Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that involves multiple joints bilaterally. It is characterized by an inflammation of the tendon (tenosynovitis) resulting in both cartilage destruction and bone erosion. While until the 1990s RA frequently resulted in disability, inability to work, and increased mortality, newer treatment options have made RA a manageable disease. Here, great progress has been made in the development of disease-modifying anti-rheumatic drugs (DMARDs) which target inflammation and thereby prevent further joint damage. The available DMARDs are subdivided into (1) conventional synthetic DMARDs (methotrexate, hydrochloroquine, and sulfadiazine), (2) targeted synthetic DMARDs (pan-JAK- and JAK1/2-inhibitors), and (3) biologic DMARDs (tumor necrosis factor (TNF)-α inhibitors, TNF-receptor (R) inhibitors, IL-6 inhibitors, IL-6R inhibitors, B cell depleting antibodies, and inhibitors of co-stimulatory molecules). While DMARDs have repeatedly demonstrated the potential to greatly improve disease symptoms and prevent disease progression in RA patients, they are associated with considerable side-effects and high financial costs. This review summarizes our current understanding of the underlying pathomechanism, diagnosis of RA, as well as the mode of action, clinical benefits, and side-effects of the currently available DMARDs.

Ameliorated Autoimmune Arthritis and Impaired B Cell Receptor-Mediated Ca2+ Influx in Nkx2-3 Knock-out Mice

“…Specifically, although the anti-rhG1 and anti-CCP-IgG1 antibody levels were similar in the arthritic Nkx2-3 −/− mice and the controls, the anti-CCP-IgG2a antibodies were produced in lesser amounts. Additionally, the concentrations of signature cytokines of GIA [ 5 ], and likewise, RA [ 2 ], IFNγ and IL-17 were markedly lower, whereas the concentrations of IL-1β, IL-4 and IL-6 were markedly higher in Nkx2-3 −/− than in BALB/c mice. Overall, these markers suggest a stronger Th2 activation (primarily indicated by IL-4 and anti-CCP IgG2a) in Nkx2-3 −/− mice instead of the characteristic Th1/Th17 dominated immune response seen in GIA of BALB/c mice [ 5 , 8 , 28 ].…”

“…The disease primarily affects the small joints, where a chronic, progressive inflammation leads to cartilage and bone destruction, associated with severe pain and disability [ 1 ]. Despite intensive research, no definitive cause(s) of the disease are known, and therefore, unfortunately, no curative treatment is available to date [ 2 ]. So, finding the potential pathogenic factors and mechanisms in the background of RA is of utmost importance because they might provide a basis for future therapies.…”

“…RA is a chronic, progressive disease, usually lasting for decades [ 2 , 9 , 10 ]. According to our present view on RA pathogenesis, the patients are diagnosed only in the final inflammatory/destructive phase of the disease, when the typical symptoms (pain, swollen joints) appear [ 10 ].…”

“…The development of autoreactive T cells and starting of autoantibody production might be the key elements of this preclinical/latent phase of RA [ 10 ] and likewise, during the initiation period of its model PGIA [ 8 ]. These processes most likely take place not only locally, in the joints, but, importantly, in the lymphatic tissues like the lymph nodes and the spleen [ 2 , 8 ].…”

Human Amniotic Mesenchymal Stem Cells Promote Endogenous Bone Regeneration

“…In addition to various defects, bone disorders also include joint diseases associated with an autoimmune disorder, such as rheumatoid arthritis (RA) ( 5 ), osteoarthritis (OA) ( 6 ), and ankylosing spondylitis (AS) ( 7 ). Typically, these joint diseases are treated by drugs (for example, glucocorticoid, immunosuppressive agents, non-steroidal anti-inflammatory drugs, and disease modifying antirheumatic drug) to reduce the symptoms and improve the joint function; however, therapeutic interventions are essential in the advanced stage characterized by loss of articular cartilage, subchondral sclerosis, osteophyte formation, and joint capsule thickening ( 8 ). Nowadays, tissue engineering is gaining increasing attention and is expected to resolve these clinical issues.…”