PURPOSE:To evaluate the primary efficacy and safety of satralizumab, an anti-interleukin-6 receptor antibody, in patients with thyroid eye disease (TED). DESIGN:SatraGO-1 (NCT05987423) and SatraGO-2 (NCT06106828) are identically designed, 72-week, double-masked, placebo-controlled, multicenter, 2-stage randomization phase 3 trials. PARTICIPANTS:Aged ≥18 years with active, moderate to severe TED (Clinical Activity Score [CAS] ≥3 for ≤12 months) or inactive TED (CAS <3 for ≥6 months). METHODS:Participants (SatraGO-1: N = 131; SatraGO-2: N = 127) were randomized 1:1 to receive loading doses of subcutaneous satralizumab or placebo at weeks 0, 2, and 4, followed by every-4-week dosing through week 20 (part I). MAIN OUTCOME MEASURES:The primary endpoint was the proportion of participants with active TED who achieved a proptosis response (≥2-mm reduction from baseline) at week 24. Secondary endpoints included the proportion of participants with a ≥2-point CAS reduction, disease inactivation (CAS of 0 or 1), and an ≥1-grade diplopia reduction at week 24. Efficacy outcomes were also reported for the combined active and inactive TED population. Safety was assessed in all participants exposed to study treatment. RESULTS:In participants with active TED, the satralizumab arm of both trials consistently showed an increased proportion achieving a proptosis response (SatraGO-1: 49.0% vs. 31.2%, P = 0.0715; SatraGO-2: 52.9% vs. 23.4%, P = 0.0011), CAS reduction (SatraGO-1: 78.0% vs. 54.9%, P = 0.0120; SatraGO-2: 89.6% vs. 63.3%, P = 0.0009), CAS of 0 or 1 (SatraGO-1: 68.0% vs. 45.1%, P = 0.0146; SatraGO-2: 68.8% vs. 40.8%, P = 0.0042), and diplopia reduction (SatraGO-1: 44.4% vs. 34.4%, P = 0.3371; SatraGO-2: 60.7% vs. 25.8%, P = 0.0044) vs. placebo, although not all comparisons reached statistical significance. Similar clinical benefits were observed in the combined active and inactive TED population. Satralizumab was well tolerated, with low rates of serious adverse events, treatment discontinuations, and infections, and no serious infections. CONCLUSIONS:Satralizumab demonstrated clinically meaningful improvements in proptosis, CAS, and diplopia, and had a favorable safety profile in participants with TED. Interleukin-6 pathway inhibition with subcutaneous satralizumab represents an efficacious and well-tolerated treatment option for patients with TED.
