Thyroid associated opthalmopathy
Conditions
Interventions
Trade Name: Mabthera
Product Name: mabthera
Pharmaceutical Form: Injection
Trade Name: metotrexate
Product Name: metotrexate
Pharmaceutical Form: Tablet
Trade Name: Solu-Medrol
Product Name: Solu-Me
Sponsors
Department of Endocrinology, Sahlgrenska University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria • Man or woman between 18-70 years. • TAO with CAS of = 4 (less than 3 months). • Euthyroid for at least 6 weeks Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Exclusion criteria • Dysthyroid optic neuropathy (DON) • Ulcerative Keratitis • Previous treatment with steroids for TAO (do not include prophylaxis for TAO in connection with radio iodine treatment) • Previous Treatment with Rituximab (MabThera®) • Positive Hepatitis B or C serology. • Receipt of a live vaccine within 4 weeks prior RTX+MTX to randomization • History of recurrent significant infection or history of recurrent bacterial infections • Patient who may not attend to the protocol according to the investigators opinion. • Pregnancy or lactation • Significant cardiac, including significant or uncontrolled arrhythmia, or pulmonary disease (including obstructive pulmonary disease). • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications • Concomitant malignancies or previous malignancies. • Previous active tuberculosis • Alkoholism • Alkoholic related liver disease or other chronical liver disease • Bone marrow depression with leukopenia, thrombocytopenia or significant anemia • Reumatoid or other significant pulmonary disease • Allergy to the active substance or any other substance in the medications or murine proteins • Active, severe infections (such as tuberculosis, sepsis or opportunistic infections) • Patients with severe immunosuppression • Severe cardiac failure or severe uncontrolled heart disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary scientific question 1. To evaluate the effect of RTX+MTX in patients with active TAO unresponsive to steroids or active TAO relapsing after steroid treatment. ;Secondary Objective: To characterize the group of steroid resistant patients Compare RTX+MTX or poGC+MTX on CAS week 32 and 46 Compare RTX+MTX or poGC+MTX on severity of disease week 32 and 46 Compare quality of life effect of RTX+MTX or poGC+MTX Compare the side-effects in RTX+MTX or poGC+MTX Describe the number of relapses later than 6 weeks but before 52 weeks after 12 weeks iv steroids Evaluate if impaired adrenal GC production occurs after 12 weeks iv steroid treatment Evaluate the QoL in patients on intravenous steroids Describe side-effects in RTX+MTX and intravenous steroids Do the side-effects differ according to GCd receptor polymorphism? To characterize the GC resistant group in the GC receptor, genetic and immunologic markers Compare genetic and immunological markers in the steroid-responding patients that relapses compared to the non-relapsing patients Describe how immunologic markers changes under treatment ;Primary end point(s): The primary outcome measurement is the responder analysis in Clinical activity score (CAS) according to Mourrits et al (Mourits MP, Prummel MF, Wiersinga WM, Koornneef L. Clinical activity score as a guide in the management of patients with Graves' ophthalmopathy. Clin Endocrinol (Oxf) 1997;47(1):9-14) and the consensus statement from EUGOGO ((Bartalena L et al European Journal of Endocrinology 2008 158 273-285) in the responder analysis. A responder is defined as an improvement in CAS =2 compared with before treatment. This can be analyzed at four occasions 1. At 4 weeks iv Steroid treatment compared to baseline 2. In the responder group 12 weeks compared to baseline 3. In the non-repsonder group 18 weeks compared to 4 weeks 4. In the relapse group at 32 and 46 weeks compared to 18 weeks ;Timepoint(s) of evaluation of this end point: Se abo | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Mean/Median change in CAS is a secondary measurement outcome and can be evaluated at: 1. 12 weeks in the responder group compared to baseline 2. 18 weeks in the non-responder group compared to 4 weeks 3. In the relapse group at 32 and 46 weeks compared to 18 weeks in relapse RTX+MTX and poGC+MTX, respectively Main outcome meausrements is CAS, proptosis, strabismus, side effects ;Timepoint(s) of evaluation of this end point: Se above E 5:2 | — |
Countries
Sweden
Outcome results
None listed