Rituximab Treatment of Patients with Severe, Corticosteroid-Resistant Thyroid-Associated Ophthalmopathy

Khanna, Dinesh; Chong, Kelvin; Afifiyan, Nikoo F.; Hwang, Catherine J.; Lee, Diana K.; Garneau, Hélène Chokron; Goldberg, Robert A.; Darwin, Christine; Smith, Terry J.; Douglas, Raymond S.

doi:10.1016/j.ophtha.2009.05.029

Cited by 155 publications

(132 citation statements)

References 40 publications

(50 reference statements)

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“…To date, clinical studies have shown that RTX can be employed in patients with active moderate-to-severe GO either as first-line treatment or when IVMP therapy fails (114,115,116,117,118,119).…”

Section: Rituximabmentioning

confidence: 99%

“…One possible explanation is that subclinical DON was already present in these patients at the time of therapy and that the release of cytokines induced by RTX might have resulted in increased intraorbital edema with optic nerve compression. To date, RTX has been employed in another ten patients with dysthyroid optic neuropathy (DON) (116,118,121) and has induced significant improvement of vision. We therefore suggest caution in employing RTX in very severe GO, particularly if subclinical DON is suspected, until randomized controlled trials will provide evidence of its superiority over standard treatment with high-dose IVMP.…”

Section: Efficacy and Dosing Of Rtx In Gomentioning

confidence: 99%

“…The infusion of 1000 mg twice, with a 2-week interval, has been employed as the standard treatment of RA and other autoimmune diseases. This dose has been initially used in most open studies (115,118) and in case reports (107,114) in patients with GO. Rapid and complete peripheral B-cell depletion following very low-dose (100 mg) RTX was shown in a study by Salvi et al (112).…”

Section: Efficacy and Dosing Of Rtx In Gomentioning

confidence: 99%

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THERAPY OF ENDOCRINE DISEASE: Endocrine dilemma: management of Graves’ orbitopathy

Campi

Vannucchi

Salvi

2016

European Journal of Endocrinology

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Management of Graves' orbitopathy (GO) must be based on the correct assessment of activity and severity of the disease. Activity is usually assessed with the Clinical Activity Score, whereas severity is classified according to a European Group On Graves' Orbitopathy (EUGOGO) consensus statement as mild, moderate-to-severe, and sight-threatening. Myopathic and chronic congestive forms are uncommon clinical presentations of GO. Restoration and maintenance of stable euthyroidism are recommended in the presence of GO. In moderate-to-severe disease, steroids have been widely employed and have shown to possess an anti-inflammatory activity, but about 20 -30% of patients are not responsive and present recurrence. Some novel immunosuppressors have already been employed in clinical studies and have shown interesting results, although the lack of randomized and controlled trials suggests caution for their use in clinical practice. Potential targets for therapy in GO are the thyroid-stimulating hormone and the insulin-like growth factor 1 receptor on the fibroblasts, inflammatory cytokines, B and T cells, and the PIK3/mTORC1 signaling cascades for adipogenesis. A recent open study has shown that tocilizumab, an anti-sIL-6R antibody, inactivates GO. Consistent reports on the efficacy of rituximab have recently been challenged by randomized controlled trials. As the main goal of treatment is the well-being of the patient, the therapeutic strategy should be addressed to better suit the patient needs, more than improving one or more biological parameters. The increasing availability of new therapies will expand the therapeutic options for GO patients and allow the clinician to really personalize the treatment to better suit the patients' personal needs.

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Section: Rituximabmentioning

confidence: 99%

Section: Efficacy and Dosing Of Rtx In Gomentioning

confidence: 99%

Section: Efficacy and Dosing Of Rtx In Gomentioning

confidence: 99%

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THERAPY OF ENDOCRINE DISEASE: Endocrine dilemma: management of Graves’ orbitopathy

Campi

Vannucchi

Salvi

2016

European Journal of Endocrinology

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“…The potential use of RTX in GO has previously been reported in the literature (17,(26)(27)(28)(29). However, the difference and importance of the present study is that the GO of this patient was the most severe of the published cases.…”

Section: Discussionmentioning

confidence: 50%

Clinical efficacy of combined rituximab treatment in a woman with severe Graves' ophthalmopathy

Liu

Guo

Liu

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The present study reports the case of a female Chinese patient with Graves' disease (GD) and severe Graves' ophthalmopathy (GO) in its active phase, who was treated with propylthiouracil and oral prednisolone for 2 months at a local hospital. However, a lack of improvement in symptoms meant that the patient was transferred to the First Affiliated Hospital of Xi'an Jiaotong University (Xi'an, China), whereupon the patient received high-dose intravenous methylprednisolone pulse therapy, although with limited efficacy. Subsequently, rituximab (RTX; anti-CD20 monoclonal antibody) combined with orbital irradiation treatment was initiated. The patient responded positively to the combined treatment; the clinical symptoms and enlargement of the extraocular muscles were ameliorated, and there were marked decreases in the clinical activity and NOSPECS grading scores. Furthermore, the serum levels of anti-thyrotropin receptor antibodies (TRAb) were markedly decreased at 2 months following RTX therapy. The patient was maintained in a euthyroid state by treatment with methimazole during and following RTX therapy. It was concluded that RTX treatment may attenuate severe GO by depleting lymphocytes, and may promote the recovery of GD by reducing the serum levels of TRAb.

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“…Initial studies by Fassi et al and Salvi et al 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 [9-11] Khanna et al have treated six patients with active and severe Gravis' orbitopathy, unresponsive to glucocorticoids with RTX, and have observed a decrement in the CAS from 5.5-1.8 at eight week, which remained low at sixth month [12]. In all these studies, there was no relapse in patient treated with RTX.…”

Section: Discussionmentioning

confidence: 99%

Rituximab therapy in steroid resistant thyroid associated ophthalmopathy

Devarbhavi¹,

Maiti²,

Sinha³

et al. 2017

Case Rep Int

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Introduction:Thyroid associated ophthalmopathy (TAO) is the most frequent extrathyroidal manifestation of Graves' disease. Considerable number of TAO is also found with euthyroid or hypothyroid state and responds to present mainstay of therapy i.e corticosteroid. However, some patients with TAO are resistant to steroid therapy and may progress to vision threatening orbitopathy. Radiotherapy, surgical decompression and cyclosporine in combination with oral or intravenous glucocorticoid were the other options in such cases. But recently rituximab a monoclonal anti CD20 antibody which was successfully used in other

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Rituximab Treatment of Patients with Severe, Corticosteroid-Resistant Thyroid-Associated Ophthalmopathy

Cited by 155 publications

References 40 publications

THERAPY OF ENDOCRINE DISEASE: Endocrine dilemma: management of Graves’ orbitopathy

THERAPY OF ENDOCRINE DISEASE: Endocrine dilemma: management of Graves’ orbitopathy

Clinical efficacy of combined rituximab treatment in a woman with severe Graves' ophthalmopathy

Rituximab therapy in steroid resistant thyroid associated ophthalmopathy

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