Efficacy and safety of etoricoxib in the treatment of osteoarthritis

Osteoarthritis is a progressive disease that affects millions of people worldwide, but for which there are no curative options and indeed a limited number of medical treatment options. The American College of Rheumatology recommendations suggest administering either a traditional NSAID or a COX-2-selective inhibitor for pain relief. Traditional NSAIDs, such as naproxen, may have a higher risk of gastrointestinal (GI) events, while COX-2-selective inhibitors may have a higher risk of thrombotic cardiovascular (CV) events (with traditional NSAIDs and COX-2-selective agents appearing to have a similar CV risk). Etoricoxib, introduced in 2002, has been approved in over 60 countries worldwide for osteoarthritis. Large-scale studies addressing the efficacy, GI tolerability and potential for CV events with etoricoxib have now been published. Several patient types appear to benefit from etoricoxib, including those with CV risk factors and those requiring gastroprotective agents. In patients with CV risk factors, the benefits and risks of all NSAIDs should be weighed carefully in each patient, balancing the potential risks of treatment against the potential relief for pain and disability.     

Clinical pharmacology of celecoxib, a COX-2 selective inhibitor

NSAIDs are extensively used worldwide; nonetheless, they are associated with adverse gastrointestinal (GI) effects. COX-2 inhibitors (coxibs) have been developed to reduce pain and inflammation without associated GI and bleeding risks. Celecoxib was the first COX-2 inhibitor introduced on the market, and it still remains so, whereas rofecoxib and valdecoxib were withdrawn due to excess cardiovascular (CV) risk. There is consequently a concern that CV toxicity reflects a class effect of all COX-2 inhibitors. Celecoxib possesses anti-inflammatory and analgesic properties, and the evidence for CV risk is rather small and comparable to that of other traditional NSAIDs in short-term treatments (of < 4 weeks). It could be suggested that the use of low doses of celecoxib (100 mg b.i.d.) in short-treatment, especially in patients with previous experience of GI events and the recommendation of avoiding use of celecoxib in patients with CV history or risk, contribute in the decision-making process of prescribing COX-2 or NSAIDs.     

Risks versus benefits of cyclooxygenase-2-selective nonsteroidal antiinflammatory drugs.

PURPOSE: A summary of the basic science underlying the current controversies regarding cyclooxygenase-2 (COX-2)-selective nonsteroidal antiinflammatory drugs (NSAIDs), including data on their cardiovascular safety, their gastrointestinal (GI) benefits, cost-effectiveness, physician-prescribing trends, and recommendations for prescribing these agents is presented. SUMMARY: A number of randomized controlled trials (RCTs) have reported that COX-2-selective NSAIDs increase cardiovascular events, although there appear to be gradations of risks among the COX-2-selective NSAIDs. In addition, traditional NSAIDs may increase the risk for cardiovascular events, complicating the interpretation of RCTs that use traditional NSAIDs as comparators. Selective inhibitors of COX-2-selective NSAIDs are effective antiinflammatory and analgesic drugs with improved upper-GI safety compared to traditional NSAIDs. Data on the cost-effectiveness of COX-2-selective NSAIDs indicate that they should be limited to patients at high risk for upper-GI adverse effects. However, they had been increasingly used in patients with lower GI risks until recent events reversed that trend. Circumstances under which COX-2-selective NSAIDs may be appropriate are in patients at high GI risk and in patients who did not respond to multiple traditional NSAIDs. The national spotlight in the United States on NSAID-related adverse events and recent lawsuits against health care providers prescribing COX-2-selective NSAIDs further highlights the need for provider-patient communication and risk disclosure. The relative cardiovascular risks of NSAIDs are similar in magnitude to other currently prescribed therapies. CONCLUSION: Health care providers must consider the efficacy, GI and cardiovascular risks, concomitant medications, and costs when determining the appropriateness of COX-2-selective NSAID therapy.     

