Rheumatoid arthritis is an inflammatory arthritis occurring in people who suffer from recurrent bouts of joint pain, swelling and deformity. Apart from inflammation of the joints, there are abnormal changes in blood vessels in these people which puts them at an increased risk of cardiovascular diseases such as heart attack prematurely and reduction in life-expectancy. Excess number of deaths due to cardiovascular cause were consistently observed in people suffering from rheumatoid arthritis.
A drug that controls the inflammation and also prevents changes in blood vessels will be highly useful in these people. Statins (e.g. lovastatin, simvastatin) have shown lot of promise in this regard.
Statins inhibit an enzyme of the lipid metabolism called as HMG-CoA reductase; therefore they are called as HMG-CoA reductase inhibitors. Process of atherosclerosis i.e. clogging of blood vessels with cholesterol is accelerated in inflammatory arthritis. The levels of good (high density lipoprotein) cholesterol are abnormally low while those of bad (low density lipoprotein) cholesterol are higher in inflammatory arthritis. Statins reduce the low density lipoprotein cholesterol levels and inhibit atherosclerosis. As atherosclerosis is the culprit for vascular events like heart attack and stroke, the risk of these diseases is also reduced.
Apart from lowering lipid levels, the statins were found to have anti-inflammatory action in recent studies. In inflammatory arthritis, statins may suppress the inflammatory response of the synovial membrane which lines the joint cavity. Statins act on blood cells like lymphocytes and macrophages which are responsible for inflammation and inhibit the release of harmful chemicals like cytokines from these cells. As inflammation is responsible for clinical features of inflammatory arthritis, statins markedly improve the clinical picture in these patients. Statins not only relieve pain and stiffness, but also retard the ongoing process of joint destruction.
Leung et al found that atorvastatin suppressed immune responses and cytokine release in mice. Abud-Mendoza C et al found that simvastatin showed marked improvement in signs and symptoms in patients with refractory rheumatoid arthritis which was unresponsive to methotrexate, a powerful drug. Similarly, atorvastatin was shown to be highly effective in rheumatoid arthritis in a recent randomized controlled
trial.
Inflammation in rheumatoid arthritis is not confined to the joints only. Low-grade inflammation exists in blood vessels also. This along with malfunction of endothelial cells lining blood vessels may accelerate the atherosclerotic process leading to vascular events such as heart attack at younger age as compared with normal population. Statins suppress this inflammation and inhibit release of harmful free radicals. Statins also improve the function of endothelial cells. Statins also reduce the levels of C-reactive protein, an independent risk factor for heart disease. Thus statins act as protectors against vascular events and may reduce the morbidity due to these diseases.
Statins should be used in rheumatoid arthritis unresponsive to treatment with disease modifying anti-Rheumatic drug (DMARD) as adjuvant therapy. They can also be used in protection against vascular diseases. The existing statins are mainly developed to act as lipid modulating agents rather than anti-inflammatory drugs. Further research is required for developing new statins who have more potent anti-inflammatory action. Recently, a new statin, Geranylgeranyl pyrophosphate (GGPP) has been found to have potent anti-inflammatory effects. Further trials are required to prove its efficacy and safety.
Thus statins will play increasingly important role in management of inflammatory arthritis due to their multiple benefits. They improve the quality of life by relieving the symptoms of arthritis and at the same time protect a person from premature death due to cardiovascular causes.
References:
1. McInnes IB, McCarey DW, Sattar N (2004) Do statins offer therapeutic potential in inflammatory arthritis? Annals of the Rheumatic Diseases 63, 1535-37.:
2. Leung BP, Sattar N, Crilly A, Prach M, Mccarey DW, Payne H, Madhok R et al (2003)A Novel Anti-Inflammatory Role for Simvastatin in Inflammatory Arthritis. The journal of immunology 170, 1524-30.:
3. Abud-Mendoza C, de la Fuente H, Cuevas Orta E, et al (2003) Therapy with statins in patients with refractory rheumatic diseases: a preliminary study. Lupus 12, 607-611.:
4. McCarrey DW, McInnes IB, Madhok R, et al (2004) Trial of atorvastatin in Rheumatoid Arthritis (TARA), double-blind, randomized, placebo-controlled trial. Lancet 363, 2015-2021.:
5. Mason J C, Ahmed Z, Mankoff R, Lidington E A, Ahmad S, Bhatia V, et al (2002) Statin-induced expression of decay-accelerating factor protects vascular endothelium against complement-mediated injury. Circulation Research 91, 696-703.
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