Pathogenesis and Current Treatment Strategies in Rheumatoid Arthritis: A Systematic Review Article

Abstract Rheumatoid arthritis (RA) is a chronic, symmetrical, and inflammatory autoimmune disease that initially affects small joints, progressing to larger joints, and eventually the skin, eyes, heart, kidneys, and lungs. It has been recorded that RA affects 0.5%–1% of the adult population of developed regions. It initially affects small joints, progressing to larger joints, and eventually the skin, eyes, heart, kidneys, and lungs. Often, the bone and cartilage of joints are destroyed, and tendons and ligaments weaken. All this damage to the joints causes deformities and bone erosion, usually very painful for a patient. RA by producing inflammatory cytokines and proteinases, such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases that perpetuate joint destruction by abnormal proliferation of synovium. Under the influence of synovial cells, cytokines such as – Interleukin (IL)-1 and IL-17 chondrocytes are destroyed by apoptosis. Again the extracellular matrix secretes a proteinase called MMPs that damages the type 2 collagen fibers of the cartilage matrix causing biomechanical changes to the joint movements. This way with destruction of articular cartilage of the joint surface by hyperplastic synovium leads to a reduction of joint space. The difference between the hyaline cartilage of the articular surface and other hyaline cartilage is that articular hyaline cartilage never undergoes regeneration. With limited membrane permeability and poor gastrointestinal stability, monoclonal antibodies (mABs) do not have good oral bioavailability (<1%). For this reason, they are usually not administered orally, and parenteral administration is mostly by intravenous, subcutaneous (SC), and intramuscular (IM) injections. When mABs are injected IM or SC, the absorption process from the site of injection is through the interstitial space and into the lymphatic system, with subsequent draining into the systemic circulation. Although IM and SC routes of administration offer lower bioavailability because of proteolytic degradation in the interstitial fluid or the lymphatic system, the SC route is the most widely used due to convenience and the possibility of patient self-administration. For these last two routes of administration, the peak plasma concentration after a single dose is achieved 3–7 days after administration, due to the slow absorption into the systemic circulation. Other potential routes of administration include intravitreal, intraperitoneal, and pulmonary. CRD NUMBER-42024601637.