Short-Term Efficacy and Safety of Haizao Yuhu Decoction Plus Methimazole versus Methimazole Monotherapy for Graves’ Disease: A Prospective Study Using Propensity Score-Matching

Wenbin Huang,1,2,* Fengyun Cheng,1,* Xiaoju Liu,1 Xingjia Li,1 Sicong Zhou,2 Rong Lin,3 Fenxia Zhu,4,5 Xiaodong Mao,6 Chao Liu,1,6 Shuhang Xu1 1Department of Endocrinology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China; 2Department of Thyroid Vascular Surgery, Second People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, 350003, People’s Republic of China; 3Department of Endocrinology, Xiamen Hospital of Traditional Chinese Medicine, Xiamen Hospital Beijing University of Chinese Medicine, Xiamen, 361000, People’s Republic of China; 4Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China; 5Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People’s Republic of China; 6Key Laboratory of TCM Syndrome and Treatment of Ying-Bing (Thyroid Disease) of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuhang Xu, Email [email protected] Chao Liu, Email [email protected]: To investigate the efficacy and safety of the early addition of Haizao Yuhu Decoction (HYD) with methimazole (MMI) versus the monotherapy of MMI in treating Graves’ disease (GD).Methods: This was a prospective observational study. A total of 198 patients with GD were assigned to either the HYD combined with MMI group or the MMI monotherapy group according to clinical judgment and patient preference. To minimize confounding bias, propensity score matching (PSM) was performed to balance baseline characteristics between the two groups. Primary (thyroid function, MMI dose) and secondary outcomes (general conditions, thyrotrophin receptor antibody [TRAb], thyroid size, peak systolic velocity of the superior thyroid artery [STA-PSV], the Thyroid-related Patient-Reported Outcome 39 [ThyPRO39] scores, traditional Chinese medicine [TCM] syndrome scores, and safety) were measured at 0 (V1), 4 (V2), 8 (V3) and 12 weeks of treatment (V4).Results: Each group consisted of 54 GD patients after a 1:1 PSM. A greater decline in free thyroxine (FT4) (16.67 [7.64, 24.43] pmol/L vs 9.82 [3.49, 19.02] pmol/L, P = 0.018) and free triiodothyronine (FT3) (5.32 [3.10, 10.33] pmol/L vs 3.46 [1.16, 7.63] pmol/L, P = 0.043) was observed at V2 in the combination group than in the MMI group. The cumulative dose of MMI during the 12-week treatment was significantly lower in the combination group than in the MMI group (814.20 [600.00, 1050.00] mg vs 1007.10 [782.10, 1125.00] mg, P = 0.004). The combination group showed more pronounced reductions in the STA-PSV, TCM syndrome scores, and ThyPRO scores (P = 0.032, 0.010, and 0.044, respectively). The cumulative incidence of adverse events in the combination group was significantly lower than that in the MMI group (5.56% [3/54] vs 18.52% [10/54], P = 0.038).Conclusion: The combination of HYD and MMI serves as an effective and safe treatment of GD, accelerating thyroid function recovery, reducing thyroid hormone levels and ATD dosage, alleviating hyperthyroid symptoms, and lowering the risk of adverse events.Keywords: Haizao Yuhu decoction, Graves’ disease, methimazole, thyroid function, antithyroid drugs