Trial Outcomes & Findings for Switching Anti-TNF-Alpha Agents in Rheumatoid Arthritis (RA) (NCT NCT00796705)

Last Updated: 2012-10-04

Results Overview

The DAS28 is a score on a scale (0 to 10) indicating current activity of rheumatoid arthritis (\>5.1=high disease activity; \<=3.2=low disease activity; \<2.6=remission); a continuous variable which is a composite of 4 variables(the number of tender joints out of 28, the number of swollen joints out of 28 joints, serum C-reactive protein in mg/L (CRP) and subject assessment of disease activity measure on a visual analogue scale (VAS) of 100 mm).

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

13 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2012-10-04

Participant Flow

Subject recruitment occurred between November 2008 and November 2010 at 16 sites located in the United States. All sites utilized a rheumatology clinic and outside referrals for recruitment.

Each subject signed an informed consent prior to undergoing any screening procedures. At the screening visit, subjects underwent procedures to establish inclusion/exclusion criteria.

Participant milestones

Participant milestones
Measure	Non-Switcher/Adalimumab Alternating With Placebo Participants defined as adalimumab failures \[1\] at screening who were randomized to remain on adalimumab (one 40 milligram \[mg\] subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 millilitre \[mL\] SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. \[1\] Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab.	Non-Switcher/Etanercept Participants defined as etanercept failures \[1\] at screening who were randomized to receive etanercept (one 50 mg subcutaneous injection) once weekly for a total of 12 weeks in a blinded (masked) fashion. \[1\] Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Switcher/Adalimumab to Etanercept Participants defined as adalimumab failures \[1\] at screening who were randomized to switch from adalimumab to etanercept (one 50 mg subcutaneous injection) once weekly for a total of 12 weeks in a blinded (masked) treatment fashion. \[1\] Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab.	Switcher/Etanercept to Adalimumab Alternating With Placebo Participants defined as etanercept failures \[1\] at screening who were randomized to switch from etanercept to adalimumab (one 40 mg subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 mL SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. \[1\] Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.
Overall Study STARTED	3	4	4	2
Overall Study COMPLETED	3	4	4	2
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Switching Anti-TNF-Alpha Agents in Rheumatoid Arthritis (RA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Non-Switcher/Adalimumab Alternating With Placebo n=3 Participants Participants defined as adalimumab failures \[1\] at screening who were randomized to remain on adalimumab (one 40 milligram \[mg\] subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 millilitre \[mL\] SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. \[1\] Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab.	Non-Switcher/Etanercept n=4 Participants Participants defined as etanercept failures \[1\] at screening who were randomized to receive etanercept (one 50 mg subcutaneous injection) once weekly for a total of 12 weeks in a blinded (masked) fashion. \[1\] Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Switcher/Adalimumab to Etanercept n=4 Participants Participants defined as adalimumab failures \[1\]at screening who were randomized to switch from adalimumab to etanercept (one 50 mg subcutaneous injection) once weekly for a total of 12 weeks in a blinded (masked) treatment fashion. \[1\] Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab.	Switcher/Etanercept to Adalimumab Alternating With Placebo n=2 Participants Participants defined as etanercept failures \[1\] at screening who were randomized to switch from etanercept to adalimumab (one 40 mg subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 mL SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. \[1\] Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Total n=13 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	11 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Age Continuous	53 years STANDARD_DEVIATION 4.0 • n=5 Participants	65 years STANDARD_DEVIATION 9.4 • n=7 Participants	39 years STANDARD_DEVIATION 13.7 • n=5 Participants	60 years STANDARD_DEVIATION 6.4 • n=4 Participants	53 years STANDARD_DEVIATION 14.0 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	13 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	3 participants n=5 Participants	4 participants n=7 Participants	4 participants n=5 Participants	2 participants n=4 Participants	13 participants n=21 Participants
Disease Activity Score Using C-reactive Protein (DAS28[CRP])	5.6 Scores on a scale STANDARD_DEVIATION 0.66 • n=5 Participants	5.4 Scores on a scale STANDARD_DEVIATION 0.44 • n=7 Participants	4.8 Scores on a scale STANDARD_DEVIATION 0.62 • n=5 Participants	5.3 Scores on a scale STANDARD_DEVIATION 0.19 • n=4 Participants	5.3 Scores on a scale STANDARD_DEVIATION 0.56 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: Intent-to-treat

