Anti-TNF Agents for the Treatment of Rheumatoid Arthritis

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00837434
• Collaborator: Autoimmunity Centers of Excellence (Other), Rho Federal Systems Division, Inc. (Industry)
• Enrollment: 63
• Locations: 7
• Arms: 2
• Duration (Months): 58.1
• Patients Per Site: 9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Rheumatoid arthritis (RA) is a chronic disease that leads to inflammation and progressive joint damage. RA is a systemic inflammatory autoimmune disorder affecting almost 1% of the United States population. Current therapies target the immune system early in the disease process before joint damage occurs, and include drugs such as methotrexate (MTX) and tumor necrosis factor (TNF)-blocking agents. The primary purpose of this study is to determine the effectiveness of two TNF inhibitors, etanercept and adalimumab, on memory B lymphocytes (B-cells) in the peripheral blood of participants with RA.

Additionally, there are 4 optional sub-studies as part of the trial:

• B-Cell Kinetic Sub-Study to look at changes in B-cell subsets over time and how quickly reductions in B-cell memory occur

• Vaccine Response Sub-Study to assess B cell memory in response to immunization with hepatitis B,-hepatitis A, and diphtheria/tetanus vaccines, and to determine whether T-cell vaccine responses are altered with TNF blockade

• Tonsil Biopsy Sub-Study to evaluate how TNF blockade affects memory B-cells in the tonsil dendritic cells and germinal cells

• Synovial Biopsy Sub-Study to evaluate how TNF blockade affects changes in memory B-cells in lymphoid tissue.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Etanercept; Drug: Adalimumab	Phase 4

Detailed Description

RA is characterized by persistent inflammation of peripheral joints, causing pain, stiffness, swelling and warmth. Over the past 10 years, advancements in biotechnology have revolutionized RA therapeutics with biologically-derived immunomodulating compounds. TNF-alpha inhibitors constitute the largest class of these new biologic therapies. The purpose of this study is to determine the effectiveness two TNF inhibitors, etanercept and adalimumab, on memory B lymphocytes (B-cells) in the peripheral blood of participants with RA.

This study will last 24 weeks. Participants will be randomized into one of two treatment groups. Participants in one group will receive a dose of etanercept once every week for 24 weeks. Participants in the other group will receive a dose of adalimumab once every 2 weeks for 24 weeks.

This study consists of seven study visits after randomization and will occur at study entry and Weeks 4, 8, 12, 16, 20 and 24. Blood collection will occur at all study visits. A written participant assessment, vital signs, and physical exam will occur at study entry and Weeks 12 and 24. Follow-up calls to assess safety are scheduled for Weeks 4, 8, 16, and 20.

Additionally, participants will be offered the opportunity to enter one of four sub-studies as mentioned in the brief summary above: B Cell Kinetic Sub-Study, Vaccine Response Sub-Study, Tonsil Biopsy Sub-Study, and Synovial Biopsy Sub-Study. More information on these sub-studies is in the protocol.

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: A Partially Blinded, Randomized, Multi-Center, Phase IV Trial to Evaluate Mechanism of Action of Anti-TNF Agents in Rheumatoid Arthritis
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Etanercept Participants receive a subcutaneous injection of etanercept once every week for 24 weeks	Drug: Etanercept; 50 mg dose of etanercept by subcutaneous injection; Other Names: Enbrel®
Experimental: Adalimumab Participants receive a subcutaneous injection of adalimumab once every 2 weeks for 24 weeks	Drug: Adalimumab; 40 mg dose of adalimumab by subcutaneous injection; Other Names: Humira®)

Outcome Measures

Primary Outcome Measures

1. Percentage of CD27+ Switched Memory B Cells at Week 12 [Week 12]

   Analysis of the steady state composition of the B cell compartment were performed using ex-vivo multicolor flow cytometry on Ficoll isolated peripheral blood mononuclear cells (PBMCs). CD27+ switched memory B cells are a subset of B cells and are assessed by flow cytometry. CD27+ switched memory B cells are expressed as a percent of B cells. Lower CD27+ memory B cells indicate a decrease in the generation of B cell memory which may be caused by blocking lymphotoxin (LT) and tumor necrosis factor (TNF) signaling.