Celecoxib: a review of its use in the management of arthritis and acute pain

Celecoxib (Celebrex), the first cyclo-oxygenase (COX) 2-selective inhibitor (coxib) to be introduced into clinical practice, has been available for almost a decade. It is approved in one or more countries worldwide for the relief of the signs and symptoms of osteoarthritis (OA), rheumatoid arthritis (RA), juvenile rheumatoid arthritis (in patients aged > or =2 years) and ankylosing spondylitis (AS), the management of acute pain in adults, the treatment of primary dysmenorrhoea and the reduction in the number of adenomatous colorectal polyps in familial adenomatous polyposis.Celecoxib remains an effective and useful altenative to nonselective NSAIDs in the treatment of acute or chronic musculoskeletal pain. In the latter setting, it offers the prospect of improved gastrointestinal (GI) tolerability and, in patients not taking aspirin for cardioprophylaxis, a GI safety advantage. Currently available evidence of an increase in cardiovascular (CV) risk with celecoxib is inconsistent; any increase in risk is likely to be small and similar to that with nonselective NSAIDs. As with all NSAIDs, the potential GI, CV and renal risks of celecoxib must be weighed against the potential benefits in each individual; it is a rational choice for patients at low CV risk who require NSAID therapy, especially those at increased risk of NSAID-induced GI toxicity, but also those unresponsive to, or intolerant of, other NSAIDs. If selected, celecoxib, like all NSAIDs, should be used at the lowest effective dose for the shortest possible duration.     

Prevention of nonsteroidal anti-inflammatory drug–associated gastrointestinal symptoms and ulcer complications

Nonsteroidal anti-inflammatory drugs (NSAIDs) produce symptoms of dyspepsia and peptic ulcer disease in up to 50% and up to 20%, respectively, of individuals taking them. Risk factors for NSAID-related gastric injury include age >70 years, history of ulcer disease, use of multiple agents (e.g., ≥2 NSAIDs, or an NSAID plus aspirin—even at cardioprotective doses), high doses of an NSAID, and concurrent use of corticosteroids or anticoagulants. In NSAID users, infection with Helicobacter pylori can produce additive or synergistic gastric mucosal injury. Several clinical strategies can decrease the risk for dyspepsia, ulceration, and the more serious complications in NSAID users. Proton pump inhibitor (PPI) co-therapy has been shown to lower the incidence of dyspepsia in those taking NSAIDs. In those with an active ulcer, PPI therapy produces ulcer healing even in “tough-to-treat” individuals who require ongoing NSAID therapy. Maintenance of ulcer healing is significantly greater in those who receive ongoing PPI treatment compared with placebo, and adverse events and treatment withdrawals are fewer compared with their occurrence in persons treated with misoprostol. In those not receiving aspirin therapy, the use of an NSAID that is a selective inhibitor of cyclooxygenase (COX)-2 may result in fewer gastrointestinal symptoms compared with a traditional agent; however, studies have failed to show any decrease in healthcare resource utilization (including outpatient or emergency room visits, hospitalization rate, or use of any resource) with COX-2–selective therapy.     

Gastrointestinal bleeding rates among managed care patients newly started on cox-2 inhibitors or nonselective NSAIDs

