Nonsteroidal Anti-inflammatory COX-2 Research Articles

Exploring COX-Independent Pathways: A Novel Approach for Meloxicam and Other NSAIDs in Cancer and Cardiovascular Disease Treatment.

As a fundamental process of innate immunity, inflammation is associated with the pathologic process of various diseases and constitutes a prevalent risk factor for both cancer and cardiovascular disease (CVD). Studies have indicated that several non-steroidal anti-inflammatory drugs (NSAIDs), including Meloxicam, may prevent tumorigenesis, reduce the risk of carcinogenesis, improve the efficacy of anticancer therapies, and reduce the risk of CVD, in addition to controlling the body's inflammatory imbalances. Traditionally, most NSAIDs work by inhibiting cyclooxygenase (COX) activity, thereby blocking the synthesis of prostaglandins (PGs), which play a role in inflammation, cancer, and various cardiovascular conditions. However, long-term COX inhibition and reduced PGs synthesis can result in serious side effects. Recent studies have increasingly shown that some selective COX-2 inhibitors and NSAIDs, such as Meloxicam, may exert effects beyond COX inhibition. This emerging understanding prompts a re-evaluation of the mechanisms by which NSAIDs operate, suggesting that their benefits in cancer and CVD treatment may not solely depend on COX targeting. In this review, we will explore the potential COX-independent mechanisms of Meloxicam and other NSAIDs in addressing oncology and cardiovascular health.

Royal Jelly, A Super Food, Protects Against Celecoxib-Induced Renal Toxicity in Adult Male Albino Rats.

Celecoxib is a COX-2 nonsteroidal anti-inflammatory drug (NSAID). It is widely used for the treatment of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. This study aimed to explore the effect of long-term administration of celecoxib on kidney of male albino rats, and to study the potential effect of treatment discontinuation on such tissues. The study also examined the alleged ameliorative effect of royal jelly (RJ). Fifty, male albino rats were divided into 5 equal groups; 10 each. Group 1: rats received no drug (control group). Group 2: rats received celecoxib (50 mg/kg/day, orally for 30 successive days). Group 3: rats received celecoxib (50 mg/kg/day, orally) and royal jelly (300 mg/kg/day, orally) for 30 successive days. Group 4: rats received celecoxib for 30 successive days, then rats were left untreated for another 30 days. Group 5: rats received celecoxib and RJ for 30 successive days, then rats were left untreated for another 30 days. Long-term celecoxib administration caused significant elevation in kidney function tests, with ameliorative effects of RJ against celecoxib-induced renal toxicity. Long-term celecoxib administration caused renal toxicity in male albino rats, with ameliorative effects of RJ.

Involvement of opioid antagonists on COX-2 activity

Pain is a complex process involving complex molecular and cellular mechanisms and pharmacotherapeutic strategies including nonsteroidal anti-inflammatory drugs (NSAIDs). The main mechanism of action of them, both for their adverse and therapeutic effects, is the inhibition of cyclooxygenases (COXs), one of its isoforms is COX-2 with selective inhibitors such as celecoxib, rofecoxib, and etoricoxib. The objective of this study was to evaluate the nociceptive interaction of COX-2 NSAIDs with other drugs due to the scarce information available in this regard. Antinociception was assessed by the formalin hind paw test evaluated from dose-response curves obtained before and after the i.p. administration of 1,0 mg/kg of naltrexone (NTX), or naltrindole (NTI), or nor-binaltorphimine (nor-BNI) in the assay, using at least 6-8 animals for each of at least 4 doses. Analgesic ratio (AR) expressed as the relation between ED50 of phase II / phase I of FHP indicates the following order of relative potency: celecoxib > parecoxib > etoricoxib. Administration of naltrexone or naltrindole induced a significant reduction of the analgesic activity of celecoxib, etoricoxib and parecoxib, reflected by an increase in the respective ED50 in both phases of FHP assay. However, norbinaltorphimine lack of effect. The results of the work demonstrate that opioid receptors MOR and DOR play a key role in coxib-induced antinociception in the FHP trial and while the KOR opioid receptor seems not to be involved in this antinociception.

