Celecoxib is used in the management of osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, pain, ankylosing spondylitis, and dysmenorrhea. There currently is no evidence establishing superiority of selective COX-2 inhibitors relative to prototypical NSAIAs in the management of these conditions, and the principal benefit of selective COX-2 inhibitors is a potential reduction in the incidence of certain adverse effects (e.g., GI toxicity). Both COX-2 inhibitors and prototypical NSAIAs have been associated with an increased risk of cardiovascular events. A decision to use a selective COX-2 inhibitor rather than a prototypical NSAIA usually is based on an individual assessment of the risk of ulcer complications from NSAIA therapy. There is some evidence that therapy with a COX-2 inhibitor may be no more effective in reducing the risk of NSAIA-induced GI complications than a combined regimen of a prototypical NSAIA and a proton-pump inhibitor.
Celecoxib also is used to reduce the number of adenomatous colorectal polyps in adults with familial adenomatous polyposis (FAP).
The potential benefits and risks of celecoxib therapy as well as alternative therapies should be considered prior to initiating therapy with the drug. The lowest possible effective dosage and shortest duration of therapy consistent with treatment goals of the patient should be employed.
Celecoxib is used for the management of the signs and symptoms of osteoarthritis in adults. Medical management of osteoarthritis of the hip or knee includes both pharmacologic therapy to reduce pain and nonpharmacologic therapy to maintain and/or improve joint mobility and limit functional impairment (e.g., patient education, weight loss when necessary, aerobic and muscle-strengthening exercise programs, physical therapy and range-of-motion exercises, assistive devices for ambulation and activities of daily living, patellar taping, appropriate footwear or bracing). Pain management is considered an adjunct to nonpharmacologic measures, and is most effective when combined with nonpharmacologic strategies.
A variety of drugs have been used for management of pain in patients with osteoarthritis, including oral agents (e.g., acetaminophen, NSAIAs, tramadol), intraarticular agents (e.g., glucocorticoids, sodium hyaluronate), and topical agents (e.g., capsaicin, methylsalicylate). Factors to consider when making treatment decisions for the management of pain in patients with osteoarthritis include the presence of risk factors for serious adverse GI effects or renal toxicity (which may affect decisions regarding use of NSAIAs), existing comorbidities and concomitant therapy, and the adverse effects profiles and costs of specific therapies.
Because there is evidence that acetaminophen can be effective and because of its relative safety and low cost, the American College of Rheumatology (ACR) and other clinicians recommended use of the drug as the initial analgesic for many osteoarthritis patients. Acetaminophen appears to be as effective as NSAIAs for relief of mild to moderate joint pain in many patients with osteoarthritis; however, the drug is not effective in all patients and may not provide adequate relief in those with moderate to severe pain or when joint inflammation is present. An NSAIA can be considered an alternative initial drug of choice for patients with osteoarthritis, especially for those who have moderate to severe pain and signs of joint inflammation, and also can be considered in patients who fail to obtain adequate symptomatic relief with acetaminophen. NSAIAs that are selective inhibitors of COX-2 (e.g., celecoxib) are associated with a lower incidence of adverse GI effects than prototypical NSAIAs. Both COX-2 inhibitors and prototypical NSAIAs have been associated with an increased risk of cardiovascular events. A decision to use a selective COX-2 inhibitor (e.g., celecoxib) rather than a prototypical NSAIA usually is based on an individual assessment of the risk for GI toxicity. If a prototypical NSAIA (e.g., diclofenac, diflunisal, fenoprofen, ibuprofen, indomethacin, ketoprofen, meclofenamate, naproxen, piroxicam, sulindac, tolmetin) is used in osteoarthritis patients at risk for GI complications, concomitant use of misoprostol or a proton-pump inhibitor (e.g., omeprazole) can be considered for preventive therapy. However, in a study comparing the efficacy of celecoxib (200 mg twice daily) versus diclofenac sodium (75 mg twice daily) plus omeprazole (20 mg daily) in preventing recurrent ulcer bleeding in H. pylori-negative arthritis (principally osteoarthritis) patients with a recent history of ulcer bleeding while receiving long-term NSAIA therapy, the protective efficacy was unexpectedly low for both regimens (recurrent ulcer bleeding probabilities of 4.9 versus 6.4%, respectively, during the 6-month study) and it appeared that neither could completely protect patients at high risk.
In several double-blind, placebo-controlled, or comparative studies of up to 12 weeks' duration, celecoxib was at least as effective as naproxen and more effective than placebo in the symptomatic management of osteoarthritis of the knee or hip in patients who experienced exacerbation of symptoms (e.g., pain, joint stiffness) following discontinuance of standard therapy with NSAIAs or other analgesics. While celecoxib and naproxen generally are comparably effective in the management of osteoarthritis, current data suggest that adverse GI effects occur less frequently with celecoxib.