Outcome measures

Outcome measures
Measure	Non-Switcher/ Adalimumab or Etanercept n=7 Participants Participants defined as adalimumab failures \[1\] at screening who were randomized to remain on adalimumab (one 40 milligram \[mg\] subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 millilitre \[mL\] SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion and participants defined as etanercept failures \[2\] at screening who were randomized to receive etanercept (one 50 mg SQ injection) once weekly for a total of 12 weeks in a blinded (masked) fashion. 1. Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab. 2. Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Switcher/ Adalimumab to Etanercept or Etanercept to Adalimuma n=6 Participants Participants defined as adalimumab failures \[1\]at screening who were randomized to switch from adalimumab to etanercept (one 50 mg SQ injection) once weekly for a total of 12 weeks in a blinded (masked) treatment fashion and participants defined as etanercept failures \[2\] at screening who were randomized to switch from etanercept to adalimumab (one 40 mg SQ injection) alternating with adalimumab placebo (1.0 mL SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. 1. Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab. 2. Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Switcher/Adalimumab to Etanercept Participants defined as adalimumab failures \[1\]at screening who were randomized to switch from adalimumab to etanercept (one 50 mg subcutaneous injection) once weekly for a total of 12 weeks in a blinded (masked) treatment fashion. \[1\] Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab.	Switcher/Etanercept to Adalimumab Alternating With Placebo Participants defined as etanercept failures \[1\] at screening who were randomized to switch from etanercept to adalimumab (one 40 mg subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 mL SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. \[1\] Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.
Change in the Disease Activity Score Using C-reactive Protein (DAS28[CRP]) From Baseline to Week 12 in Non-Switchers Versus Switchers.	-1.4 Scores on a scale Standard Deviation 0.90	-1.7 Scores on a scale Standard Deviation 1.09	—	—

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: Intent-to-treat

Outcome measures

Outcome measures
Measure	Non-Switcher/ Adalimumab or Etanercept n=3 Participants Participants defined as adalimumab failures \[1\] at screening who were randomized to remain on adalimumab (one 40 milligram \[mg\] subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 millilitre \[mL\] SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion and participants defined as etanercept failures \[2\] at screening who were randomized to receive etanercept (one 50 mg SQ injection) once weekly for a total of 12 weeks in a blinded (masked) fashion. 1. Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab. 2. Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Switcher/ Adalimumab to Etanercept or Etanercept to Adalimuma n=4 Participants Participants defined as adalimumab failures \[1\]at screening who were randomized to switch from adalimumab to etanercept (one 50 mg SQ injection) once weekly for a total of 12 weeks in a blinded (masked) treatment fashion and participants defined as etanercept failures \[2\] at screening who were randomized to switch from etanercept to adalimumab (one 40 mg SQ injection) alternating with adalimumab placebo (1.0 mL SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. 1. Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab. 2. Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Switcher/Adalimumab to Etanercept n=4 Participants Participants defined as adalimumab failures \[1\]at screening who were randomized to switch from adalimumab to etanercept (one 50 mg subcutaneous injection) once weekly for a total of 12 weeks in a blinded (masked) treatment fashion. \[1\] Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab.	Switcher/Etanercept to Adalimumab Alternating With Placebo n=2 Participants Participants defined as etanercept failures \[1\] at screening who were randomized to switch from etanercept to adalimumab (one 40 mg subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 mL SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. \[1\] Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.
Change in the Disease Activity Score Using C-reactive Protein (DAS28[CRP]) From Baseline to Week 12.	-2.0 Scores on a scale Standard Deviation 0.22	-0.9 Scores on a scale Standard Deviation 0.92	-1.7 Scores on a scale Standard Deviation 0.94	-1.5 Scores on a scale Standard Deviation 1.81

