A 12-month regimen of thionamide antithyroid drug (ATD) combined with a single dose of adjuvant rituximab was found to increase the likelihood of remission among adolescents and young adults with Graves hyperthyroidism. These findings were published in the Journal of Clinical Endocrinology & Metabolism.
These results came from an investigator-initiated, open-label, single arm, single stage, phase 2 trial. Research participants (N=27) aged 12-20 years with Graves hyperthyroidism were recruited between 2016 and 2018 from 5 pediatric and 4 adult endocrine centers in the United Kingdom. They received a single 500 mg rituximab infusion within 6 weeks of a diagnosis of Graves hyperthyroidism and were given 12 months of ATD. Remission and safety were assessed.
The participants were aged mean 15.3 years, 24 were girls or women, body mass index (BMI) was 21.7 kg/m2, and free triiodothyronine (FT3) was 10.85 pmol/L.
The Graves’ hyperthyroidism remission rate was 48% at 24 months, which exceeded the expectation of 20%.
Among those in remission at 24 months (n=13), 2 had increased thyroid receptor antibody (TRAb) titers and low thyroid stimulating hormone (TSH), suggesting a relapse was likely. Of the 14 participants who relapsed at 24 months, 13 received an additional 12- to 24-month course of ATD and 1 patient returned to low TSH and high FT3 levels at 24 months.
Stratified by remission status, TRAb titers at baseline were lower in the remission group, but group differences did not reach significance (median, 6.50 u/l vs 9.65 u/l; P =.30). At 28 weeks, the remission cohort had lower B cell lymphocyte counts than the remission group (median, 18.0 vs 46.5; P =.064), respectively, which increased among both groups at 52 weeks (median, 48.9 vs 62.8; P =.33), respectively.
There were no significant differences among the remission and relapse groups for time to normalization for TSH (median group difference, 47 days; P =.17), FT3 (median group difference, 31 days; P =.24), or free thyroxine (FT4) (median group difference, 13 days; P =.73).
There were 363 adverse events reported during the trial, of which 6 were considered serious but not related to the trial interventions. There were 13 adverse reactions that “could have” been related to the trial interventions, 4 “probably related’ and 1 indeterminate. One of the 17 adverse reactions was considered moderate in severity.
The researchers acknowledged limitations to the trial and “feel that the next step is to conduct a randomized, concurrently controlled trial.” They also said it is unknown whether the addition of rituximab only delayed a potential relapse in the study participants.
“This trial has indicated that rituximab may alter the clinical course of Graves hyperthyroidism in the young, with no unacceptable side effects,” the study authors concluded. “A formal randomized controlled trial is warranted.”
Disclosure: Some study authors declared affiliations with pharmaceutical companies. Please see the original reference for a full list of authors’ disclosures.
Cheetham T, Cole M, Abinun M, et al. Adjuvant rituximab – exploratory trial in young people with Graves’ disease. J Clin Endocrinol Metab. Published October 23rd, 2021. doi:10.1210/clinem/dgab763