Upper Gastrointestinal Adverse Events Research Articles

P097 The risks of adverse events with analgesics in patients with inflammatory arthritis: a systematic review of observational studies

Abstract Background/Aims Analgesics are widely prescribed in patients with inflammatory arthritis (IA) despite limited evidence of efficacy and uncertainties about potential harms. The assessment of harms is complex as some drug-related adverse events (AE), including myocardial infarctions, are part of the IA comorbidity spectrum. As trials have limited follow-up periods and often exclude patients with comorbidities, safe prescribing requires an understanding of analgesic harms in “real-world” settings. We consequently undertook the first systematic review of observational studies reporting risks of adverse events with analgesics in adults with rheumatoid arthritis (RA) and spondyloarthritis (SpA). Methods A pre-specified protocol was PROSPERO-registered (CRD42019154277). Systematic searches were conducted in Web of Science/Embase/Medline without language/date restriction on the 18/1/22. Due to marked methodological and statistical heterogeneity, studies were combined in a structured narrative synthesis. Results Studies: Of 6,444 citations screened, thirty-five studies met eligibility criteria, comprising 21 cohort (200 to 143,433 patients); 12 case-control (41 to 7,102 cases); 1 self-controlled case series; 1 case-crossover. Two evaluated opioids in RA, 23 oral NSAIDs in RA, 9 oral NSAIDs in SpA, and 1 NSAIDs and opioids in RA. None evaluated paracetamol/gabapentinoids. Fourteen were rated “good”, 19 “fair” and 1 “poor” quality. Adverse Event Risks: All studies of opioids reported significantly increased risks of fractures/serious infection. For NSAIDs renal, upper gastrointestinal (UGI), and cardiovascular (CV) events were most often reported. There was consistent evidence that NSAIDs significantly increased renal (3/3 studies) and UGI (3/4 studies) AEs. Findings with CV AEs varied: 7/18 studies showed significantly increased risks; 3/18 showed significantly reduced risks, and 3/18 showed significantly increased risks with some NSAIDs and reduced risks with others. There was no evidence NSAIDs increased risks of lower/functional gastrointestinal AEs, or fractures. With regards to mortality, one study showed a significantly reduced risk of death with NSAID use in SpA; the other showed a significantly reduced risk of death with NSAID use in inflammatory polyarthritis (but not RA). Differences Between RA And SpA: More studies reported a significantly reduced risk of CV events/fractures/deaths with NSAIDs in SpA (6/10) than RA (4/24). Differences Between IA and Non-IA Populations: Two of four studies found significant differences in AE risks in RA/SpA compared to OA/controls. One reported a significantly higher risk of myocardial infarction in SpA than OA and another a significantly lower risk of composite CV events in RA than controls. Conclusion Observational study data on risks of analgesic harms in IA are limited. All studies of opioids showed increased risks of harms. Studies of NSAIDs gave variable results, reflecting heterogeneity and potential confounding. Overall, oral NSAIDs increased renal and UGI AEs, with some evidence they reduced fractures/mortality in SpA. Further high-quality observational studies are needed to better characterise analgesic harms in IA. Disclosure C.R. White: None. O. Babatunde: None. J. Higgs: None. S. Muller: None. C.D. Mallen: None. S.L. Hider: None. I.C. Scott: None.

Efficacy and safety profiles of mood stabilizers and antipsychotics for bipolar depression: a systematic review.

The whole picture of psychotropics for bipolar depression (BPD) remains unclear. This review compares the differences in efficacy and safety profiles among common psychotropics for BPD. MEDLINE, EMBASE, and PsycINFO were searched for proper studies. The changes in the depressive rating scale, remission/response rates, nervous system adverse events (NSAEs), gastrointestinal adverse events (GIAEs), metabolic parameters, and prolactin were compared between medication and placebo or among medications with the Cohen's d or number needed to treat/harm. The search provided 10 psychotropics for comparison. Atypical antipsychotics (AAPs) were superior to lithium and lamotrigine at alleviating acute depressive symptoms. Lithium was more likely to induce dry mouth and nausea. Cariprazine and aripiprazole seemed to be associated with an increased risk of akathisia and upper GIAEs. Lurasidone was associated with an increased risk of developing akathisia and hyperprolactinemia. Olanzapine, olanzapine-fluoxetine combination (OFC), and quetiapine were associated with an increased risk of NSAEs, metabolic risk, dry mouth, and constipation. Cariprazine, lurasidone, OFC, or quetiapine was optimal monotherapy for BPD. Further studies are needed to assess the efficacy and safety of lamotrigine for treating BPD. Adverse events varied widely across different drug types due to variations in psychopharmacological mechanisms, dosages, titration, and ethnicities.

