Elsevier

Annales d'Endocrinologie

Volume 78, Issue 1, February 2017, Pages 20-26
Annales d'Endocrinologie

Original article
Treatment by rituximab on six Grave's ophthalmopathies resistant to corticosteroidsTraitement par rituximab de six orbitopathies dysthyroïdiennes résistantes aux corticoïdes

https://doi.org/10.1016/j.ando.2016.12.002Get rights and content

Abstract

Objectives

Graves’ ophthalmopathy occurs in 50% of Graves’ disease cases. Treatment is based on smoking cessation, and control of the euthyroidism and ocular repercussions associated with the disease. The active orbital forms are treated with glucocorticoids. Non-validated therapies have also been recently tested. Rituximab has been effectively used several times to treat corticosteroid-resistant Graves’ ophthalmopathy associated with an optic neuropathy, but its use could be proposed only in inflammatory ophthalmopathies after failure of the corticosteroids. We present six cases treated since early 2012 at the University Hospital Center of Tours, France.

Methods

Six patients were treated at the University Hospital Center of Tours, France, between September 2012 and April 2014. The patients had a Mourits’ score greater than three after treatment with corticosteroids and/or a severe NOSPECS score and/or orbital inflammation resistant to maximal treatment with intravenous injections of methylprednisolone and an optic neuropathy. They twice received one gram of rituximab by slow intravenous injection two weeks apart. Efficacy was assessed by a decrease of the orbital inflammatory clinical Mourits’ score, and visual acuity and visual field testing.

Results

The inflammatory score of patients improved and treatment helped to stop the progression of the sequelae due to neuropathy. The orbital inflammatory clinical score, and the visual acuity and visual field improved but orbital decompression was necessary to complete the treatment.

Conclusion

Rituximab has been used for the treatment of active corticosteroid-resistant Graves’ ophthalmopathies. We also had positive results on patients with visual threat and optic neuropathy, when combined with surgical decompression.

Résumé

Introduction

L’orbitopathie basedowienne survient dans 50 % des maladies de Basedow. Son traitement repose sur l’arrêt du tabac, l’euthyroïdie et le traitement du retentissement oculaire (symptômes et séquelles). Le traitement de l’orbitopathie active aiguë repose sur la corticothérapie, cependant plusieurs autres thérapeutiques non validées sont à l’étude. Le rituximab a été utilisé à plusieurs reprises efficacement pour traiter des atteintes orbitaires graves avec atteinte du nerf optique, quand celles-ci étaient résistantes aux corticoïdes, mais son utilisation ne pourrait être proposée que dans l’indication inflammatoire après échec des corticoïdes. Nous présentons ici six cas traités au centre hospitalier universitaire de Tours depuis début 2012.

Matériels et méthodes

Six patients ont été traités au centre hospitalier universitaire de Tours entre septembre 2012 et avril 2014, présentant un score de Mourits supérieur à trois, persistant après la corticothérapie, et/ou un score NOSPECS sévère, et/ou avec une inflammation orbitaire résistante à un traitement maximal par bolus de Solumédrol®, et une neuropathie optique. Ils ont reçu un gramme de rituximab en perfusion lente intraveineuse, à deux reprises à deux semaines d’intervalle. L’efficacité a été évaluée sur la diminution du score inflammatoire clinique orbitaire de Mourits, l’acuité visuelle et le champ visuel.

Résultats

Les patients traités ont amélioré leur score inflammatoire et le traitement a permis d’éviter l’aggravation des séquelles de la maladie dans les formes avec neuropathie. Le score inflammatoire orbitaire a été amélioré ainsi que l’acuité visuelle et le champ visuel. Un traitement par décompression orbitaire a été nécessaire en complément dans tous les cas.

Conclusion

Le rituximab a été utilisé dans les orbitopathies dysthyroïdiennes actives résistantes aux corticoïdes. Nous avons eu également des résultats positifs pour nos patients avec menace visuelle et neuropathie optique résistantes aux corticoïdes, en complément de la décompression chirurgicale.

Section snippets

Objectives

Graves’ ophthalmopathy is a disfiguring and potentially blinding disease, which greatly affects the appearance of patients and their quality of life. It affects the eyelid and the area around the orbit combining proptosis, oculomotor disorders, and eyelid abnormalities. The incidence of Graves’ disease is 16 per 100,000 for women and three per 100,000 for men per year [1]. Graves’ ophthalmopathy occurs in 50% of these patients and can be severe in 3–5% of cases. The symptoms can range from a

Methods

Six patients were treated with rituximab between September, 2012 and April, 2014 for Graves’ ophthalmopathies at the Tours University Hospital Center, France. They had a Mourits’ inflammatory clinical orbital score greater than 3 and were initially treated for inflammatory Graves’ ophthalmopathy with glucocorticoid therapy. The protocol consisted of 15 mg/kg intravenous injections (with doses up to 1000 mg) of methylprednisolone every fifteen days for two months and then 7.5 mg/kg every two weeks

Results

The three men and three women of the study all had a thyroidectomy prior to rituximab treatment. One patient did not stop smoking prior to treatment. Three patients were non-smokers; the other two were ex-smokers. All patients exhibited oculomotor disorders. Visual acuity was abnormal for four patients. The Mourits’ score was greater than or equal to three for five patients. Five patients had proptosis of greater than 18 mm. All six patients had visual field defects. Four patients had emergency

Discussion

Rituximab therapy was beneficial in second intention for the six patients in this study, based on three criteria, who had severe ophthalmopathy with inflammatory signs resistant to corticosteroids, decreased visual acuity and/or visual field defects.

Anti-CD20 treatments have made it possible to exploit the role of B cells in autoimmunity to treat a number of diseases.

B lymphocytes not only produce autoantibodies, but also activate CD4+ T cells, thus playing a role in inflammation. They are also

Conclusion

We successfully used rituximab to treat Graves’ ophthalmopathies without significant side effects resulting in improvement of the symptoms of patients who responded inadequately to corticosteroids, however some patients had orbital decompression shortly before treatment by rituximab. We had positive results on patients with visual threat and optic neuropathy, combined or not with an initial surgical orbital decompression. The description of cases treated with rituximab in centers caring for

Disclosure of interest

The authors declare that they have no competing interest.

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