Stopping TNF Alpha Inhibitors in Rheumatoid Arthritis

Background: * Rheumatoid arthritis (RA) is often treated with drugs known as tumor necrosis factor (TNF) inhibitors, that can help decrease joint pain and swelling and can even result in RA remission. However, TNF inhibitors may increase risk of serious infections or some types of cancer. * It is not clear if people whose RA has been in remission for a long time need to stay on the TNF inhibitor to remain in remission. If they can stop taking the TNF inhibitor without having their symptoms come back, they will be spared the side effects of these medicines. Some studies have shown that people can stay in remission after stopping a TNF inhibitor, but other studies have not confirmed it. Researchers want to see if people with RA in remission on a TNF inhibitor can stay in remission without this medicine. Also there may be a clinical, imaging (MRI, ultrasound), laboratory profile that will help to determine which patients remain in remission after stopping these drugs. Objectives: * To see whether RA remission can continue after discontinuing use of a TNF inhibitor. * To determine if clinical, imaging and immunological measurements can predict which participants will flare and which will remain in remission after discontinuing TNF inhibitor. Eligibility: -Individuals at least 18 years of age who have RA that is being controlled with TNF inhibitors. We plan to randomize 291 patients. Design: * The study has seven visits over about 2 years. Six visits occur in the first year of the study, about 12 weeks apart. The final study visit is 1 year after the end of the treatment phase. * At the first visit, participants will be screened with a physical exam and medical history. They will complete a questionnaire about their RA symptoms. A blood sample will be collected. They will continue to take their RA medicines during this time. * The second visit will repeat tests from the first visit. These tests will confirm that the RA is in remission. Imaging studies will be performed on the hands, wrists, feet, and their connected joints. After this visit, participants will stop taking their TNF inhibitors and will start to have injections of a study drug. This drug will be either the participant's original TNF inhibitor or a placebo. * There will be follow-up visits at weeks 12, 24, and 36. Participants will have a medical history and joint exam. They will also provide blood samples and answer questions about their RA symptoms. * At the sixth visit (week 48), participants will repeat the tests and imaging studies from the second visit. They will stop taking the study injections. * Continued RA treatment after this visit will be decided by the participant and his or her rheumatologist. Participants may take any recommended medicine, including the TNF inhibitor they had been taking before the study. They will also receive a questionnaire to complete at home and mail back before the final study visit. * At the final visit (week 100), participants will repeat the tests and imaging studies from the second and sixth visits.

Sex

All

Minimum age

18 Years

* 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 months
* Treated with greater than 5 mg of prednisone (or equivalent) daily in the last 3 months
* Treated with intramuscular or intravenous corticosteroids in the last 6 months for RA activity
* 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 months
* 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 randomization
* Absence of documentation of negative hepatitis B serologies, absence of completion of treatment for chronic hepatitis B, or absence of suppressive antiviral treatment
* 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.

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