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Stopping Tumor Necrosis Factor-Alpha Inhibitors in Rheumatoid Arthritis

Phase 4
18 Years
Open (Enrolling)
Rheumatoid Arthritis

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Trial Information

Stopping Tumor Necrosis Factor-Alpha Inhibitors in Rheumatoid Arthritis

Remission of rheumatoid arthritis (RA) is an achievable goal with currently available
medications, including the anti-tumor necrosis factor (anti-TNF) agents. However, it is
uncertain if patients with RA in clinical remission while treated with anti-TNF agents and
background disease-modifying antirheumatic drugs (DMARD) would remain in remission if
anti-TNF therapy was stopped. If remission can be sustained off anti-TNF agents, then
patients may be spared the potential toxicity and costs of these medications.

The Stopping Anti-Tumor Necrosis Factor Agents in Rheumatoid Arthritis (STARA) study is a
multicenter, randomized, double-blind, placebo-controlled noninferiority trial that will
test differences in time to relapse between patients with RA in remission who discontinue
anti-TNF agents and patients with RA in remission who continue anti-TNF agents. The
secondary objectives of the study are: 1) to determine if discontinuation of anti-TNF agents
results in a difference in progression of joint damage on radiographs; 2) to determine if
discontinuation of anti-TNF agents results in a difference in physical function, and 3) to
identify predictors of relapse.

Eligible subjects will have RA in remission for at least six months while taking etanercept,
infliximab, or adalimumab. An eight-week run-in period prior to randomization will be used
to confirm remission. Subjects will then be randomized in a 2:1 ratio to receive one of two
blinded treatments: 1) matching placebo or 2) their currently used anti-TNF agent,
respectively. All subjects will maintain their current background DMARD. Clinical
assessments will be performed every 12 weeks. The primary outcome is 48-week relapse-free
status. Secondary outcomes include change from baseline radiographic joint damage score at
48 weeks and 100 weeks, and change from baseline physical function score at 48 weeks.
Subjects who relapse before week 48 will discontinue study medication and receive treatment
through their rheumatologist. Blinded treated will end at week 48 and subjects will be
followed for 52 additional weeks. This study will provide important new information on the
best treatment approach for patients with RA in remission.

Inclusion Criteria

- Study personnel will evaluate participant eligibility using a checklist of inclusion
and exclusion criteria as outlined below. Clinical information will be obtained from
subjects by interview and from the medical record.

At the screening visit, potential participants will be included if:

- Age greater than or equal to 18 years

- Have RA, as defined by the 1987 revised American College of Rheumatology criteria

- In sustained clinical remission for the last 6 months while receiving treatment with
either etanercept, infliximab, or adalimumab, and greater than or equal to 1 DMARD
(methotrexate, hydroxychloroquine, sulfasalazine, leflunomide, minocycline,
cyclosporine, azathioprine, gold, penicillamine). DAS28 should be less than 2.6 on
each visit over the preceding 6 months, with at least one visit 2-4 months before
enrollment. If there is no visit 6 months before enrollment, the nearest visit in
the 6-12 month period before enrollment should be considered and have a DAS28 less
than 2.6.

Potential participants will be excluded if:

- Had dose increase of anti-TNF agent or DMARD in the last 6 months

- Had change of anti-TNF agent or DMARD in the last 6 months

- Treated currently with golimumab or certolizumab

- Treated with greater than 10 mg of prednisone (or equivalent) daily in the last 6

- Treated with greater than 5 mg of prednisone (or equivalent) daily in the last 3

- Treated with intramuscular or intravenous corticosteroids in the last 6 months for RA

- Treated with anakinra, abatacept, or tocilizumab in the last 6 months

- Treated with rituximab in the last 12 months

- Treated with an investigational RA drug in the last 6 months

- Pregnant (or anticipate pregnancy during the study period) or lactating women

- Absence of documentation in the medical record of clinical remission for the last 6

- Unwilling to discontinue anti-TNF agent

- Absence of documentation of negative tuberculin skin test, negative QuantiFERON-TB
Gold test, or treatment for latent tuberculosis prior to starting treatment with the
anti-TNF agent

- Treatment of solid malignancy or non-melanoma skin cancer within the past 5 years, or
any history of melanoma or hematologic or lymphoproliferative malignancy

- Absence of documentation of age-appropriate cancer screening at the time of

- Absence of documentation of negative hepatitis B serologies, hepatitis C serologies,
or absence of completion of treatment for chronic hepatitis B

- Unable to provide informed consent

- Anticipate not being available or able to comply with the schedule of study visits

Study entry is not limited by gender or ethnicity. Children are excluded because
inflammatory polyarthritis developing before age 16 is considered juvenile idiopathic
arthritis and not RA. Patients who developed RA while age 17 would be eligible, but given
the time needed to achieve remission, these patients would in most cases be 18 or older by
the time they would meet other criteria for study entry.

Participants will largely be recruited from the practices of study investigators. To
identify potential subjects, investigators may search rosters of patients in their
practice for patients who meet the inclusion criteria. The number of patients screened
and reasons for exclusion will be tabulated at each site. Subjects may also be recruited
by physician referral. Information about the study will be mailed to local
rheumatologists and posted on the NIAMS website. We do not anticipate self-referral of
subjects but eligible self-referred subjects will not be excluded.

During the course of the study, enrollment of subjects treated with a particular anti-TNF
agent may be suspended or terminated to permit adequate representation of patients treated
with each of the 3 anti-TNF medications, due to problems procuring medication, or due to
other unforeseen issues.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Outcome Measure:

Remission by Disease Activity Score - 28 over 48 weeks

Outcome Time Frame:

48 weeks

Safety Issue:


Principal Investigator

Michael M Ward, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)


United States: Federal Government

Study ID:




Start Date:

January 2013

Completion Date:

December 2018

Related Keywords:

  • Rheumatoid Arthritis
  • Rheumatoid Arthritis
  • Autoimmune Diseases
  • Anti-TNF
  • Arthritis
  • Arthritis, Rheumatoid



National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892