Longitudinal Model-Based Meta-Analysis in Rheumatoid Arthritis: An Application Toward Model-Based Drug Development

Abstract

Summary-level longitudinal data on the clinical efficacy of drugs for rheumatoid arthritis (RA) are available in the literature. This information can be used to optimize the clinical development of new drugs for RA. The aim of this study was twofold: first, to quantify the time course of the ACR20 score across approved drugs and patient populations, and second, to apply this knowledge in the decision-making process for a specific compound, canakinumab. The integrated analysis included data from 37 phase II-III studies describing 13,474 patients. It showed that, with the tested doses/regimens of canakinumab, there was only a low probability that this drug would be better than the most effective current treatments. This finding supported the decision not to continue with clinical development of canakinumab in RA. This paper presents the first longitudinal model-based meta-analysis of ACR20. The framework can be applied to any other compound targeting RA, thereby supporting internal and external decision making at all clinical development stages.

Cytokines as Therapeutic Targets in Rheumatoid Arthritis and Other Inflammatory Diseases

“…Secondary outcomes were also improved, and there were no safety concerns. However, integrated model-based analysis that included data from published trials suggested there was only a low probability that canakinumab would be better than the most effective treatments (Demin et al, 2012), and larger phase III trials have never been performed in RA. The high cost of canakinumab is also a limiting factor to its clinical utility.…”

Anti-Inflammatory Therapy for Atherosclerosis: Contribution to and Lessons of Rheumatology

“…Примечательно, что вна-чале канакинумаб разрабатывался для лечения РА. Однако при анализе исследований II-III фаз была прогнозирована низкая вероятность более высокой эффективности кана-кинумаба по сравнению с другими ГИБП [24], что, к сожа-лению, привело к приостановке дальнейших клинических испытаний этого препарата при РА.…”

Role of Interleukin 1 in the Development of Human Diseases

“…Однако интегральный анализ материалов 37 исследований фаз II-III (более 13 тыс. пациентов с РА) показал низкую веро-ятность более высокой эффективности канакинумаба по сравнению с другими ГИБП при РА [180]. Это привело к приостановке дальнейших клинических испытаний дан-ного препарата при РА.…”