Secondary Outcome Measures

1. Percentage of Participants Fulfilling DAS-28-CRP "Good or Moderate Response" Criteria at Week 12 [Week 12]

   Good responders: change in DAS28-CRP (Baseline-Week12) > 1.2 and Week 12 DAS-CRP score was <\= 3.2. If the conditions for non-response* or good response were not met, the DAS28-CRP response was considered moderate. Participants with measurements for designated time points were included in the analysis. [*Non-responders had any of 4 conditions: change in DAS28-CRP (Baseline -Week 12) <0.6; 0.6 <\= change in DAS28-CRP ( Baseline-Week 12) < 1.2 with Week 12 DAS28-CRP score > 5.1; a flare that required prednisone > 10 mg/day (or equivalent) beyond Week 8 or the inability to taper prednisone to <\= 10 mg/day by Week 8; or the participant required prednisone > 20 mg/day at any time point].

2. Percentage of Participants Fulfilling DAS-28-CRP "Good or Moderate Response" Criteria at Week 24 [Week 24]

   Good responders had: change in DAS28-CRP (Baseline-Week 24) > 1.2 and the Week 24 DAS-CRP score was <= 3.2. If the conditions for non-response* or good response were not met then the DAS28-CRP response was considered moderate.[*Non-responders had any of the 4 conditions: change in DAS28-CRP (Baseline -Week 24) <0.6; 0.6 <\= change in DAS28-CRP ( Baseline-Week 24) < 1.2 with Week 24 DAS28-CRP score > 5.1 ; a flare that required prednisone > 10 mg/day (or equivalent) beyond Week 8 or the inability to taper prednisone to <= 10 mg/day by Week 8; or the participant required prednisone > 20 mg/day at any time point]. Participants with measurements for designated time points were included in the analysis.

3. Percentage of Participants Meeting ACR20 Response Criteria at Week 12 [Week 12]

   The American College of Rheumatology (ACR) 20 Responder Index is defined as someone who achieved at least 20% improvement in the tender and swollen 28-joint count, and 20% improvement in at least three of the following 5 measures: Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm) Patient's global assessment of disease activity (VAS 100 mm) Physician's global assessment of disease activity (VAS 100 mm) Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) Acute phase reactant (CRP). Participants with measurements for designated time points were included in the analysis.

4. Percentage of Participants Meeting ACR20 Response Criteria at Week 24 [Week 24]

   The American College of Rheumatology (ACR) 20 Responder Index is defined as someone who achieved at least 20% improvement in the tender and swollen 28-joint count, and 20% improvement in at least three of the following 5 measures: Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm) Patient's global assessment of disease activity (VAS 100 mm) Physician's global assessment of disease activity (VAS 100 mm) Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) Acute phase reactant (CRP). Participants with measurements for designated time points were included in the analysis.

5. Percentage of Participants Meeting ACR50 Response Criteria at Week 12 [Week 12]

   The American College of Rheumatology (ACR) 50 Responder Index is defined as someone who achieved at least 50% improvement in the tender and swollen 28-joint count, and 50% improvement in at least three of the following 5 measures: Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm) Patient's global assessment of disease activity (VAS 100 mm) Physician's global assessment of disease activity (VAS 100 mm) Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) Acute phase reactant (CRP). Participants with measurements for designated time points were included in the analysis.

6. Percentage of Participants Meeting ACR50 Response Criteria at Week 24 [Week 24]

   The American College of Rheumatology (ACR) 50 Responder Index is defined as someone who achieved at least 50% improvement in the tender and swollen 28-joint count, and 50% improvement in at least three of the following 5 measures: Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm) Patient's global assessment of disease activity (VAS 100 mm) Physician's global assessment of disease activity (VAS 100 mm) Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) Acute phase reactant (CRP). Participants with measurements for designated time points were included in the analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of RA*

• Disease duration as defined from the onset of symptoms of at least 3 months prior to study entry

• Active RA with DAS28 > 4.4, clinically requiring the addition of anti-TNF therapy

• Stable dose of MTX between 7.5 mg and 25 mg weekly for at least 8 weeks prior to study entry

• Able and willing to self-administer subcutaneous injections or have available qualified person(s) or caregiver to administer subcutaneous injections

• For females, agree to use accepted methods of contraception during the duration of the study and for 150 days after study completion*. *More information on these criterion can be found in the protocol.