Selective COX-2 inhibitor continues to be a safe alternative in patients with nonselective NSAIDs hypersensitivity

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause different types of allergic and pseudo allergic reactions. This results in difficulties in clinical practice. Most cases of NSAID hypersensitivity are mediated by the inhibition of cyclooxygenase-1 enzyme (COX-1), which results in depletion of the protective prostaglandin E2, and promotes the unrestrained synthesis of inflammatory mediators from mast cells. Selective COX-2 inhibitors are considered safe alternatives in patients with NSAID allergy, although hypersensitivity reactions to COX-2 inhibitors have also been reported. Our study aimed to report the experience in Qatar for using COX2 inhibitors as an alternative treatment for nonselective NSAID allergy.Methods: Data of patients who underwent open challenge with a single dose of oral celecoxib 200 mg were retrieved from the procedure log of the Allergy and immunology Division in Hamad medical corporation, Doha, Qatar, from 2013 to 2022. The challenge was considered positive if the patient developed cutaneous or respiratory symptoms.Results: A total of 31 patients were identified; 4 with a history of celecoxib allergy. The remaining 27 (23 females and 4 males); with mean ( ± SD, range) age of 42 ( ± 12, 20–65) years had hypersensitivity to one (n = 11) or more than one (n = 16) nonselective NSAID, manifested as cutaneous, respiratory, or anaphylactic symptoms. Those 4 patients with celecoxib allergy were challenged and only one with a historical reaction of anaphylaxis developed anaphylaxis during the challenge. Celecoxib was well tolerated in all 27 patients with hypersensitivity reactions to nonselective NSAIDs. Also, patients were contacted by telephone call at 24 hours and after 1 week with no evidence of delayed reactions.Conclusions: Selective COX-2 and nonselective NSAIDs have similar overall efficacy as analgesic, anti-inflammatory, and antipyretic agents. Hypersensitivity reaction to COX-2 inhibitors has been reported; however, it is rare. So, it is safer to challenge the patients with COX-2 inhibitors before prescribing them as alternative medication in patients with Nonselective NSAID allergies. We plan to conduct a single-/double-blind placebo-controlled study for more patients, especially using graded challenges for high-risk profile candidates. Also, it may be of significance to test more than one type of selective COX-2 to avoid drug-specific reactions.

Non-steroidal anti-inflammatory drugs for acute gout.

Non-steroidal anti-inflammatory drugs for acute gout.

Meloxicam in pain syndrome treatment of comorbid diseases patients

The issue nonsteroidal anti-inflammatory drugs (NSAIDs) use safety is associated with a high frequency of adverse events (AEs) from the gastrointestinal tract and cardiovascular risks. Patients with lower back pain (LBP) and osteoarthritis (OA), as a rule, have comorbid diseases, such as arterial hypertension (AH), coronary heart disease (CHD), gastrointestinal tract (GIT) diseases, which significantly complicates the appointment of NSAIDs. The main guideline in NSAIDs appointment is the selective ability to inhibit cyclooxygenase-1 and -2 (COX). The ratio of the activity of NSAIDs when blocking COX-1/COX-2 allows us to judge their potential toxicity. And, then higher the selectivity of NSAIDs, then lower its toxicity. For example, the ratio of COX-1/COX-2 in meloxicam is 0.33, diclofenac – 2.2, tenoxicam – 15, piroxicam – 33, indomethacin – 107. To the predominantly selective COX-2 NSAIDs include meloxicam, which has little effect on the GIT, the lowest relative risk (RR) of complications from the cardiovascular system (CVS). The therapeutic efficacy of meloxicam is comparable to piroxicam and diclofenac. A number of studies have shown the high efficacy of meloxicam, both with per oral (p/o) administration (7.5–15 mg/d), and with intramuscular (i/m) administration (1.5 ml), and when injected into trigger zones. Both with p/o and the injectable form of meloxicam has minimal GIT AEs and absence local reaction in the injection area. The drug can be recommended both as a combination therapy and prescribed in monotherapy.

