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Cyclo-oxygenase-2 inhibitors or nonselective NSAIDs plus gastroprotective agents: what to prescribe in daily clinical practice?

ABSTRACT: Two strategies for prevention of upper gastrointestinal (UGI) events for nonselective nonsteroidal anti-inflammatory drug (nsNSAID) users are replacement of the nsNSAID by a cyclo-oxygenase-2-selective inhibitor (coxib) or co-prescription of a gastroprotective agent (GPA).To identify whether and in whom either of these strategies should be preferred in daily practice.A nested case-control study was conducted using three European primary care databases. We selected a cohort including all naive nsNSAID+GPA (?80% GPA adherence) and coxib users (without GPA use) aged ?50 years. Cases with an UGI event (i.e. symptomatic UGI ulcer or bleeding) were matched to cohort members without an UGI event on age, sex and number of individual UGI risk factors (i.e. UGI event history, age ?65 years, concomitant use of anticoagulants, antiplatelets, or glucocorticoids) and calendar time. Conditional logistic regression analysis was used to calculate odds ratios (ORs) with 95% CI, while adjusting for potential confounders.Within the NSAID cohort (n = 617,220), 398 UGI cases were identified. The risk of UGI events was equivalent for coxib and nsNSAID+GPA (?80% adherence) users (OR: 1.02; 95%CI: 0.77-1.37). In concurrent glucocorticoid users, the risk of UGI events was significantly elevated for nsNSAID+GPA (?80% adherence) compared with coxib users (OR: 9.01; 95%CI: 1.61-50.50).The risk of UGI events was similar in nsNSAID+GPA (?80% adherence) and coxibs users. In patients concurrently using glucocorticoids, a significant increase in the risk of UGI events for nsNSAID+GPA users was observed and coxibs should be preferred.

SUBMITTER: Masclee GM

PROVIDER: S-EPMC3687334 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Cyclo-oxygenase-2 inhibitors or nonselective NSAIDs plus gastroprotective agents: what to prescribe in daily clinical practice?

Masclee G M C GM Valkhoff V E VE van Soest E M EM Schade R R Mazzaglia G G Molokhia M M Trifirò G G Goldstein J L JL Hernández-Díaz S S Kuipers E J EJ Sturkenboom M C J M MC

Alimentary pharmacology & therapeutics 20130528 2

<h4>Background</h4>Two strategies for prevention of upper gastrointestinal (UGI) events for nonselective nonsteroidal anti-inflammatory drug (nsNSAID) users are replacement of the nsNSAID by a cyclo-oxygenase-2-selective inhibitor (coxib) or co-prescription of a gastroprotective agent (GPA).<h4>Aim</h4>To identify whether and in whom either of these strategies should be preferred in daily practice.<h4>Methods</h4>A nested case-control study was conducted using three European primary care databas ...[more]

PMID: 23710837

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Project description:ObjectiveTo assess the comparative efficacy of traditional non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase-2 inhibitors in patients with acute gout.DesignSystematic review and meta-analysis.Data sourcesMedline, Web of Science, China National Knowledge Infrastructure and Wanfang Data published as of 4 April 2020.MethodsWe performed meta-analysis of randomised controlled trials (RCTs) of traditional non-selective NSAIDs versus cyclo-oxygenase-2 inhibitors and RCTs of various cyclo-oxygenase-2 inhibitors in patients with acute gout. The main outcome measures were mean change in pain Visual Analogue Scale (VAS) score and 5-point Likert scale score on days 2-8.ResultsTwenty-four trials involving five drugs were evaluated. For pain Likert scale, etoricoxib was comparable to indomethacin (standardised mean difference (SMD): -0.09, 95% CI: -0.27 to 0.08) but better than diclofenac 50 mg three times a day (SMD: -0.53, 95% CI: -0.98 to 0.09). Regarding pain VAS score, etoricoxib was comparable to diclofenac 75 mg two times per day (SMD: -1.63, 95% CI: -4.60 to 1.34) and diclofenac 75 mg four times a day (SMD: -1.82, 95% CI: -5.18 to 1.53), while celecoxib was comparable to diclofenac 100 mg four times a day (SMD: -2.41, 95% CI: -5.91 to 1.09). Etoricoxib showed similar patients' global assessment of response (SMD: -0.10, 95% CI: -0.27 to 0.07) and swollen joint count (SMD: -0.25, 95% CI: -0.74 to 0.24), but better investigator's global assessment of response (SMD: -0.29, 95% CI: -0.46 to 0.11) compared with indomethacin. Etoricoxib showed more favourable pain VAS score than celecoxib (SMD: -2.36, 95% CI: -3.36 to 1.37), but was comparable to meloxicam (SMD: -4.02, 95% CI: -10.28 to 2.24). Etoricoxib showed more favourable pain Likert scale than meloxicam (SMD: -0.56, 95% CI: -1.10 to 0.02). Etoricoxib 120 mg four times a day was more likely to achieve clinical improvement than celecoxib 200 mg two times per day (OR: 4.84, 95% CI: 2.19 to 10.72).ConclusionAlthough cyclo-oxygenase-2 inhibitors and traditional non-selective NSAIDs may be equally beneficial in terms of pain relief, cyclo-oxygenase-2 inhibitors (especially etoricoxib) may confer a greater benefit.

