Adjuvant Rituximab - exploratory trial in young people with Graves' disease.

OBJECTIVE: Remission rates in young people with Graves' hyperthyroidism are <25% after two years of thionamide antithyroid drug (ATD). We explored whether rituximab, a B lymphocyte depleting agent, would increase remission rates when administered with a short course of ATD. DESIGN: This was an open label multi-centre single arm phase 2 trial in young people (12-20y) 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 500mg rituximab and 12 months of ATD titrated according to thyroid function. ATD were stopped after 12 months and primary outcome assessed at 24 months. Participants had relapsed at 24 months if: TSH was suppressed and FT3 was raised; they had received ATD between months 12 and 24; they had thyroid surgery/radioiodine. RESULTS: Twenty-seven participants were recruited and completed the trial with no serious side effects linked to treatment. Daily carbimazole dose at 12 months was <5mg in 21/27 participants. 13/27 participants were in remission at 24 months (48%, 90% one-sided confidence interval 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. CONCLUSIONS: Adjuvant rituximab, administered with a 12 month course of ATD, may increase the likelihood of remission in young people with Graves' hyperthyroidism. A randomised trial of adjuvant rituximab in young people with Graves' hyperthyroidism is warranted.