Prescription Habits Related to Chronic Pathologies of Elderly People in Primary Care in the Western Part of Romania: Current Practices, International Recommendations, and Future Perspectives Regarding the Overuse and Misuse of Medicines

The European Commission’s 2019 report regarding the state of health profiles highlighted the fact that Romania is among the countries with the lowest life expectancy in the European Union. Therefore, the objectives of the present study were to assess the current prescription habits of general physicians in Romania related to medicines taken by the elderly population for chronic conditions in both urban and rural setting and to discuss/compare these practices with the current international recommendations for the elderly (American—Beers 2019 criteria and European—STOPP/START v.2, 2015 criteria). A total of 2790 electronic prescriptions for chronic pathologies collected from 18 community pharmacies in the western part of Romania (urban and rural zones) were included. All medicines had been prescribed by general physicians. We identified the following situations of medicine overuse: 15% of the analyzed prescriptions involved the use of nonsteroidal anti-inflammatory drugs (NSAIDs) for >2 weeks, 12% involved the use of a proton-pump inhibitor (PPI) for >8 weeks, theophylline was the bronchodilator used as a monotherapy in 3.17% of chronic obstructive pulmonary disease cases, and zopiclone was the hypnotic drug of choice for 2.31% of cases. Regarding the misuse of medicines, 2.33% of analyzed prescriptions contained an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II receptor blocker (ARB) for patients with renal failure in addition to vitamin K antagonists (AVKs) and NSAIDs in 0.43% of cases. Prescriptions for COX2 NSAIDs for periods longer than 2 weeks for patients with cardiovascular disorders accounted for 1.33% of prescriptions, and trihexyphenidyl was used as a monotherapy for patients with Parkinson’s disease in 0.18% of cases. From the included medical prescriptions, 32.40% (the major percent of 2383 prescriptions) had two potentially inappropriate medications (PIMs). Rural zones were found to be risk factor for PIMs. Decreasing the chronic prescription of NSAIDs and PPIs, discontinuing the use of hypnotic drugs, and avoiding potentially harmful drug–drug associations will have long term beneficial effects for Romanian elderly patients.

Pain management after complex spine surgery: A systematic review and procedure-specific postoperative pain management recommendations.

BACKGROUNDComplex spinal procedures are associated with intense pain in the postoperative period. Adequate peri-operative pain management has been shown to correlate with improved outcomes including early ambulation and early discharge.OBJECTIVESWe aimed to evaluate the available literature and develop recommendations for optimal pain management after complex spine surgery.DESIGN AND DATA SOURCESA systematic review using the PROcedure SPECific postoperative pain managemenT methodology was undertaken. Randomised controlled trials and systematic reviews published in the English language from January 2008 to April 2020 assessing postoperative pain after complex spine surgery using analgesic, anaesthetic or surgical interventions were identified from MEDLINE, EMBASE and Cochrane Databases.RESULTSOut of 111 eligible studies identified, 31 randomised controlled trials and four systematic reviews met the inclusion criteria. Pre-operative and intra-operative interventions that improved postoperative pain were paracetamol, cyclo-oxygenase (COX)-2 specific-inhibitors or non-steroidal anti-inflammatory drugs (NSAIDs), intravenous ketamine infusion and regional analgesia techniques including epidural analgesia using local anaesthetics with or without opioids. Limited evidence was found for local wound infiltration, intrathecal and epidural opioids, erector spinae plane block, thoracolumbar interfascial plane block, intravenous lidocaine, dexmedetomidine and gabapentin.CONCLUSIONSThe analgesic regimen for complex spine surgery should include pre-operative or intra-operative paracetamol and COX-2 specific inhibitors or NSAIDs, continued postoperatively with opioids used as rescue analgesics. Other recommendations are intra-operative ketamine and epidural analgesia using local anaesthetics with or without opioids. Although there is procedure-specific evidence in favour of intra-operative methadone, it is not recommended as it was compared with shorter-acting opioids and due to its limited safety profile. Furthermore, the methadone studies did not use non-opioid analgesics, which should be the primary analgesics to ultimately reduce overall opioid requirements, including methadone. Further qualitative randomised controlled trials are required to confirm the efficacy and safety of these recommended analgesics on postoperative pain relief.

Targeting nerve growth factor, a new option for treatment of osteoarthritis: a network meta-analysis of comparative efficacy and safety with traditional drugs.

