Safety Of Cyclooxygenase-2 Inhibitors Research Articles

Efficacy and safety of cyclooxygenase 2 inhibitors for desmoid tumor management: a systematic review.

ABSTRACTThe efficacy and safety of cyclooxygenase 2 (COX2) inhibitors for the treatment of desmoid-type fibromatosis (DF) are unclear. Therefore, we systematically reviewed related literature to assess the efficacy and safety of COX2 inhibitors for DF treatment. We searched pertinent literature between January 1999 and August 2017 to identify relevant studies using the keywords “Fibromatosis, aggressive” and “Cyclooxygenase inhibitors.” Thereafter, we screened and determined the quality of the studies using the Grading of Recommendations Assessment, Development, and Evaluation system and extracted the article data. The critical outcomes selected were the efficacy and adverse effects of COX2 inhibitors. Efficacy was evaluated in terms of clinical benefit when patients showed complete response, partial response, and stable disease. Thirty-one articles were identified from the database search, and one was identified through the reviewers’ manual search. Finally, we retrieved six studies, including three case reports, comprising 89 patients after the first and second screenings. Fifty-three patients were excluded because three studies were reported from the same institution; hence, in total, 36 patients were included. Clinical benefit was noted in 64% of the patients. Three adverse effects were identified from the records of the six extracted studies. The strategy of watchful waiting using COX2 inhibitors with few side effects is weakly recommended for DF, especially DF patients with pain.

Safety of Cyclooxygenase-2 Inhibitors in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

ObjectiveOur aim was to assess the safety of cyclooxygenase-2 (COX-2) inhibitors in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials.MethodsA comprehensive literature search was undertaken in the databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with COX-2 inhibitors in patients with OA were eligible for inclusion. Two authors appraised titles, abstracts and full-text papers for suitability and then assessed the studies for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective outcomes reporting. The primary outcomes of interest were gastrointestinal disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, hepatobiliary disorders, renal and urinary disorders, as well as overall severe and serious AEs, drug-related AEs and mortality. Secondary outcomes were withdrawals due to AEs (i.e. the number of participants who stopped the treatment due to an AE) and total number of AEs (i.e. the number of patients who experienced any AE at least once).ResultsDatabase searches identified 2149 records from which, after exclusions, 40 trials were included in the meta-analysis. The use of COX-2 inhibitors in OA was associated with a significant increased risk of drug-related AEs compared with placebo (relative risk (RR) 1.26, 95% CI 1.09–1.46; I2 = 24%). The risk of upper gastrointestinal complications (including dyspepsia, gastritis and heartburn) was significantly increased with COX-2 inhibitors versus placebo (RR 1.19, 95% CI 1.03–1.38; I2 = 0%), particularly for abdominal pain, which increased by 40% with COX-2 inhibitors (RR 1.40, 95% CI 1.08–1.80; I2 = 0%). The risk of hypertension increased by 45% overall (RR 1.45, 95% CI 1.01–2.10; I2 = 25%); however, when rofecoxib was removed from the analysis the risk of hypertension in the COX-2 inhibitor group was no longer significant (RR 1.21, 95% CI 0.80–1.83; I2 = 20%). The overall risk of heart failure and edema was increased by nearly 70% with COX-2 inhibitors versus placebo (RR 1.68, 95% CI 1.22–2.31; 0%) and this level of risk did not change appreciably when rofecoxib was excluded (RR 1.67, 95% CI 1.21–2.29; 0%).ConclusionsIn our analysis, COX-2 inhibitors were associated with an increased risk of upper gastrointestinal AEs, especially abdominal pain. We also found an increased risk of cardiovascular AEs with COX-2 inhibitors, namely hypertension, heart failure and edema.Electronic supplementary materialThe online version of this article (10.1007/s40266-019-00664-x) contains supplementary material, which is available to authorized users.

Tolerability of selective cyclooxygenase 2 inhibitors used for the treatment of rheumatological manifestations of inflammatory bowel disease.

Tolerability of selective cyclooxygenase 2 inhibitors used for the treatment of rheumatological manifestations of inflammatory bowel disease.

The safety of COX-2 inhibitors

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed drugs worldwide, but they can cause serious gastrointestinal (GI) side effects. NSAIDs are capable of damaging the whole gastrointestinal tract. Cyclooxygenase-2 (COX-2) inhibitors (coxibs) have been developed with the aim of maintaining the anti-inflammatory benefits but reducing gastrotoxicity. There is a good evidence that these drugs effectively prevent gastroduodenal ulcers and ulcer complications. Little is known about the side effects of these agents in the small and large intestine. There is an increasing evidence that COX-2 is constitutively expressed in the gastrointestinal tract and is important for the maintenance of bowel integrity. There have also been growing concerns about the potential for coxibs to increase the frequency of adverse cardiovascular events. The purpose of this review is to summarize recent knowledge about the safety profile of selective COX-2 inhibitors.

