Cost-effectiveness analysis of biologics and biosimilars & pathway-based meta-analysis of transcriptomics : a quantitative synthesis of psoriasis

Abstract

Psoriasis is an immunological disease that presents as excessive cell proliferation and inflammation in the skin and nails of patients. The chronic and disfiguring nature of the disease greatly impairs patients’ quality of life. Despite considerable research effort, the etiology of psoriasis remains ambiguous, and so is the treatment decision making. This thesis aims to take advantage of the wealth of existing research data through quantitative synthesis to help address the above problems. This thesis explores the psoriasis disease from perspectives including economics and transcriptomics. The first study presented an economic evaluation of psoriasis biologic treatments through a cost effectiveness analysis on four common first-line biologics for moderate-to-severe psoriasis, adalimumab, etanercept, secukinumab, and ustekinumab, in the Hong Kong local setting, with reference to the treatment effectiveness data synthesized from previous clinical trials. The cost effectiveness of biosimilars ABP501 and GP2015, relatively inexpensive biological products that are made similar to a reference biologic, was also evaluated. Results suggested that the less expensive etanercept treatment was the most cost effective among the biologics compared, and the biosimilar alternatives are both cost effective when compared to their reference drug. The second study describes a novel pathway-level meta-analysis approach for paired and partially paired omics samples to compare transcriptomics profiles of psoriatic lesional and non-lesional samples. Six psoriasis transcriptomics datasets were included in the analysis, comprising a total of 448 skin samples. Results revealed associations between psoriasis and pathways of cell cycle, DNA replication, signal transduction, and the immune system. The corresponding R software for the proposed meta-analysis framework was also developed and presented, thus allowing applications involving omics data in other biomedical fields. The results from the two studies summarized and consolidated information on different aspects of psoriasis through the synthesis of evidence from multiple published sources. Findings from the current study could be extended to further exploration in disease mechanisms and treatment choices of psoriasis.