ESPE2021 Free Communications Thyroid (6 abstracts)
Adjuvant Rituximab – exploratory trial in young people with Graves’ disease
Tim Cheetham 1 , Michael Cole 1 , Mario Abinun 1 , Amit Alalhabadia 2 , Tim Barratt 3 , Jeremy Kirk 3 , Justin Davies 4 , Paul Dimitri 2 , Amanda Drake 5 , Robert Murray 6 , Caroline Steele 7 , Nicola Zammitt 5 , Sonya Carnell 1 , Denise Howell 1 , Jonathan Prichard 1 , Gillian Watson 1 , John Matthews 1 & Simon Pearce 1
1Newcastle University, Newcastle upon Tyne, United Kingdom.;2Sheffield University, Sheffield, United Kingdom.;3Birmingham University, Birmingham, United Kingdom.;4Southampton University, Southampton, United Kingdom.;5Edinburgh University, Edinburgh, United Kingdom.;6Leeds University, Leeds, United Kingdom.;7Leeds Teaching Hospitals NHS trust, Leeds, United Kingdom
Objective: Remission rates in young people with Graves’ hyperthyroidism are 25% or less after a 2-yr course of thionamide antithyroid drug (ATD). Immunomodulatory agents could potentially improve outcome by facilitating immune tolerance. We wanted to explore whether rituximab, a B lymphocyte depleting agent, would increase remission rates when administered with a short course of ATD.
Design: This was an investigator-initiated open label multi-centre single arm phase 2 trial in young people (12-20 years) with Graves’ hyperthyroidism. The trial used an A’Hern design to distinguish an encouraging remission rate of 40% from an unacceptable rate of 20%, with power of 80% and Type I error of 10%. Participants presenting with Graves’ hyperthyroidism received a single 500mg dose of rituximab (RTX) followed by up to 12 months of ATD titrated according to thyroid function. The primary endpoint was relapse at 24 months (12 months without ATD) as judged by suppressed serum TSH and raised FT3; or they had restarted ATD between months 12 and 24; or they had thyroid surgery or radioiodine therapy at any time following RTX.
Results: Twenty-seven participants were recruited from 6 UK centres. All completed the trial and there were no serious side effects linked to treatment. The daily ATD dose at 12 months was 5mg or less in 20/27 participants. 13 of the 27 participants were in remission at 24 months (48%, 90% one-sided confidence interval 35%, 100%); this number exceeded the critical value (9) for the A’Hern design and provided evidence that the remission rate exceeded 40%. Two of the 13 participants in remission had low TSH and elevated thyroid receptor antibody titre and were considered at high risk of relapse. B lymphocyte count at 28 weeks, expressed as a percentage of baseline value, was related to likelihood of remission but there was no evidence of a difference between remission/relapse groups in terms of total ATD dose received or time to non-suppressed TSH.
Conclusions: This trial indicates that adjuvant rituximab, administered with a 12 month course of ATD, may increase the likelihood of remission in young people with Graves’ hyperthyroidism. B cell count at 6 months may be a pointer towards a favourable outcome. This data suggests that a formal randomised trial of adjuvant rituximab in young people with Graves’ hyperthyroidism is warranted.
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