Table 1.

FDA approved therapies available for RA along with major adverse effects.

DMARDs	Binding Target	Administration Route	Processes Affected	Major Adverse Effects/Risk of Infection	References
Conventional Synthetic DMARDs
Methotrexate, Sulfasalazine, Chloroquine, Hydroxy-chloroquine	Unknown targets	Oral/ subcutaneous/ intra-muscular	Immuno-inflammatory reactions by increased adenosine release and binding to cell surface receptors	Gastrointestinal toxicity; hepatic dysregulations; pneumonitis	(19)
Biological DMARDs
Adalimumab, Certolizumab, Etanercept, Golimumab, Infliximab	Tumor necrosis factor (TNF)	Intravenous infusion/ subcutaneous injection	Stromal cell activation, angiogenesis, cytokine and chemokine expression, MMP production	Flares in patients with MS; high risk of Herpes zoster; reactivation of tuberculosis	(20)
Tocilizumab, Sarilumab	IL-6R	Intravenous infusion/ subcutaneous injection	T-cell migration and activation, FLS inflammatory response, osteoclast activation	Gastrointestinal perforations; severe liver failure	(21)
Abatacept	T-cell co-stimulation signal (CD80/CD86)	Intravenous infusion/ subcutaneous injection	Effector T-cell and dendritic cell activation, B -cell infiltration, osteoclastogenesis	Moderate chances of serious infections	(20)
Rituximab	CD20 (cell marker expressed on B-cells)	Intravenous infusion	Circulating B-cells, a proportion of tissue B-cells and plasmablasts, autoantibody titers	Risk of Herpes zoster; rare risk of progressive multifocal leuko-encephalopathy	(22)
Targeted Synthetic DMARDs
Tofacitinib	JAK1/3	Oral	Cytokine-dependent feedback loops and downstream effects	Risk of venous thromboembolism; Herpes zoster (baricitinib, tofacitinib); Hepatitis B reactivation (baricitinib)	(23)
Baricitinib	JAK1/2	Oral
Upadacitinib, Filgotinib	JAK1	Oral

MMP, matrix metalloproteinase enzymes; IL-6R, interleukin-6 receptor; FLS, fibroblast-like synoviocytes; JAK, Janus kinase; MS, multiple sclerosis.