Multiplexed imaging reveals an IFN-γ-driven inflammatory state in nivolumab-associated gastritis

SummaryImmune checkpoint blockade using PD-1 inhibition is an effective approach for treating a wide variety of cancer subtypes. While lower gastrointestinal (GI) side effects are more common, upper gastrointestinal adverse events are rarely reported. Here, we present a case of nivolumab-associated autoimmune gastritis. To elucidate the immunology underlying this condition, we leverage multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to identify the presence and proportion of infiltrating immune cells from a single section of biopsy specimen. Using MIBI-TOF, we analyze formalin-fixed, paraffin-embedded human gastric tissue with 28 labels simultaneously. Our analyses reveal a gastritis characterized by severe mucosal injury, interferon gamma (IFN-γ)-producing gastric epithelial cells, and mixed inflammation that includes CD8 and CD4 T cell infiltrates with reduced expression of granzyme B and FOXP3, respectively. Here, we provide a comprehensive multiplexed histopathological mapping of gastric tissue, which identifies IFN-γ-producing epithelial cells as possible contributors to the nivolumab-associated gastritis.

Aspirin and other non-steroidal anti-inflammatory drugs for the prevention of dementia.

Aspirin and other non-steroidal anti-inflammatory drugs for the prevention of dementia.

Long-Term Efficacy and Safety of Evocalcet in Japanese Patients with Secondary Hyperparathyroidism Receiving Hemodialysis

Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD), and as the disease progresses SHPT is associated with systemic consequences, termed CKD-mineral and bone disorder. Currently, cinacalcet is indicated for the treatment of SHPT; however, cinacalcet is associated with upper gastrointestinal adverse events. Evocalcet has been developed to address these issues, but the long-term safety and efficacy of evocalcet need to be evaluated. To more accurately reflect clinical practice, this phase 3, multicenter, open-label study was specifically designed without a cinacalcet washout period, and focused on those patients who switched from cinacalcet to evocalcet. A total of 137 SHPT patients undergoing hemodialysis were enrolled, of whom 113 switched from cinacalcet to evocalcet. The most frequent type of adverse drug reaction was decreased adjusted calcium. The incidence of gastrointestinal-related adverse events did not increase in a dose-dependent manner as the dose of evocalcet was increased. The percentage of patients achieving the target intact parathyroid hormone concentration increased from 40.9% to 72.3% with 52-week treatment. The corrected serum calcium and phosphorus levels remained largely unchanged throughout the study. The long-term safety and efficacy of evocalcet was confirmed using a clinically relevant intra-subject dose-adjustment strategy in SHPT patients undergoing hemodialysis.

Differential benefit risk assessment of DOACs in the treatment of venous thromboembolism: focus on dabigatran.

Venous thromboembolism includes deep vein thrombosis and pulmonary embolism and is a serious medical condition that requires anticoagulation as part of treatment. Currently, standard therapy consists of parenteral anticoagulation followed by a vitamin K antagonist (VKA). The pharmacokinetic and pharmacodynamic profiles of the direct oral anticoagulants (DOACs) differ from VKAs, which overcome some of the limitations of VKAs and have practical implications on their use in clinical situations. Dabigatran is a prodrug that undergoes primarily renal elimination and does not affect cytochrome P450 enzymes. Assays to quantify the degree of anticoagulation and the therapeutic level of DOAC are either unavailable for routine clinical use or require specific calibration. Routine monitoring of DOACs is not recommended at this time. Dabigatran, rivaroxaban, and apixaban are DOACs that have been studied for treatment of venous thromboembolism. Clinical trials comparing DOACs with standard therapy have shown them to be non-inferior for acute and extended therapy. Each DOAC has a unique benefit and harm profile that should be considered prior to use. The distinguishing characteristics of dabigatran include a requirement of parenteral anticoagulation prior to acute treatment, clinical trial results comparing it with a VKA for extended treatment, association with upper gastrointestinal adverse events, and increased risk of gastrointestinal bleed. Rivaroxaban is the only DOAC that has once-daily dosing while apixaban is the only DOAC that has lower risk of overall, major, and gastrointestinal bleeding compared with VKA. A common drawback of DOACs is the lack of an available reversal agent. Clinical trials of reversal agents are ongoing and one application for approval has been submitted to the US Food and Drug Administration. Selection of a DOAC for acute and extended therapy requires a shared decision-making approach that includes a comprehensive assessment of the benefits and harms of each individual DOAC.

