On NSAIDs and COX-2s from the ACR

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An excerpt from:

American College of Rheumatology

Guidelines for the Management of Rheumatoid Arthritis

2002

NSAIDs. The initial drug treatment of RA usually

involves the use of salicylates, NSAIDs, or a selective

cyclooxygenase 2 (COX-2) inhibitor to reduce joint

pain and swelling and to improve joint function. These

agents have analgesic and antiinflammatory properties

but do not alter the course of the disease or prevent joint

destruction. Thus, they should not be used as the sole

treatment for RA.

Choice of available agents is based on considerations

of efficacy, safety, convenience, and cost. Some

salicylates and all available nonsalicylate NSAIDs inhibit

the production of prostaglandins by inhibiting one or

both of the cyclooxygenase enzyme isoforms, COX-1

and COX-2. COX-1 is produced constitutively and is

present in many cells, including platelets, cells of the

gastric and intestinal mucosa, and endothelial cells.

Production of COX-2 can be increased many times over,

particularly by cells at sites of inflammation. Data sug-

gest that although selective COX-2 inhibitors have a

significantly lower risk of serious adverse gastrointestinal

(GI) effects than do nonselective NSAIDs (41,42),

they are no more effective than nonselective NSAIDs

and may cost as much as 15-20 times more per month of

treatment than generic NSAIDs.

Patients with RA are nearly twice as likely as

patients with osteoarthritis to have a serious complication

from NSAID treatment (43). Risk factors for the

development of NSAID-associated gastroduodenal ulcers

include advanced age, history of ulcer, concomitant

use of corticosteroids or anticoagulants, higher dosage

of NSAID, use of multiple NSAIDs, or a serious underlying

disease (44). Advanced age is defined as 75 years or

older.

The following approaches may be considered for

patients with RA who would benefit from an NSAID but

who are at increased risk of serious adverse GI effects:

use of low-dose prednisone instead of an NSAID, use of

a nonacetylated salicylate, use of a highly selective

COX-2 inhibitor, or use of a combination of an NSAID

and a gastroprotective agent.

Gastroprotective agents,

which are effective in decreasing NSAID-associated

gastroduodenal ulceration, include high-dose H2 blockers

(45), proton-pump inhibitors (46,47), and oral prostaglandin

analogs (48).

While symptoms of dyspepsia are often improved

by treatment with H2 blockers, one study showed that

asymptomatic patients with RA who were receiving both

NSAIDs and low-dose H2 blockers were at higher risk of

GI complications than those receiving NSAIDs alone

(49). Therefore, routine use of H2 blockers to prevent

dyspepsia or to protect against NSAID-induced gastropathy

is not recommended.

In two recent large trials comparing highly selective

COX-2 agents with traditional NSAIDs, the patients

in the selective COX-2 agent group had significantly

fewer GI events (41,42). There are several caveats,

however. If antiplatelet therapy is indicated (e.g., as risk

reduction for cardiovascular disease), an agent such as

low-dose aspirin should be used because, unlike nonselective

NSAIDs, the selective COX-2 inhibitors have no

effect on platelet adhesion or aggregation (41). The

addition of low-dose aspirin may partially ameliorate the

benefit of less GI toxicity associated with highly selective

COX-2 agents (42). Moreover, the use of a highly

selective COX-2 agent has been reported to be associated

with a higher rate of thrombotic events (including

more myocardial infarctions) compared with traditional

NSAIDs (41). Use of NSAIDs and selective COX-2

inhibitors should be avoided in conditions associated

with diminished intravascular volume or edema, such as

congestive heart failure, nephrotic syndrome, or cirrhosis,

and in patients with serum creatinine levels greater than or equal to

2.5 mg/dl (50).

http://www.rheumatology.org/research/guidelines/raguidelines02.pdf

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Mayo Clinic in Rochester

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