OBJECTIVE: While cyclooxygenase-2 (COX-2) inhibitors were introduced to the U.S. market with the promise of less gastrointestinal (GI) toxicity than nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), additional research is needed to examine this outcome in the naturalistic setting. The objective of this study was to examine whether use of COX-2 inhibitors is associated with reduced risk of GI bleed in a managed care population. METHODS: Adult patients in a multistate managed care organization that were initiated on a nonselective NSAID between January 1999 and August 2002 were identified and matched using propensity scoring with patients in the same managed care organization that were initiated on a COX-2 inhibitor. Matching variables included age, gender, geographical state, comorbidity index, corticosteroid use, warfarin use, arthritis indication, and history of recent GI bleed. Patients were followed until they switched or discontinued their NSAID or COX-2 inhibitor, disenrolled from the health plan, developed a GI bleed, or reached the end of the 1-year follow-up period. A GI bleed was defined as an inpatient hospitalization for GI bleed or at least 2 medical claims with a primary diagnosis for GI bleed. The relative risk (RR) of GI bleed was calculated using proportional hazards regression. RESULTS: Overall, 35,007 pairs of COX-2 inhibitor and nonselective NSAID users were evaluated. Mean age was 63 years, and 65% were female. There were 375 cases of GI bleed among 19,201 follow-up years for COX-2 users (19.5 cases per 1,000 person-years) versus 228 cases of GI bleed among 12,680 follow-up years for NSAID users (18.0 cases per 1,000 person-years). The risk of GI bleed was not significantly different for COX-2 users compared with nonselective NSAID users (RR 1.07; 95% confidence interval [CI], 0.90-1.26). Even among high-risk patients, there was no reduction in the risk of a GI bleed among users of COX-2 inhibitors (RR 0.995; 95% CI, 0.84 -1.19). CONCLUSION: Overall, within this managed care population, COX-2 inhibitor users did not have a reduced risk of a GI bleed compared with patients with similar baseline characteristics using nonselective NSAIDs.     

Should nonsteroidal anti-inflammatory drugs (NSAIDs) be prescribed to the older adult?

The prevalence of chronic pain increases with age, exceeding 50% in individuals aged ≥65 years. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a mainstay of chronic pain management but carry significant dose-related risks of cardiovascular, renal, haematological and other systemic adverse events (AEs). Older patients have an increased risk of these AEs and are more likely to take multiple medications that can potentially interact with NSAIDs. In particular, older patients are more likely to have cardiovascular disease and a natural age-related decline in renal function, increasing the risks of cardiovascular, haematological and renal AEs. Given these risks, recent guidelines for the management of chronic pain in the elderly recommend using NSAIDs rarely and only in carefully selected patients. NSAIDs currently available in the US fall into three categories: nonselective NSAIDs that act via inhibition of cyclo-oxygenase (COX)-1 and COX-2; celecoxib, a selective inhibitor of COX-2; and topical NSAIDs that inhibit both COX-1 and COX-2 but result in much less systemic NSAID exposure than oral formulations. Topical NSAIDs have demonstrated efficacy similar to oral NSAIDs, with an incidence of AEs similar to placebo; however, these agents are an option only in patients with localized pain in superficial joints. Safe pain management in older patients therefore requires cautious choice of selective and nonselective oral NSAIDs, topical NSAIDs or non-NSAID analgesics. This article discusses the risks and benefits of NSAID therapy, reviews its mechanism of action as the source of adverse effects and provides recommendations for maximizing NSAID safety, particularly in older patients. Articles cited in this review were identified via a search of PubMed (January 2005 to November 2009) and a manual search of reference lists from the articles identified in that search. Priority was given to articles discussing NSAID use in older populations, clinical trials of high quality, reports on NSAID safety and AEs, and treatment guidelines.     

NSAID-induced peptic ulcers and Helicobacter pylori infection: implications for patient management.

