Efficacy of Tocilizumab in Patients With Moderate-to-Severe Corticosteroid-Resistant Graves Orbitopathy: A Randomized Clinical Trial

Pérez-Moreiras, J.V.; Gómez-Reino, Juan J.; Pérez‐Pampín, Eva; Lopez, Angel Romo; Alvarez, Fernando M. Rodríguez; Laguarta, Jesús M. Castillo; Cabello, Aurora del Estad; Sorroche, María Gessa; Gregori, Enrique España; Sales‐Sanz, Marco; Maneiro, José Ramón; Rituerto, Maria A. Tome Martinez de; Pampín, Eva Pérez; Álvarez, Alejandro; Troyano, J; Niño, Cristina; Vico, Eva Aladro; Zorrilla, Maria C. Montañez; Sanz, Marco Sales; Ucero, Ana M. Martín; Revenga, Marcelino; Lazaro, Antonia M. Pérez; Todolí, José; Alejos, Alba M. Gonzalez; Díaz, César; Marcos, Jose Miguel; Polo, Angel Dominguez; Lavilla, L; Ginés, Cilia Peralta; Escobar, Antonio J. Gómez; Díaz, Concepción; Sarabia, Federico Navarro; Hernández, Tomás Martín; Navarro, Elena; Rubio, Esteban; Blandón, Rafael Villanueva; Maiquez, María P.

doi:10.1016/j.ajo.2018.07.038

Cited by 206 publications

(230 citation statements)

References 31 publications

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“…Randomisation was to either 8 mg/kg body weight TCZ or placebo administered intravenously at weeks 0, 4, 8, and 12, and follow-up for an additional 28 weeks. The authors reported a significant difference in the proportion of patients achieving a CAS < 3 and exophthalmos size change from baseline in patients treated with tocilizumab [75].…”

Section: Specific Immunosuppressantmentioning

confidence: 96%

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Interruption of autoimmunity for thyroid eye disease: B-cell and T-cell strategy

Strianese

2019

Eye

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Recent new insights into the molecular basis of thyroid eye disease have led to the use of more specific therapies such as monoclonal antibodies This review explores the traditional immunosuppressant therapy for TED, highlighting the basis for emergent recent medications, possible treatment options and, eventually possible new general recommendation for management of TED. Data has been retrieved from the literature searching on Pubmed. Steroid therapy remains the first line therapy for moderate/severe and severe vision threatening TED The use of some traditional nonspecific immunosuppressant such as mycophenolate, cyclosporine and azathioprine seems useful in combination with steroid therapy to achieve stable results in the long term; methotrexate is useful as steroid-sparing medications and in steroid resistant or intolerant patients. In recent years, many scientific reports have showed the effectiveness of biological immunosuppressive agents in the management of TED. Etanercept, adalimumab, and tocilizumab have shown to be effective in reduction of the inflammatory signs with the possible advantage to prevent relapse of the disease. Particularly Tociliuzumab seems very effective as second line therapy, after steroid failure. Teprotumumab may control the disease activity and it seems to be very effective in preventing severity disease progression. Infliximab might be useful in severe TED with optic nerve compression resistant to steroid and decompression. Indeed, the actual incidence of adverse effects is not well assessed yet, therefore the use should be limited at those cases that really need an alternative therapy to steroid, handled by an expert multidisciplinary team.

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Section: Specific Immunosuppressantmentioning

confidence: 96%

“…Tocilizumab seems to be effective for treatment of steroid-resistant patients with low incidence of complication [73,75].…”

Section: Conclusion and General Recommendationmentioning

confidence: 99%

Interruption of autoimmunity for thyroid eye disease: B-cell and T-cell strategy

Strianese

2019

Eye

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“…Importance of those findings is difficult to assess given the absence of controls. A subsequent, multicenter study from many of the same investigators examined 32 patients with glucocorticoidresistant, moderate-to-severe TAO in a randomized, placebo-controlled trial (80 proptosis (1.5 mm) than did patients in the placebo group (0.0 mm, P = 0.01), but this relatively modest effect may not prove durable. The authors considered that their study was limited by the relatively small recruitment size and the potentially long interval between initial disease presentation and enrolment in the trial.…”

Section: Biologicals Targeting Cytokines and Their Potential In Taomentioning

confidence: 99%

“…A recent systematic review and metaanalysis of 11 studies including 167 patients supported the promising effects of rituximab for the management of TAO (128), but large, multicenter, randomized clinical trials are needed. Tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, was evaluated in a placebocontrolled, randomized clinical trial of 32 patients with moderate-to-severe and active TAO from several Spanish centers (80). Outcomes in terms of inactivation and overall improvement appeared to be significantly better compared to placebo, although it should be noted that in the follow-up visit at 40 weeks, differences were less impressive (80).…”

Section: The Road Beyond Initial Investigation Of Biologicals -Restormentioning

confidence: 99%

Will biological agents supplant systemic glucocorticoids as the first-line treatment for thyroid-associated ophthalmopathy?

