Comparison of the Effectiveness of Two Glucocorticoid Regimens for Treatment of Graves' Orbitopathy

Study Overview
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Brief Summary
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The goal of this interventional study is to compare the effectiveness of two different glucocorticoid regimens for treatment of active moderate-to-severe Graves' orbitopathy. The main questions it aims to answer are: Are the two glucocorticoid regimens similarly effective? Do the two glucocorticoid regimens have similar safety profile? The patients involved are treated with one of the two glucocorticoid regimens. Their ocular status, therapeutic response and quality of life reassessed during the treatment, at its end, and 3 month later.

Detailed Description
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Systemic glucocorticoids are the mainstay of treatment for active moderate-to-severe Graves' orbitopathy. However, there are a number of different glucocorticoid regimens with different total dosage, schemes of administration and duration. The goal of this interventional study is to compare the effectiveness of two different glucocorticoid regimens for treatment of active moderate-to-severe Graves' orbitopathy. The main questions it aims to answer are: Are the two glucocorticoid regimens similarly effective? Do the two glucocorticoid regimens have similar safety profile? The patients involved are treated with one of the two glucocorticoid regimens. The first group is treated with modified monthly regimen, including 3 pulses of 3 infusions of 500 mg methylprednisolone administered in three consecutive months, with application of 125 mg methylprednisolone intramuscularly once per week between the pulses. Total cumulative dose - 5.5. g., duration - 3 months. After completion of the venous infusions, a low dose peroral glucocorticoid therapy is prescribed for the next 3 months. The second group is treated with weekly glucocorticoid regimen: 6 infusions of 500 mg methylprednisolone during the first 6 weeks followed by 6 infusions of 250 mg methylprednisolone during the next 6 weeks. Total cumulative dose - 4.5 g., duration - 3 months. Patients' ocular status and therapeutic response are assessed at 1st, 3rd and 6th months; quality of life - at 3rd and 6th month.

Official Title
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Comparison of the Efficacy of Two Different Glucocorticoid Regimens for Treatment of Active Moderate-to-severe Graves' Orbitopathy

Conditions
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Graves Ophthalmopathy

Intervention / Treatment
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* Drug: Methylprednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active moderate-to-severe Graves' orbitopathy Without previous treatment with glucocorticoids or orbital radiotherapy Euthyroid state Exclusion Criteria: Uncontrolled hyper- or hypothyroidism Previously treated Graves' orbitopathy Mild or sight-threatening form of Graves' orbitopathy Inactive moderate-to-severe Graves' orbitopathy Contraindications for glucocorticoid treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Modified monthly regimen<br>Treatment with 3 pulses of 3 infusions of 500 mg methylprednisolone on 3 consecutive months with intramuscular administration of 125 mg methylprednisolone per week between the pulses. Additional low dose peroral treatment after completion of the pulses. | Drug: Methylprednisolone<br>* methylprednisolone applied as intravenous infusions or intramuscularly<br>* Other names: Urbason;|
| Weekly regimen<br>Treatment with 6 infusions of 500 mg methylprednisolone during the first 6 weeks, followed by 6 infusions of 250 mg methylprednisolone during the next 6 weeks. | Drug: Methylprednisolone<br>* methylprednisolone applied as intravenous infusions or intramuscularly<br>* Other names: Urbason;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the changes in the overall therapeutic response assessed using Bartalena's criteria during the treatment with the two glucocorticoid regimens | Comparison of the changes in the overall therapeutic response assessed using Bartalena's criteria and classified as full, partial and no response during the treatment with the two glucocorticoid regimens | 6 months | 
| Comparison of the changes in clinical activity score, assessed using a 7- or 10-point scale and expressed in points during the treatment with the two glucocorticoid regimens | Comparison of the changes in clinical activity score, assessed using a 7-point scale at baseline or 10-point scale during the follow-up and expressed in points as recommended by European Thyroid Association and European Group on Graves' orbitopathy during the treatment with the two glucocorticoid regimens | 6 months | 
| Comparison of the changes in lid aperture expressed in mm during the treatment with the two glucocorticoid regimens | Comparison of the changes in lid aperture measured by ruler and expressed in mm during the treatment with the two glucocorticoid regimens | 6 months | 
| Comparison of the changes in proptosis expressed in mm during the treatment with the two glucocorticoid regimens | Comparison of the changes in proptosis measured by Hertel's exophthalmometer and expressed in mm during the treatment with the two glucocorticoid regimens | 6 months | 
| Comparison of the changes in visual acuity expressed in decimals during the treatment with the two glucocorticoid regimens | Comparison of the changes in visual acuity measured by Snellen chart and expressed in decimals during the treatment with the two glucocorticoid regimens | 6 months | 
| Comparison of the changes in diplopia assessed using Gorman's classification system during the treatment with the two glucocorticoid regimens | Comparison of the changes in diplopia assessed using Gorman's classification system and classified as gr. 0 absent, gr. I intermittent, gr. II inconstant, gr. III constant during the treatment with the two glucocorticoid regimens | 6 months | 
| Comparison of the changes in soft tissue involvement evaluated using the colour atlas proposed by European Group on Graves' orbitopathy during the treatment with the two glucocorticoid regimens | Comparison of the changes in soft tissue involvement evaluated using the colour atlas proposed by European Group on Graves' orbitopathy and categorized as gr. 0-I absent or mild, gr. II-III moderate or severe during the treatment with the two glucocorticoid regimens | 6 months | 
| Comparison of the changes in subjective symptoms whose severity was reported by patients themselves using subjective scale during the treatment with the two glucocorticoid regimens | Comparison of the changes in subjective symptoms whose severity was reported by patients themselves and were graded as 0-I absent or mild, gr. II-III moderate or severe during the treatment with the two glucocorticoid regimens | 6 months | 
| Comparison of the changes in quality of life assessed by disease-specific questionnaire recommended by European Group on Graves' orbitopathy (GO-QoL) аnd expressed as percentages during the treatment with the two glucocorticoid regimens | Comparison of the changes in quality of life during the treatment with the two glucocorticoid regimens assessed by disease-specific questionnaire recommended by European Group on Graves' orbitopathy (GO-QoL) аnd expressed as percentages, which includes two subscales - one evaluating the impact of Graves' orbitopathy on patients' visual functioning (QoL-VF) and the other related to the changes of physical appearance as a result of the disease (QoL-AP) | 6 months | 
| Incidence of treatment-emerged adverse events in the two glucocorticoid regimens groups | Number and type of adverse reactions in the study groups reported by patients themselves or found by the laboratory tests or during clinical examination. | 6 months |