JCEM: An exploratory trial of adjuvant rituximab therapy in young people with Graves disease

Background: Graves disease (GD) is a challenging disease for young people and their families
.
The remission rate of standard antithyroid drugs (ATD) after 1-3 years of treatment is low, about 20%-30%, so it is recommended to extend the treatment time
.
For most patients who still relapse after ATD treatment, you can choose to continue ATD treatment, or choose surgery (total thyroidectomy) or radioactive iodine (RI) treatment
.
It is not ideal for these patients to take thyroxine (T4) for a long time, because adults with normal thyroid stimulating hormone (TSH) concentration will have less well-being in thyroid hormone replacement therapy
compared with the control group , and receive RI or thyroidectomy The quality of life of patients treated for GD will also decrease .
The purpose of this study was to investigate whether the short-term use of the B lymphocyte depleting agent rituximab (RTX) combined with ATD can improve the remission rate of GD
.

Methods: The main purpose of this trial is to determine whether a 500mg dose of RTX combined with a 12-month sulfamide drug (tabazole [CBZ] or propylthiouracil [PTU]) will significantly improve the achievement of patients with Graves hyperthyroidism Proportion of long-term relief
.
The secondary goal is to examine the safety of the trial treatment regimen by determining the nature and frequency of adverse events (AEs), and to examine the relationship between the remission/relapse status after 24 months and the following parameters: 1.
TRAb during RTX injection Titer 2.
Immune cell response, especially the number of B cells (CD19+ cells) at 28 weeks and 52 weeks, expressed as a percentage of the baseline value 3.
The cumulative dose of ATD 4.
Free T4 (FT4) and free 3,5.
3'- The time required for triiodothyronine (FT3) to return to normal after RTX injection
.
This is an open-label, multi-center Phase 2 trial for patients with Graves' hyperthyroidism aged 12-20 years
.
Participants with Graves hyperthyroidism received 500 mg of RTX and 12 months of ATD, which were evaluated based on thyroid function
.
ATDS was discontinued after 12 months, and the main results were evaluated at 24 months
.
If thyroid stimulating hormone is suppressed and free 3'-triiodothyronine (FT3) rises, participants relapse at 24 months; they receive ATD treatment between 12 and 24 months; or they receive thyroid surgery/ Radioactive iodine therapy
.
Clinicians diagnose GD based on clinical and biochemical indicators, including suppressed serum TSH levels at the time of diagnosis (TSH levels cannot be recorded according to the local reference range, so they are lower than the detection threshold) and serum free thyroid hormone concentration (above the local reference range), And TRAb is elevated
.
Participants were less than 6 weeks before starting antithyroid medication (CBZ or PTU) for the first time and had no previous history of autoimmune thyroid disease
.
Patients with severe heart and lung disease, kidney or liver disease (including hepatitis B and hepatitis C) were excluded
.

Results: A total of 27 participants were recruited and the trial was completed without any serious side effects related to the treatment
.
Of the 27 participants, 21 had a daily dose of methimazole less than 5 mg at 12 months
.
Thirteen of the 27 participants were in remission at 24 months (48%, 90% one-sided CI, 35%-100%); this exceeded the critical value of the experimental design and provided evidence of remission
.
The B lymphocyte count at 28 weeks, expressed as a percentage of baseline, is related to the likelihood of remission
.

Table 1 Inclusion and exclusion criteria

Table 2 Summary of patient biochemistry and remission status

Figure 1 Thyroid receptor antibody (TRAb) levels were centrally measured at baseline, 12 months and 24 months
.
Relapsed patients are shown in red
.

Figure 2 Box plot shows the distribution of B-cell lymphocyte counts in patients in remission and non-remission at 28 weeks, expressed as a percentage of the baseline value: the red line indicates the median
.

Table 3 Serious adverse reactions experienced by trial participants

Table 4 The number and percentage of all participants for each non-serious adverse event or adverse reaction reported by system organ category (N = 27)

Conclusion: The adjuvant RTX combined with a 12-month course of ATD may increase the possibility of remission in young patients with Graves hyperthyroidism
.
It is necessary to conduct randomized trials of the adjuvant RTX in young people with hyperthyroidism
.

Original source:

Cheetham T, Cole M, Abinun M,et al.
Adjuvant Rituximab-exploratory trial in young people with Graves' disease .
J Clin Endocrinol Metab 2021 Oct 23