Cyclo-oxygenase (COX)-2 selective and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are important in managing acute and chronic pain secondary to inflammation. As a greater understanding of the risks of gastrointestinal (GI), cardiovascular (CV) and renal events with NSAIDs use has emerged, guidelines have evolved to reflect differences in risks among NSAIDs. Updated guidelines have yet to reflect new evidence from recent trials which showed similar CV event rates with celecoxib compared to naproxen and ibuprofen, and significantly better GI tolerability for celecoxib. This practice advisory paper aims to present consensus statements and associated guidance regarding appropriate NSAID use based on a review of current evidence by a multidisciplinary group of expert clinicians. This paper is especially intended to guide primary care practitioners within Asia in the appropriate use of NSAIDs in primary care. Following a literature review, group members used a modified Delphi consensus process to determine agreement with selected recommendations. Agreement with a statement by 75% of total voting members was defined a priori as consensus. For low GI risk patients, any nonselective NSAID plus proton pump inhibitor (PPI) or celecoxib alone is acceptable treatment when CV risk is low; for high CV risk patients, low-dose celecoxib or naproxen plus PPI is appropriate. For high GI risk patients, celecoxib plus PPI is acceptable for low CV risk patients; low-dose celecoxib plus PPI is appropriate for high CV risk patients, with the alternative to avoid NSAIDs and consider opioids instead. Appropriate NSAID prescription assumes that the patient has normal renal function at commencement, with ongoing monitoring recommended. In conclusion, appropriate NSAID use requires consideration of all risks.

OBJECTIVE: This study examined the degree of gastrointestinal (GI) risk and patient-reported outcomes including GI-related symptoms, adherence to non-steroidal anti-inflammatory drugs (NSAIDs), disease activity and quality of life (QoL) in patients with ankylosing spondylitis (AS).
METHODS: Cross-sectional, observational study conducted at six nationwide, university-based hospitals of Korea. AS patients treated with NSAIDs for at least 2 weeks were included between March and September 2016. Demographic and clinical data were gathered through a medical chart review and patient survey. GI risk was estimated using Standardized Calculator of Risk for Events (SCORE). NSAIDs adherence was investigated with Morisky Medication Adherence Scale-8 (MMAS-8). Disease activity and QoL were examined with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and EuroQol-3L (EQ-5D, EQ-visual analog scale [EQ-VAS]), respectively. Path analysis was implemented to estimate pathways of GI risk, GI symptoms and NSAIDs adherence to QoL.
RESULTS: A total of 596 patients (age: 38.9 ± 12.6 years, male: 82.1%) participated in the study, of which 33.2% experienced GI symptoms during NSAID treatment, and 34.2% of them showed ongoing GI symptoms upon enrollment. According to SCORE, 37.1% of patients showed moderate to very high GI risk. No patient showed high adherence according to MMAS-8, so 55.3% of patients with moderate adherence were considered adherent. BASDAI and QoL of the total patients were 3.5 ± 2.0, 0.6 ± 0.3 (EQ-5D), and 67.4 ± 19.8 (EQ-VAS), respectively. From path analyses, higher GI risk significantly lowered QoL.
CONCLUSIONS: This study suggests timely therapeutic strategies should be implemented to manage GI risk during NSAID treatment in order to effectively manage AS.

COX2-selective and nonselective (ns) nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for chronic pain management. There are marked differences in the risk of adverse gastrointestinal (GI) and cardiovascular (CV) events among different NSAIDs. In 2017, publication of two randomized controlled trials and an individual patient-data meta-analysis provided robust data on the relative GI and CV tolerability profiles of currently available NSAIDs. The PRECISION study showed similar CV-event rates with celecoxib vs naproxen and ibuprofen, but GI tolerability was better for celecoxib. In the CONCERN study of high-GI-risk patients, celecoxib was associated with fewer adverse GI-tract events than naproxen. The meta-analysis showed no significant difference between celecoxib and ns-NSAIDs in the rate of acute myocardial infarction, and celecoxib was the only COX2-selective NSAID with a lower risk of adverse CV and GI events vs ns-NSAIDs. These data add to the body of knowledge about the relative tolerability of different NSAIDs and were used to propose an updated treatment algorithm. The decision about whether to use an NSAID and which one should be based on a patient\'s risk of developing adverse GI and CV events. Lower- and upper-GI-tract events need to be considered. Celecoxib has a better lower-GI-tract tolerability profile than ns-NSAIDs plus a proton-pump inhibitor. In addition, the latest data suggest that long-term use of celecoxib 200 mg/day may be appropriate for patients at increased CV risk.