Objective: Osteoarthritis (OA) is the most common joint disease and leading cause of pain and disability in the elderly population. Most guidelines recommend the use of non-steroidal anti-inflammatory drugs (NSAIDs) and opioids for the non-operative treatment of OA. Monoclonal nerve growth factor (NGF) antibodies are new drugs with the potential to provide pain relief and functional improvement in OA. We compared the efficacy (pain reduction and functional improvement), and safety of monoclonal NGF antibodies with NSAIDs and opioids in the treatment of OA with a Bayesian network meta-analysis.Results: 38 articles, comprising 41 trials and 20489 patients with OA were included. Overall from the network meta-analysis, anti-NGFs were the most effective drugs for pain relief (Standardized Mean Difference or SMD compared with placebo 4.25, 95% CI 2.87 to 5.63, Surface Under the Cumulative RAnking curve or SUCRA=93.7%) and for functional improvement (SMD 4.90, 95% CI 3.46 to 6.33, SUCRA=98.3%). Although anti-NGFs were associated with higher risk of peripheral sensation abnormality (paresthesia and pruritus), they were not associated with higher risk of other AEs (headaches and nausea) or with higher withdrawal rates related to AEs.Conclusions: Monoclonal NGF antibodies provide significantly greater pain relief and functional improvement in OA compared to NSAIDs and opioids. Monoclonal NGF antibodies are not associated with severe AEs. More studies are needed to confirm these findings.Methods: PubMed, CNKI, Web of Science, Scopus, Embase and Cochrane Library databases were searched for relevant studies (OA treated with anti-NGFs, opioids, selective COX-2 inhibitors or NSAIDs) published between January 1999 to January 2020. Bayesian network and conventional meta-analyses were conducted. Pain relief, functional improvement and AEs were assessed.

Descriptive Analysis of Cross-Reactive Anaphylaxis as a Different Clinical Subtype of Nonsteroidal Anti-Inflammatory Drug (NSAID) Hypersensitivity

Introduction: The European Network of Drug Allergy and the European Academy of Allergy and Clinical Immunology have classified hypersensitivity reactions induced by nonsteroidal anti-inflammatory drugs (NSAIDs) into 5 phenotypes according to the pathophysiology, clinical manifestations, number of drugs involved, and the presence of underlying diseases. This classification does not include anaphylaxis as part of NSAID cross-reactivity. The objective of this study was to characterize a group of patients with anaphylactic NSAID cross-reactivity. Method: This was a retrospective, descriptive, observational study. Patients who developed anaphylaxis to one NSAID plus another acute reaction (anaphylactic or not) to at least one other NSAID of a different chemical group were included. Demographic and clinical characteristics and the diagnostic approach were studied. Results: A total of 38 patients were included, 28 (73.7%) of whom were women. The mean age was 40 ± 17.7 years. The main organs affected in the anaphylactic reaction were the skin and the respiratory system, occurring in 35 (92.1%) and 33 (86.8%) patients, respectively. Thirty-two (84.3%) patients presented with cutaneous and respiratory involvement simultaneously. The main anti-inflammatory agent involved in anaphylactic reactions was acetylsalicylic acid in 9 (23.7%) patients, followed by dipyrone in 8 (21.1%). The most frequent allergic comorbidity was rhinitis in 20 (52%) patients. Skin tests were performed in 15 (39.5%) patients, showing positivity in 12 (80%), mainly to mites. A total of 36 of 38 patients were challenged with alternative drugs, and 35 (97.2%) tolerated meloxicam and/or etoricoxib. Conclusion: In the present study, NSAID cross-anaphylaxis was more frequent in women, and acetylsalicylic acid and dipyrone were the main triggers. Rhinitis was the main allergic comorbidity, and there was a high incidence of atopy. The majority tolerated selective COX-2 NSAIDs.

PIH21 EFFICACY AND SAFETY OF IMRECOXIB, CELECOXIB AND DICLOFENAC IN PATIENTS WITH OSTEOARTHRITIS: A NETWORK META-ANALYSIS