The conflicting data about the influence of Helicobacter pylori infection on the ulcer risk in patients receiving NSAIDs can be accounted for by the heterogeneity of study designs and the diversified host response to H. pylori. Factors that will affect the outcome include the choice of H. pylori diagnostic tests, previous ulcer complications, concurrent use of acid suppressants, NSAID-naive versus long-term users, low-dose aspirin (acetylsalicylic acid) versus non-aspirin NSAIDs and whether the result was derived from a pre-specified endpoint or post hoc subgroup analysis. Current evidence suggests that H. pylori eradication reduces the ulcer risk for patients who are about to start receiving NSAIDs but not for those who are already on long-term NSAID therapy. Since treatment with a proton pump inhibitor (PPI) worsens H. pylori-associated corpus gastritis, H. pylori should be tested for, and eradicated if present, before starting long-term prophylaxis with PPIs. Patients with H. pylori infection and a history of ulcer complications who require NSAIDs should receive concomitant PPIs or misoprostol after curing the infection. Among patients receiving low-dose aspirin, who have H. pylori infection and previous ulcer complications, long-term treatment with a PPI further reduces the risk of complicated ulcers if H. pylori eradication fails or if patients use concomitant non-aspirin NSAIDs. Current data on the gastric safety of COX-2 selective NSAIDs in H. pylori-infected patients are conflicting. Limited data suggest that the gastroduodenal sparing effect of rofecoxib is negated by H. pylori infection in patients who have had prior upper gastrointestinal events. In light of potential cardiovascular risk with COX-2 selective NSAIDs, it is important to weigh the potential adverse effects against the benefits for an individual patient.     

GP and Patient Perspectives on Treatment with Non-steroidal Anti-inflammatory Drugs for the Treatment of Pain in Osteoarthritis

Summary

Two nationwide surveys were carried out using an electronic poll of 2000 GPs and postal questionnaires were sent to 30000 patients with osteoarthritis (OA).

Both surveys found a high level of gastrointestinal (GI) side-effects in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). Almost every GP (97%) reported experience of patients suffering GI symptoms while on an NSAID, 38% reported patients who had been hospitalised and 4% reported patients who had died owing to NSAID-induced side-effects. Most GPs (92%) said they were concerned about GI safety when prescribing an NSAID and almost a third (32%) said they were concerned about litigation from patients who had experienced a bleed.

Use of NSAIDs in OA remained high, with 44% of GPs prescribing conventional NSAIDs to at least three quarters of their patients, 57% of GPs using simple analgesia and just 12% using a cyclo-oxygenase-2 (COX-2) selective inhibitor in over 74% of patients.

Some 45% of patients reported receiving NSAIDs compared with 43% on simple analgesia and 4% on COX-2 selective inhibitors.

Most GPs (69%) stated that their main therapeutic objective in using an NSAID to treat OA was to control pain without GI side-effects. Almost a quarter (24%) said they used low-dose NSAIDs in the hope that this would control pain without GI side-effects.

Dissatisfaction with treatment was the most common reason reported by GPs for patients on an NSAID to re-present, with 73% citing either breakthrough pain or incomplete pain relief as the most common reason for patient dissatisfaction. This mirrored the patients' perception, with 63% citing inadequate pain relief as their main reason for dissatisfaction with current painkillers compared to 17% who cited stomach upsets or irritation.

Patient and GP appear to be united in their concern at the GI risks of NSAID treatment. In the light of this and recent data on the efficacy, safety profile and cost-effectiveness of COX-2 selective inhibitors, GPs should re-examine their medical management of OA.     

GP and patient perspectives on treatment with non-steroidal anti-inflammatory drugs for the treatment of pain in osteoarthritis

Two nationwide surveys were carried out using an electronic poll of 2,000 GPs and postal questionnaires were sent to 30,000 patients with osteoarthritis (OA). Both surveys found a high level of gastro-intestinal (GI) side-effects in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). Almost every GP (97%) reported experience of patients suffering GI symptoms while on an NSAID, 38% reported patients who had been hospitalised and 4% reported patients who had died owing to NSAID-induced side-effects. Most GPs (92%) said they were concerned about GI safety when prescribing an NSAID and almost a third (32%) said they were concerned about litigation from patients who had experienced a bleed. Use of NSAIDs in OA remained high, with 44% of GPs prescribing conventional NSAIDs to at least three quarters of their patients, 57% of GPs using simple analgesia and just 12% using a cyclo-oxygenase-2 (COX-2) selective inhibitor in over 74% of patients. Some 45% of patients reported receiving NSAIDs compared with 43% on simple analgesia and 4% on COX-2 selective inhibitors. Most GPs (69%) stated that their main therapeutic objective in using an NSAID to treat OA was to control pain without GI side-effects. Almost a quarter (24%) said they used low-dose NSAIDs in the hope that this would control pain without GI side-effects. Dissatisfaction with treatment was the most common reason reported by GPs for patients on an NSAID to re-present, with 73% citing either breakthrough pain or incomplete pain relief as the most common reason for patient dissatisfaction. This mirrored the patients' perception, with 63% citing inadequate pain relief as their main reason for dissatisfaction with current painkillers compared to 17% who cited stomach upsets or irritation. Patient and GP appear to be united in their concern at the GI risks of NSAID treatment. In the light of this and recent data on the efficacy, safety profile and cost-effectiveness of COX-2 selective inhibitors, GPs should re-examine their medical management of OA.     