PA32540 (a coordinated-delivery tablet of enteric-coated aspirin 325 mg and immediate-release omeprazole 40 mg) versus enteric-coated aspirin 325 mg alone in subjects at risk for aspirin-associated gastric ulcers: Results of two 6-month, phase 3 studies

Discontinuations and/or interruptions in aspirin therapy for secondary cardioprotection due to upper gastrointestinal (UGI) complications or symptoms have been shown to increase the risk for subsequent cardiovascular events. PA32540 is a coordinated-delivery, combination tablet consisting of enteric-coated aspirin (EC-ASA) 325 mg and immediate-release (IR) omeprazole 40 mg. Two identically-designed, 6-month, randomized, double-blind trials evaluated PA32540 vs. EC-ASA 325 mg in a secondary cardiovascular disease prevention population taking aspirin 325 mg daily for ≥3 months and at risk for ASA-associated gastric ulcers (GUs). The combined study population was 1049 subjects (524 randomized to PA32540, 525 to EC-ASA 325 mg). The primary endpoint was the occurrence of endoscopically-determined gastric ulceration over 6 months. Safety outcomes included the rates of major adverse cardiovascular events (MACE) and UGI symptoms. Significantly fewer PA32540-treated subjects (3.2%) developed endoscopic GUs vs. EC-ASA 325 mg-treated subjects (8.6%) (P < .001). Overall occurrence of MACE was low (2.1%), with no significant differences between treatments in types or incidence of MACE. PA32540-treated subjects had significantly fewer UGI symptoms (P < .001) and significantly fewer discontinuations due to pre-specified UGI adverse events (1.5% vs. 8.2%, respectively; P < .001). PA32540 reduced the incidence of endoscopic GUs compared to EC-ASA 325 mg, but with a similar cardiovascular event profile. Due to fewer UGI symptoms, continuation on aspirin therapy was greater in the PA32540 treatment arm.

Bisphosphonates and glucocorticoid-induced osteoporosis: Efficacy and tolerability

In this review, the efficacy concern relating to bisphosphonates therapy for glucocorticoid-induced osteoporosis is considered. Sole the randomised clinical trials that including more than 50 patients in each treatment arm were considered. This review also covered the safety of bisphosphonates in the setting of glucocorticoid-induced osteoporosis with specific focus on atrial fibrillation, osteonecrosis of the jaw, upper gastrointestinal adverse events and esophageal cancer risk, atypical fractures and renal safety. These last adverse events have been selected due to the rationale of a possible additive, pathophysiologic or synergetic, deleterious effect of bisphosphonates and glucocorticoid on these organs. The available evidence for glucocorticoid-induced osteoporosis treatment and management is much less important than for post-menopausal osteoporosis. However, based on randomised clinical trials with lumbar spine BMD as the primary endpoint after one year, bisphosphonates can be considered as efficacious. Alendronate, etidronate, risedronate and zoledronate prevented declines in spine BMD in adults receiving glucocorticoid. Treatment and prevention studies in glucocorticoid-induced osteoporosis have a short duration and have included smaller population than in post-menopausal osteoporosis. However in this setting, the safety profile of bisphosphonates in glucocorticoid-induced osteoporosis was good. Long-term use of bisphosphonates in patients treated with glucocorticoid might be cautiously monitored in order to prevent adverse effects.