Smith

Bartalena

2019

European Journal of Endocrinology

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In this article, the two authors present their opposing points of view concerning the likelihood that glucocorticoids will be replaced by newly developed biological agents in the treatment of active, moderate-to-severe thyroid-associated ophthalmopathy (TAO). TAO is a vexing, disfiguring and potentially blinding autoimmune manifestation of thyroid autoimmunity. One author expresses the opinion that steroids are nonspecific, frequently fail to improve the disease and can cause sometimes serious side effects. He suggests that glucocorticoids should be replaced as soon as possible by more specific and safer drugs, once they become available. The most promising of these are biological agents. The other author argues that glucocorticoids are proven effective and are unlikely to be replaced by biologicals. He reasons that while they may not uniformly result in optimal benefit, they have been proven effective in many reports. He remains open minded about alternative therapies such as biologicals but remains skeptical that they will replace steroids as the first-line therapy for active, moderate-to-severe TAO without head-to-head comparative clinical trials demonstrating superiority. Despite these very different points of view, both authors are optimistic about the availability of improved medical therapies for TAO, either as single agents or in combination. Further, both agree that better treatment options are needed to improve the care of our patients with active moderate-to-severe TAO.

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“…Es konnte nachgewiesen werden, dass Patienten, die nach 6 Wochen noch kein Therapieansprechen zeigten, sich nach 12 Wochen nur zu 28 % bessern, und Patien-ten, die sich innerhalb der ersten 6 Wochen verschlechtern, auch nach 12 Wochen nicht ansprechen[50]. Bei Patienten, bei denen vor allem die entzündliche Weichteilsymptomatik nicht genug auf die i. v. Steroidtherapie anspricht, hat sich Tocilizumab[55] als effektiv erwiesen. Allerdings müssen die Ergebnisse der 2018 publizierten Studie noch an einer größeren Patientenzahl bestätigt werden.…”

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Update endokrine Orbitopathie

Eckstein¹,

Oeverhaus²,

Stöhr³

et al. 2020

Augenheilkunde up2date

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ZusammenfassungDie endokrine Orbitopathie ist eine Autoimmunerkrankung, die am häufigsten zusammen mit einer Schilddrüsenüberfunktion vom Typ Basedow auftritt. Die Patienten weisen spezifisch TSH-Rezeptor-Autoantikörper auf. Diese stimulieren die Schilddrüse und führen zu einer von der Hypophyse nicht mehr kontrollierten Schilddrüsenüberfunktion. Die TSH-Rezeptor-Autoantikörper und vornehmlich infiltrierende T-Zellen und Makrophagen verursachen krankhafte Veränderungen der Orbitafibroblasten mit dem Endresultat einer Fettvermehrung in der Orbita, Entzündungsreaktion und Fibrose. Die Folge sind Lidretraktion, Augenbewegungsstörung, Exophthalmus und eine mehr oder weniger ausgeprägte entzündliche Weichteilsymptomatik. Die chronische Entzündungsreaktion verläuft in drei Phasen: aktive Phase, Plateauphase und inaktive Phase. In der aktiven Phase kann man mit einer antientzündlichen Therapie (i. v. Steroide und Orbitaspitzenbestrahlung – bei ausbleibenden Erfolg Kombination mit einer immunmodulatorischen Therapie) die endokrine Orbitopathie bessern. Eine Vollheilung ist jedoch mit den aktuell verfügbaren Therapieoptionen selten. Dies ändert sich möglicherweise in der Zukunft, wenn neue zielgerichtete Therapien zum Einsatz kommen, die aktuell in Studien getestet werden. Meist müssen bleibende Defekte chirurgisch in folgender Reihenfolge korrigiert werden: 1. Orbitadekompression, 2. Augenmuskelchirurgie und 3. Lidchirurgie. Eine schlechte Kontrolle der Schilddrüsenfunktion, Nikotinkonsum und hohe TSH-Rezeptor-Autoantikörper-Spiegel sind die stärksten Risikofaktoren für einen schweren Verlauf der Erkrankung. Seltenere Formen wie die endokrine Orbitopathie ohne begleitende Schilddrüsenerkrankung und die endokrine Orbitopathie assoziiert mit einer Autoimmunthyreoiditis vom Typ Hashimoto verlaufen meist mild und häufig asymmetrisch.

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Efficacy of Tocilizumab in Patients With Moderate-to-Severe Corticosteroid-Resistant Graves Orbitopathy: A Randomized Clinical Trial

Cited by 206 publications

References 31 publications

Interruption of autoimmunity for thyroid eye disease: B-cell and T-cell strategy

Interruption of autoimmunity for thyroid eye disease: B-cell and T-cell strategy

Will biological agents supplant systemic glucocorticoids as the first-line treatment for thyroid-associated ophthalmopathy?

Update endokrine Orbitopathie

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