Concomitant use of gastroprotective drugs among elderly NSAID/COX-2 selective inhibitor users: a nationwide register-based study

BACKGROUND AND OBJECTIVES: NSAIDs and cyclo-oxgenase (COX)-2-selective inhibitors have been associated with gastrointestinal (GI) complications among the elderly. It is recommended that gastroprotective drugs (i.e. misoprostol, proton pump inhibitors or high doses of histamine H2 receptor antagonists) be taken concomitantly to prevent NSAID-induced GI complications among older people. However, there are concerns that the rate of concomitant use of gastroprotective drugs in elderly NSAID users is too low. This study aimed to investigate the extent to which elderly users of NSAIDs/COX-2-selective inhibitors are concurrently taking gastroprotective drugs, and to determine the factors associated with concomitant use of gastroprotective drugs and NSAIDs/COX-2-selective inhibitors in a nationwide population of older people. METHODS: We analysed data on age, sex and dispensed drugs for people>or=75 years of age registered in the Swedish Prescribed Drug Register from October to December 2005 (n=732,230) and located 41,626 NSAID/COX-2-selective inhibitor users. Logistic regression analysis was used for analysing the association between the use of different NSAIDs/COX-2-selective inhibitors and gastroprotective drugs, and between individual characteristics and use of gastroprotective drugs. RESULTS: Gastroprotective drugs were used by 22% of NSAID/COX-2-selective inhibitor users. Celecoxib, ketoprofen, meloxicam and etoricoxib were most commonly used concomitantly with gastroprotective drugs. Meloxicam and celecoxib were most strongly associated with gastroprotective drugs, after adjustment for age, sex and number of other drugs. Furthermore, NSAID/COX-2-selective inhibitor+oral corticosteroid users, NSAID/COX-2-selective inhibitor+selective serotonin reuptake inhibitor users and users of two or more NSAIDs/COX-2-selective inhibitors were more likely to concomitantly use gastroprotective drugs compared with NSAID/COX-2-selective inhibitor only users, after adjustment for age, sex and number of other drugs. However, users of NSAIDs/COX-2-selective inhibitors+anticoagulants (both warfarin and low-dose aspirin [acetylsalicylic acid]) did not show an increased likelihood of concomitant use of gastroprotective drugs, after adjustment for age, sex and number of other drugs. CONCLUSION: Our results indicate that gastroprotective drugs are not prescribed to elderly NSAID users according to guidelines. Furthermore, COX-2-selective inhibitors were used with gastroprotective drugs more often than were traditional NSAIDs. Greater awareness of factors contributing to NSAID/COX-2-selective inhibitor-induced GI complications is warranted, particularly with respect to advanced age and concurrent use of anticoagulants.     

NSAID induced gastrointestinal damage and designing GI-sparing NSAIDs

ABSTRACT

NSAIDs are widely used to treat pain and rheumatic conditions, but they induce adverse events in different body systems, although the major, most frequent events occur in the upper and lower gastrointestinal (GI) tracts.

Areas covered: This review is focused on damage caused by NSAIDs in the upper and lower GI tracts, the different mechanisms of damage and the GI-sparing NSAIDs designed to minimize adverse events based on understanding of these mechanisms.

