Association Between Efficacy and Pharmacokinetics of DMB-3115 and its Originator Ustekinumab in Patients with Chronic Plaque Psoriasis: An Exposure-Response Analysis.
Hironori Konishi, Takeyuki Shindo, Kazuya Ishiwata, Jun Morita
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引用次数: 0
Abstract
Introduction: DMB-3115 is a biosimilar to ustekinumab (Stelara®). Although a single-dose study conducted in Europe showed that the pharmacokinetics of DMB-3115 was equivalent to that of ustekinumab, another single-dose study in Japan suggested that the maximum serum concentration (Cmax) of DMB-3115 might be slightly lower than that of ustekinumab in the Japanese population. Thus, we conducted a post hoc analysis of randomized controlled studies.
Methods: The single-dose DMB-3115-1 and DMB-3115-3 studies enrolled healthy participants. The DMB-3115-2 study enrolled patients with moderate-to-severe chronic plaque psoriasis. It comprised 2 periods (Weeks 0-28 and 28-52), and we used the data through Week 12, during which patients received the assigned treatments at Weeks 0 and 4. Across all studies, participants were randomized to receive subcutaneous DMB-3115 or Stelara. We conducted regression analysis to investigate the relationships between the Cmax and efficacy outcomes using the data of participants receiving DMB-3115 or Stelara in the DMB-3115-2 study. We also conducted population pharmacokinetic (PK) analysis using the data of participants receiving DMB-3115 in the DMB-3115-1, -2, and -3 studies. Based on its results, we simulated the Cmax in the Japanese population.
Results: In the regression analysis, the combined Cmax of DMB-3115 and ustekinumab was not statistically associated with the percent change in Psoriasis Area and Severity Index (PASI) score from baseline to Week 12 or PASI-75 achievement (at least 75% improvement from baseline) at Week 12. Additionally, the gradual slopes of the regression line and curve suggested that the difference in Cmax is not expected to have a meaningful impact on clinical efficacy. In the population PK analysis, the simulated maximum concentrations in the Japanese population were within the range of those observed in the DMB-3115-2 study.
Conclusion: The difference in Cmax of DMB-3115 is not expected to have a meaningful impact on its efficacy.
期刊介绍：
Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
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