Cyclooxygenase-2 inhibitors efficacy

Simon LS, Lanza FL, Lipsky PE, Hubbard RC, Talwalker S, Schwartz BD, Isakson PC, Geis GS. Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibitor efficacy and safety in two placebo-controlled trials in osteoarthritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects. Arthritis Rheum 1998 41(9) 1591-602. 

The efficacy and safety of cyclooxygenase-2 (COX-2) selective inhibitors (e.g., celecoxib) have not been fully assessed in gouty arthritis, but they are more costly than conventional NSAIDs and are unlikely to result in fewer GI complications because of the short duration of therapy. 

The discovery of two cyclooxygenase isoforms (COX-1 and COX-2) led to the concept that the constitutive COX-1 isoform tends to be homeostatic in function, while COX-2 is induced during inflammation and tends to facilitate the inflammatory response. On this basis, highly selective COX-2 inhibitors have been developed and marketed on the assumption that such selective inhibitors would be safer than nonselective COX-1 inhibitors but without loss of efficacy. 

Altman R, Luciardi HL, Muntaner J, etal, Efficacy assessment of meloxicam, a preferential cyclooxygenase-2 inhibitor, in acute coronary syndromes without ST-segment elevation the Nonsteroidal Anti-Inflammatory Drugs in Unstable Angina Treatment-2 (NUT-2) pilot study, Circulation 2002 106 191-195. 

The analgesic efficacy and safety profiles of the nonsalicylate NSAIDs make them appropriate alternatives to aspirin for treatment of mild to moderate pain. Most NSAIDs are used primarily for their anti-inflammatory effects, but they are also effective analgesics that relieve pain associated with a variety of ocular conditions. The nonsalicylate NSAIDs consist of the propionic acid derivatives, cyclooxygenase-2 (COX-2) inhibitors, and several other less commonly used agents (Table 7-2). 

Cannon GW, Caldwell JR, Holt P, McLean B, Seidenberg B, Bolognese J, Ehrich E, Mukhopadhyay S, Daniels B. Rofecoxib, a specific inhibitor of cyclooxygenase 2, with clinical efficacy comparable rvith that of diclofenac sodium results of a one-year, randomized, clinical trial in patients with osteoarthritis of the knee and hip. Rofecoxib Phase III Protocol 035 Study Group. Arthritis Rheum 2000 43(5) 978-87. 

Morrison BW, Christensen S, Yuan W, Brovm J, Amlani S, Seidenberg B. Analgesic efficacy of the cyclooxygenase-2-specific inhibitor rofecoxib in post-dental surgery pain a randomized, controlled trial. Chn Ther 1999 21(6) 943-53. 

Blockade of prostaglandin synthesis through inhibition of cyclooxygenase (both COX-1 and COX-2 enzymes) is believed to be the principal mechanism by which NSAIDs relieve pain and inflammation" " (Fig. 90-3). Given the similar efficacy of nonspecific NSAIDs and COX-2 inhibitors, toxicity and cost play major roles in determining the medication chosen for a given patient. To understand the differences between nonspecific NSAIDs and COX inhibitors, the next section will review the COX-2 paradigm." " ... 

Jahr JS, Donkor KN, Sinatra RS. Non-selective non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors (COX-2Is), and acetaminophen in acute perioperative pain analgesic efficacy, opiate-sparing effects, and adverse effects. In Sinatra R, de Leon-Casasola O, Ginsberg B, Viscusi ER, eds. Acute Pain Management, 2nd ed. 

Ott E, Nussmeier NA, Duke PC, et al. Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. J Thorac Cardiovasc Surg 2003 125 1481-1492. 

Individuals with inherited familial adenomatous polyposis (FAP) develop numerous polyps, the premalignant precursors to colorectal carcinoma. A remarkable heterogeneity in patient response was observed in a clinical trial with a cyclooxygenase-2-inhibitor, celocoxib, which is known to be efficacious in FAP. SELDl proteomic profile revealed that a putative marker at 16,961.4 Da was a strong discriminator between response and nonresponse [134]. 

---