Expert commentary: Among the new NSAIDs, COX-2 selective inhibitors have been extensively investigated, and some were approved for human use. Celecoxib demonstrated its safety for the entire GI tract, compared to traditional NSAIDs. However, coxibs, like traditional NSAIDs, are toxic to the cardiovascular (CV) system. Other GI-sparing agents include nitric oxide-NSAIDs and phosphatidylcholine-associated NSAIDs. Testing in animal models and humans they showed GI advantages over the parent NSAID compounds, but none obtained regulatory approval or were further investigated. Hydrogen sulfide-releasing NSAIDs are currently under clinical development, and more data are needed before clinical use. Alternative therapies, such as modulating gut microbiota, are being explored. Currently, clinicians must continue prescribing traditional NSAIDs or coxibs, associated with/without proton pump inhibitor therapy, based on the presence of GI/CV risk factors.     

Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis

Rofecoxib is a selective cyclo-oxygenase (COX)-2 inhibitor which has little or no effect on the COX-1 isoenzyme at doses up to 1000 mg/day. Rofecoxib has greater selectivity for COX-2 than celecoxib, meloxicam, diclofenac and indomethacin. In well-controlled clinical trials, rofecoxib 12.5 to 500 mg/day has been evaluated for its efficacy in the treatment of osteoarthritis, acute pain and rheumatoid arthritis [lower dosages (5 to 125 mg/day) were generally used in the chronic pain indications]. In the treatment of patients with osteoarthritis, rofecoxib was more effective in providing symptomatic relief than placebo, paracetamol (acetaminophen) and celecoxib and was similar in efficacy to ibuprofen, diclofenac, naproxen and nabumetone. Overall, both the physician's assessment of disease status and the patient's assessment of response to therapy tended to favour rofecoxib. In patients with postsurgical dental pain, pain after spinal fusion or orthopaedic surgery, or primary dysmenorrhoea, rofecoxib provided more rapid and more sustained pain relief and reduced requirements for supplemental morphine use after surgery than placebo. Rofecoxib was more efficacious than celecoxib in patients with acute dental pain and pain after spinal fusion surgery, although celecoxib may have been used at a subtherapeutic dose. In comparison with traditional nonsteroidal anti-inflammatory drugs (NSAIDs) ibuprofen, diclofenac and naproxen sodium, rofecoxib was similar in efficacy in the treatment of acute pain. Although naproxen sodium provided more rapid pain relief than rofecoxib in patients with primary dysmenorrhoea, the reverse was true after orthopaedic surgery: rofecoxib provided more rapid pain relief and less supplemental morphine was needed. Rofecoxib was as effective as naproxen in providing symptomatic relief for over 8700 patients with rheumatoid arthritis. Compared with traditional NSAID therapy, rofecoxib had a significantly lower incidence of endoscopically confirmed gastroduodenal ulceration and, in approximately 13,000 patients with osteoarthritis and rheumatoid arthritis, a lower incidence of gastrointestinal (GI) adverse events. Rofecoxib was generally well tolerated in all indications with an overall tolerability profile similar to traditional NSAIDs. The most common adverse events in rofecoxib recipients were nausea, dizziness and headache. In conclusion, rofecoxib is at least as effective as traditional NSAID therapy in providing pain relief for both chronic and acute pain conditions. Rofecoxib provides an alternative treatment option to traditional NSAID therapy in the management of symptomatic pain relief in patients with osteoarthritis. Initial data from patients with primary dysmenorrhoea and postoperative pain are promising and further trials may confirm its place in the treatment of these indications. Rofecoxib has also shown promising results in patients with rheumatoid arthritis and is likely to become a valuable addition to current drug therapy for this patient population. Importantly, rofecoxib is associated with a lower incidence of GI adverse events than traditional NSAIDs making it a primary treatment option in patients at risk of developing GI complications or patients with chronic conditions requiring long term treatment.     

