Comparison of the therapeutic effects of 15 mg and 30 mg initial daily prednisolone doses in patients with subacute thyroiditis: a multicenter, randomized, open-label, parallel-controlled trial

Abstract

Introduction

Current guidelines recommendations for the initial dose of prednisolone (PSL) in the treatment of subacute thyroiditis (SAT) are based on low-quality studies. We designed a randomized controlled trial (RCT) to compare the efficacy and safety of using a low initial dose of PSL with a standard initial dose of PSL in SAT patients.

Patients and methods

This open-label RCT was conducted at five hospitals in China from June 2019 to January 2022. SAT patients with moderate-to-severe pain or a poor response to non-steroidal anti-inflammatory drugs (NSAIDs) were randomly assigned in a 1:1 ratio to the experimental and control groups. The initial dose of PSL was 15 mg/d in the experimental group and 30 mg/d in the control group. The primary outcome was the total duration of PSL treatment, with non-inferiority prespecified with a margin of 7 days. Clinical trial registration number: ChiCTR1900023884.

Results

The full analysis set included 60 patients (30 in each group). The mean duration of PSL treatment in the experimental and control group was 34.62 ± 14.12 and 41.18 ± 16.89 days, respectively, meeting the non-inferiority criterion (p_{non-inferiority} = 0.0006). The total dose of PSL used in the experimental group was lower than in the control groups (330 vs 595 mg, p < 0.0001). There were no differences in the mean time to pain relief and complete resolution, the occurrence of recurrence, hypothyroidism, or adverse events between the groups.

Conclusions

The initial dose of 15 mg/d of PSL was not inferior to the dose of 30 mg/d in terms of efficacy and showed a similar safety profile. A low initial dose of PSL could be recommended for Chinese adult SAT patients who have a suboptimal response using NSAIDs or experience moderate-to-severe pain.

KEY MESSAGES

1. Low initial dose (15 mg/d) of prednisolone was non-inferior to the standard initial dose of prednisolone (30 mg/d) in treatment duration, time to pain relief, or the prevalence of hypothyroidism, recurrence, and adverse reactions in the treatment of subacute thyroiditis.

2. Patients with subacute thyroiditis administered a low initial dose of prednisolone had a lower total dose of prednisolone compared to those receiving the standard dose of prednisolone.

Keywords:

• Initial dose
• prednisolone
• subacute thyroiditis
• randomized controlled trial

Acknowledgments

We thank all patients with subacute thyroiditis who participated in this study as well as the researchers at various study centers. We thank Arshad Makhdum, PhD, from Liwen Bianji (Edanz) (www.liwenbianji.cn), for editing the English text of a draft of this manuscript.

Author contributions

JJZ, AHJ and JZ contributed equally to this work. Conceptualization: SYX, LS and LG; Data curation: JJZ, WLX, AHJ, and JZ; Formal analysis: JJZ, AHJ and JZ; Funding acquisition: SYX; Investigation: SYX, AHJ, JZ, BG, JX, YX, XRJ, YJ, JW, and WLX; Methodology: SYX and JJZ; Project administration: SYX; Resources: SYX; Software: JJZ; Supervision: SYX and LS; Validation: JJZ; Writing –original draft: JJZ, SYX, AHJ, and JZ; Writing – Review & editing: SYX, JJZ, AHJ, JZ, BG, JX, YX, XRJ, YJ, JW, LS. All authors read and approved the final manuscript. All authors agree to be accountable for all aspects of the work.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, Shaoyong Xu, upon reasonable request.

Additional information

Funding

This work was supported by the Young Talents Project of Hubei Provincial Health Commission, China under Grant number WJ2021Q012; Science and Technology Research Key Project of Education Department of Hubei Province, China under Grant number D20212602; Sanuo Diabetes Charity Foundation, China; and Xiangyang Science and Technology Plan Project, China under Grant number 2019ZD12.