The rationale for B lymphocyte depletion in Graves’ disease. Monoclonal anti-CD20 antibody therapy as a novel treatment option

Fassi, Daniel El; Nielsen, Claus Henrik; Hasselbalch, Hans Carl; Hegedűs, László

doi:10.1530/eje.1.02140

Cited by 64 publications

(49 citation statements)

References 87 publications

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“…Patients treated with RTX were studied at 4,8,12,16,20,30,50, and 70-75 weeks, while those treated with IVGC were studied at 8, 20, 30, and 50 weeks after the first drug infusion (Fig. 1).…”

Section: Patientsmentioning

confidence: 99%

“…The rationale of the present study is based on the potential effect of RTX treatment on B-cell-mediated immunity in GD and TAO (15,16). When compared with the natural course of Graves' hyperthyroidism, TAO has a self-limiting evolution with an active phase lasting a relatively limited time (6-18 months) and followed by clinical stabilization.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of Graves’ disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study

Salvi¹,

Vannucchi²,

Campi³

et al. 2007

eur j endocrinol

237

187

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Introduction: Hyperthyroid Graves' disease (GD) is a B-cell-mediated condition caused by TSH receptor antibodies (TRAb), which decline when GD remits. Anti-CD20 monoclonal antibody rituximab (RTX) induces transient B-cell depletion that may potentially modify the active inflammatory phase of thyroid-associated ophthalmopathy (TAO). Methods: Nine patients with GD, (seven with active TAO, two with mild lid signs) were studied. The trial was only approved as an open pilot study; thus we compared the effect of RTX therapy to that of i.v. glucocorticoids (IVGC) in 20 consecutive patients. Patients were treated with RTX (1000 mg i.v. twice at 2-week interval) or with IVGC (500 mg i.v. for 16 weeks). TAO was assessed by the clinical activity score (CAS) and severity was classified using NOSPECS (No signs or symptoms; Only signs (lid); Soft tissue involvement; Proptosis, Extraocular muscle involvement; Corneal involvement; Sight loss). Thyroid function and lymphocyte count were measured by standardized methods. Results: All patients attained peripheral B-cell depletion with the first RTX infusion. Minor side effects were reported in three patients. Thyroid function was not affected by RTX therapy and hyperthyroid patients required therapy with methimazole. After RTX, the changes in the levels of thyroglobulin antibodies, thyroperoxidase antibodies and TRAb were neither significant nor correlated with CD20C depletion (PZNS). CAS values before RTX were 4.7G0.5 and decreased to 1.8G0.8 at the end of follow-up (P!0.0001) and more significantly compared with IVGC (P!0.05). Proptosis decreased significantly after RTX both in patients with active TAO (ANOVA; P!0.0001) and those with lid signs (ANOVA; P!0.003). The degree of inflammation (class 2) decreased significantly in response to RTX (ANOVA; P!0.001). Relapse of active TAO was not observed in patients treated with RTX, but occurred in 10% of those treated with IVGC, who also experienced adverse effects more frequently (45 vs 33% of patients). Conclusions: RTX positively affects the clinical course of TAO, independently of either thyroid function or circulating antithyroid antibodies, including TRAb. If our findings are confirmed in large controlled studies, RTX may represent a useful therapeutic tool in patients with active TAO.

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Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Treatment of Graves’ disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study

Salvi¹,

Vannucchi²,

Campi³

et al. 2007

eur j endocrinol

237

187

View full text Add to dashboard Cite

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“…18,19 The B-cell population typically reaches normal levels 9-12 months after infusion of rituximab. 18 Despite its depletion of B cells, rituximab typically does not result in low immunoglobulin levels, although IgM can be decreased after multiple retreatments.…”

Section: Rituximab Treatment In Thyroid Eye Diseasementioning

confidence: 99%

“…18 Despite its depletion of B cells, rituximab typically does not result in low immunoglobulin levels, although IgM can be decreased after multiple retreatments. 19 Available dosing regimens for rituximab include four consecutive weekly intravenous infusions of 375 mg/m 2 of body surface area (typically used for haematologic disorders) or two intravenous infusions of 1000 mg given 2 weeks apart (typically used in autoimmune disease). 1 Rituximab is considered to be relatively safe, with mild infusion-related reactions being the most commonly reported adverse event.…”

Section: Rituximab Treatment In Thyroid Eye Diseasementioning

confidence: 99%

“…Because immunoglobulin levels are usually maintained, there are relatively few infection-related adverse events, although rarely a fatal reactivation of JC virus causing progressive multifocal leukoencephalopathy has been reported. 18,19 Through B-lymphocyte depletion and subsequent decreased production of pathogenic antibodies, rituximab shows promise as an effective treatment for TED and has been increasingly described in recent case reports and case series. 20 Intra-thyroidal B-lymphocyte depletion in GD has been reported after the use of rituximab 21 as early as 7 days after treatment.…”

Section: Rituximab Treatment In Thyroid Eye Diseasementioning

confidence: 99%

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Rituximab in the Treatment of Thyroid Eye Disease: A Review

Ostrowski

Bussey

Shayesteh

et al. 2015

Neuro-Ophthalmology

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Graves disease is an autoimmune thyroid disease classically characterised by a clinical triad consisting of hyperthyroidism, diffuse goitre, and thyroid eye disease. Thyroid eye disease is an immunologically mediated condition in which humoral immunity is thought to play a central role. Thyroid eye disease is traditionally treated with high-dose glucocorticosteroids and surgical orbital decompression. However, responses are inadequate and alternative treatment options are needed. Rituximab, an anti-CD20 monoclonal antibody, shows promise as a novel therapeutic option for thyroid eye disease. There are 43 cases of thyroid eye disease treated with rituximab in the medical literature, and larger studies are warranted to determine the long-term effectiveness of rituximab. Rituximab may represent an attractive new treatment option for thyroid eye disease, especially in the case of disease that is refractory to current treatment strategies.

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Distribution of Lymphocyte Subpopulations in Thyroid Glands of Human Autoimmune Thyroid Disease

Zha

Huang

Lin

et al. 2014

J. Clin. Lab. Anal.

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Based on CD20+ B cells predominantly infiltrating in all HT thyroid tissues we suggested CD20 antibody might be of help for HT treatment. Furthermore based on FoxP3+ Tregs abundantly infiltrating in some of the AITD thyroid specimens, we considered that activating the Tregs' function in comparison to increasing the Tregs' number only, may be a more effective approach to the treatment of AITD in some cases.

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The rationale for B lymphocyte depletion in Graves’ disease. Monoclonal anti-CD20 antibody therapy as a novel treatment option

Cited by 64 publications

References 87 publications

Treatment of Graves’ disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study

Treatment of Graves’ disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study

Rituximab in the Treatment of Thyroid Eye Disease: A Review

Distribution of Lymphocyte Subpopulations in Thyroid Glands of Human Autoimmune Thyroid Disease

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