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Corticosteroids

Overview

CorticosteroidsCorticosteroids have long been employed in the treatment of rheumatoid arthritis and remain a key component of symptom management. They produce potent, rapid suppression of inflammation with consequent improvements in joint pain and swelling. Studies showing that corticosteroids can reduce the rate of joint damage in rheumatoid arthritis patients led to their initial classification as disease-modifying agents. However, rheumatologists caution that the disease-modifying properties of corticosteroids are limited, and they should not be administered as a monotherapy to rheumatoid arthritis patients with active disease. Instead, true Disease-modifying antirheumatic drugs, either conventional or biological, should be initiated, and corticosteroids used as supplemental therapy to control symptoms as needed.

Corticosteroids are associated with many side effects. Insomnia, night sweats, mood changes, and altered glucose metabolism may occur shortly after beginning corticosteroids. Prolonged corticosteroid therapy can lead to adrenal atrophy, and abrupt cessation can cause adrenal insufficiency, hypotension, and even death. Long-term use of systemic corticosteroids is associated with osteoporosis, hypertension, cataracts, acne, abnormal fat deposition, and excessive hair growth. These side effects generally occur less often with corticosteroid injections, but injection site infections, post-injection flares, and crystal-induced synovitis can occur with parenteral delivery.

A wide variety of generic corticosteroids, salts, and formulations are available in the markets under study. This section assesses two of the most commonly prescribed agents, orally administered prednisone (Pfizer’ s Deltasone, generics) and intra-articular (IA) methylprednisolone acetate (Pfizer’s Depo-Medrol, generics).

Mechanism Of Action

Corticosteroids act as anti-inflammatory and immunosuppressive agents through multiple effects: inhibiting synthesis of proinflammatory mediators (prostaglandins, leukotrienes, and cytokines); disrupting cellular activation, migration, and proliferation; and blocking edema formation. Corticosteroids can also inhibit the expression of COX-2 and the activity of collagenase and other cartilage-damaging enzymes.

Formulation

CorticosteroidsRheumatologists employ a wide variety of corticosteroid formulations and doses to relieve rheumatoid arthritis symptoms. Oral corticosteroids are often used as bridge therapy, meaning they are initiated by primary care physicians or rheumatologists upon diagnosis, but then discontinued when the slower-acting, conventional Disease-modifying antirheumatic drug therapy takes effect. Intravenous corticosteroids are occasionally used as bridge therapy, as well. In addition, oral and intravenous corticosteroids are used during periodic flare-ups to control symptoms during times of high disease activity.

For alleviating severe rheumatoid arthritis symptoms, high doses of intravenous corticosteroids can be used on a short-term basis (up to 1 g per day for three days). The intravenous treatment can be repeated after four to six weeks if necessary. Alternatively, oral corticosteroids can be initiated at a high dose (e.g., 30-40 mg prednisone daily) and then gradually tapered down in 5 mg steps to a continuous dosage of 5-10 mg per day. For milder symptoms, a low dose of oral corticosteroids can be used as short-term or long-term therapy. Because of the serious side effects associated with corticosteroids, rheumatologists prefer to discontinue these drugs as soon as possible. However, abrupt cessation of corticosteroids can cause adrenal insufficiency, hypotension, and even death, so doses must be carefully tapered to a level where these drugs may be safely discontinued.

To minimize side effects and to prevent problems with abrupt discontinuation of systemic therapy, intramuscular or IA injections are used for relief of localized, aggressive joint flare-ups. A single intramuscular dose of a depot corticosteroid, such as methylprednisolone acetate or triamcinilone acetonide (both 40 mg/mL), is preferred by rheumatologists when rapid control is required. Furthermore, physicians and researchers have expressed concern that repeated corticosteroid injections into joints can actually exacerbate progressive cartilage damage. As a result, many rheumatologists consider this strategy a last resort and will not use it in more than one joint at a time. The ACR also recommends that intra-articular injections not be administered in the same joint more than once within three months.

Prednisone

Methylprednisolone Acetate

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