SECONDARY outcome

Timeframe: Week 12

Population: Intent-to-treat

Outcome measures

Outcome measures
Measure	Non-Switcher/ Adalimumab or Etanercept n=3 Participants Participants defined as adalimumab failures \[1\] at screening who were randomized to remain on adalimumab (one 40 milligram \[mg\] subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 millilitre \[mL\] SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion and participants defined as etanercept failures \[2\] at screening who were randomized to receive etanercept (one 50 mg SQ injection) once weekly for a total of 12 weeks in a blinded (masked) fashion. 1. Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab. 2. Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Switcher/ Adalimumab to Etanercept or Etanercept to Adalimuma n=4 Participants Participants defined as adalimumab failures \[1\]at screening who were randomized to switch from adalimumab to etanercept (one 50 mg SQ injection) once weekly for a total of 12 weeks in a blinded (masked) treatment fashion and participants defined as etanercept failures \[2\] at screening who were randomized to switch from etanercept to adalimumab (one 40 mg SQ injection) alternating with adalimumab placebo (1.0 mL SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. 1. Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab. 2. Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Switcher/Adalimumab to Etanercept n=4 Participants Participants defined as adalimumab failures \[1\]at screening who were randomized to switch from adalimumab to etanercept (one 50 mg subcutaneous injection) once weekly for a total of 12 weeks in a blinded (masked) treatment fashion. \[1\] Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab.	Switcher/Etanercept to Adalimumab Alternating With Placebo n=2 Participants Participants defined as etanercept failures \[1\] at screening who were randomized to switch from etanercept to adalimumab (one 40 mg subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 mL SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. \[1\] Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.
Participants With a Disease Activity Score Using C-reactive Protein (DAS28[CRP]) Value <= 3.2 (Low Disease Activity) at Week 12	1 participants	1 participants	2 participants	1 participants

SECONDARY outcome

Timeframe: Week 12

Population: Intent-to-treat

Outcome measures

Outcome measures
Measure	Non-Switcher/ Adalimumab or Etanercept n=3 Participants Participants defined as adalimumab failures \[1\] at screening who were randomized to remain on adalimumab (one 40 milligram \[mg\] subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 millilitre \[mL\] SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion and participants defined as etanercept failures \[2\] at screening who were randomized to receive etanercept (one 50 mg SQ injection) once weekly for a total of 12 weeks in a blinded (masked) fashion. 1. Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab. 2. Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Switcher/ Adalimumab to Etanercept or Etanercept to Adalimuma n=4 Participants Participants defined as adalimumab failures \[1\]at screening who were randomized to switch from adalimumab to etanercept (one 50 mg SQ injection) once weekly for a total of 12 weeks in a blinded (masked) treatment fashion and participants defined as etanercept failures \[2\] at screening who were randomized to switch from etanercept to adalimumab (one 40 mg SQ injection) alternating with adalimumab placebo (1.0 mL SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. 1. Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab. 2. Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Switcher/Adalimumab to Etanercept n=4 Participants Participants defined as adalimumab failures \[1\]at screening who were randomized to switch from adalimumab to etanercept (one 50 mg subcutaneous injection) once weekly for a total of 12 weeks in a blinded (masked) treatment fashion. \[1\] Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab.	Switcher/Etanercept to Adalimumab Alternating With Placebo n=2 Participants Participants defined as etanercept failures \[1\] at screening who were randomized to switch from etanercept to adalimumab (one 40 mg subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 mL SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. \[1\] Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.
Participants With a Disease Activity Score Using C-reactive Protein (DAS28[CRP]) Value < 2.6 (Remission) at Week 12	0 participants	0 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Intent-to-treat

The EULAR definition of a Moderate Response is a decrease from baseline in the DAS28\[CRP\] value of ≥ 1.2.