Pharmacokinetic and clinical evaluation of esomeprazole and ASA for the prevention of gastroduodenal ulcers in cardiovascular patients

Introduction: Low-dose aspirin (ASA, 75 – 325 mg/day) is widely used for the primary and secondary prevention of cardiovascular (CV) diseases. However, the value of primary prevention ASA is uncertain as the reduction in occlusive events needs to be weighed against the significant increase in major bleedings. Prevention with antisecretory drugs has been proposed to reduce the incidence of ASA-induced gastrointestinal (GI) bleedings, but non-adherence to gastro-protection is of concern, as it significantly increases the risk of upper GI adverse events. Beside patients and physicians education, one approach to overcome non-adherence is the development of fixed-dose combination.Area covered: This review explores the results of clinical studies on the influence of the combination esomeprazole (ESA) and ASA on pharmacokinetic (PK) parameters, and the role for such combination in prevention of CV events in patients at risk of gastric ulcers.Expert opinion: Patients at risk of ASA-induced gastroduodenal ulcer might benefit from a fixed ASA and proton pump inhibitor (PPI) combination. PK and PD parameters suggest there is no significant interaction between these drugs. Nevertheless, attention must be paid on the appropriate use of such combination, that is, still balancing the risk:benefit ratio in a real-life setting, and any increase in the proportion of patients receiving ASA and PPI should be considered as a warning signal.

A fixed-dose combination of naproxen and esomeprazole magnesium has comparable upper gastrointestinal tolerability to celecoxib in patients with osteoarthritis of the knee: Results from two randomized, parallel-group, placebo-controlled trials

Background. Non-steroidal anti-inflammatory drugs are associated with poor upper gastrointestinal (UGI) tolerability and increased ulcer risk, but patient adherence to gastroprotective co-therapy is frequently inadequate. A fixed-dose combination of enteric-coated naproxen 500 mg and immediate-release esomeprazole magnesium 20 mg was evaluated: efficacy is reported by Hochberg et al. (Curr Med Res Opin 2011;27:1243–53); tolerability findings are reported here.Patients and methods. In two 12-week double-blind, placebo-controlled, multicenter, phase III studies (PN400-307 and PN400-309), patients aged ≥ 50 years with symptomatic knee osteoarthritis randomly (2:2:1) received naproxen/esomeprazole magnesium BID, celecoxib 200 mg QD, or placebo. Tolerability end-points included: modified Severity of Dyspepsia Assessment (mSODA); heartburn severity; and UGI adverse events (AEs).Results. Overall, 619 (PN400-307) and 615 (PN400-309) patients were randomized; mSODA scores improved (baseline to week 12) in each group, with no significant treatment differences between naproxen/esomeprazole magnesium and celecoxib (95% CIs: PN400-307: –0.4, 1.9; PN400-309: –1.8, 0.6). Naproxen/esomeprazole magnesium-treated patients reported significantly more heartburn-free days versus celecoxib (95% CIs: PN400-307: 2.1, 12.7; PN400-309: 2.5, 13.4). UGI AE incidence (PN400-307: 17.3%; PN400-309: 20.3%) was similar between treatment groups. UGI AEs resulted in few discontinuations (< 4%, either study).Conclusions. Naproxen/esomeprazole magnesium has comparable UGI tolerability to celecoxib in patients with osteoarthritis.

Meta-analysis

To compare cyclooxygenase-2 (Cox-2) inhibitors alone with NSAIDs plus proton pump inhibitors (PPIs) in preventing gastrointestinal adverse events: upper gastrointestinal (UGI) adverse events and gastrointestinal symptoms in Osteoarthritis and Rheumatoid arthritis. PubMed, the Cochrane Library, EMBASE, ISI Web of Knowledge, Chinese Biomedical Literature Database, and reference lists of relevant papers for articles published 1990-2010.12 were searched. The related data matching standards set for this study were extracted. Statistical analyses were carried out using RevMan (5.0) software. The meta-analysis of six randomized controlled trials with a total of 6219 patients revealed that there was no difference in the UGI adverse events between Cox-2 inhibitors and nonselective NSAIDs with concurrent use of PPIs [relative risk (RR) 0.61, 95% confidence interval (CI) 0.34-1.09]. There was no significant difference in gastrointestinal symptoms (RR 1.10, 95% CI: 0.88-1.39) and the cardiovascular adverse events (RR 1.67, 95% CI: 0.78-3.59) between the two groups. Cox-2 inhibitors are no better than nonselective NSAIDs with PPIs in regard to UGI adverse events, gastrointestinal symptoms and cardiovascular adverse events in Osteoarthritis and Rheumatoid arthritis. On the basis of the current evidence and the combined wishes of the patient, clinicians should carefully consider and weigh both gastrointestinal and cardiovascular risk before selecting NSAID plus PPIs or Cox-2 inhibitors.

