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Lessons From the Success and Failure of Targeted Drugs for Rheumatoid Arthritis: Perspectives for Effective Basic and Translational Research

  • Mingyo Kim (Division of Rheumatology, Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital) ;
  • Yong-ho Choe (Division of Rheumatology, Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital) ;
  • Sang-il Lee (Division of Rheumatology, Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital)
  • Received : 2022.01.17
  • Accepted : 2022.02.16
  • Published : 2022.02.28
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Abstract

Rheumatoid arthritis (RA) is a representative autoimmune disease that is primarily characterized by persistent inflammation and progressive destruction of synovial joints. RA has a complex and heterogeneous pathophysiology, involving interactions among various immune and joint stromal cells and a diverse network of cytokines and intracellular signaling pathways. With improved understanding of RA, over the past decades, therapeutic strategies have become considerably advanced and now included targeted molecular therapies, such as tumor necrosis factor inhibitors, IL-6 blockers, B-cell depletion agents, as well as inhibitors of T-cell co-stimulation and Janus kinases. However, a considerable proportion of RA patients experience refractory disease and interrupted treatment owing to the associated risk of developing serious infections and cancers. In contrast, although IL-1β, IL-17A, and p38α play significant roles in RA pathogenesis, several drugs targeting these factors have not been approved because of their low efficacy and severe adverse effects. In this review, we provide an overview of the working mechanism, advantages, and limitations of the currently available targeted drugs for RA. Additionally, we suggest potential mechanistic causes for clinically approved and failed drugs. Thus, this review provides perspectives on approaches for basic and translational studies that hold promise for identifying future next-generation therapeutics for RA.

Keywords

Acknowledgement

This study was supported by a grant from National Research Foundation of Korea (NRF-2020R1C1C1007944) and from the Korea Health Technology R&D project through the Korea Health Industry Development Institute (KHIDI) funded by the Korean Ministry of Health and Welfare (grant number: HI14C1277). We would like to thank Editage (www.editage.co.kr) for English language editing.

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