B-cell Depletion Therapy With Rituximab for Thyroid Eye Disease
| Status: | Recruiting |
|---|---|
| Conditions: | Ocular, Ocular, Endocrine |
| Therapuetic Areas: | Endocrinology, Ophthalmology |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 6/9/2018 |
| Start Date: | January 2016 |
| End Date: | July 2019 |
| Contact: | Kelly Reckley, BS |
| Email: | reckleyka@upmc.edu |
| Phone: | 412-647-2637 |
Thyroid eye disease (TED) is an autoimmune inflammation of the orbital tissues that develops
in up to 50% of patients with Graves' disease. Although about 80% respond to IVGC initially,
the relapse rate is high and about 75% require further surgery despite initial response.
Although the natural history of TED is associated with spontaneous remissions after about 1
to 3 years, many irreversible serious ophthalmic and orbital complications can arise during
this time. Therefore, there is a need for improved intervention strategies in the early
active inflammatory phase of TED, to avoid progression to the cicatricial stage where disease
manifestations can only be addressed in a rehabilitative fashion. The primary
immunopathogenesis of Graves' disease is considered to be activation of B cells that then
produce autoantibody against thyrotropin receptors in the thyroid (TRAb). Like in many
autoimmune diseases, the inflammatory CD4+ T cell subset known as Th17 cells is also
increased in blood of patients with active Graves' disease; the putative Th17 cytokine,
IL-17, is also increased in serum and tears of TED patients. There is also an emerging
pathogenic role for Th17 cells that co-express the chemokine receptor CXCR5 and drive
autoantibody production. The contribution of Th17 cells to TED is not well defined. This
study is an observational, longitudinal, prospective study of patients receiving treatment
for thyroid eye disease.
in up to 50% of patients with Graves' disease. Although about 80% respond to IVGC initially,
the relapse rate is high and about 75% require further surgery despite initial response.
Although the natural history of TED is associated with spontaneous remissions after about 1
to 3 years, many irreversible serious ophthalmic and orbital complications can arise during
this time. Therefore, there is a need for improved intervention strategies in the early
active inflammatory phase of TED, to avoid progression to the cicatricial stage where disease
manifestations can only be addressed in a rehabilitative fashion. The primary
immunopathogenesis of Graves' disease is considered to be activation of B cells that then
produce autoantibody against thyrotropin receptors in the thyroid (TRAb). Like in many
autoimmune diseases, the inflammatory CD4+ T cell subset known as Th17 cells is also
increased in blood of patients with active Graves' disease; the putative Th17 cytokine,
IL-17, is also increased in serum and tears of TED patients. There is also an emerging
pathogenic role for Th17 cells that co-express the chemokine receptor CXCR5 and drive
autoantibody production. The contribution of Th17 cells to TED is not well defined. This
study is an observational, longitudinal, prospective study of patients receiving treatment
for thyroid eye disease.
All enrolled subjects will receive Intravenous Glucocorticoid (IVGC) therapy, which is
currently the standard of care for TED patients. Subjects will receive the IVGC therapy at a
facility chosen by them and their physician. If their disease does not respond to IVGC
therapy, they will receive rituximab and/or surgical decompression and/or radiation which is
also currently standard of care at a facility chosen by them and their physician. Prior to
initiation of treatment and during the course of treatment, study patients will get research
labs done along with routine labs and fill out questionnaires regarding their disease
symptoms.
We will obtain 30 mL or 2 tablespoons of blood from subjects at initial evaluation and
approximately Wk4, Wk 12, Wk 26, Wk 38, and Wk 52 (this may vary depending on when the
patient comes in for their follow up visits, but the schedule approximates what is typical
for standard of care in these patients) for mechanistic studies.
currently the standard of care for TED patients. Subjects will receive the IVGC therapy at a
facility chosen by them and their physician. If their disease does not respond to IVGC
therapy, they will receive rituximab and/or surgical decompression and/or radiation which is
also currently standard of care at a facility chosen by them and their physician. Prior to
initiation of treatment and during the course of treatment, study patients will get research
labs done along with routine labs and fill out questionnaires regarding their disease
symptoms.
We will obtain 30 mL or 2 tablespoons of blood from subjects at initial evaluation and
approximately Wk4, Wk 12, Wk 26, Wk 38, and Wk 52 (this may vary depending on when the
patient comes in for their follow up visits, but the schedule approximates what is typical
for standard of care in these patients) for mechanistic studies.
Inclusion Criteria:
1. Willing and able to give informed consent
2. Age 18 to 75 years of age
3. Diagnosis of Thyroid Eye Disease (TED) with a CAS of ≥ 3. (Thyroid status can be
euthyroid, hyper or hypothyroid.)
4. Willingness to practice birth control for at least 12 months post treatment.
5. Normal organ function, except if abnormal due to tumor involvement.
6. Men and women of reproductive potential must agree to use an acceptable method of
birth control during treatment and for twelve months after completion of treatment.
7. Subject has provided written informed consent.
8. Documentation of CD20 + status (for B cell malignancies).
9. ANC: > 1000/mm3
10. Adequate bone marrow function as indicated by a total white blood cell count of > 4 x
109/, hemoglobin of > 7 g/dl or a platelet count >100,000/mm³
11. Adequate renal function as indicated by creatinine of <2.5.
12. Adequate liver function, as indicated by AST or ALT <2x Upper Limit of normal unless
related to primary disease.
Exclusion Criteria:
Patients will be excluded from the study based on the following criteria:
1. Brittle insulin dependent diabetes [The term "brittle" refers to cases of diabetes in
which there is an instability that leads to a disruption of life and often recurrent
and/ or prolonged hospitalization]
2. Pregnant or nursing patients
3. Significant medical comorbidities that would make the risk of high dose steroids
intolerable such as severe CHF, CAD, arrhythmias, renal insufficiency, infection or
immune deficiency, systemic autoimmune disease, severe glaucoma etc.
4. Absolute neutrophil count < 1500/mm³.
5. Contraindication to use of rituximab
6. Positive PPD and/or Quantiferon Gold TB test without prior anti-tuberculous therapy;
active TB
7. HIV or hepatitis infection or declined consent for HIV or hepatitis testing
8. Use of rituximab in the prior 24 months for any reason other than TED
9. Unwillingness to practice birth control for at least 12 months post treatment
10. Pregnancy (a negative serum pregnancy test should be performed for all women of
childbearing potential within 7 days of treatment), or lactating.
11. Inability to comply with study and/or follow-up procedures.
12. History of HIV.
13. Presence of active infection.
14. Presence of CNS metastases.
15. New York Heart Association Classification III or IV heart disease (See Appendix D).
16. Concomitant malignancies or previous malignancies within the last five years, with the
exception of adequately treated basal or squamous cell carcinoma of the skin or
carcinoma in situ of the cervix.
17. History of psychiatric disorder.
18. At the Investigator's discretion, receipt of a live vaccine within 4 weeks prior to
randomization.
We found this trial at
1
site
4200 Fifth Ave
Pittsburgh, Pennsylvania 15260
Pittsburgh, Pennsylvania 15260
(412) 624-4141
Principal Investigator: Niveditha Mohan, MD
Phone: 412-647-2637
University of Pittsburgh The University of Pittsburgh is a state-related research university, founded as the...
Click here to add this to my saved trials