Exclusion Criteria:

• Positive PPD test - a tuberculosis (TB) skin test: (> 5 mm induration regardless of prior Bacille Calmette-Guerin [BCG] vaccine administration) without evidence of ongoing treatment for at least 30 days or completed treatment

• History of positive PPD or chest x-ray findings indicative of prior TB infection, without documentation of either treatment for TB infection or chemoprophylaxis for TB exposure

• Prednisone dose > 10 mg/day (or equivalent dose of another corticosteroid) within 30 days prior to study entry

• Definitive diagnosis of another autoimmune disease that may require immunosuppression for treatment*

• Concomitant use of DMARDSs (e.g., disease-modifying antirheumatic drugs)*

• Any immunosuppressive therapy other than MTX, NSAIDs, or corticosteroids*

• Current or previous use of any biologic agent

• Presence of open leg ulcers

• Chronic or persistent infection that might be worsened by immunosuppressive treatment*

• Active infection or severe infections requiring hospitalization or treatment with intravenous (IV) antibiotics, IV antivirals, or IV antifungals within 30 days prior to study entry

• Received oral antibiotics, antivirals, or antifungals within 14 days prior to study entry

• Certain abnormal laboratory values*

• Any medical condition that, in the opinion of the investigator, would interfere with the study

• History of malignancy other than treated localized carcinoma in situ of the cervix or adequately treated non-metastatic squamous or basal cell skin carcinoma within 10 years prior to study entry

• Any Investigational agent within the earlier of 4 weeks or 5 half-lives prior to study entry

• History of drug or alcohol abuse within 6 months prior to study entry

• Known allergy or hypersensitivity to study products

• Inability or unwillingness to follow the protocol

• Any condition or treatment that, in the opinion of the investigator, places the participant at an unacceptable risk

• Pregnant or breastfeeding *More information on these criterion are in the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35294
2	University of California, San Francisco	San Francisco	California	United States	94143
3	Yale University School Medicine	New Haven	Connecticut	United States	06519
4	University of Chicago	Chicago	Illinois	United States	60637
5	Feinstein Institute for Medical Research	Manhasset	New York	United States	11030
6	University of Rochester	Rochester	New York	United States	14642
7	Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Autoimmunity Centers of Excellence
• Rho Federal Systems Division, Inc.

Investigators

• Study Chair: Jennifer A. Anolik, MD, PhD, University of Rochester
• Study Chair: Inaki Sanz, MD, University of Rochester
• Study Chair: R. John Looney, MD, University of Rochester
• Principal Investigator: Meggan Mackay, MD, The Feinstein Institute for Medical Research NS-LIJ Health System
• Principal Investigator: Jeffrey Curtis, MD, University of Alabama at Birmingham

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)

Publications

• Bingham CO 3rd. Emerging therapeutics for rheumatoid arthritis. Bull NYU Hosp Jt Dis. 2008;66(3):210-5. Review.
• Otomo K, Koike T. [TNF inhibitors for treatment of rheumatoid arthritis]. Nihon Naika Gakkai Zasshi. 2008 Oct 10;97(10):2405-12. Review. Japanese.
• Soen S. [Daily practice using the guidelines for prevention and treatment of osteoporosis. The effects of anti-TNF therapy on bone and joint manifestations in rheumatoid arthritis]. Clin Calcium. 2008 Aug;18(8):1169-75. doi: CliCa080811691175. Review. Japanese.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00837434
• Other Study ID Numbers: DAIT ARA06; NIAID CRMS ID#: 20001
• First Posted: Feb 5, 2009
• Last Update Posted: Sep 22, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): tumor necrosis factor (TNF) blockade; inflammatory autoimmune disorder
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Adalimumab; Etanercept

Study Results

Participant Flow

Recruitment Details	Participants were to be recruited from seven sites in the United States. Recruitment occurred at six sites. The first site was activated in April 2009. The first participant was randomized in July 2009 and the last participant was randomized in July 2013.