Non-steroidal anti-inflammatory drug (NSAIDs) are widely prescribed for relief of the symptoms of osteoarthritis. The efficacy and safety of different NSAIDs are still studied, especially between the cyclooxygenase-2 inhibitor (COX-2) and non-selective NSAIDs (ns-NSAIDs). A new Cox-2 NSAID called imrecoxib was approved by China Food and Drug Administration in 2011, and the efficacy and safety compared with other NSAIDs stay unexplored. This study is aimed to access the overall efficacy and safety of imrecoxib, celecoxib (COX-2), diclofenac (ns-NSAIDs) based on the existing literature. 25 randomized controlled trials (RCTs) published from the time of database establishment to Nov 19, 2019 were systematically reviewed in 8 databases, which compared any of imrecoxib, celecoxib, diclofenac and placebo. The primary outcome was the mean change of different drugs on patient’s pain score (VAS mm); the sencondary outcomes were the rate of total adverse events and gastrointestinal (GI) events. The rate of adverse events was adjusted with standardized doses. Literature with less than 4-week treatment duration were excluded. Celecoxib (standardized mean difference [SMD] -0.52 [95%CI -0.96 to -0.09]) was significantly more effective than placebo, while imrecoxib (-0.67 [-1.97 to 0.63]) and diclofenac (-0.49 [-1.06 to 0.08]) were more effective than placebo. Celecoxib (odds ratio [OR] 1.04 [95%CI 0.84 to 1.28]) and diclofenac (1.27 [0.89 to 1.81]) were more unsafe than placebo, whereas imrecoxib was not. Similar results could be found in the analysis of the rate of GI events, celecoxib (1.05 [0.83 to 1.32]) and diclofenac (1.39 [0.95 to 2.03]) were more unsafe than placebo. It seemed that imrecoxib was associated with better efficacy and fewer adverse events. Since there were sparse RCTs have been reported for imrecoxib, the conclusion should be adopted with caution. Meanwhile, a nocebo effect was observed in the analysis of the rate of adverse events, which need further discussion.

PHARMACOKINETICS OF ORAL MAVACOXIB IN CARIBBEAN FLAMINGOS (PHOENICOPTERUS RUBER RUBER).

Mavacoxib is a selective cyclooxygenase-2 nonsteroidal anti-inflammatory drug that has been used for management of osteoarthritis and other inflammatory conditions in dogs. The main advantage of mavacoxib over other nonsteroidal anti-inflammatory drugs is its longer plasma half-life, leading to decreased dosing frequency. This study determined the pharmacokinetics of mavacoxib in Caribbean flamingos (Phoenicopterus ruber ruber) after a single-dose oral administration of 6 mg/kg (n = 6). Plasma mavacoxib concentrations were determined using liquid chromatography with mass spectrometry, and pharmacokinetic analysis was performed using noncompartmental methods. Mean peak plasma concentration (Cmax) was (mean; range) 2.97 (2.19--4.06) µg/ml; mean time to peak plasma concentration (Tmax) was 18.68 (4.00-48.00) hr; mean area under the curve (AUC) was 455 (292-637) hr * µg/ml; and mean terminal half-life (T1/2) was 74.47 (49.57-161.43) hr. Based on the results of this study, mavacoxib dosed at 6 mg/kg orally in Caribbean flamingos reaches plasma concentrations above the therapeutic concentration established for dogs, but further studies are needed to determine appropriate dosing recommendations in flamingos.

Abstract P372: U.S. National Estimates of Prescription Nonsteroidal Anti-inflammatory Drugs Among Patients With Cardiovascular Disease

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain, fever, and inflammation, but their ubiquitous use has led to concerns over increased risk of adverse cardiovascular (CV) events, particularly in patients with established CV disease (CVD). In 2005, the FDA revised labels for all NSAIDs to include a boxed warning highlighting the potential for increased CV risk. However, little is known regarding real-world prescribing of NSAIDs among patients with CVD. Our objective was to characterize the use of prescription NSAIDs among patients with CVD from 1988-2016 in the U.S. Methods: Using cross-sectional National Health and Nutrition Examination Survey (NHANES) data from 1988-1994 and 1999-2016, we included participants aged ≥18 years with hypertension (defined by self-report, mean blood pressure ≥140/90, or use of an antihypertensive medication), or aged ≥20 years with ≥1 of the following self-reported heart disease conditions: congestive heart failure (CHF), coronary heart disease (CHD), angina, myocardial infarction (MI), or stroke. Survey-weighted data were analyzed to assess prevalence and trends of prescription NSAID use within each CVD population in 6-year examination periods. Results: Overall, prescription NSAID use declined among all U.S. CVD populations over the study period. Prevalence of prescription NSAID use was highest during the 1999-2004 examination years, but thereafter, declined during the 2005-2010 examination years for those with hypertension (13.9% to 8.8%), CHF (14.6% to 8.5%), CHD (16.3% to 7.0%), angina (17.6% to 9.73%), MI (16.1% to 8.2%), and stroke (15.7% to 8.8%). Use of prescription NSAIDs since the 2005-2010 examination years has remained consistent in all CVD populations. These decreases were driven in part by reduced use of COX-2-selective NSAIDs, whereas non-selective NSAID use among all CVD populations was relatively steady from 1999 to 2016. Conclusions: Prescription NSAID use among patients with CVD appears to have declined from 1988 to 2016, primarily because of less COX-2 NSAID use following removal of 2 approved agents. Otherwise, the prevalence of prescription NSAIDs has remained somewhat stable and relatively high among these high-risk CV populations. Our results suggest additional efforts may be needed to limit the use of NSAIDs among patients with CVD, given that these agents are known to be associated with adverse CVD outcomes.

