incorporated	San Jose	California
United States	Arthritis and Rheumatic Care Center	South Miami	Florida
United States	Arthritis Northwest, PLLC	Spokane	Washington
United States	Arizona Arthritis & Rheumatology Research	Sun City	Arizona
United States	Health Point Medical Group, Inc.	Tampa	Florida
United States	Spring Clinical Research	Tomball	Texas
United States	Via Christi Hospitals Wichita, Inc.	Wichita	Kansas
United States	Clinical Research Center of Reading, LLC	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Bulgaria,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Correlation of Antidrug Antibody Titers With Efficacy Measures.	Correlation of antidrug antibody titers with efficacy measures analysed using Spearman correlation coefficient.	1 day	No
Secondary	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	No

External Links

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