Arm/Group Title	Etanercept	Adalimumab
Arm/Group Description	Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Period Title: Overall Study
STARTED	43	20
COMPLETED	34	19
NOT COMPLETED	9	1

Baseline Characteristics

Arm/Group Title	Etanercept	Adalimumab	Total
Arm/Group Description	Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.	Total of all reporting groups
Overall Participants	39	19	58
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.7 (9.4)	52.7 (14.0)	52.0 (11.0)
Sex: Female, Male (Count of Participants)
Female	31 79.5%	15 78.9%	46 79.3%
Male	8 20.5%	4 21.1%	12 20.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 20.5%	1 5.3%	9 15.5%
Not Hispanic or Latino	31 79.5%	18 94.7%	49 84.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 12.8%	1 5.3%	6 10.3%
White	30 76.9%	18 94.7%	48 82.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	4 10.3%	0 0%	4 6.9%
Region of Enrollment (participants) [Number]
United States	39 100%	19 100%	58 100%
Detection of Either IgM-Rheumatoid Factor or Antibodies to Cyclic Citrullinated Peptide (participants) [Number]
Positive	30 76.9%	14 73.7%	44 75.9%
Negative	9 23.1%	5 26.3%	14 24.1%
Detection of IgM-Rheumatoid Factor (IgM RF) (participants) [Number]
Positive	24 61.5%	9 47.4%	33 56.9%
Negative	15 38.5%	10 52.6%	25 43.1%
Detection of Antibodies to Cyclic Citrullinated Antibody Peptide (participants) [Number]
Positive	25 64.1%	11 57.9%	36 62.1%
Negative	14 35.9%	8 42.1%	22 37.9%
Methotrexate Dosage (mg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg]	17.4 (4.0)	18.8 (3.8)	17.9 (3.9)
Years with Rheumatoid Arthritis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	5.8 (7.7)	4.3 (5.2)	5.3 (7.0)
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	1.4 (0.7)	1.3 (0.6)	1.4 (0.7)
C-reactive Protein (CRP) Level (mg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/L]	14.1 (25.5)	13.3 (24.3)	13.8 (24.9)
Tender Joint Count (Joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Joints]	12.2 (6.6)	12.6 (7.2)	12.3 (6.7)
Swollen Joint Count at Baseline (Joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Joints]	9.9 (6.2)	9.4 (5.9)	9.7 (6.0)
Patient's Global Assessment of Disease Activity- Visual Analog Scale (PtGADA-VAS) (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	5.9 (2.6)	7.3 (2.0)	6.4 (2.5)
Disease Activity Score Using C-reactive Protein (DAS28-CRP) (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	5.2 (1.0)	5.4 (0.7)	5.3 (0.9)

Outcome Measures

1. Primary Outcome

Title	Percentage of CD27+ Switched Memory B Cells at Week 12
Description	Analysis of the steady state composition of the B cell compartment were performed using ex-vivo multicolor flow cytometry on Ficoll isolated peripheral blood mononuclear cells (PBMCs). CD27+ switched memory B cells are a subset of B cells and are assessed by flow cytometry. CD27+ switched memory B cells are expressed as a percent of B cells. Lower CD27+ memory B cells indicate a decrease in the generation of B cell memory which may be caused by blocking lymphotoxin (LT) and tumor necrosis factor (TNF) signaling.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The Per Protocol population includes subjects with a baseline and week 12 (plus or minus 1 week) assessment that received at least 75% of the planned doses of either etanercept or adalimumab prior to week 12 and who did not have any serious protocol deviations.

Arm/Group Title	Etanercept	Adalimumab
Arm/Group Description	Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Measure Participants	30	18
Mean (Standard Deviation) [Percentage of B Cells]	13.2 (7.3)	13.8 (7.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Adalimumab
	Comments	Null Hypothesis: Mean percentage of CD27+ switched memory cells in the peripheral blood at Week 12 does not differ between individuals treated with etanercept and those treated with adalimumab after adjusting for baseline CD27+ switched memory cells. Alt. hypothesis: Mean percentage of CD27+ switched memory cells in the peripheral blood at Week 12 in individuals treated with etanercept is lower than in those treated with adalimumab after adjusting for baseline CD27+ switched memory cells.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3
	Comments
	Method	ANCOVA
	Comments	P-value for testing treatment effect uses week 12 CD27+ switched memory as the outcome variable and adjusts for baseline CD27+ switched memory