Risk of acute myocardial infarction during use of individual NSAIDs: A nested case-control study from the SOS project.

BackgroundUse of selective COX-2 non-steroidal anti-inflammatory drugs (NSAIDs) (coxibs) has been associated with an increased risk of acute myocardial infarction (AMI). However, the risk of AMI has only been studied for very few NSAIDs that are frequently used.ObjectivesTo estimate the risk of AMI for individual NSAIDs.MethodsA nested case-control study was performed from a cohort of new NSAID users ≥18 years (1999–2011) matching cases to a maximum of 100 controls on database, sex, age, and calendar time. Data were retrieved from six healthcare databases. Adjusted odds ratios (ORs) of current use of individual NSAIDs compared to past use were estimated per database. Pooling was done by two-stage pooling using a random effects model (ORmeta) and by one-stage pooling (ORpool).ResultsAmong 8.5 million new NSAID users, 79,553 AMI cases were identified. The risk was elevated for current use of ketorolac (ORmeta 2.06;95%CI 1.83–2.32, ORpool 1.80; 1.49–2.18) followed, in descending order of point estimate, by indometacin, etoricoxib, rofecoxib, diclofenac, fixed combination of diclofenac with misoprostol, piroxicam, ibuprofen, naproxen, celecoxib, meloxicam, nimesulide and ketoprofen (ORmeta 1.12; 1.03–1.22, ORpool 1.00;0.86–1.16). Higher doses showed higher risk estimates than lower doses.ConclusionsThe relative risk estimates of AMI differed slightly between 28 individual NSAIDs. The relative risk was highest for ketorolac and was correlated with COX-2 potency, but not restricted to coxibs.

The safety profile of parecoxib for the treatment of postoperative pain: a pooled analysis of 28 randomized, double-blind, placebo-controlled clinical trials and a review of over 10 years of postauthorization data.

BackgroundNonselective, nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors are associated with safety issues including cardiovascular, renal, and gastrointestinal (GI) events.ObjectiveTo examine the safety of parecoxib, a COX-2 inhibitor, for the management of postoperative pain.DesignPooled analysis of 28 placebo-controlled trials of parecoxib and review of postauthorization safety data.Main outcome measuresPrespecified safety events commonly associated with COX-2 inhibitors and/or NSAIDs. In the clinical trial analysis, the frequency of each event was compared between treatment groups using a chi-square test. In the postauthorization review, the number of confirmed cases, along with outcome, was presented for each event.ResultsIn the clinical trial analysis, GI-related events occurred in ~0.2% of patients in the parecoxib and placebo groups. Renal failure and impairment was similar between parecoxib (1.0%) and placebo (0.9%). The occurrence of arterial (parecoxib=0.3%; placebo=0.2%) and venous (parecoxib=0.2%; placebo=0.1%) cardiovascular embolic and thrombotic events was similar between groups. Hypersensitivity reactions including anaphylactic reactions (parecoxib=8.7%; placebo=8.6%), hypotension (parecoxib=2.6%; placebo=2.1%), angioedema (parecoxib=2.5%; placebo=2.8%), and severe cutaneous adverse reactions (0% in both groups) were similar between groups. Incision site or other skin/tissue infections occurred in <0.1% of patients in both groups. The occurrence of these events (total reports/serious reports) in the postauthorization database, based on 69,567,300 units of parecoxib, was as follows: GI ulceration-related events (35/35), renal failure and impairment (77/68), cardiovascular embolic and thrombotic events (66/64), hypersensitivity reactions including hypotension-related events (32/25) and severe cutaneous adverse events (17/17), and masking signs of inflammation (18/18). A majority of reported outcomes were classified as recovered or recovering.ConclusionsPotentially serious safety events occur infrequently with parecoxib, which high-lights its safety in patients with postoperative pain.