Outcome measures

Outcome measures
Measure	Non-Switcher/ Adalimumab or Etanercept n=3 Participants Participants defined as adalimumab failures \[1\] at screening who were randomized to remain on adalimumab (one 40 milligram \[mg\] subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 millilitre \[mL\] SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion and participants defined as etanercept failures \[2\] at screening who were randomized to receive etanercept (one 50 mg SQ injection) once weekly for a total of 12 weeks in a blinded (masked) fashion. 1. Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab. 2. Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Switcher/ Adalimumab to Etanercept or Etanercept to Adalimuma n=4 Participants Participants defined as adalimumab failures \[1\]at screening who were randomized to switch from adalimumab to etanercept (one 50 mg SQ injection) once weekly for a total of 12 weeks in a blinded (masked) treatment fashion and participants defined as etanercept failures \[2\] at screening who were randomized to switch from etanercept to adalimumab (one 40 mg SQ injection) alternating with adalimumab placebo (1.0 mL SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. 1. Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab. 2. Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Switcher/Adalimumab to Etanercept n=4 Participants Participants defined as adalimumab failures \[1\]at screening who were randomized to switch from adalimumab to etanercept (one 50 mg subcutaneous injection) once weekly for a total of 12 weeks in a blinded (masked) treatment fashion. \[1\] Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab.	Switcher/Etanercept to Adalimumab Alternating With Placebo n=2 Participants Participants defined as etanercept failures \[1\] at screening who were randomized to switch from etanercept to adalimumab (one 40 mg subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 mL SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. \[1\] Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.
Participants With a Decrease in Disease Activity Score Using C-reactive Protein (DAS28[CRP]) Value of >1.2 From Baseline to Week 12 (European League Against Rheumatism (EULAR) Definition of a Moderate Response)	3 participants	1 participants	2 participants	1 participants

SECONDARY outcome

Timeframe: Week 12

Population: Intent-to-treat

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)

Outcome measures

Outcome measures
Measure	Non-Switcher/ Adalimumab or Etanercept n=3 Participants Participants defined as adalimumab failures \[1\] at screening who were randomized to remain on adalimumab (one 40 milligram \[mg\] subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 millilitre \[mL\] SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion and participants defined as etanercept failures \[2\] at screening who were randomized to receive etanercept (one 50 mg SQ injection) once weekly for a total of 12 weeks in a blinded (masked) fashion. 1. Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab. 2. Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Switcher/ Adalimumab to Etanercept or Etanercept to Adalimuma n=4 Participants Participants defined as adalimumab failures \[1\]at screening who were randomized to switch from adalimumab to etanercept (one 50 mg SQ injection) once weekly for a total of 12 weeks in a blinded (masked) treatment fashion and participants defined as etanercept failures \[2\] at screening who were randomized to switch from etanercept to adalimumab (one 40 mg SQ injection) alternating with adalimumab placebo (1.0 mL SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. 1. Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab. 2. Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Switcher/Adalimumab to Etanercept n=4 Participants Participants defined as adalimumab failures \[1\]at screening who were randomized to switch from adalimumab to etanercept (one 50 mg subcutaneous injection) once weekly for a total of 12 weeks in a blinded (masked) treatment fashion. \[1\] Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab.	Switcher/Etanercept to Adalimumab Alternating With Placebo n=2 Participants Participants defined as etanercept failures \[1\] at screening who were randomized to switch from etanercept to adalimumab (one 40 mg subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 mL SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. \[1\] Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.
Participants With an ACR 20 Response at Week 12	3 participants	2 participants	3 participants	1 participants

SECONDARY outcome

Timeframe: Week 12

Population: Intent-to-treat

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)

Outcome measures

Outcome measures
Measure	Non-Switcher/ Adalimumab or Etanercept n=3 Participants Participants defined as adalimumab failures \[1\] at screening who were randomized to remain on adalimumab (one 40 milligram \[mg\] subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 millilitre \[mL\] SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion and participants defined as etanercept failures \[2\] at screening who were randomized to receive etanercept (one 50 mg SQ injection) once weekly for a total of 12 weeks in a blinded (masked) fashion. 1. Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab. 2. Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Switcher/ Adalimumab to Etanercept or Etanercept to Adalimuma n=4 Participants Participants defined as adalimumab failures \[1\]at screening who were randomized to switch from adalimumab to etanercept (one 50 mg SQ injection) once weekly for a total of 12 weeks in a blinded (masked) treatment fashion and participants defined as etanercept failures \[2\] at screening who were randomized to switch from etanercept to adalimumab (one 40 mg SQ injection) alternating with adalimumab placebo (1.0 mL SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. 1. Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab. 2. Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Switcher/Adalimumab to Etanercept n=4 Participants Participants defined as adalimumab failures \[1\]at screening who were randomized to switch from adalimumab to etanercept (one 50 mg subcutaneous injection) once weekly for a total of 12 weeks in a blinded (masked) treatment fashion. \[1\] Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab.	Switcher/Etanercept to Adalimumab Alternating With Placebo n=2 Participants Participants defined as etanercept failures \[1\] at screening who were randomized to switch from etanercept to adalimumab (one 40 mg subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 mL SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. \[1\] Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.
Participants With an ACR 50 Response at Week 12	2 participants	0 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Week 12

