Rituximab for the treatment of thyroid eye disease

Thyroid eye disease affects 50% of patients with the autoimmune condition, Graves' disease. Symptoms include eye pain, redness, swelling, protrusion (proptosis), double vision, and in severe cases, reduction in vision. Currently treatment options include steroids and radiotherapy, but relapses are common. Surgery is reserved for severe cases. Rituximab is a medication given by intravenous infusion which has been shown to benefit patients with other autoimmune conditions like rheumatoid arthritis. This review was designed to investigate whether rituximab is effective and safe as a treatment option for patients with thyroid eye disease. There is a lack of evidence from randomised controlled trials to support the use of rituximab for thyroid eye disease. Rigorous studies looking at patients with active thyroid eye disease, comparing rituximab treatment with either steroids or placebo, need to be conducted in order to answer this question.

Authors' conclusions: 

There is currently insufficient evidence to support the use of rituximab in patients with TAO. There is a need for large RCTs, investigating rituximab versus placebo or corticosteroids in patients with active TAO to make adequate judgement on the efficacy and safety of this novel therapy for this condition.

Read the full abstract...

Thyroid associated ophthalmopathy (TAO) is the most frequent extrathyroidal manifestation of Graves' disease, affecting up to 50% of patients, and has a great impact on quality of life. Rituximab is a human/murine chimeric monoclonal antibody that targets CD20, a transmembrane protein expressed on the surface of pre-B and mature B lymphocytes, but not on stem cells, pro-B lymphocytes or plasma cells. Preliminary work has shown that blocking the CD20 receptor on B-lymphocytes with rituximab affects the clinical course of TAO, by reducing inflammation and the degree of proptosis.


The aim of this review was to investigate the effectiveness and safety of rituximab for the treatment of TAO.

Search strategy: 

We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to April 2013), EMBASE (January 1980 to April 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to April 2013), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and the EU Clinical Trials Register (www.clinicaltrialsregister.eu). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 15 April 2013. We manually searched references of review articles and used the Science Citation Index to identify additional studies citing trials. We contacted the lead investigators of relevant trials on ClinicalTrials.gov and the WHO ICTRP for information and data from as yet unpublished clinical trials. We contacted experts in the field for information about any ongoing trials. We contacted the manufacturers of rituximab for details of any sponsored trials.

Selection criteria: 

We sought to include randomised controlled trials (RCTs) of rituximab treatment by intravenous infusion for the treatment of patients with TAO, compared with placebo or intravenous glucocorticoid treatment.

Data collection and analysis: 

Two review authors independently scanned titles and abstracts, as well as independently screened the full reports of the potentially relevant studies. At each stage, the results were compared and disagreements were solved by discussion.

Main results: 

No studies were identified that met the inclusion criteria. There are three ongoing studies which are likely to meet inclusion criteria once published, and thus be included in future updates of this review.