Physicians' communication of risks from non-steroidal anti-inflammatory drugs and attitude towards providing adverse drug reaction information to patients.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for orthopaedic conditions, therefore this study aimed to explore orthopaedic physicians' perceptions of their role in NSAID-risk communication, their attitudes towards the necessity of informing patients about adverse drug reactions (ADR), and factors associated with these. Self-administered questionnaires were mailed to all 206 orthopaedic physicians working at hospitals in Northeastern Thailand. Attitudes were assessed using 17 statements and total scores classed as poor, moderate and good attitude. Sixty-six questionnaires were returned (32.04%). The responses showed that 75% of physicians claimed to communicate NSAID ADR information, more frequently about gastrointestinal (GI) complications, than about renal and cardiovascular (CVS) complications. ADR management (36%) and monitoring (30%) were not frequently communicated. The time spent with patients was associated with provision of ADR and monitoring advice. Renal function was the risk factor of greatest concern for prescribing any NSAID, followed by history of GI complications, and allergy for non-selective NSAIDs, and history of CVS diseases and age for selective COX-2 NSAIDs. Most physicians (41) had moderate attitude towards providing information and 24 good attitude. Fewer physicians working in tertiary hospitals than general and community hospital physicians considered that time limitations prevented counseling and that patient information leaflets offered easily accessible information. Additionally, more physicians who did not inform patients about ADRs agreed that ADR communication can lead to anxiety and discontinuing treatment. The study indicates that, although orthopaedic physicians had positive attitudes towards providing ADR information to patients, improvement is needed in communicating NSAID risk information.

Selective COX-2 Inhibitor (Meloxicam) and Tooth-Supporting Bone Quality. A Histomorphometric Study in Rats.

The effects of the non-steroidal anti-inflammatory drugs (NSAIDs) on bone quantity and quality were investigated for years. However, there is lack of information on the impact of NSAIDs on the quality of tooth-supporting alveolar bone in absence of periodontal inflammation. Thus, the aim of this study was to evaluate histometrically the influence of a selective COX-2 NSAID (Meloxicam) on the inter-radicular bone mineral density in rats. Forty-nine adult male Wistar rats were randomly divided into four experimental groups: Subcutaneous injection of 0.9% sterile saline for 15 days (G1; n=12) and 45 days (G2; n=11); and subcutaneous injection of Meloxicam for 15 days (G3; n=13) and 45 days (G4; n=13). Mineral density was histometrically determined in the inter-radicular area of the 1st mandibular molars and data analysis performed by two-way ANOVA (a=5%). Results showed no interaction between time and treatment (p>0.05) and that meloxicam did not affect the alveolar bone density. In contrast, it was found that inter-radicular alveolar bone density increased with time (91.88±3.08% and 92.86±2.38% for groups 15 and 45 days, respectively) (p<0.05). Within the limits of this study, daily administration of a selective COX-2 inhibitor (Meloxicam) did not affect the quality of the inter-radicular alveolar bone in absence of periodontal infection.

COX-2-dependent and independent effects of COX-2 inhibitors and NSAIDs on proatherogenic changes in human monocytes/macrophages

It is the second decade of controversy regarding the cardiovascular effects of cyclo-oxygenase-2 (COX-2) inhibitors. At this time, celecoxib is the only available COX-2-specific inhibitor for treatment of pain and...

Non-steroidal anti-inflammatory drugs for chronic low back pain.

