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Switching Anti-TNF-alpha Agents in Patients With RA With An Inadequate Response to TNF-alpha Inhibition

Phase 4
18 Years
Not Enrolling
Rheumatoid Arthritis

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Trial Information

Switching Anti-TNF-alpha Agents in Patients With RA With An Inadequate Response to TNF-alpha Inhibition

Over the past 10 years, advancements in biotechnology have revolutionized Rheumatoid
Arthritis (RA) therapeutics with biologically-derived immunomodulating compounds. Tumor
Necrosis Factor (TNF) alpha inhibitors constitute the largest class of these new biologic
therapies. The purpose of this study is to determine the effectiveness of switching to an
alternative TNF-alpha inhibitor in comparison to continuing treatment with an existing
TNF-alpha inhibitor in adults suffering from RA who have had inadequate clinical response to
the study drugs etanercept and adalimumab.

This study will last approximately 16 weeks. Participants will be randomized into two arms
and receive injections once per week for 12 weeks. Participants in the adalimumab arm will
receive alternating subcutaneous adalimumab and adalimumab placebo injections. Participants
in the etanercept arm will receive subcutaneous etanercept injections.

This study consists of thirteen study visits after randomization. Study visits will occur on
a weekly basis for 12 weeks prior to a follow-up visit at Week 16. A vital signs measurement
and adverse event assessment will occur at each visit. A physical exam, assessment of tender
and swollen joints, medication assessment, and blood collection will occur at Weeks 4, 8,
12, and 16.

Inclusion Criteria:

- Diagnosis of Rheumatoid Arthritis

- Current treatment with either etanercept or adalimumab for at least 12 weeks prior to

- Disease Activity Score (DAS) C-reactive Protein (CRP) 28 ≥ 4.4

- Treatment with concomitant Disease-Modifying Anti-Rheumatic Drugs (DMARDs) is
permitted but not required as described below:

1. Methotrexate - maximum dose of 25 mg per os (PO), intra-muscular (IM), or SQ

2. Leflunomide - maximum dose of 20 mg PO daily.

3. Sulfasalazine - maximum dose of 1,500 mg PO twice daily.

4. Hydroxychloroquine - maximum dose of 400 mg PO daily.

- If taking DMARD(s), subjects must be on stable doses for at least 12 weeks prior to

- If treated with prednisone (or equivalent corticosteroid), on a stable dose of <= 10
mg/day for 28 days prior to randomization.

- Agree to use appropriate form of contraception. More information on this criterion
can be found in the protocol.

Exclusion Criteria:

- Diagnosis of another autoimmune disease likely to require immunosuppression. More
information on this criterion can be found in the protocol.

- Failing treatment with etanercept if previously treated with adalimumab

- Failing treatment with adalimumab if previously treated with etanercept

- Intraarticular injection within 4 weeks prior to randomization

- Concomitant use of DMARDs other than those described in Inclusion Criteria within 12
weeks of randomization.

- Concurrent use of any biologic agent other than etanercept or adalimumab

- Concomitant immunosuppressive therapy other than the Disease-Modifying Anti-Rheumatic
Drugs (DMARDs), non-steroidal anti-inflammatory drugs (NSAIDs), or corticosteroids
specified in the protocol

- Presence of open leg ulcers

- Chronic or persistent infection that may be worsened by immunosuppressive treatment.
More information on this criterion can be found in the protocol.

- Active infection or severe infections requiring hospitalization or treatment with
intravenous antibiotics, antivirals, or antifungals within 30 days prior to

- History of positive Purified Protein Derivative (PPD) or chest x-ray findings
indicative of prior tuberculosis infection

- Any medical condition or treatment that, in the opinion of the investigator, would
put the subject at risk by participation in the study

- History of malignancy. More information on this criterion can be found in the

- Certain abnormal laboratory values. More information on this criterion can be found
in the protocol.

- Investigational biological or chemical agents within 4 weeks prior to randomization.

- History of drug or alcohol abuse within a year prior to randomization

- Treatment with natalizumab, rituximab, or another B-cell depleting therapy within a
year prior to randomization

- Treatment with infliximab, abatacept, tocilizumab, golimumab, or certolizumab pegol
within 12 weeks prior to randomization.

- Known allergy or hypersensitivity to study products

- Any psychiatric disorder that prevents the participant from providing informed

- Inability to follow protocol instructions

- Pregnant or breastfeeding

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Change in the Disease Activity Score Using C-reactive Protein (DAS28[CRP]) From Baseline to Week 12 in Non-Switchers Versus Switchers.

Outcome Description:

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).

Outcome Time Frame:

Baseline, Week 12

Safety Issue:


Principal Investigator

Larry Moreland, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Pittsburgh


United States: Federal Government

Study ID:




Start Date:

November 2008

Completion Date:

October 2010

Related Keywords:

  • Rheumatoid Arthritis
  • Arthritis
  • Arthritis, Rheumatoid



University of AlabamaBirmingham, Alabama  
Stanford UniversityStanford, California  94305
Oklahoma Medical Research FoundationOklahoma City, Oklahoma  73104
University of PittsburghPittsburgh, Pennsylvania  15261
University of UtahSalt Lake City, Utah  
Duke University Medical CenterDurham, North Carolina  27710
University of RochesterRochester, New York  14642
University of Chicago Medical CenterChicago, Illinois  60637
Baylor Research InstituteDallas, Texas  75246
Altoona Center for Clinical ResearchDuncansville, Pennsylvania  16635
Yale New Haven HospitalNew Haven, Connecticut  06520
Sarasota Arthritis Research CenterSarasota, Florida  34239
Tampa Medical GroupTampa, Florida  33614
Justus Fiechtner, MD, PCLansing, Michigan  48910
Feinstein Institute for Medical Research NS-LIJManhassett, New York  14642
Carolina Bone and JointCharlotte, North Carolina  28210