Cheetham, T.D., Cole, M., Abinun, M. et al. (15 more authors) (2022) Adjuvant rituximab—exploratory trial in young people with Graves disease. The Journal of Clinical Endocrinology & Metabolism, 107 (3). pp. 743-754. ISSN 0021-972X
Abstract
Context
Remission rates in young people with Graves hyperthyroidism are less than 25% after 2 years of thionamide antithyroid drug (ATD).
Objective
We explored whether rituximab (RTX), a B-lymphocyte–depleting agent, would increase remission rates when administered with a short course of ATD.
Methods
This was an open-label, multicenter, single-arm, phase 2 trial in young people (ages, 12-20 years) with Graves hyperthyroidism. An A’Hern design was used to distinguish an encouraging remission rate (40%) from an unacceptable rate (20%). Participants presenting with Graves hyperthyroidism received 500 mg RTX and 12 months of ATD titrated according to thyroid function. ATDs were stopped after 12 months and primary outcome assessed at 24 months. Participants had relapsed at 24 months if thyrotropin was suppressed and free 3,5,3′-triiodothyronine was raised; they had received ATD between months 12 and 24; or they had thyroid surgery/radioiodine.
Results
A total of 27 participants were recruited and completed the trial with no serious side effects linked to treatment. Daily carbimazole dose at 12 months was less than 5 mg in 21 of 27 participants. Thirteen of 27 participants were in remission at 24 months (48%, 90% one-sided CI, 35%-100%); this exceeded the critical value (9) for the A’Hern design and provided evidence of a promising remission rate. B-lymphocyte count at 28 weeks, expressed as a percentage of baseline, was related to likelihood of remission.
Conclusion
Adjuvant RTX, administered with a 12-month course of ATD, may increase the likelihood of remission in young people with Graves hyperthyroidism. A randomized trial of adjuvant RTX in young people with Graves hyperthyroidism is warranted.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | thyrotoxicosis; Graves disease; thionamide; rituximab; adolescents; children |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 04 Mar 2022 10:50 |
Last Modified: | 04 Mar 2022 10:50 |
Status: | Published |
Publisher: | The Endocrine Society |
Refereed: | Yes |
Identification Number: | 10.1210/clinem/dgab763 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:184268 |