Table 1.
Key clinical studies on novel treatment approaches of GH
| Therapeutics [ref.] | Mechanism of action | Study design/patient population | Key findings | Common/important toxicities |
|---|---|---|---|---|
| RTX [14] | B cell depletion | • Prospective, controlled, nonrandomized study • 20 patients with untreated GH, rendered euthyroid after ~4 months of methimazole, then withdrawn • Intervention: → 10 RTX group (i.v. RTX 375 mg/m2 weekly for 4 doses) → 10 control group (observation alone) |
• 4/10 (40%) in RTX group remained in remission with median FU of 25 months • 10/10 (100%) in control group relapsed by 14 months |
Serum sickness-like reactions; iridocyclitis; polyarthritis; inflammatory bowel disease |
| RTX [16] | B cell depletion | • Prospective, single-arm, phase 2 study • 13 patients with relapsing GH • Intervention: 2 doses of i.v. RTX 1 g with a 2-week interval |
• 9/13 (69%) euthyroid and remained in remission after a median FU of 18 months (all responders achieved significant reduction in TSH-R-Ab levels) | |
| ATX-GD-59 [22] | Antigen-specific immunotherapy which reinstates immune tolerance to TSH-R | • Open-label, phase 1, single-arm study • 10 patients with untreated GH • Intervention: 10 doses of intradermal ATX-GD-59 over 18 weeks |
• 5/10 (50%) euthyroid by week 18, 3 of them remained relapse-free for 1 year after last dose of study drug • 2/10 (20%) had reduction in fT3/fT4 levels • Response in serum thyroid hormones correlated with reductions in both TSH-R-Ab and TSI levels |
Mild injection site reactions |
| Iscalimab [26] | Anti-CD40 MAb blocking the CD40-CD154 costimulatory pathway | • Open-label, phase 2, single-arm, proof-of-concept study • 15 patients with untreated GH • Intervention: 5 doses of i.v. iscalimab (10 mg/kg) over 12 weeks |
• 7/15 (47%) euthyroid by week 24, 4/7 (57%) responders relapsed by week 36 • Marked reduction in TSH-R-Ab levels, 4/15 (27%) achieved normal TSH-R-Ab levels by week 20 |
Nil |
FU, follow-up; GH, Graves' hyperthyroidism; i.v., intravenous; MAb, monoclonal antibody; RTX, rituximab; TSH-R, thyrotropin receptor; TSH-R-Ab, thyrotropin receptor autoantibody; TSI, thyroid-stimulating immunoglobulin.