Nonsteroidal anti-inflammatory drugs versus selective COX-2 inhibitors in the upper gastrointestinal tract

There are enough basic data supporting the use of coxibs with regard to the upper GI tract in patients with the need for continuous treatment of joint pain. The clinical studies available clearly show that coxibs induce fewer lesions and complications in volunteers and in patients when compared with NSAIDs. However, in Helicobacter pylori- positive patients the advantage seems less clear. The combination of NSAID plus PPI is not worse with regard to duodenal ulcers and recurrent clinical complications and is more cost effective than the use of coxibs. Similarly, with the concomitant use of aspirin even in low doses no major advantage of coxibs has been demonstrated. The combination of coxibs and PPI in high-risk patients needs to be studied. It is unclear at the moment how important are the changes in the lower GI tract. Considering the current controversy regarding cardiovascular events, there is no major reason to prefer coxibs to conventional NSAID plus PPI in patients needing long-term treatment.     

GI risk and risk factors of NSAIDs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used drugs in the United States. Ulcers are found at endoscopy in 15% to 30% of patients using NSAIDs regularly. The annual incidence of upper gastrointestinal (GI) complications such as bleeding with regular NSAID use is approximately 1.0% to 1.5%, whereas the annual rate of upper GI clinical events (complicated plus symptomatic uncomplicated ulcers) is approximately 2.5% to 4.5%. Upper GI symptoms such as dyspepsia also occur in many patients taking NSAIDs--at a relative risk of about 1.5 to 2 compared with that in patients without NSAID use. Important risk factors for upper GI clinical events include older age, prior history of upper GI events, use of corticosteroids or anticoagulants, and high-dose or multiple NSAIDs (including NSAID plus low-dose aspirin). Lower GI clinical events such as bleeding may also occur with NSAIDs, although they are less common and less well studied than upper GI events. The decision to employ a protective strategy to decrease NSAID-associated GI clinical events is based on risk stratification. Strategies employed include the use of non-NSAID analgesics, use of lowest effective dose of NSAID, use of medical cotherapy (eg, proton pump inhibitor, misoprostol), or use of coxibs.     

Lumiracoxib: the evidence of its clinical impact on the treatment of osteoarthritis

INTRODUCTION: The symptoms of osteoarthritis (OA) include joint pain, stiffness, and a reduced ability to perform normal daily activities, which result in decreased quality of life. There is currently no known cure or means of preventing the progression of joint damage due to OA. Therefore, treatment focuses on the control of symptoms, including the use of various agents [including nonselective and selective nonsteroidal antiinflammatory drugs (NSAIDs)] to provide pain relief and reduce inflammation. Lumiracoxib is a selective cyclooxygenase-2 (COX-2) inhibitor for the treatment of OA. AIMS: To review the evidence for the treatment of OA with lumiracoxib. EVIDENCE REVIEW: There is evidence that lumiracoxib reduces the pain and stiffness associated with OA, and is as effective as nonselective NSAIDs, and the COX-2 inhibitor celecoxib. There is some evidence that lumiracoxib treatment results in a lower incidence of upper gastrointestinal (GI) ulcer complications compared with nonselective NSAIDs. However, evidence suggests that there is no GI benefit in patients receiving concomitant aspirin medication. With the exception of GI ulcers, the evidence indicates that lumiracoxib has a tolerability profile similar to nonselective NSAIDs: low risk of cardiovascular (CV) events and a low incidence of edema. Changes in liver function occur in some patients, largely at doses >100 mg. The cost effectiveness of lumiracoxib compared with nonselective NSAIDs remains to be determined. CLINICAL VALUE: Lumiracoxib is an alternative treatment option for OA which provides effective pain relief without the GI complications associated with nonselective NSAIDs, and with a low risk of CV events. Lumiracoxib is contraindicated in patients with current, previous, or at risk of, hepatic impairment.