Upper gastrointestinal tolerability of alendronate sodium monohydrate 10 mg once daily in postmenopausal women: A 12-week, randomized, double-blind, placebo-controlled, exploratory study

Background: The dissolution profiles of generic oral bisphosphonate alendronate (ALN) sodium for the treatment of postmenopausal osteoporosis differ by formulation, suggesting potential differences in the risk for upper gastrointestinal (GI) irritation. Objective: This study compared the tolerability profile of ALN monohydrate with that of placebo, with a focus on upper GI irritation, in postmenopausal women with osteoporosis. Methods: This multicenter, double-blind, placebo-controlled estimation study enrolled postmenopausal women with osteoporosis. Patients were randomized in a 2:1 ratio to receive ALN monohydrate 10 mg or placebo once daily for 12 weeks. Tolerability was monitored throughout the study and up to 14 days after administration of the final dose. Primary end points were the proportions of patients with upper GI adverse events (AEs); upper GI AEs that were rated as serious or study drug related or that led to study discontinuation; and esophageal AEs. Between-treatment differences and associated 95% CIs were assessed using the Wilson score method. Results: Of 438 patients who were randomized, 367 (mean age, 65.5 years; history of osteoporotic fracture, 6.8%; ALN monohydrate, 237; placebo, 130) completed the study. The proportion of patients with a history of upper GI disorders at baseline was numerically greater in the ALN monohydrate group than in the placebo group (117 [40.2%] and 45 [30.6%], respectively). The proportions of patients with active baseline upper GI disease were 83 (28.5%) and 30 (20.4%) in the ALN monohydrate and placebo groups, respectively. The proportions of patients who experienced an upper GI AE during the study period were 66 (22.7%) and 30 (20.4%) (95% CI, −6.2 to 10.0). The proportions of patients with upper GI AEs that were rated as serious or study drug related or that led to study discontinuation were 20.3% and 12.9% (95% CI, −0.3% to 14.1%). Three serious AEs in the active-treatment group (breast cancer, 2; wrist fracture, 1) were not considered related to the study drug, nor was the 1 serious AE in the placebo group (wrist fracture). One patient (ALN monohydrate) had an esophageal AE (nonserious spasm). Approximately 8% of patients who received ALN monohydrate reported dyspepsia, compared with none who received placebo. Within each treatment group, the rates of upper GI AEs were numerically higher in patients with a history of upper GI disease. Conclusions: In these postmenopausal women who received ALN monohydrate or placebo, upper GI AEs were common (20.4%–22.7%). The proportion of patients who experienced upper GI AEs considered drug related or that led to discontinuation was appar- ently greater with ALN monohydrate compared with placebo.

PGI3 RISK OF UPPER GASTROINTESTINAL ADVERSE EVENTS AND THE EFFECT OF ACID-SUPPRESSIVE THERAPY IN PATIENTS RECEIVING ACETYLSALICYLIC ACID FOR CARDIOVASCULAR RISK MANAGEMENT

Risk of upper gastrointestinal adverse events and the effect of acid-suppressive theraphy in patients receiving acetylsalicylic acid for cardiovascular risk management

Randomized, active-controlled study of once-weekly alendronate 280 mg high dose oral buffered solution for treatment of Paget’s disease

