Strategies toward rheumatoid arthritis therapy; the old and the new

Abstract

Currently, medications used to treat rheumatoid arthritis (RA) are glucocorticoids (GCs) and nonsteroidal anti‐inflammatory drugs (NSAIDs), predominantly used for controlling the pain and inflammation, disease‐modifying antirheumatic drugs (DMARDs), administered as first‐line medication for newly diagnosed RA cases, and biological therapies, used to target and inhibit specific molecules of the immune and inflammatory responses. NSAIDs and other GCs are effective in alleviating the pain, inflammation, and stiffness due to RA. DMARDs that are used for RA therapy are hydroxychloroquine, methotrexate, leflunomide, and sulfasalazine. The biological therapies, on the contrary, are chimeric anti‐CD20 monoclonal antibody, rituximab, inhibitors of tumor necrosis factor‐α (TNF‐α) like etanercept, infliximab, and adalimumab, a recombinant inhibitor of interleukin‐1 (IL‐1), anakinra, and costimulation blocker, abatacept. Moreover, newly under evaluation biological therapies include new TNF‐α inhibitors, JAK inhibitors, anti‐interleukin‐6‐receptor monoclonal antibodies (mABs), and antibodies against vital molecules involved in the survival and development of functional B cells. The new strategies to treat RA has improved the course of the disease and most of the patients are successful in remission of the clinical manifestations if the diagnosis of the disease occur early. The probability of remission increase if the diagnosis happens rapidly and treat‐to‐target approach are implemented. In this review article, we have attempted to go through the treatment strategies for RA therapy both the routine ones and those which have been developed over the past few years and currently under investigation.

The Role of NF-κB in Physiological Bone Development and Inflammatory Bone Diseases: Is NF-κB Inhibition “Killing Two Birds with One Stone”?

“…Rheumatoid arthritis (RA) is a chronic inflammatory disease with progressive joint destruction over time [6][7][8]. Biologics such as anti-TNF-α antibodies have been shown to be effective in cases where existing drugs have not been effective [47]. The characteristic feature of RA is the proliferation and infiltration of synovial cells and angiogenesis of the joint area [6][7][8].…”

“…However, these biologics cause serious side effects, such as triggering an autoimmune anti-antibody response or weakening the body's immune defenses. Therefore, alternative small-molecule-based therapies for inhibition of these cytokines' effects is a hot topic both in academia and industry [47,48].…”

“…Thus, to suppress the classical NF-κB pathway, experiments have been conducted [34,35,[49][50][51][52][53][54] possible when treatments centered on rheumatox are not enough to control the disease. These guidelines are widely accepted internationally [47]. Anti-TNF-α neutralized antibodies directly inhibit the binding of TNF-α to its receptor and suppress excessive inflammation that induces RANKL expression in synovial cells.…”

Er Miao San, a traditional Chinese herbal formula, attenuates complete Freund’s adjuvant-induced arthritis in rats by regulating Th17/Treg cells

“…The main objective of treatment is to relieve joint pain and prevent joint damage, in order to improve a patient's quality of life. Currently, drugs used in the clinical treatment of RA include steroidal anti-inflammatories, disease-modifying antirheumatic drugs (DMARDs), non-steroidal anti-inflammatory drugs (NSAIDs) and biological preparations (Abbasi et al 2019).…”

Role of Signal Transduction Pathways and Transcription Factors in Cartilage and Joint Diseases

“…Based on accumulating knowledge that some inflammatory cytokines, such as tumor necrosis factor α (TNFα), interleukin 1 (IL-1), and IL-6, play critical roles in the onset and progression of rheumatoid arthritis, specific inhibitory reagents for these cytokines have been developed [5,6]. For instance, anti-TNFα antibodies, soluble TNF receptor 2-conjugated Fc domain of IgG1, anti-IL-6 receptor antibody, and IL-1 receptor antagonist have exhibited dramatic effects on rheumatoid arthritis patients [6,7]. Furthermore, specific inhibitors of Janus kinases (JAKs), the downstream tyrosine kinases of IL-6, are also effective for rheumatoid arthritis patients [8,9].…”