Trial Information

Systemic Immunosupressive Therapy for Eye Diseases (SITE) Cohort Study

BACKGROUND:

Ocular inflammatory diseases, including uveitis, scleritis, and mucous membrane pemphigoid,
are major blinding eye diseases. For some patients, corticosteroid therapy is insufficient
to control ocular inflammatory disease, such that immunosuppressive therapy is required.
Immunosuppressive therapy for eye diseases has most commonly employed antimetabolite, T-cell
inhibitor, and/or alkylating agent therapies. It has been suggested, based on studies of
patients with severe systemic immunologic or other systemic diseases, that such treatments
may result in an increased risk of cancer and other long-term morbidities. In these
studies, it has been difficult to determine whether the excess risk arose from the
underlying systemic diseases or the treatment.

AIMS:

The Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study will evaluate
directly whether immunosuppressive therapy for ocular inflammatory diseases is associated
with an excess risk of mortality and of cancer. The study is expected to generate critical
information in deciding whether immunosuppressive therapy is warranted for such patients,
and whether certain immunosuppressive agents should be avoided. In addition, the study will
evaluate the frequency of short-term complications with such therapy, and the ocular
benefits of therapy.

METHODS:

The SITE Study will have a classic retrospective cohort design. A database will be
constructed through a chart review of patients seen here in the Uveitis clinic of the NEI
since 1977 and 3 other sites. Patients exposed to immunosuppressive therapies will be
compared to two groups: 1) an external standard, the general United States population; and
2) an internal comparison group, patients with the same ocular inflammatory diseases who did
not receive immunosuppression. Approximately 10000-15000 patients will be accrued from four
centers which pioneered the use of immunosuppressive therapy for eye diseases, beginning
19-29 years ago. Patients who received immunosuppressive therapy for eye diseases, and
patients with the same ocular inflammatory diagnoses who did not, will be identified by the
chart reviews. Those who subsequently have died will be identified through a search of the
National Death Index and/or the Social Security Death Index.

In addition to overall mortality, cause-specific mortality will be evaluated, as obtained
from death certificate coding. The data collected here at the NIH will be compared to the
National Death Index separately from the data from the other centers, via a direct query
from our center. Abstracted data without identifiers other than study number and letter
codes that could not be used to identify subjects by anyone outside the LI will be sent to
the central database. The outcomes of mortality, cause-specific mortality, and cancer
incidence will be analyzed using a relative incidence approach. Description of the
short-term complications of immunosuppression and of the beneficial effects of
immunosuppression on eye diseases also will be evaluated. This study's chair is John Kempen
at the Wilmer Eye Institute of the Johns Hopkins School of Medicine. We will be a
participating center.