Chronic back pain is an important health problem. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat people with low back pain, especially people with acute back pain. Short term NSAID use is also recommended for pain relief in people with chronic back pain. Two types of NSAIDs are available and used to treat back pain: non-selective NSAIDs and selective COX-2 NSAIDs. In 2008, a Cochrane review identified a small but significant effect from NSAIDs compared to placebo in people with chronic back pain. This is an update of the Cochrane review published in 2008 and focuses on people with chronic low back pain. To determine if NSAIDs are more efficacious than various comparison treatments for non-specific chronic low back pain and if so, which type of NSAID is most efficacious. We searched CENTRAL, MEDLINE, EMBASE, PubMed and two clinical trials registry databases up to 24 June 2015 for randomized controlled trials (RCTs) published in English, German or Dutch. We also screened references cited in relevant reviews. We included RCTs (double-blind and single-blind) of NSAIDs used to treat people with chronic low back pain. Two review authors independently screened trials for inclusion in this Cochrane review according to the inclusion criteria. One review author extracted the data, and a second review author checked the data. Two review authors independently evaluated the risk of bias of all included trials. If data were clinically homogeneous, we performed a meta-analysis and assessed the quality of evidence using the GRADE approach. We included 13 trials in this Cochrane review. Ten studies were at 'low' risk of bias. Six studies compared NSAIDs with placebo, and included 1354 participants in total. There is low quality evidence that NSAIDs are more effective than placebo, with a mean difference in pain intensity score from baseline of -3.30 (95% CI -5.33 to -1.27) on a 0 to 100 visual analogue scale (VAS) with a median follow-up of 56 days (interquartile range (IQR) 13 to 91 days). Four studies measured disability using the Roland Morris Disability Questionnaire. There is low quality evidence that NSAIDs are more effective than placebo on disability, with a mean difference from baseline of -0.85 (95% CI -1.30 to -0.40) on a scale from 0 to 24 with a median follow-up of 84 days (IQR 42 to 105 days). All six placebo controlled studies also reported adverse events, and suggested that adverse events are not statistically significant more frequent in participants using NSAIDs compared to placebo (RR 1.04, 95% CI 0.92 to 1.17). Due to the relatively small sample size and relatively short follow-up in most included trials, it is likely that the proportion of patients experiencing an adverse event is underestimated.Two studies compared different types of non-selective NSAIDs, namely ibuprofen versus diclofenac and piroxicam versus indomethacin. The trials did not find any differences between these NSAID types, but both trials had small sample sizes. One trial reported no differences in pain intensity between treatment groups that used selective or non-selective NSAIDs. One other trial compared diflunisal with paracetamol and showed no difference in improvement from baseline on pain intensity score. One trial showed a better global improvement in favour of celecoxib versus tramadol.One included trial compared NSAIDs with 'home-based exercise'. Disability improved more in participants who did exercises versus participants receiving NSAIDs, but pain scores were similar. Six of the 13 included RCTs showed that NSAIDs are more effective than placebo regarding pain intensity. NSAIDs are slightly more effective than placebo regarding disability. However, the magnitude of the effects is small, and the level of evidence was low. When we only included RCTs at low risk of bias, differences in effect between NSAIDs and placebo were reduced. We identified no difference in efficacy between different NSAID types, including selective versus non-selective NSAIDs. Due to inclusion of RCTs only, the relatively small sample sizes and relatively short follow-up in most included trials, we cannot make firm statements about the occurrence of adverse events or whether NSAIDs are safe for long-term use.

Nonsteroidal Antiinflammatory Drugs for Axial Spondyloarthritis: A Cochrane Review.

To determine the benefits and harms of nonsteroidal antiinflammatory drugs (NSAID) in axial spondyloarthritis (axSpA). Systematic review using Cochrane Collaboration methodology. randomized controlled trials (RCT) and quasi-RCT (to June 2014), investigating NSAID versus any control for axSpA, and observational studies of longterm effects (≥ 6 mos) of NSAID on radiographic progression or adverse events. Main outcomes were pain, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index, radiographic progression, number of withdrawals because of adverse events, and number of serious adverse events. Risk of bias was assessed. Thirty-five RCT, 2 quasi-RCT, and 2 cohort studies were included. Twenty-nine RCT and 2 quasi-RCT (n = 4356) were included in pooled analyses [traditional NSAID vs placebo (n = 5), cyclooxygenase-2 (COX-2) vs placebo (n = 3), COX-2 vs traditional NSAID (n = 4), NSAID vs NSAID (n = 24), naproxen vs other NSAID (n = 3), and low- vs high-dose NSAID (n = 5)]. Compared with placebo, both traditional and COX-2 NSAID were consistently more efficacious at 6 weeks and equally safe after 12 weeks. No significant differences in benefits or harms between the 2 NSAID classes and no important differences in benefits or withdrawals because of adverse events between different NSAID were found, especially if studies with high risk of bias were excluded. Single studies suggest NSAID may retard radiographic progression, especially by continuous rather than on-demand NSAID use. High-quality evidence indicates that both traditional and COX-2 NSAID are efficacious for treating axSpA, and harms are not different from placebo in the short term. Various NSAID are equally effective.