Management of Rheumatoid Arthritis: An Overview

Abstract

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease of unknown etiology, primarily affecting the joints, then extra-articular manifestations can occur. Due to its complexity, which is based on an incompletely elucidated pathophysiological mechanism, good RA management requires a multidisciplinary approach. The clinical status of RA patients has improved in recent years due to medical advances in diagnosis and treatment, that have made it possible to reduce disease activity and prevent systemic complications. The most promising results were obtained by developing disease-modifying anti-rheumatic drugs (DMARDs), the class to which conventional synthetic, biologic, and targeted synthetic drugs belong. Furthermore, ongoing drug development has led to obtaining molecules with improved efficacy and safety profiles, but further research is needed until RA turns into a curable pathology. In the present work, we offer a comprehensive perspective on the management of RA, by centralizing the existing data provided by significant literature, emphasizing the importance of an early and accurate diagnosis associated with optimal personalized treatment in order to achieve better outcomes for RA patients. In addition, this study suggests future research perspectives in the treatment of RA that could lead to higher efficacy and safety profiles and lower financial costs.

Keywords: DMARDs; Janus kinase inhibitors; anti-citrullinated protein antibodies; extra-articular manifestations; proteins; rheumatoid arthritis; rheumatoid factor; targets.

Figure 1

Immunological processes in the pre-RA phase. ACPA, anti-citrullinated protein antibodies; APC, antigen-presenting cells; RF, rheumatoid factor.

Figure 2

The involvement of air pollution and microbiota in the pathogenesis of RA. ACPA, anti-citrullinated protein antibodies; APC, antigen-presenting cells; IFN, interferon gamma; IL, interleukin; NF-KB, nuclear factor kappa-light-chain-enhancer of activated B cells; NLR, nod-like receptor; RA, rheumatoid arthritis; ROS, reactive oxygen species; TLR, toll-like receptor; TNF-α, tumor necrosis factor alpha; UVB, ultraviolet B radiation; VDR, vitamin D receptor.

Figure 3

Pathological mechanisms in RA. IL, interleukin; FLS, fibroblast-like synoviocytes; MMP, matrix metalloproteinase; RANKL, receptor activator of nuclear factor-kB ligand; ROS, reactive oxygen species.

Figure 4

Molecular structure of the most widely used csDMARDs.

Figure 5

Status and future targeted therapies in RA. AMG, human monoclonal antibody; CD20, membrane-embedded surface molecule; CXCR, α-chemokine receptor; IL, interleukin; CD80, ligand for the protein CD28; JAK, Janus kinase; MAPK, mitogen-activated protein kinases; MMP, matrix, metallopeptidase; TNF-α, tumor necrosis factor alpha.