Valdecoxib for Postoperative Pain Management After Cesarean Delivery: A Randomized, Double-Blind, Placebo-Controlled Study

Nonsteroidal anti-inflammatory drugs (NSAIDs) help to relieve pain following cesarean delivery, but concern over their use has arisen because of the potential for antiplatelet and gastrointestinal side effects as well as breast-feeding problems. Cyclooxygenase-2 (COX-2) inhibitors also provide analgesia in this setting, and inhibition of platelets is comparatively minimal. This randomized, double-blind, placebo-controlled study examined the analgesic efficacy and safety of valdecoxib, a selective COX-2 inhibitor, in women given spinal anesthesia for elective cesarean section. General concern about the safety of COX-2 inhibitors led to discontinuance of the study after 47 healthy ASA physical status I-II women had completed it. Participants were randomized to receive 20 mg of valdecoxib or placebo orally every 12 hours for 72 hours postoperatively. Pain-whether at rest or on movement-was comparable in the valdecoxib and control groups. Pain scores, whether estimated verbally on a 0-to-10 scale or using a categorical rating scale (none, mild, moderate, severe), declined over time at similar rates in the two groups. There were no group differences in the need for intravenous morphine, the time to the first request for pain relief, or total analgesic use in morphine equivalents. Side effects including vaginal bleeding, nausea, sedation, and hypertension were similarly frequent in the two groups. Most patients were satisfied (or very satisfied) with their analgesia. Neither success in breast-feeding nor functional activity was a function of analgesia. The investigators recommend that valdecoxib not be used routinely to relieve postcesarean pain because it does not provide superior analgesia and because of possible thrombotic cardiovascular events. Although it is not clear whether these findings can be applied to all COX-2 inhibitors, NSAIDs remain the preferred analgesic for relieving pain following cesarean delivery.

A European??s Perspective of COX-2 Drug Safety

Regulators require less evidence to take action on drug safety concerns than would be required to grant drug efficacy claims. Such an asymmetrical view of risk points to the need for large studies to judge the safety of novel medicines compared with standard therapy as smaller sample sizes might produce unreliable and misleading toxicity signals. Large studies conducted in the classical manner are expensive and difficult to conduct. In addition, tight entry criteria and strictly protocolized care results in such trials having poor external validity. If the safety of medicines is to be judged efficiently, novel, easier to conduct, and less-expensive solutions are required. Such trials could have improved external validity were they incorporated into normal care. This paper discusses the safety of cyclooxygenase-2 inhibitors and describes the sort of studies that could be carried out to gather better safety information on their use versus standard nonsteroidal anti-inflammatory drugs.

Lumiracoxib, a highly selective COX-2 inhibitor

Lumiracoxib (Prexige®, Novartis AG) is a highly selective inhibitor of cyclooxygenase-2 that has been approved in 22 countries including the UK for analgesic therapy in chronic and acute pain. For patients with osteoarthritis, the recommended initial dose is 100 or 200 mg once daily, in one or two divided doses. In patients with primary dysmenorrhea, or following dental or orthopedic surgery with moderate-to-severe acute pain, the recommended dose is 400 mg once daily. The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) tested the efficacy and gastrointestinal safety of the drug against two traditional nonselective nonsteroidal anti-inflammatory drugs, naproxen and ibuprofen. The results from this trial demonstrated that lumiracoxib reduces gastrointestinal ulcer complication rates by 66% overall and 79% among nonaspirin users in a population without gastroprotection. Lumiracoxib was not associated with a statistically significant difference in cardiovascular morbidity and mortality compared with nonselective nonsteroidal anti-inflammatory drugs. However, in view of the ongoing debate about the safety of cyclooxygenase-2 inhibitors, the use of this drug class should be limited to patients with increased risk of gastrointestinal complications until results of randomized trials in cardiovascular high-risk populations are published.

Safety of COX-2 inhibitors in asthma patients with aspirin hypersensitivity.

To review the safety of cyclooxygenase-2 (COX-2) inhibitors in asthma patients with aspirin hypersensitivity. Clinical studies were identified using MEDLINE (1966-September 2002). Key search terms included cyclooxygenase inhibitors, aspirin, asthma, and hypersensitivity. English-language articles were identified and included. References from the identified articles were also reviewed. The literature provides information regarding the safety of COX-2 inhibitors in asthma patients with aspirin-exacerbated respiratory disease (AERD). The mechanism of AERD involves inhibition of cyclooxygenase, particularly COX-1. Inhibition of COX-1 causes an increased production of certain inflammatory mediators, which results in the reactions seen with AERD. Considering this mechanism, COX-2 inhibitors may be an alternative to aspirin or nonsteroidal antiinflammatory drugs (NSAIDs) in a patient with AERD. This article analyzes 4 studies to evaluate the safety of COX-2 inhibitors in this population. The 4 studies evaluated included a total of 172 patients with AERD. All patients included demonstrated intolerance to aspirin or NSAIDs and tolerated the selective COX-2 inhibitor administered. COX-2 inhibitors provide a potentially safe alternative for treatment of inflammatory conditions in patients with AERD.

Outcomes studies of the gastrointestinal safety of cyclooxygenase-2 inhibitors.

Short-term endoscopic studies of the highly selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) rofecoxib and celecoxib have shown that these agents are well tolerated and have efficacy equivalent to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) with fewer adverse effects on the upper gastrointestinal (GI) tract. These studies are limited, however, as the detection of endoscopic lesions is not well correlated with symptomatic ulcers and ulcer complications. Outcomes studies of the GI safety are, therefore, essential to understanding how coxibs are likely to perform in a clinical practice setting. Four large outcomes studies (Vioxx Gastrointestinal Outcomes Research, VIGOR; Assessment of Difference Between Vioxx and Naproxen to Ascertain Gastrointestinal Tolerability and Effectiveness trial, ADVANTAGE; Celecoxib Long-term Arthritis Safety Study, CLASS; and the Successive Celecoxib Efficacy and Safety Studies, SUCCESS) examined the GI safety of rofecoxib and celecoxib in over 39,000 patients with osteoarthritis or rheumatoid arthritis. Results of these studies showed that patients taking a supratherapeutic dose of rofecoxib or celecoxib had significantly lower rates of GI-related adverse events than those taking a nonselective NSAID (naproxen, ibuprofen, or diclofenac). Reduced risk of upper GI events was seen in patients with multiple risk factors and in patients using low-dose aspirin and corticosteroids concomitantly with a coxib. Results of large outcomes studies provide support for the COX-2 hypothesis and demonstrate the long-term safety and tolerability of coxibs.