Population: Intent-to-treat

The American College of Rheumatology (ACR) 70 Responder Index is defined as someone who achieved at least 70% improvement in the tender and swollen 28- joint count, and 70% improvement in at least three of the following 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)

Outcome measures

Outcome measures
Measure	Non-Switcher/ Adalimumab or Etanercept n=3 Participants Participants defined as adalimumab failures \[1\] at screening who were randomized to remain on adalimumab (one 40 milligram \[mg\] subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 millilitre \[mL\] SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion and participants defined as etanercept failures \[2\] at screening who were randomized to receive etanercept (one 50 mg SQ injection) once weekly for a total of 12 weeks in a blinded (masked) fashion. 1. Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab. 2. Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Switcher/ Adalimumab to Etanercept or Etanercept to Adalimuma n=4 Participants Participants defined as adalimumab failures \[1\]at screening who were randomized to switch from adalimumab to etanercept (one 50 mg SQ injection) once weekly for a total of 12 weeks in a blinded (masked) treatment fashion and participants defined as etanercept failures \[2\] at screening who were randomized to switch from etanercept to adalimumab (one 40 mg SQ injection) alternating with adalimumab placebo (1.0 mL SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. 1. Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab. 2. Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.	Switcher/Adalimumab to Etanercept n=4 Participants Participants defined as adalimumab failures \[1\]at screening who were randomized to switch from adalimumab to etanercept (one 50 mg subcutaneous injection) once weekly for a total of 12 weeks in a blinded (masked) treatment fashion. \[1\] Adalimumab failures: participants with rheumatoid arthritis \[RA\] on adalimumab treatment for at least 12 weeks prior to treatment randomization that experienced inadequate clinical response to adalimumab.	Switcher/Etanercept to Adalimumab Alternating With Placebo n=2 Participants Participants defined as etanercept failures \[1\] at screening who were randomized to switch from etanercept to adalimumab (one 40 mg subcutaneous \[SQ\] injection) alternating with adalimumab placebo (1.0 mL SQ injection of normal saline 0.9%) once weekly for a total of 12 weeks in a blinded (masked) fashion. \[1\] Etanercept failures: participants with rheumatoid arthritis \[RA\] on etanercept treatment for at least 12 weeks prior to randomization that experienced inadequate clinical response to etanercept.
Participants With an ACR 70 Response at Week 12	0 participants	0 participants	0 participants	0 participants

Adverse Events

Non-Switcher/Adalimumab

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Non-Switcher/Etanercept

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Switcher/Adalimumab to Etanercept

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Switcher/Etanercept to Adalimumab