(See Cautions: GI Effects.)
In controlled clinical studies in adults with osteoarthritis, therapy with celecoxib (100 mg twice daily or 200 mg once daily) resulted in improvement in the Western Ontario and McMasters Universities (WOMAC) osteoarthritis index; WOMAC is a 24-item questionnaire that measures pain, stiffness, and functioning. Following initiation of celecoxib 100 or 200 mg twice daily in patients with joint pain as a result of symptomatic exacerbation of osteoarthritis, pain relief generally occurs within 24-48 hours and therapy with the drug is associated with greater reductions in joint pain than placebo. In placebo-controlled and comparative studies in patients with symptomatic exacerbation of osteoarthritis of the hip or knee, 31-36% of patients receiving celecoxib 100 mg twice daily for 12 weeks improved as measured by patient and physician assessment of the arthritic condition; improvement occurred in 29-36% of patients receiving celecoxib 200 mg twice daily, 29-37% of patients receiving naproxen 500 mg twice daily, and 17-24% of patients receiving placebo twice daily. Celecoxib dosages of 100 mg twice daily and 200 mg once daily were comparably effective in patients with osteoarthritis as measured by joint pain, disease activity, functionality, and health-related quality of life. Celecoxib dosages of 200 mg twice daily do not appear to provide additional benefit compared with dosages of 100 mg twice daily or 200 mg once daily in these patients.
Rheumatoid Arthritis in Adults
Celecoxib is used for the management of the signs and symptoms of rheumatoid arthritis in adults. Although current data suggest that the efficacy of celecoxib is similar to that of prototypical NSAIAs but with a lower risk of adverse GI effects, both selective COX-2 inhibitors and prototypical NSAIAs have been associated with an increased risk of cardiovascular events. A decision to use a selective COX-2 inhibitor (e.g., celecoxib) rather than a prototypical NSAIA usually is based on an individual assessment of the risk for GI toxicity. There is some evidence that therapy with a COX-2 inhibitor may be no more effective in reducing the risk of NSAIA-induced GI complications than a combined regimen of a prototypical NSAIA and a proton-pump inhibitor.
(See Uses: Osteoarthritis.)
In the management of rheumatoid arthritis in adults, NSAIAs may be useful for initial symptomatic treatment; however, NSAIAs do not alter the course of the disease or prevent joint destruction. Disease modifying antirheumatic drugs (DMARDs) (e.g., azathioprine, cyclosporine, etanercept, oral or injectable gold compounds, hydroxychloroquine, infliximab, leflunomide, methotrexate, minocycline, penicillamine, sulfasalazine) have the potential to reduce or prevent joint damage, preserve joint integrity and function, and reduce total health care costs, and all patients with rheumatoid arthritis are candidates for DMARD therapy. DMARDs should be initiated early in the disease course and should not be delayed beyond 3 months in patients with active disease (i.e., ongoing joint pain, substantial morning stiffness, fatigue, active synovitis, persistent elevation of erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP], radiographic evidence of joint damage) despite an adequate regimen of NSAIAs. NSAIA therapy may be continued in conjunction with DMARD therapy or, depending on patient response, may be discontinued.
In double-blind, placebo-controlled studies, therapy with celecoxib was associated with greater reduction in joint tenderness/pain and swelling than placebo. In addition, several double-blind, comparative studies of up to 24 weeks' duration have demonstrated that celecoxib is at least as effective as naproxen or diclofenac in the symptomatic treatment of rheumatoid arthritis but is less likely to cause adverse GI effects.
(See Cautions: GI Effects.)Clinical studies of celecoxib generally have included adults receiving standard therapy for rheumatoid arthritis (i.e., NSAIAs with or without DMARDs and/or low-dose oral corticosteroids) who experienced symptomatic exacerbation (symptom ''flare'') within 2-14 days of discontinuing the NSAIA component of their regimen. Symptom flare was defined as a minimum of 6 tender joints and an increase of 20% in the number of tender or painful joints or involvement of at least 2 additional joints since discontinuing NSAIA therapy; a minimum of 3 swollen joints and an increase of 20% in the number of swollen joints or involvement of at least 2 additional joints since discontinuing NSAIA therapy; and either a minimum of 45 minutes of morning stiffnessand an increase of at least 15 minutes in the duration of morning stiffness or an increase in patient-assessed arthritis pain since discontinuing NSAIA therapy.
