Table 1 Modern pharmacologic therapies for rheumatoid arthritis

From: Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies

Classification Name Mechanism of action Potential mechanisms Side Effect Reference
Conventional synthetic DMARDs Methotrexate Analog of folic acid Folate-dependent processes; Adenosine signaling; Methyl-donor production; Reactive oxygen species; Adhesion-molecule expression; Cytokine profiles Eicosanoids and MMPs. Increased liver enzymes, pulmonary damage. 83
Leflunomide/ Teriflunomide Pyrimidine synthesis inhibitor DHODH-dependent pathway; Leukocyte adhesion; Rapidly dividing cells; NF-kB; Kinases; Interleukins; TGF-β. Hypertension, diarrhea and nausea, hepatotoxicity. 153
Sulfasalazine Anti-inflammatory and immunosuppression Cyclooxygenase and PGE2; Leukotriene production and chemotaxis; Inflammatory cytokines (IL-1, IL-6, TNF-α); Adenosine signaling; NF-kB activation. Gastrointestinal, central nervous system, and hematologic adverse effect. 154
Chloroquine /Hydroxychloroquine Immunomodulatory effects Toll-like receptors; Lysosomotropic action; Monocyte-derived pro-inflammatory cytokines; Anti-inflammatory effects; Cellular immune reactions; T cell responses; Neutrophils; Cartilage metabolism and degradation. Gastrointestinal tract, skin, central nervous system adverse effect and retinal toxicity. 155
Biological DMARDs Antibody-based therapies   
TNF-α targeted therapy Infliximab TNF-α inhibitor Phagocytosis and pro-inflammatory cytokines; Chemoattractant; Adhesion molecules and chemokines; Treg cell function; Function of osteoclasts, leukocytes, endothelial and synovial fibroblasts. Infection (pneumonia and atypical tuberculosis) injection-site reaction.  
Adalimumab Hypertension.  
Etanercept Severe /anaphylactoid transfusion reaction. 156
Certolizumab pegol   
B-cell targeted therapy Rituximab B cell depleting Fc receptor gamma-mediated antibody-dependent cytotoxicity and phagocytosis; Complement-mediated cell lysis; antigen presentation; B cell apoptosis; Depletion of CD4+ T cells. Infection, hypertension, hypogammaglobulinemia, viral reactivation, vaccination responses.  
Ofatumumab Late-onset neutropenia.  
Belimumab Inhibitors of B cell function Severe/anaphylactoid transfusion reaction. 157
T-cell targeted therapy Abatacept CD28/CTLA4 system Autoantigen recognition; Immune cell infiltrate; T cells activation. Infection, malignancy. 158
Belatacept CD80/CD86   
Interleukin targeted therapy Tocilizumab IL-6 inhibition Innate and the adaptive immune system perturbation; Acute-phase proteins. Infections (most notably skin and soft tissue), increases in serum cholesterol, transient decreases in neutrophil count and abnormal liver function. 159
Anakinra IL-1 inhibition Inflammatory responses; Matrixenzyme. Injection site reactions, infections, neutropenia, malignancy.  
Canakinumab 160
Secukinumab IL-17 inhibition Mitochondrial function; Autophagosome formation. Infections, nasopharyngitis, candidiasis, neutropenia, safety data of mental health is limited. 161
Growth and differentiation factors Denosumab RANKL inhibitor Maturation and activation of osteoclast. Low Ca2+ and phosphate in the blood, muscle cramps, cellulitis, and numbness. 162
Mavrilimumab GM-CSF inhibitor Activation, differentiation, and survival of macrophages, dendritic cells, and neutrophils; T helper 1/17 cell; modulation of pain pathways. Safety file needs further research. 143
Small molecules
JAK pathway Tofacitinib JAK1 and JAK3 inhibitor T-cell activation, pro-inflammatory cytokine production, synovial inflammation, and structural joint damage. Zoster infection (advice is to vaccinate beforehand) and other potential side-effects should be monitored carefully through further study.  
Baricitinib JAK1 and JAK2 inhibitor 163, 164
Filgotinib JAK1 inhibitor  
Future drug and target Toll like receptors;165 Bruton’s tyrosine kinase;151 Phosphoinositide-3-kinase pathway;166 Transforming growth factor-beta;167 Neuropathways;168 Dendritic cell169