Current and emerging therapeutic strategies for preventing inflammation and aggrecanase-mediated cartilage destruction in arthritis

Dancevic, Carolyn M; McCulloch, Daniel R

doi:10.1186/s13075-014-0429-9

Table 1 Current and emerging arthritis treatments and their mode of action and side effects

From: Current and emerging therapeutic strategies for preventing inflammation and aggrecanase-mediated cartilage destruction in arthritis

Therapeutic agent	Mode of action	Side effects
DMARDs
Methotrexate [39]	Inhibits purine and pyrimidine synthesis and suppresses cytokine synthesis	Abdominal discomfort, alopecia, oral ulcerations and cytopenia, diarrhea, nausea, alopecia, vomiting, hepatotoxicity, and infections
Chloroquine, quinachrine, and hydroxychloroquine [40]	Anti-inflammatory, inhibition of cytokine diffusion
Sulfasalazine [41]	Decreases pain and swelling
Leflunomide [42]	Inhibits de novo pyrimidine synthesis
Biological agents
Infliximab [47],[54]	TNF inhibitors	Nausea, upper respiratory tract infections, dyspepsia, and headaches
Golimumab [44]
Adalimumab [46]
Etanercept [45]
Rituximab [50]	B-cell inhibitor (CD20)
Abatacept	T-cell inhibitor
Tocilizumab [43],[48]	IL-6R inhibitor
Anakinra	IL-1R inhibitor
Corticosteroids/NSAIDs
Prednisolone [54]	Anti-inflammatory	Weight gain, immunosuppression, altered glycemic control, glaucoma, hypertension, and osteoporosis
Aspirin (acetylsalicylic acid)	Anti-inflammatory	Gastrointestinal ulcer perforation and bleeding, renal impairment, and platelet dysfunction
Ibuprofen	Anti-inflammatory
Naproxen	Anti-inflammatory
Therapeutic agent	Mode of action	Key observations
Statins
Simvastatin [56]-[58],[66]	Anti-inflammatory	Suppression of macrophage infiltration and bone destruction (rat), decreased MMP-3 (rat), decreased migration and invasion of fibroblast-like synoviocytes (cells), and mild improvements in DAS28 scores and swollen joint counts (human)
Atorvastatin [59],[60],[64]	Anti-inflammatory Cartilage anabolism Cartilage protection	Decreased systemic TNF-α (human); reduction in C-reactive protein and erythrocyte sedimentation and improved DAS28 scores (human); and decreased IL-1β and MMP-13 and increased aggrecan and ColIIa1 (in vitro human osteoarthritic chondrocytes)
Rosuvastatin [63]	Anti-inflammatory	Reduction of C-reactive protein (human)
Mevastatin [65]	Anti-inflammatory Cartilage protection	Reduction in IL-1β, MMP-3, and MMP-13 (rabbit)

Common arthritis treatments that target inflammation and pain are shown. Disease-modifying anti-rheumatic drugs (DMARDs) used for rheumatoid arthritis target systemic inflammation, whereas biological agents target localized inflammatory cytokines. Corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) are often used for both rheumatoid arthritis and osteoarthritis treatments. Cholesterol-lowering drugs (statins) target inflammation and prevent cartilage breakdown in varying rheumatoid arthritis and osteoarthritis contexts. DAS28, Disease Activity Score in 28 Joints; IL, interleukin; MMP, matrix metalloproteinase; TNF, tumor necrosis factor.

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