Effects of Biological Therapies on Molecular Features of Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease primarily affecting the joints, and closely related to specific autoantibodies that mostly target modified self-epitopes. Relevant findings in the field of RA pathogenesis have been described. In particular, new insights come from studies on synovial fibroblasts and cells belonging to the innate and adaptive immune system, which documented the aberrant production of inflammatory mediators, oxidative stress and NETosis, along with relevant alterations of the genome and on the regulatory epigenetic mechanisms. In recent years, the advances in the understanding of RA pathogenesis by identifying key cells and cytokines allowed the development of new targeted disease-modifying antirheumatic drugs (DMARDs). These drugs considerably improved treatment outcomes for the majority of patients. Moreover, numerous studies demonstrated that the pharmacological therapy with biologic DMARDs (bDMARDs) promotes, in parallel to their clinical efficacy, significant improvement in all these altered molecular mechanisms. Thus, continuous updating of the knowledge of molecular processes associated with the pathogenesis of RA, and on the specific effects of bDMARDs in the correction of their dysregulation, are essential in the early and correct approach to the treatment of this complex autoimmune disorder. The present review details basic mechanisms related to the physiopathology of RA, along with the core mechanisms of response to bDMARDs.

Effectiveness and safety of aerobic exercise for rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials

“…Nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs) are commonly used in clinical practice [ 9 , 10 ]. The advent of biological therapeutics as an important segment of pharmacological treatment has been a major advance in the treatment of RA [ 11 ]. Medicine has achieved certain effects; however, there are disadvantages of adverse drug reactions, such as gastrointestinal adverse reactions, high cost and limited efficacy [ 12 , 13 ], and nonpharmacological therapies are providing emerging support.…”

CS-semi5 Inhibits NF-κB Activation to Block Synovial Inflammation, Cartilage Loss and Bone Erosion Associated With Collagen-Induced Arthritis

“…The most commonly used medications in RA patients are disease-modifying antirheumatic drugs (DMARDs), which are limited by gastrointestinal toxicity. However, DMARDs do not relive cartilage erosion, joint damage or bone loss in RA patients (Lopez-Pedrera et al, 2020). Chondroitin sulfate (CS) and glucosamine are glycosaminoglycans that are considered to be symptomatic slow-acting drugs for osteoarthritis (SYSADOA) (Henrotin et al, 2014).…”

MicroRNA-4423-3p inhibits proliferation of fibroblast-like synoviocytes by targeting matrix metalloproteinase 13 in rheumatoid arthritis

“…In recent years, research has begun to focus on the mechanisms of epigenetics in autoimmune diseases. miRNAs bind to messenger RNAs to affect target gene expression and affect disease progression [ 31 ]. The research on epigenetic correlation of RA has mainly focused on miRNAs [ 32 ].…”