Wei Zhu1, Lei Ye, Liyun Shen, Qin Jiao, Fengjiao Huang, Rulai Han, Xiaofang Zhang, Shu Wang, Weiqing Wang, Guang Ning. 1. Shanghai Key Laboratory for Endocrine Tumors (W.Z., L.Y., L.S., F.H., R.H., X.Z., S.W., W.W., G.N.), Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200025, P. R. China; Department of Ophthalmology (Q.J.), Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200025, P. R. China; and Laboratory for Endocrine and Metabolic Diseases of Institute of Health Science (G.N.), Shanghai JiaoTong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, P. R. China.
Abstract
BACKGROUND: For patients with active moderate-to-severe Graves' ophthalmopathy (GO), a course of 4.5 g iv glucocorticoids (GCs) is the recommended therapy. The weekly protocol is preferred because of the potential safety concerns with the daily protocol. However, evidence for the superiority of different administration protocols is lacking. METHODS: We conducted a prospective, randomized trial to compare the efficacy and safety of two protocols of iv 4.5 g methylprednisolone in a total of 80 patients in our institute. The patients were randomized to receive iv methylprednisolone weekly or daily. The response rate (a composite response endpoint including lid width, soft tissue involvement, proptosis, intraocular pressure, Clinical Activity Score [CAS], diplopia, and visual acuity) was evaluated as the primary outcome, and adverse effects were recorded at each visit. GO-associated serum cytokines were measured. RESULTS: We found a significantly greater response rate for the weekly protocol vs the daily protocol at the 12th week (76.92 vs 41.03%; P = .0025) and a similar response rate at the fourth week. Seven patients on the daily protocol worsened when tapering iv methylprednisolone to oral prednisone in the fourth week. Patients in both groups showed significant CAS response, and at the 12th week, patients on the weekly protocol showed a nonsignificant trend toward greater CAS response. Weekly protocol showed significant prolonged retreatment-free survival. Severe side effects were only observed in two cases, both of which were on the daily protocol. Furthermore, we observed sustained decreased levels of serum CXCL10 in the 12th week compared to the baseline level (P = .0009) in the patients on the weekly protocol. CONCLUSIONS: The weekly protocol of iv methylprednisolone therapy is more efficient and safer than the daily protocol for patients with active moderate-to-severe GO.
RCT Entities:
BACKGROUND: For patients with active moderate-to-severe Graves' ophthalmopathy (GO), a course of 4.5 g iv glucocorticoids (GCs) is the recommended therapy. The weekly protocol is preferred because of the potential safety concerns with the daily protocol. However, evidence for the superiority of different administration protocols is lacking. METHODS: We conducted a prospective, randomized trial to compare the efficacy and safety of two protocols of iv 4.5 g methylprednisolone in a total of 80 patients in our institute. The patients were randomized to receive iv methylprednisolone weekly or daily. The response rate (a composite response endpoint including lid width, soft tissue involvement, proptosis, intraocular pressure, Clinical Activity Score [CAS], diplopia, and visual acuity) was evaluated as the primary outcome, and adverse effects were recorded at each visit. GO-associated serum cytokines were measured. RESULTS: We found a significantly greater response rate for the weekly protocol vs the daily protocol at the 12th week (76.92 vs 41.03%; P = .0025) and a similar response rate at the fourth week. Seven patients on the daily protocol worsened when tapering iv methylprednisolone to oral prednisone in the fourth week. Patients in both groups showed significant CAS response, and at the 12th week, patients on the weekly protocol showed a nonsignificant trend toward greater CAS response. Weekly protocol showed significant prolonged retreatment-free survival. Severe side effects were only observed in two cases, both of which were on the daily protocol. Furthermore, we observed sustained decreased levels of serum CXCL10 in the 12th week compared to the baseline level (P = .0009) in the patients on the weekly protocol. CONCLUSIONS: The weekly protocol of iv methylprednisolone therapy is more efficient and safer than the daily protocol for patients with active moderate-to-severe GO.