The effect of B cell depletion therapy on anti‐<scp>TSH</scp> receptor antibodies and clinical outcome in glucocorticoid‐refractory Graves' orbitopathy

Mitchell, Anna L.; Gan, Earn H; Morris, Margaret; Johnson, K.; Neoh, C; Dickinson, A J; Perros, Petros; Pearce, Simon H. S.

doi:10.1111/cen.12141

Cited by 72 publications

(76 citation statements)

References 25 publications

(34 reference statements)

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“…This study suggests that the natural history of AAD is modifiable and that Addison's disease is potentially remediable by disease-modifying drugs targeted at the immune response. This is in line with Type 1 diabetes mellitus and Graves' ophthalmopathy, in which immunomodulatory drugs administered early on in natural history have also shown some success (105,106,107). The low but detectable serum cortisol at diagnosis demonstrates the persistence of adrenal steroidogenesis in some patients, which has the potential to be rescued by either immunomodulatory or regenerative approaches.…”

Section: Regenerative Medicine In Autoimmune Addison's Diseasesupporting

confidence: 61%

MANAGEMENT OF ENDOCRINE DISEASE: Regenerative therapies in autoimmune Addison’s disease

Gan

Pearce

2017

European Journal of Endocrinology

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The treatment for autoimmune Addison's disease (AAD) has remained virtually unchanged in the last 60 years. Most patients have symptoms that are relatively well controlled with exogenous steroid replacement, but there may be persistent symptoms, recurrent adrenal crisis and poor quality of life, despite good compliance with optimal current treatments. Treatment with conventional exogenous steroid therapy is also associated with premature mortality, increased cardiovascular risk and complications related to excessive steroid replacement. Hence, novel therapeutic approaches have emerged in the last decade attempting to improve the long-term outcome and quality of life of patients with AAD. This review discusses the recent developments in treatment innovations for AAD, including the novel exogenous steroid formulations with the intention of mimicking the physiological biorhythm of cortisol secretion. Our group has also carried out a few studies attempting to restore endogenous glucocorticoid production via immunomodulatory and regenerative medicine approaches. The recent advances in the understanding of adrenocortical stem cell biology, and adrenal plasticity will also be discussed to help comprehend the science behind the therapeutic approaches adopted.

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Section: Regenerative Medicine In Autoimmune Addison's Diseasesupporting

confidence: 61%

MANAGEMENT OF ENDOCRINE DISEASE: Regenerative therapies in autoimmune Addison’s disease

Gan

Pearce

2017

European Journal of Endocrinology

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“…Whether this might have led to a diminished benefit in the US patients is not yet known. A similar use of steroids was usually the case for the pretrial case series that reported benefit with the use of RTX (10,15,31), and there are no clinical data to indicate that a longer washout from steroids would in any way potentiate RTX response. The protocol employed in the 2 RCTs is outlined in Table 3.…”

Section: Analysis Of the Randomized Trials Characteristicsmentioning

confidence: 90%

MANAGEMENT OF ENDOCRINE DISEASE: Rituximab therapy for Graves’ orbitopathy – lessons from randomized control trials

Stan

Salvi

2017

European Journal of Endocrinology

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Rituximab (RTX) use in open-label series has been associated with very encouraging responses in patients with active and moderate-to-severe Graves' orbitopathy (GO). Recently, randomized controlled trials of RTX have been performed in such patients to answer the question of clinical efficacy and the safety profile of this agent. That data, reported separately, focused on Clinical Activity Score (CAS) and indicated in one trial a strong benefit of RTX in comparison with IV glucocorticoids, whereas the other trial noted the absence of a benefit by comparison with placebo. The outcome was reanalyzed post hoc here, using EUGOGO criteria, and the results were not significantly different. The authors comment further on the differences between the two trials regarding populations treated, methodology, analysis of outcomes and the adverse effect profile of RTX. The populations treated appear different with younger patients, lower TRAb and shorter duration of disease prevalent in the Italian trial, all elements favoring a better response. Smoking, usually diminishing a response, was also more prevalent in some patients. The combined outcome proposed by EUGOGO revealed similar results with CAS regarding RTX efficacy; yet, it might be a more comprehensive outcome. The adverse events of concern relate mainly to the risk of DON, which seems to be increased by the use of RTX in a certain subset of patients. Based on available data, a multicenter trial using the EUGOGO-proposed outcomes might be the next best step to define the role of RTX in GO therapy.

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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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The effect of B cell depletion therapy on anti‐TSH receptor antibodies and clinical outcome in glucocorticoid‐refractory Graves' orbitopathy

Cited by 72 publications

References 25 publications

MANAGEMENT OF ENDOCRINE DISEASE: Regenerative therapies in autoimmune Addison’s disease

MANAGEMENT OF ENDOCRINE DISEASE: Regenerative therapies in autoimmune Addison’s disease

MANAGEMENT OF ENDOCRINE DISEASE: Rituximab therapy for Graves’ orbitopathy – lessons from randomized control trials

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

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