Systemic safety analysis of mycophenolate in Graves’ orbitopathy

Lee, A C H; Riedl, Michaela; Frommer, Lara; Diana, Tanja; Kahaly, George J.

doi:10.1007/s40618-019-01161-z

Cited by 23 publications

(24 citation statements)

References 41 publications

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“…Furthermore, both the response rate to immunosuppressive treatment and the beneficial effect of GC as well as the associated health-related quality of life can be increased significantly when combining IVGC with the well-tolerated and efficacious drug mycophenolate, 36,86 with oral GC to cyclosporine, 104 IV immunoglobulins, 105 or orbital irradiation. 53,106 2.…”

Section: Resultsmentioning

confidence: 99%

Glucocorticoids in Graves’ orbitopathy: mechanisms of action and clinical application

Längericht

Krämer

Kahaly

2020

Therapeutic Advances in Endocrinology

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Background: Graves’ orbitopathy (GO) is the most frequent extrathyroidal manifestation of the autoimmune Graves’ disease. GO significantly impacts quality of life and has a psycho-social morbidity. Inflammation and swelling of the orbital tissue often leads to proptosis, diplopia, and decrease of visual acuity. Due to the inflammatory background of the disease, glucocorticoids (GC) have been used as a first-line treatment for decades. Methods: PubMed and MeSH database were searched for original articles, clinical trials, reviews, and meta-analyses published between 1 January 2000 and 31 March 2020 and pertaining to both the mechanism of action and immunological effects of GC as well as to the treatment of GO by GC. The publications were evaluated according to their setting and study design. Results: GC act through genomic (trans-activation and trans-repression) and rapid non-genomic mechanisms. GC in general, and the intravenous (IV) administration of GC in particular, markedly decrease the activity and number of the most potent antigen-presenting dendritic cells. According to the internationally acknowledged European Thyroid Association Guidelines for the management of GO, weekly IVGC application over 12 weeks is recommended as first-line treatment for patients with active and severe GO. The daily and cumulative dose should be tailored according to clinical severity, for example, 4.5 g of IV methylprednisolone for the inflammatory component versus 7.5 g in the presence of diplopia and severe proptosis. Fast and significant improvements in orbital symptoms and signs are noted in 65–70% of patients. Long-term experience over decades, and worldwide availability at low cost, underline the clinical and therapeutic relevance of GC. Adverse events are rarely severe, dose-dependent, and usually reversible, hence easy to handle by medical investigators. Oral GC application on a daily basis is characterized by high bioavailability but reduced efficacy and increased toxicity. Conclusion: IVGC still represents the standard of care in active/severe GO. Innovative biologicals, like monoclonal antibodies targeting the thyrotropin/Insulin-like growth factor-1 receptors or pro-inflammatory cytokines (e.g., Interleukin-6) should be compared with standard GC treatment with respect to short- and long-term efficacy, safety, costs, and global availability.

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Section: Resultsmentioning

confidence: 99%

Glucocorticoids in Graves’ orbitopathy: mechanisms of action and clinical application

Längericht

Krämer

Kahaly

2020

Therapeutic Advances in Endocrinology

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“…Post hoc analysis showed that the combination group demonstrated more significant improvement in CAS, swelling of eyelids or caruncle, orbital pain, chemosis, downgaze duction and elevation, as well as visual functioning subscale in the GO-specific quality of life (GO-QoL) questionnaire. Although a direct comparison between the two trials is not possible, several important differences in baseline characteristics between the two study populations (higher mean age, more prevalent smoking, longer disease duration, and greater proportion of TSH-R-Ab positive patients) may explain the lower response rates in the EUGOGO trial [50].…”

Section: Mycophenolatementioning

confidence: 99%

“…The safety data of mycophenolate in GO from both trials were also systemically analyzed [50]. Adverse events and serious adverse events were more common in the combination group of the EUGOGO trial than in the MMF group of the Chinese trial.…”

Section: Mycophenolatementioning

confidence: 99%

“…However, the US trial [62] found that RTX did not offer additional benefit over placebo in terms of CAS and other secondary endpoints. A subsequent joint post hoc analysis suggested that several differences in baseline characteristics (younger age, lower TSH-R-Ab, shorter duration of GO) may explain the favorable treatment outcomes in the Italian trial [63]. In fact, B cell infiltration was absent in some immunohistochemically analyzed GO orbital tissues [36], and this might explain why some patients failed to respond to RTX.…”

Section: Rituximabmentioning

confidence: 99%

“…A few patients in the RTX groups of both randomized trials developed a transient increase in proptosis or visual loss, and 2 patients even developed frank DON. It is postulated that massive lysis of intraorbital B cells due to RTX therapy may cause cytokine release syndrome with subsequent edema and expansion of orbital tissue, leading to progression of subclinical or impending DON [63]. Based on the latest evidence, the EUGOGO recommends that RTX be considered as one of the second-line treatment options after failure of IVGC, but it should not be used in patients with impending DON or long duration of disease [2].…”

Section: Rituximabmentioning

confidence: 99%

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Novel Approaches for Immunosuppression in Graves’ Hyperthyroidism and Associated Orbitopathy

Lee¹,

Kahaly²

2020

Eur Thyroid J

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Background: Both Graves’ hyperthyroidism (GH) and Graves’ orbitopathy (GO) are associated with significant adverse health consequences. All conventional treatment options have limitations regarding efficacy and safety. Most importantly, they do not specifically address the underlying immunological mechanisms. We aim to review the latest development of treatment approaches in these two closely related disorders. Summary: Immunotherapies of GH have recently demonstrated clinical efficacy in preliminary studies. They include ATX-GD-59, an antigen-specific immunotherapy which restores immune tolerance to the thyrotropin receptor; iscalimab, an anti-CD40 monoclonal antibody which blocks the CD40-CD154 costimulatory pathway in B-T cell interaction; and K1-70, a thyrotropin receptor-blocking monoclonal antibody. Novel treatment strategies have also become available in GO. Mycophenolate significantly increased the overall response rate combined with standard glucocorticoid (GC) treatment compared to GC monotherapy. Tocilizumab, an anti-interleukin 6 receptor monoclonal antibody, displayed strong anti-inflammatory action in GC-resistant cases. Teprotumumab, an anti-insulin-like growth factor 1 receptor monoclonal antibody, resulted in remarkable improvement in terms of disease activity, proptosis, and diplopia. Further, rituximab appears to be useful in active disease of recent onset without impending dysthyroid optic neuropathy. Key Messages: Therapeutic advances will continue to optimize our management of GH and associated orbitopathy in an effective and safe manner.

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Advances in the Treatment of Thyroid Eye Disease Associated Extraocular Muscle Myopathy and Optic Neuropathy

Amarikwa

Sears

et al. 2022

Curr Neurol Neurosci Rep

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Systemic safety analysis of mycophenolate in Graves’ orbitopathy

Cited by 23 publications

References 41 publications

Glucocorticoids in Graves’ orbitopathy: mechanisms of action and clinical application

Glucocorticoids in Graves’ orbitopathy: mechanisms of action and clinical application

Novel Approaches for Immunosuppression in Graves’ Hyperthyroidism and Associated Orbitopathy

Advances in the Treatment of Thyroid Eye Disease Associated Extraocular Muscle Myopathy and Optic Neuropathy

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