Table 1.

Overview of available treatments for RA.

Category	Example	Mechanism	FDA Approval	Side Effects	Reference
NSAID	Naproxen Ibuprofen Celecoxib	Interruption of the inflammatory cycle: blocked formation of prostaglandins through the inhibition of COX-1/COX-2 enzymes	1900 (Aspirin) *	Gastrointestinal problems including indigestion and gastric ulcers Cardiovascular, renal, or hepatic complications	[7,28]
Corticosteroids	Dexamethasone Prednisone	Modification of inflammatory mechanisms and immune responses by the activation of the cytosolic glucocorticoid receptor	1955 (Prednisone)	Bone-thinning, diabetes, high blood pressure, weight gain, immunosuppression, and psychological effects	[7,30]
csDMARD	Methotrexate Leflunomide	Interferes with deoxyribonucleotides metabolism Impedes immune cell proliferation and promotes apoptosis of these cells	1953 (Methotrexate) **	Increased risk of developing lymphoma Decreased production of hematoblast Liver, lung, skin, and epithelial damage	[31,32]
bDMARD	Etanercept Infliximab Rituximab	Inhibition of cytokines (TNF and IL) Co-stimulation blockers by binding to CD80/CD86 Anti-B-cell-agents that cause depletion, inactivation, or prevent differentiation	1998 (Etanercept)	Increased risk of frequent and severe infections Bone marrow suppression and hepatotoxicity	[27,28]
tsDMARD	Tofacitinib Upadacitinib	Binding to the adenosine triphosphate-binding site of Janus kinase (JAK) and suppression of the enzyme activity of JAK, thereby suppressing cytokine signal transduction and cytokine action	2012 (Tofacitinib)	Neutropenia/ lymphopenia/ anemia, severe infection, malignancy, major adverse cardiovascular events, and venous thromboembolism	[29]

* Not the year of approval, in 1900 aspirin was introduced to the market in the form of tablets [33]. ** MTX was not the first sDMARD approved, but it is the initial second-line drug and is considered the gold standard for RA treatment [34].