The American College of Rheumatology criteria for a 20% improvement (ACR 20 response) in measures of disease activity were used as the principal measure of clinical response in studies evaluating the efficacy of celecoxib. An ACR 20 response is achieved if the patient experiences a 20% improvement in the number of tender and swollen joints and a 20% or greater improvement in at least 3 of the following 5 criteria: patient pain assessment; patient global assessment; physician global assessment; patient self-assessed disability; and laboratory measures of disease activity (i.e., ESR or C-reactive protein level). In placebo-controlled and comparative studies in adults with rheumatoid arthritis who had symptom flare, an ACR 20 response was achieved in 30-40% of patients who received celecoxib 100 mg twice daily for 12 weeks, 39-44% of patients who received celecoxib 200 mg twice daily for 12 weeks, 36-42% of patients who received naproxen 500 mg twice daily for 12 weeks, and 23-29% of placebo-treated patients. While celecoxib 100 mg twice daily generally was as effective as celecoxib 200 mg twice daily, some patients experienced additional benefit from the higher dosage. Dosages of 400 mg twice daily provided no additional benefit compared with dosages of 100-200 mg twice daily.
Celecoxib is used for the management of the signs and symptoms of juvenile rheumatoid arthritis in children 2 years of age or older. Efficacy of celecoxib was established in pediatric patients with pauciarticular course, polyarticular course, or systemic onset juvenile rheumatoid arthritis (active systemic disease not present at study entry) in a double-blind, active-controlled study of 12 weeks' duration; pediatric patients 2-17 years of age were randomized to receive celecoxib 3 mg/kg (up to a maximum dose of 150 mg) twice daily, celecoxib 6 mg/kg (up to a maximum dose of 300 mg) twice daily, or naproxen 7.5 mg/kg (up to a maximum dose of 500 mg) twice daily. Response was measured using the juvenile rheumatoid arthritis definition of improvement (i.e., a 30% or greater improvement in at least 3 of 6 and a 30% or greater deterioration in no more than 1 of 6 core set criteria that included physician and patient/parent global assessments, active joint count, limitation of motion, functional assessment, and erythrocyte sedimentation rate: JRA DOI 30). Results of this study indicate that celecoxib is as effective as naproxen in the management of juvenile rheumatoid arthritis. Evaluation at week 12 indicated that clinical response (JRA DOI 30) was achieved in 69, 80, or 67% of pediatric patients receiving celecoxib 3 mg/kg twice daily, celecoxib 6 mg/kg twice daily, or naproxen 7.5 mg/kg twice daily, respectively. The manufacturer states that safety and efficacy of celecoxib therapy beyond 6 months in pediatric patients with juvenile arthritis have not been established.
Clinical trials indicate that either celecoxib or a prototypical NSAIA is effective in the management of juvenile rheumatoid arthritis. Celecoxib may have a lower risk of adverse GI effects compared with prototypical NSAIAs and may be useful in children who have experienced adverse GI effects with prototypical NSAIAs. In addition, celecoxib may be useful in children who have experienced other adverse effects with prototypical NSAIAs (e.g., naproxen-induced pseudoporphyria). It remains to be determined whether long-term cardiovascular risks in children exposed to celecoxib are similar to those observed in adults receiving celecoxib or other NSAIAs.
(See Cautions: Cardiovascular Effects.)
Celecoxib is used for the management of the signs and symptoms of ankylosing spondylitis in adults. Clinical trials indicate that either selective COX-2 inhibitors or prototypical NSAIAs are effective for initial symptomatic management of ankylosing spondylitis. Although celecoxib may have a lower risk of adverse GI effects compared with prototypical NSAIAs, both selective COX-2 inhibitors and prototypical NSAIAs have been associated with an increased risk of cardiovascular events. A decision to use a selective COX-2 inhibitor (e.g., celecoxib) rather than a prototypical NSAIA usually is based on an individual assessment of the risk for GI toxicity. There is some evidence that therapy with a COX-2 inhibitor may be no more effective in reducing the risk of NSAIA-induced GI complications than a combined regimen of a prototypical NSAIA and a proton-pump inhibitor.
(See Uses: Osteoarthritis.)
In placebo- and active-controlled studies of 6- and 12-weeks' duration in patients with ankylosing spondylitis, celecoxib (100 mg twice daily, 200 mg once daily, or 400 mg once daily) was more effective than placebo, as assessed by global pain intensity and global disease activity (both rated using visual analog scales) and functional impairment (measured using the Bath Ankylosing Spondylitis Functional Index [BASFI]). In the 12-week study, there was no difference in the extent of improvement in those receiving celecoxib 400 mg daily relative to those receiving celecoxib 200 mg daily, but more patients receiving the 400-mg daily dose (53%) than the 200-mg daily dose (44%) were classified as responders (defined as achieving 20% or greater improvement in the Assessment in Ankylosing Spondylitis [ASAS] response criteria). There was no change in responder rates after 6 weeks.