2. Secondary Outcome

Title	Percentage of Participants Fulfilling DAS-28-CRP "Good or Moderate Response" Criteria at Week 12
Description	Good responders: change in DAS28-CRP (Baseline-Week12) > 1.2 and Week 12 DAS-CRP score was <\= 3.2. If the conditions for non-response* or good response were not met, the DAS28-CRP response was considered moderate. Participants with measurements for designated time points were included in the analysis. [*Non-responders had any of 4 conditions: change in DAS28-CRP (Baseline -Week 12) <0.6; 0.6 <\= change in DAS28-CRP ( Baseline-Week 12) < 1.2 with Week 12 DAS28-CRP score > 5.1; a flare that required prednisone > 10 mg/day (or equivalent) beyond Week 8 or the inability to taper prednisone to <\= 10 mg/day by Week 8; or the participant required prednisone > 20 mg/day at any time point].
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The Modified Intent-to-Treat with available data population included all randomized subjects who received at least one dose of either etanercept or adalimumab. Data were not available for two participants who received Etanercept.

Arm/Group Title	Etanercept	Adalimumab
Arm/Group Description	Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Measure Participants	37	19
Number [percentage of participants]	86.5 221.8%	89.5 471.1%

3. Secondary Outcome

Title	Percentage of Participants Fulfilling DAS-28-CRP "Good or Moderate Response" Criteria at Week 24
Description	Good responders had: change in DAS28-CRP (Baseline-Week 24) > 1.2 and the Week 24 DAS-CRP score was <= 3.2. If the conditions for non-response* or good response were not met then the DAS28-CRP response was considered moderate.[*Non-responders had any of the 4 conditions: change in DAS28-CRP (Baseline -Week 24) <0.6; 0.6 <\= change in DAS28-CRP ( Baseline-Week 24) < 1.2 with Week 24 DAS28-CRP score > 5.1 ; a flare that required prednisone > 10 mg/day (or equivalent) beyond Week 8 or the inability to taper prednisone to <= 10 mg/day by Week 8; or the participant required prednisone > 20 mg/day at any time point]. Participants with measurements for designated time points were included in the analysis.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The Modified Intent-to-Treat with available data population included all randomized subjects who received at least one dose of either etanercept or adalimumab. Data were not available for five participants who received Etanercept.

Arm/Group Title	Etanercept	Adalimumab
Arm/Group Description	Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Measure Participants	34	19
Number [percentage of participants]	88.2 226.2%	84.2 443.2%

4. Secondary Outcome

Title	Percentage of Participants Meeting ACR20 Response Criteria at Week 12
Description	The American College of Rheumatology (ACR) 20 Responder Index is defined as someone who achieved at least 20% improvement in the tender and swollen 28-joint count, and 20% improvement in at least three of the following 5 measures: Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm) Patient's global assessment of disease activity (VAS 100 mm) Physician's global assessment of disease activity (VAS 100 mm) Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) Acute phase reactant (CRP). Participants with measurements for designated time points were included in the analysis.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The Modified Intent-to-Treat with available data population included all randomized subjects who received at least one dose of either etanercept or adalimumab. Data were not available for two participants who received Etanercept.

Arm/Group Title	Etanercept	Adalimumab
Arm/Group Description	Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Measure Participants	37	19
Number [percentage of participants]	67.6 173.3%	73.7 387.9%

5. Secondary Outcome

Title	Percentage of Participants Meeting ACR20 Response Criteria at Week 24
Description	The American College of Rheumatology (ACR) 20 Responder Index is defined as someone who achieved at least 20% improvement in the tender and swollen 28-joint count, and 20% improvement in at least three of the following 5 measures: Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm) Patient's global assessment of disease activity (VAS 100 mm) Physician's global assessment of disease activity (VAS 100 mm) Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) Acute phase reactant (CRP). Participants with measurements for designated time points were included in the analysis.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The Modified Intent-to-Treat with available data population included all randomized subjects who received at least one dose of either etanercept or adalimumab. Data were not available for five participants who received Etanercept.

Arm/Group Title	Etanercept	Adalimumab
Arm/Group Description	Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Measure Participants	34	19
Number [percentage of participants]	73.5 188.5%	84.2 443.2%

6. Secondary Outcome

Title	Percentage of Participants Meeting ACR50 Response Criteria at Week 12
Description	The American College of Rheumatology (ACR) 50 Responder Index is defined as someone who achieved at least 50% improvement in the tender and swollen 28-joint count, and 50% improvement in at least three of the following 5 measures: Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm) Patient's global assessment of disease activity (VAS 100 mm) Physician's global assessment of disease activity (VAS 100 mm) Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) Acute phase reactant (CRP). Participants with measurements for designated time points were included in the analysis.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The Modified Intent-to-Treat with available data population included all randomized subjects who received at least one dose of either etanercept or adalimumab. Data were not available for two participants who received Etanercept.