Daily oral tablet bisphosphonate therapy for Paget's disease of bone may cause serious upper gastrointestinal adverse events. A once-weekly alendronate 280 mg oral buffered solution was compared with an alendronate 40 mg/day tablet. While both were similarly effective, the tablet appeared to be better tolerated in this study. Although daily doses of oral bisphosphonates are a generally safe and effective treatment for Paget's disease of bone (PDB), some patients may experience upper gastrointestinal adverse events (UGI AEs) or find the dosing requirements inconvenient and become noncompliant. A once-weekly (OW) oral dose of bisphosphonate in buffered solution (OBS) may be as effective, better tolerated, and more convenient. Sixty-three patients were randomized to either alendronate (ALN) 280 mg OW OBS (n = 42) or an ALN 40 mg/day tablet (n = 21) during a 6-month, randomized, double-blind, active-controlled trial. The primary endpoint was the mean percent decrease in total serum alkaline phosphatase (total ALP) from baseline at 6 months. There were no significant differences in total ALP between groups during the 6-month period. There was a higher incidence of clinical AEs in the ALN 280 mg OW OBS (79%) vs. the ALN 40 mg/day tablet group (67%), including drug related AEs (48% and 10%, respectively), which led to study discontinuation (19.0% and 10%, respectively). Although ALN 280 mg OW OBS was similarly effective as ALN 40 mg/day in reducing total ALP in patients with PDB, the ALN 40 mg/day tablet appears to be better tolerated than ALN 280 mg OW OBS.

Risedronate for prevention of bone mineral density loss in patients receiving high-dose glucocorticoids: a randomized double-blind placebo-controlled trial

This 6-month randomized double-blind placebo-controlled trial shows that risedronate is well tolerated and effective in improving lumbar spine BMD and reducing loss of BMD at the hips in patients receiving high-dose prednisolone. Bisphosphonates have proven benefits in patients receiving chronic low-dose glucocorticoids. However, whether they are effective in preventing bone mineral density (BMD) loss during periods of high-dose glucocorticoid treatment is unclear. The objective of this paper is to study the efficacy of risedronate in preventing bone mineral density (BMD) loss in users of high-dose glucocorticoids. Adult patients with medical diseases treated with high-dose prednisolone (>0.5 mg/kg/day) were randomized to receive risedronate (5 mg/day) or placebo for 6 months in a double-blind manner, along with elemental calcium (1,000 mg/day). Changes in BMD were studied. One hundred and twenty patients were recruited (82 women, age 42.8 +/- 14.3 years, 63% corticosteroid-naive, 30% women postmenopausal) and 103 completed the study. Baseline clinical characteristics and BMD were similar in the risedronate and placebo groups. At 6 months, a significant gain in spinal BMD was observed in the risedronate group (+0.7 +/- 0.3%; p = 0.03) but a drop was detected in the placebo group (-0.7 +/- 0.4%; p = 0.12). After adjustment for baseline BMD, age, gender, body mass index and cumulative prednisolone dosages, the inter-group difference in spinal BMD remained significant (1.4%; p = 0.006). Both groups had a significant drop in hip BMD, but the magnitude was greater in the placebo arm (-0.8 +/- 0.4% in risedronate versus -1.3 +/- 0.5% the in placebo). No new fractures developed. Subgroup analysis of corticosteroid-naive patients yielded similar results. Upper gastrointestinal adverse events were numerically more frequent in the risedronate group. Risedronate improves spinal BMD in users of high-dose glucocorticoids.

An economic model of long-term use of celecoxib in patients with osteoarthritis

BackgroundPrevious evaluations of the cost-effectiveness of the cyclooxygenase-2 selective inhibitor celecoxib (Celebrex, Pfizer Inc, USA) have produced conflicting results. The recent controversy over the cardiovascular (CV) risks of rofecoxib and other coxibs has renewed interest in the economic profile of celecoxib, the only coxib now available in the United States. The objective of our study was to evaluate the long-term cost-effectiveness of celecoxib compared with nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) in a population of 60-year-old osteoarthritis (OA) patients with average risks of upper gastrointestinal (UGI) complications who require chronic daily NSAID therapy.MethodsWe used decision analysis based on data from the literature to evaluate cost-effectiveness from a modified societal perspective over patients' lifetimes, with outcomes expressed as incremental costs per quality-adjusted life-year (QALY) gained. Sensitivity tests were performed to evaluate the impacts of advancing age, CV thromboembolic event risk, different analytic horizons and alternate treatment strategies after UGI adverse events.ResultsOur main findings were: 1) the base model incremental cost-effectiveness ratio (ICER) for celecoxib versus nsNSAIDs was $31,097 per QALY; 2) the ICER per QALY was $19,309 for a model in which UGI ulcer and ulcer complication event risks increased with advancing age; 3) the ICER per QALY was $17,120 in sensitivity analyses combining serious CV thromboembolic event (myocardial infarction, stroke, CV death) risks with base model assumptions.ConclusionOur model suggests that chronic celecoxib is cost-effective versus nsNSAIDs in a population of 60-year-old OA patients with average risks of UGI events.