Project description:Objectives: We aim to evaluate the proportion and characteristics of enthesitis-related arthritis (ERA) patients in whom medications can be withdrawn in daily practice and to analyze the factors associated with flare-ups during medication tapering of these patients. Methods: We retrospectively reviewed records of patients under 16 years old diagnosed with ERA from April 2001 to March 2020 in one tertiary medical center in Taiwan. Patients were categorized by different medication uses: conventional disease modifying anti-rheumatic drugs (cDMARDs) only and cDMARDs plus biologics. Demographics, laboratory data, presence of uveitis, and medication withdrawal rate were analyzed. Subgroup analysis was performed in the patients with cDMARDs plus biologics to identify factors associated with flare-ups during medication tapering of these patients. Statistical analysis was performed using R (v3.6.0). Results: There were 75 juvenile ERA patients with a median onset age of 10.28 years old. Nineteen (25.3%) patients used cDMARDs for disease control; 56 (74.7%) patients depended on cDMARDs plus biologics. Poly-articular involvement was noted in 29 (38.7%) patients, and it occurred more frequently in the cDMARDs plus biologics subgroup (cDMARDs only, 5.3%; cDMARDs plus biologics, 53.6%; P = 0.0001). ANA positivity was observed in 18 (24.0%) patients, and it occurred more frequently in the cDMARDs plus biologics subgroup (cDMARDs, 0%; cDMARDs plus biologics, 32.1%; P = 0.0038). The overall medication withdrawal rate was 34.7%, and it occurred more frequently in patients with cDMARDs only (cDMARDs only, 84.2%; cDMARDs plus biologics, 17.9%; P < 0.001). In the subgroup analysis of patients with cDMARDs plus biologics, patients on biologics tapering with flare-up had a significantly longer time interval between disease onset and initiation of cDMARDs (biologics tapering without flare-up: 0.27 (0.11-0.73) years; biologics tapering with flare-up: 1.14 (0.39-2.02) years; ever withdrawing biologics: 0.26 (0.18-0.42) years, P = 0.0104). Conclusion: Juvenile ERA patients with polyarticular involvement had a higher risk of developing cDMARDs refractory and progressing to biologics use. Patients with a long time interval between disease onset and initiation of cDMARDs were prone to experience flare-up during tapering of biologics.

Project description:BackgroundIt has been proved that cyclo-oxygenase-2 (COX-2) is rapidly induced by inflammatory mediators. However, it is not known whether overexpression of COX-2 in the liver is sufficient to promote activation or secretion of inflammatory factors leading to hepatitis.AimTo investigate the role forced expression of COX-2 in liver by using inducible COX-2 transgenic (TG) mice.MethodsTG mice that overexpress the human COX-2 gene in the liver using the liver-specific transthyretin promoter and non-TG littermates were derived and fed the normal diet for up to 12 months. Hepatic prostaglandin E(2) (PGE(2)) content was determined using enzyme immunoassay, nuclear factor kappaB (NF-kappaB) activation by electrophoretic mobility shift assays, apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labelling and proliferation by Ki-67 immunohistochemistry.ResultsCOX-2 TG mice exhibited strongly increased COX-2 and PGE(2), elevated serum alanine aminotransferase level and histological hepatitis. Hepatic COX-2 expression in the TG mice resulted in activation of NF-kappaB and inflammatory cytokine cascade, with a marked expression of the proinflammatory cytokines tumour necrosis factor (TNF)-alpha (9.4-fold), interleukin (IL)-6 (4.4-fold), IL-1beta (3.6-fold), and of the anti-inflammatory cytokine IL-10 (4.4-fold) and chemokine macrophage inflammatory protein-2 (3.2-fold). The inflammatory response of the COX-2 TG mice was associated with infiltration macrophages and lymphocytes, increased cell proliferation and high rates of cell apoptosis. Administration of the COX-2 inhibitor celecoxib in TG mice restored liver histology to normal.ConclusionEnhanced COX-2 expression in hepatocytes is sufficient to induce hepatitis by activating NF-kappaB, stimulating the secretion of proinflammatory cytokines, recruiting macrophage and altering cell kinetics. Inhibition of COX-2 represents a mechanism-based chemopreventive approach to hepatitis.

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Cyclo-oxygenase-2 inhibitors or nonselective NSAIDs plus gastroprotective agents: what to prescribe in daily clinical practice?

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Cyclo-oxygenase-2 inhibitors or nonselective NSAIDs plus gastroprotective agents: what to prescribe in daily clinical practice?

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