Celecoxib is used to reduce the number of adenomatous colorectal polyps in adults with familial adenomatous polyposis (FAP) as an adjunct to usual care (e.g., endoscopic surveillance, surgery). Patients with FAP have an inherited mutation in the adenomatous polyposis coli (APC) gene that results in hundreds of adenomatous polyps and an almost 100% risk of colon cancer. The clinical benefit of reducing the number of polyps in individuals with FAP remains to be determined. It is not known whether use of celecoxib in patients with FAP will reduce the risk of colorectal, duodenal, or other FAP-related cancers or whether use of the drug reduces the need for endoscopic surveillance and prophylactic colectomy or other FAP-related surgery. Therefore, FAP patients receiving celecoxib should continue to receive usual care.
Efficacy of celecoxib in reducing the extent of polyposis has been evaluated in a randomized, placebo-controlled study in adults with FAP. In this study, patients with FAP were randomized to receive a 6-month regimen of celecoxib 400 mg twice daily, celecoxib 100 mg twice daily, or placebo. Patients underwent endoscopy at the beginning and end of the study to determine the number and size of polyps in specified areas (one area of the rectum and up to 4 areas of the colon); response to treatment was expressed as the mean percent change in the number of polyps and in polyp burden (expressed as the sum of polyp diameters). The mean pretreatment number of polyps was 11.5-15.5 and the mean pretreatment polyp burden was 34.8-44.7 mm. At month 6, the mean reduction in the number of polyps was 28% in patients who received celecoxib 400 mg twice daily, 12% in those who received celecoxib 100 mg twice daily, and 5% in those who received placebo; the mean reduction in polyp burden was 30.7, 14.6, and 4.9%, respectively. While administration of celecoxib (400 mg twice daily) appears to be associated with a reduction in the number of colorectal polyps in patients with FAP, the clinical benefit of reducing the number of polyps in such individuals remains to be determined and it is unclear whether the effect of celecoxib in reducing the number of polyps persists after the drug is discontinued. The manufacturer states that safety and efficacy of celecoxib therapy for longer than 6 months in patients with FAP have not been studied.
Use of celecoxib for the prevention of adenomatous colorectal polyps (colorectal adenomas) in patients without a history of FAP has been investigated in 2 long-term, National Institute of Health (NIH)-supported, multicenter studies (Adenoma Prevention with Celecoxib [APC]; Prevention of Colorectal Sporadic Adenomatous Polyps [PreSAP]). Patients included in these studies had undergone recent removal of colorectal adenomas and were at high risk of recurrent adenomas. Results of these studies indicate that administration of celecoxib (200 mg twice daily, 400 mg twice daily, or 400 mg once daily) reduces the risk of recurrent colorectal adenomas. The cumulative rate of adenoma detection during up to 3 years of treatment was 33.6-43.2% among patients receiving celecoxib compared with 49.3-60.7% among those receiving placebo. However, some clinicians state that routine use of celecoxib for the prevention of sporadic colorectal adenomas cannot be recommended because of the potential for serious cardiovascular events in celecoxib-treated patients. The studies did not evaluate whether celecoxib alters the risk of a first occurrence of colorectal adenoma or prevents the development of colorectal cancer.
Celecoxib is used in the management of acute pain, including postoperative (dental, orthopedic) pain, in adults. In pain studies evaluating the efficacy of celecoxib, the drug was effective in the relief of postoperative dental pain and postoperative orthopedic pain that was described as moderate to severe. Following administration of single doses of celecoxib, the onset of analgesia was 60 minutes. In a single-dose study, celecoxib 100 or 400 mg reportedly was more effective than placebo and as effective as aspirin 650 mg for relief of pain following dental extraction. However, limited data indicate that celecoxib 100 or 200 mg as a single dose may be less effective than single doses of ibuprofen 400 mg or naproxen sodium 550 mg for the acute relief of postoperative dental pain.
Celecoxib is used for the relief of primary dysmenorrhea in adults. In pain studies evaluating the efficacy of celecoxib, the drug was effective in the relief of moderate to severe pain associated with primary dysmenorrhea.
Celecoxib has no effect on platelet function and is not a substitute for aspirin in the prevention of adverse cardiovascular events (e.g., primary or secondary prevention of myocardial infarction).
Results from a large, prospective, population-based cohort study in geriatric individuals indicate a lower prevalence of Alzheimer's disease among patients who received an NSAIA for 2 years or longer. Similar findings have been reported from some other, but not all, observational studies.