Etoricoxib causes fewer upper gastrointestinal adverse events than diclofenac

Etoricoxib causes fewer upper gastrointestinal adverse events than diclofenac

Etoricoxib causes fewer upper gastrointestinal adverse events than diclofenac

Etoricoxib causes fewer upper gastrointestinal adverse events than diclofenac

NSAID-Associated Adverse Effects and Acid Control Aids to Prevent Them

NSAIDs are central to the clinical management of a wide range of conditions. However, NSAIDs in combination with gastric acid, which has been shown to play a central role in upper gastrointestinal (GI) events, can damage the gastroduodenal mucosa and result in dyspeptic symptoms and peptic lesions such as ulceration.NSAID-associated GI mucosal injury is an important clinical problem. Gastroduodenal ulcers or ulcer complications occur in up to 25% of patients receiving NSAIDs. However, these toxicities are often not preceded by indicative symptoms. Data obtained from the Arthritis, Rheumatism, and Aging Medical Information System have shown that 50-60% of NSAID-associated peptic ulcer cases can remain clinically silent and do not present until complications occur. Therefore, prophylactic treatment to prevent GI complications may be necessary in a substantial proportion of NSAID users, especially those in groups associated with a high risk of developing these complications. Use of cyclo-oxygenase (COX)-2 selective NSAIDs, also known as 'coxibs', substantially reduces the incidence of upper GI toxicities seen with non-selective NSAIDs. However, there are concerns regarding the cardiovascular safety of coxibs. For this reason, the US FDA recommends minimal use of coxibs and only when strictly necessary. Additionally, rofecoxib has been removed from the US market and sales of valdecoxib have been suspended. Furthermore, upper GI toxicities still occur in patients receiving coxibs. Therefore, cotherapies are required to prevent and/or heal upper GI effects associated with NSAID use. Effective prophylactic and treatment strategies include misoprostol, histamine H(2) receptor antagonists and proton pump inhibitors (PPIs). The key role that gastric acid plays in upper GI adverse events among NSAID users suggests that it is important to choose the most effective agent for acid control to alleviate symptoms, heal mucosal erosions and improve the reduced quality of life in this patient population. PPIs provide effective acid suppression, which is essential to avoid GI mucosal injury, and they are, therefore, capable of dramatically decreasing the morbidity and mortality associated with this disorder. Since many serious GI complications are not heralded by any previous symptoms, physicians need to be aware of risk factor profiles that predispose patients to serious GI problems. Physicians also need to initiate the appropriate preventative acid suppressive therapy to minimise the burden of NSAID-associated GI adverse effects.

Enteric-coated mycophenolate sodium - current and future use in transplant patients

Mycophenolate mofetil, the morpholino ester prodrug of mycophenolic acid, is an effective immunosuppressant, although there are concerns over dose reductions and discontinuations due to gastrointestinal adverse events. Enteric-coated mycophenolate sodium (Myfortic®) was formulated to improve mycophenolic acid-related upper gastrointestinal adverse events and to deliver effective mycophenolic acid protection. Enteric-coated mycophenolate sodium 720 mg and mycophenolate mofetil 1000 mg are therapeutically equivalent in de novo transplant patients. Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in maintenance patients can be achieved without compromising safety and efficacy. Recent studies demonstrate the efficacy and tolerability of enteric-coated mycophenolate sodium in adult and pediatric renal transplant patients converted from mycophenolate mofetil, and early results also suggest that enteric-coated mycophenolate sodium can provide similar efficacy and safety as mycophenolate mofetil in de novo heart transplant patients.