Rituximab (RTX) Therapy in Patients With Active TAO

Conditions

• Ophthalmopathy, Thyroid-Associated

Eligibility Criteria

Sex

ALL

Age

18 Years - 70 Years

Healthy Volunteers

Not accepted

Interventions

• Rituximab — DRUG
  Rituximab (RTX) is a mouse-human chimeric antibody designed towards (CD20) pre B and mature B lymphocytes and that blocks B-cells activation without affecting the regenerating of B cells from stem cells or the plasma cells immunoglobulin production. Rituximab is used in the treatment of hematologic malignancies (B cells lymphoma, chronic lymphatic leukaemia, Waldenströms macroglobulinemia) and autoimmune diseases with B-cell involvement such as rheumatoid arthritis, thrombocytopenic purpura, SLE).
• Iv Methylprednisolone — DRUG
  Solumedrol is an intravenous glucocorticoid that are the gold standard in TAO. All patients start with 500 mg/weeks for 4 weeks. The response is evaluated and patients are randomised to non-responders or responders. The responders continues with the gold standard treatment that is another 500 mg solumedrol/ week in 2 weeks and then 250 mg/ week in 6 weeks.
• peroral methylprednisolone and Methotrexate — DRUG
  Peroral GC (starting with 30 mg and tapering down) is combined with 15-20 mg MTX /week to reduce the needed dose of steroids

Study Details

Thyroid Associated Ophthalmopathy is condition affecting the eyes of about 10% of patients with Graves disease. Its combination of protrusion affecting the looks of the patient and pain is often severely affecting the quality of life among these patients. The standard treatment for this illness today is intravenous glucocorticoids together with methotrexate. The purpose of this study is to evaluate the effect of rituximab on patients that do not respond to or relapse after conventional therapy.

Key Dates

Start date

Dec 31, 2011

Status verified

Mar 2025

Primary completion

Sep 3, 2019

Completion

Feb 1, 2020

Study Design

Enrollment

38 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

FACTORIAL

Primary purpose

TREATMENT

Arms

• Active Comparator: Non-responder RTX+MTX
  Patients with moderate-severe TAO with an inflammatory CAS of ≥ 4 that do not respond to iv GC (deltaCAS \<2 compared to baseline after 4 weeks of iv GC ) or do relapse (deltaCAS ≥2 and total CAS ≥4) after steroid treatment compared to previous CAS measurement at 12 weeks. Rituximab (1000 mg iv with 2 weeks in between) is combined with methotrexate (15-20 mg once a week) to minimize the risk of antibody developement. MTX is always combined with RTX and is never given as a monotherapy in this study. rituximab and methotrexate
• Active Comparator: Relapse RTX+MTX
  Patients that respond to iv GC (Methylprednisolone iv) but relapse after 6 weeks will be randomised to either RTX+MTX or per oral GC (po GC+MTX) rituximab and methotrexate
• Active Comparator: Relapse po GC+MTX
  Patients that respond to iv GC but relapse after 6 weeks will be randomised to either RTX+MTX or per oral GC (po GC+MTX) This is the conventional therapy arm. methotrexate and methylprednisolone
• No Intervention: Responders without relapse
  Patients that respond to iv GC and have no relapse at 18 weeks of study.
• Active Comparator: Methylprednisolone iv
  All patients in the study have a 4 weeks period of 500 mg methylprednisolone iv/week. Depending of the response patients are classified as non- responders (and are given RTX and MTX) or responders. The responders continue with intravenous infusion of Methylprednisolone 500 mg /week in 2 weeks and thereafter 250 mg iv/week in 6 weeks.

Primary Outcome Measure

Clinical Activity Score (a Composite Measure of Ophthalmological Signs and Symptoms) [ Time Frame: At 4,12,18 and 68 weeks ]