Optimization of secukinumab dose regimens in patients with moderate-to-severe plaque psoriasis via exposure-response modeling

ABSTRACT

Background

Further dose optimization is required for patients with moderate-to-severe plaque psoriasis who do not benefit from the approved secukinumab dose regimen. This study aimed to develop an exposure-response model for secukinumab to recommend dose regimens for patients of different body weights.

Methods

We searched the PubMed and Cochrane Library databases for randomized controlled trials using PASI 75 and PASI 90 response rates as primary outcomes. A model-based meta-analysis was developed to quantitatively analyze the distribution of six secukinumab dose regimens in patients weighing 50–120 kg.

Results

Sixteen trials involving 6,197 subjects were included in the analysis. The established model accurately described the time-course characteristics of PASI 75 and PASI 90 response rates over 52 weeks. Simulations indicated that maintenance doses could be reduced to 150 mg every 4 weeks and to 150 mg every 3 weeks for patients weighing 50 and 60 kg, respectively. In contrast, maintenance doses of 300 mg every 3 weeks should be selected for patients weighing 120 kg. Patients weighing 70–110 kg remained on approved maintenance doses of 300 mg every 4 weeks.

Conclusions

Based on patient body weights, the exposure-response model recommends efficacious and economical dose regimens for patients with moderate-to-severe plaque psoriasis.

KEYWORDS:

• Dose optimization
• exposure-response model
• moderate-to-severe plaque psoriasis
• model-based meta-analysis
• psoriasis area and severity index
• secukinumab

Conflict of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

LJ Li and QS Zheng participated in conception and design of the work and revised the paper critically for important intellectual content. YX Liu and XR Wang selected studies and extracted the data, analyzed and interpreted the data. LJ Wu and RF Cai contributed to data extraction and cleaning. YX Liu and L Xu wrote the manuscript and revised the manuscript. All authors contributed to the article and approved the submitted version.

Data availability statement

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

Acknowledgments

We thank all staff of the center for drug clinical research, Shanghai University of Traditional Chinese Medicine.

Supplementary Material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17512433.2023.2259300

Additional information

Funding

This was not an industry supported study. This work was received financial support from the National Natural Science Funds of China (82174229), and Shanghai 3-year Action Plan for Inheritance, Innovation, and Development of traditional Chinese Medicine (ZY[2021-2023]-0401) and China national key research and development program (2022YFC3502000).