Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository

Rheumatoid arthritis (RA) is the most common inflammatory arthritis, affecting ~1% of the US
population. Severity of RA varies from mild synovitis to joint destruction with associated
disability and increased mortality. Methotrexate (MTX) is the major drug used to treat RA
and the anchor drug for clinical trials of investigational new drugs (INDs) in RA. Eight
biologic agents are currently FDA-approved for RA. No drug is effective in every patient,
and there is great variability in toxicity and price.

The use of concomitant MTX and biologic agents has dramatically improved the outcomes of RA
treatment in the US. This proposal is based on the premise the next major advance needed in
the treatment of RA is not additional drugs, but rather a dramatic improvement in the
efficiency and cost-effectiveness of the use of drugs for individual patients with RA. One
of the hopes for modern medicine is the realization of "personalized" medicine, which allows
accurate, quick prediction of which drug will be the most efficacious, least toxic, and
least expensive for an individual patient.

One of the major obstacles to identifying clinically useful markers of treatment response in
RA is the lack of cohorts with prospectively collected treatment response data coupled with
biological samples. Because of the importance of this issue and the paucity of funding for
such efforts, multiple efforts to establish single institution (using institutional funds)
or multisite cohorts and repositories (typically dependent on private practitioners and
pharmaceutical company support) are planned. To date, there has been no attempt to harmonize
the efforts of the US academic RA research community to create a public resource.

Recognizing that building de novo cohorts within a short time frame is not feasible, our
current proposal will fill a critical need: establishing an infrastructure of academic
investigators to lay the foundation for future collaborative large-scale registries; and
uniting the efforts of many organizations with the common goal of improving care of RA
patients. This project will facilitate future research that will result in significant,
publicly visible improvements in health care. Identifying predictors of treatment response
in RA will lead to rapid, early institution of optimal drugs rather than a "hit or miss"
sequential approach; reduce adverse events; improve patient compliance; and lead to
substantial reduction in the cost of health care. By unifying the efforts of academic
researchers, we can create unique resources, such as a bank of cryopreserved blood cells to
allow sophisticated immunologic research to dissect molecular signals of successful
treatment of RA.

In order to determine the feasibility of this infrastructure for prospectively collecting
data and samples we will enroll a small number of participants (10/site/year for each of 2
years, for a total of 200 participants).

Inclusion Criteria:

1. Age 19 years or older;

2. Diagnosis of RA based on the cumulative presence of at least 4 of 7 ACR Criteria;

3. Willing and able to provide informed consent; and

One of the following:

- Starting MTX OR

- Previous or current use of Methotrexate and starting (or switching to) any of the
following medications (with or without MTX)

- Etanercept

- Infliximab

- Adalimumab

- Rituximab

- Abatacept

- Golimumab

- Certolizumab

- Tocilizumab

There is no minimum disease activity (number of swollen joints, DAS28, CRP or ESR, etc.)
necessary for enrollment. Treatment decisions are entirely at the discretion of the
treating rheumatologist.

There are no combinations of drugs to be excluded, except those that do not include at
least one of the seven drugs noted above.

Use of corticosteroids (oral, parenteral, intra-articular) is allowed, but must be
recorded.

Exclusion Criteria:

Concomitant diagnosis of RA and systemic lupus erythematosus, juvenile arthritis,
psoriatic arthritis, hepatitis C infection, current pregnancy or lactation.