Arm/Group Title	Etanercept	Adalimumab
Arm/Group Description	Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Measure Participants	37	19
Number [percentage of participants]	29.7 76.2%	47.4 249.5%

7. Secondary Outcome

Title	Percentage of Participants Meeting ACR50 Response Criteria at Week 24
Description	The American College of Rheumatology (ACR) 50 Responder Index is defined as someone who achieved at least 50% improvement in the tender and swollen 28-joint count, and 50% improvement in at least three of the following 5 measures: Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm) Patient's global assessment of disease activity (VAS 100 mm) Physician's global assessment of disease activity (VAS 100 mm) Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) Acute phase reactant (CRP). Participants with measurements for designated time points were included in the analysis.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The Modified Intent-to-Treat with available data population included all randomized subjects who received at least one dose of either etanercept or adalimumab. Data were not available for five participants who received Etanercept.

Arm/Group Title	Etanercept	Adalimumab
Arm/Group Description	Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.	Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
Measure Participants	34	19
Number [percentage of participants]	38.2 97.9%	63.2 332.6%

Adverse Events

Time Frame	From the time of administration of the first dose of study drug until the participant completed study participation, an average of 24 weeks, or until 30 days after the participant prematurely withdrew.
Arm/Group Title	Etanercept		Adalimumab
Arm/Group Description	Participants were randomized to receive 50 mg etanercept given by subcutaneous injection every week for 24 weeks.		Participants were randomized to receive one subcutaneous injection of 40 mg adalimumab every other week for 24 weeks.
All Cause Mortality
	Etanercept		Adalimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Etanercept		Adalimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/39 (5.1%)		1/19 (5.3%)
Gastrointestinal disorders
Gastrooesophageal reflux disease	1/39 (2.6%)	1	0/19 (0%)	0
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	0/39 (0%)	0	1/19 (5.3%)	1
Psychiatric disorders
Suicide attempt	1/39 (2.6%)	1	0/19 (0%)	0
Other (Not Including Serious) Adverse Events
	Etanercept		Adalimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/39 (79.5%)		17/19 (89.5%)
Blood and lymphatic system disorders
Anaemia	9/39 (23.1%)	9	3/19 (15.8%)	3
Leukopenia	4/39 (10.3%)	7	2/19 (10.5%)	2
Lymphopenia	5/39 (12.8%)	5	3/19 (15.8%)	5
Neutropenia	3/39 (7.7%)	5	1/19 (5.3%)	1
Gastrointestinal disorders
Nausea	2/39 (5.1%)	2	1/19 (5.3%)	1
General disorders
Fatigue	1/39 (2.6%)	1	2/19 (10.5%)	2
Infections and infestations
Bronchitis	4/39 (10.3%)	4	2/19 (10.5%)	2
Gastroenteritis	2/39 (5.1%)	2	1/19 (5.3%)	1
Nasopharyngitis	4/39 (10.3%)	4	3/19 (15.8%)	4
Upper respiratory tract infection	4/39 (10.3%)	5	1/19 (5.3%)	1
Investigations
Alanine aminotransferase increased	7/39 (17.9%)	9	4/19 (21.1%)	4
Aspartate aminotransferase increased	10/39 (25.6%)	12	3/19 (15.8%)	3
Blood creatinine increased	5/39 (12.8%)	6	1/19 (5.3%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	5/39 (12.8%)	5	1/19 (5.3%)	1
Back pain	3/39 (7.7%)	3	0/19 (0%)	0
Pain in extremity	5/39 (12.8%)	6	2/19 (10.5%)	2
Nervous system disorders
Headache	6/39 (15.4%)	6	1/19 (5.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	3/39 (7.7%)	3	0/19 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis contact	3/39 (7.7%)	3	0/19 (0%)	0
Rash	4/39 (10.3%)	4	2/19 (10.5%)	2
Vascular disorders
Hypertension	2/39 (5.1%)	2	1/19 (5.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.