Summary: In 307 patients with predominantly intermediate-risk differentiated thyroid cancer, recombinant human thyrotropin (rhTSH, SNA001) was noninferior to thyroid hormone withdrawal for radioactive iodine ablation, with success rates of 43.8% versus 47.1% (risk difference -3.3 percentage points; 95% CI -14.8 to 8.3). Adverse events were less frequent with rhTSH (29.9% versus 58.8%; P<.001) in this open-label, manufacturer-sponsored trial.
PICO Summary
| Element | Detail |
|---|---|
| Population | 307 adults (aged 18 to 70; median 40; 62.5% female) with differentiated thyroid cancer, predominantly intermediate-risk, after total or near-total thyroidectomy and without distant metastasis. Open-label phase 3 randomized trial at 19 sites in China. |
| Intervention | Recombinant human thyrotropin (SNA001), 0.9 mg intramuscular injection daily for 2 days, plus 3.7 GBq radioactive iodine (n=154). |
| Comparison | Thyroid hormone withdrawal for 3 to 6 weeks, plus 3.7 GBq radioactive iodine (n=153). |
| Outcome | Primary ablation success (negative diagnostic whole-body scan plus stimulated thyroglobulin <1.0 ng/mL) at 6 to 8 months: 43.8% with rhTSH versus 47.1% with withdrawal; risk difference -3.3 percentage points (95% CI -14.8 to 8.3), meeting the prespecified noninferiority margin. Adverse events during therapy: 46 of 154 (29.9%) with rhTSH versus 90 of 153 (58.8%) with withdrawal (P<.001). No treatment-related adverse events led to discontinuation in the rhTSH group. |
rhTSH vs withdrawal for RAI ablation
RCT · intermediate-risk thyroid cancer · 6-8 months
rhTSH was noninferior to hormone withdrawal for radioactive iodine ablation success, with markedly fewer adverse events. Read as noninferiority, not superiority, in this open-label manufacturer-sponsored trial.
Expert Commentary
The verdict is a qualified positive: recombinant human thyrotropin met its noninferiority endpoint for radioactive iodine ablation, sparing patients several weeks of symptomatic hypothyroidism. It should be read as noninferiority, not superiority. The ablation success rate was numerically lower with rhTSH (43.8% versus 47.1%), and the confidence interval for the difference extended to -14.8 percentage points, so a clinically meaningful efficacy disadvantage is not fully excluded. The principal limitation is the open-label design, which is difficult to avoid given the divergent preparation protocols but is consequential for the adverse-event comparison. Withdrawal deliberately induces hypothyroidism, so a lower symptom burden with rhTSH is expected and partly tautological rather than a property of the drug itself. The trial was also conducted entirely in China and sponsored by the manufacturer, with company employees among the authors, and follow-up was only 8 months, too short to capture recurrence. Can I use this with my patients? Cautiously yes, for selected intermediate-risk patients undergoing ablation who would tolerate hormone withdrawal poorly, recognizing that the available rhTSH product and approvals vary by region. Longer follow-up reporting structural recurrence, and ideally an independent confirmatory trial, would strengthen confidence before this becomes the default preparation.
References
Tan H, Gu Y, Xiu Y, et al. Recombinant human thyrotropin plus radioactive iodine among patients with thyroid cancer: a noninferiority randomized clinical trial. JAMA Netw Open. 2024;7(11):e2443407. doi:10.1001/jamanetworkopen.2024.43407