An Observational, Retrospective, Single-center, Clinical Study to Evaluate the Efficacy of Sirolimus (Rapamycin) in Patients With Graves' Disease and Moderate-to-severe and Active Graves' Orbitopathy (GO)
Overview
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Pisa
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- GO overall response
Overview
Brief Summary
Graves' Orbitopathy (GO) is a disabling and disfiguring condition associated with Graves' Disease, due to autoimmunity against antigens expressed by the thyroid and orbital tissues, and resulting in orbital fibroblast proliferation and release of glycosaminoglycans. The current treatments available, especially glucocorticoids, are not effective in all patients. Two cases of patients with GO treated with Sirolimus have been reported with an excellent response to the drug.
The rationale for the use of Sirolimus lies in its mechanisms of action. Sirolimus is able to inhibit T-cell activation as well as fibroblast proliferation. In addition, acts indirectly on the Insulin-Like Growth Factor-1 (IGF-1) pathway, and recent clinical trials have shown that a monoclonal antibody against the IGF-1 receptor (Teprotumumab) is effective in patients with GO. Thus, Sirolimus could be used in GO as monotherapy in patients with GO.
The aim of the present drug vs standard treatment, observational study is to evaluate the efficacy of Sirolimus as a second-line treatment in patients with moderately severe, active GO.
Detailed Description
Study Design: observational
Thirty consecutive patients with moderate-to-severe and active GO treated with sirolimus (15 patients) or methylprednisolone (15 patients) observance 18 consecutive months will be compared.
Study Timeline
Baseline visit - (Time 0) Treatment period (week 1-week 12): daily administration of the trial agent (Sirolimus) or weekly administration of the standard treatment (methylprednisolone) Outcome visit (week 24)
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Retrospective
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients willing and capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
- •A moderate-to-severe GO, defined as the presence of at least one of the following criteria: an exophthalmos ≥2 mm compared with normal values for sex and race; presence of inconstant to constant diplopia; a lid retraction ≥2 mm
- •Active GO: CAS (4) ≥2 out of 7 points in the most affected eye
- •Previous GO treatment with glucocorticoids and/or orbital radiotherapy and/or orbital decompressive surgery, performed more than 24 weeks before the current treatment
- •Male and female patients of age: 18-75 years
Exclusion Criteria
- •Optic neuropathy
- •Treatment with glucocorticoids or other immunosuppressive medications, and/or selenium, and/or orbital radiotherapy and/or orbital decompressive surgery in the 24 weeks preceding the current treatment
- •Mental illness that prevents patients from comprehensive, written informed consent
Arms & Interventions
Sirolimus
Treatment with sirolimus for 12 weeks, given as a second-line treatment
Intervention: Sirolimus (Drug)
Methylprednisolone
Treatment with methylprednisolone for 12 weeks, given as a second-line treatment
Intervention: Methylprednisolone (Drug)
Outcomes
Primary Outcomes
GO overall response
Time Frame: 24 weeks
Percentage of subjects with at least two of the following compared to baseline: a) Improvement in clinical activity score (CAS) by at least 1 point ; b) Improvement in exophthalmos by at least 2 mm; c) Improvement in lid aperture by at least 2 mm; d) Improvement in eye muscle ductions ≥8 degrees; e) Improvement of visual acuity by at least 0.2/1, without worsening of any of these parameters in the contralateral eye if applicable.
Secondary Outcomes
- Change in exophthalmos(24 weeks)
- Change in the clinical activity score (CAS)(24 weeks)
- Change in quality of life(24 weeks)
- Change in eye ductions(24 weeks)
- Change in eyelid aperture(24 weeks)
- Change in diplopia(24 weeks)
Investigators
Marinò Michele
Associate Professor of Endocrinology
University of Pisa