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Non-Switcher/Adalimumab n=3 participants at risk Subjects failing Adalimumab at screening who were randomized to remain on Adalimumab	Non-Switcher/Etanercept n=4 participants at risk Subjects failing Etanercept at screening who were randomized to remain on Etanercept	Switcher/Adalimumab to Etanercept n=4 participants at risk Subjects failing Adalimumab at screening who were randomized to switch to Etanercept	Switcher/Etanercept to Adalimumab n=2 participants at risk Subjects failing Etanercept at screening who were randomized to switch to Adalimumab
Gastrointestinal disorders Abdominal distension	33.3% 1/3 • Number of events 1	0.00% 0/4	0.00% 0/4	0.00% 0/2
Gastrointestinal disorders Constipation	33.3% 1/3 • Number of events 1	0.00% 0/4	0.00% 0/4	0.00% 0/2
Gastrointestinal disorders Diarrhoea	0.00% 0/3	0.00% 0/4	0.00% 0/4	50.0% 1/2 • Number of events 7
Gastrointestinal disorders Dry mouth	33.3% 1/3 • Number of events 1	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
Gastrointestinal disorders Nausea	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
Gastrointestinal disorders Vomiting	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
General disorders Fatigue	33.3% 1/3 • Number of events 1	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
General disorders Influenza like illness	33.3% 1/3 • Number of events 1	0.00% 0/4	0.00% 0/4	0.00% 0/2
General disorders Injection site haematoma	0.00% 0/3	0.00% 0/4	0.00% 0/4	50.0% 1/2 • Number of events 1
General disorders Injection site irritation	0.00% 0/3	50.0% 2/4 • Number of events 6	0.00% 0/4	50.0% 1/2 • Number of events 1
General disorders Injection site pain	0.00% 0/3	50.0% 2/4 • Number of events 7	0.00% 0/4	0.00% 0/2
General disorders Injection site reaction	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
General disorders Pain	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
Infections and infestations Bronchitis	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
Infections and infestations Gastroenteritis viral	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
Infections and infestations Laryngitis	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
Infections and infestations Nasopharyngitis	0.00% 0/3	25.0% 1/4 • Number of events 1	0.00% 0/4	0.00% 0/2
Infections and infestations Otitis media	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
Infections and infestations Rhinitis	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
Infections and infestations Tooth abscess	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
Infections and infestations Upper respiratory tract infection	33.3% 1/3 • Number of events 1	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
Infections and infestations Viral upper respiratory tract infection	33.3% 1/3 • Number of events 1	0.00% 0/4	0.00% 0/4	0.00% 0/2
Injury, poisoning and procedural complications Excoriation	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/3	0.00% 0/4	0.00% 0/4	50.0% 1/2 • Number of events 1
Investigations Cardiac murmur	0.00% 0/3	25.0% 1/4 • Number of events 1	0.00% 0/4	0.00% 0/2
Investigations Gallop rhythm present	0.00% 0/3	25.0% 1/4 • Number of events 1	0.00% 0/4	0.00% 0/2
Investigations Haemoglobin decreased	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
Investigations White blood cell count decreased	33.3% 1/3 • Number of events 1	0.00% 0/4	0.00% 0/4	0.00% 0/2
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/3	0.00% 0/4	0.00% 0/4	50.0% 1/2 • Number of events 1
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
Musculoskeletal and connective tissue disorders Arthralgia	33.3% 1/3 • Number of events 1	25.0% 1/4 • Number of events 1	0.00% 0/4	0.00% 0/2
Musculoskeletal and connective tissue disorders Musculoskeletal pain	33.3% 1/3 • Number of events 2	25.0% 1/4 • Number of events 1	0.00% 0/4	0.00% 0/2
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	33.3% 1/3 • Number of events 2	0.00% 0/4	25.0% 1/4 • Number of events 1	50.0% 1/2 • Number of events 1
Musculoskeletal and connective tissue disorders Tendonitis	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
Nervous system disorders Dizziness	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
Nervous system disorders Headache	33.3% 1/3 • Number of events 1	0.00% 0/4	25.0% 1/4 • Number of events 1	50.0% 1/2 • Number of events 2
Respiratory, thoracic and mediastinal disorders Prolonged expiration	0.00% 0/3	0.00% 0/4	0.00% 0/4	50.0% 1/2 • Number of events 1
Respiratory, thoracic and mediastinal disorders Tonsillar hypertrophy	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2
Skin and subcutaneous tissue disorders Rash	0.00% 0/3	25.0% 1/4 • Number of events 2	0.00% 0/4	0.00% 0/2
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/3	0.00% 0/4	25.0% 1/4 • Number of events 1	0.00% 0/2

Additional Information

Associate Director, Clinical Research Operations Program

DAIT/NIAID

Phone: 301-594-7669

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place