NSAIDs are commonly prescribed for the treatment of pain and inflammation. Despite the effectiveness of NSAIDs, concerns exist regarding their tolerability. Worldwide health authorities, including the European Medicines Agency, Health Canada, and the US Food and Drug Administration, have advised that NSAIDs be prescribed at the lowest effective dosage and for the shortest duration. Effective lowering of NSAID dosage without compromising pain relief has been demonstrated in randomized, controlled trials of the recently approved NSAID lower-dose submicron diclofenac. Building on previously published work from an independently published systematic review and meta-analysis, a linear dose-toxicity relationship between diclofenac dose and serious gastrointestinal (GI) events was recently demonstrated, indicating that reductions in adverse events (AEs) may be seen even with modest dose reductions in many patients. The objective of the present study was to estimate the potential reduction in risk for NSAID dose-related AEs, corresponding savings in health care costs, and the incremental cost-effectiveness of submicron diclofenac compared with generic diclofenac in the United States.
Our decision-analytic cost-effectiveness model considered a subset of potential AEs that may be avoided by lowering NSAID dosage. To estimate the expected reductions in upper GI bleeding/perforation and major cardiovascular events with submicron diclofenac, our model used prediction equations estimated by meta-regressions using data from systematic literature reviews. Utilities, lifetime costs, and health outcomes associated with AEs were estimated using data from the literature. The face validity of the model structure and inputs was confirmed by clinical experts in the United States. Results were evaluated in 1-way and probabilistic sensitivity analyses.
The model predicted that submicron diclofenac versus generic diclofenac could reduce the occurrence of modeled GI events (by 18.0%), cardiovascular events (by 6.9%), and acute renal failure (by 18.8%), leading to a 9.8% reduction in costs of treating AEs. Submicron diclofenac was predicted to be cost-saving, with results relatively insensitive to parameter uncertainty.
Submicron diclofenac has the potential to provide clinical and economic value to patients using NSAIDs in the United States. Further investigation regarding the potential effects of submicron diclofenac on the risks for additional NSAID dose-related toxicities should be explored.

OBJECTIVE: The chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause complications in the gastrointestinal tract. The use of proton pump inhibitors (PPIs) is recommended in high-risk patients to prevent them.
OBJECTIVE: The aim of this article was to evaluate the gastroprotection measures taken in persons with chronic NSAID use.
METHODS: A descriptive cross-sectional study was conducted. The clinical records were reviewed of patients seen as outpatients at the Rheumatology Department over a 4-month period, choosing those with chronic NSAID use, and intentionally looking for gastroprotection measures according to the recommendations published by the American College of Gastroenterology.
RESULTS: A total of 417 patients (347 women; mean age: 48.12±14.2 years) were included. The most frequent diagnosis was rheumatoid arthritis (65%). Nine patients (2.1%) had a history of peptic ulcer, 48 (11.5%) patients were 65 years of age or older, 26 (6.2%) patients took NSAIDs and aspirin, and 130 (31.2%) took NSAIDs with steroids. Tests for Helicobacter pylori infection were done in just 53 cases, and there were positive results in only 9 (16%). Some risk for gastrointestinal toxicity was established in 211 cases and only 65 (30.8%) received gastroprotection. In contrast, 31 (15%) patients received gastroprotection when there was no indication for it.
CONCLUSIONS: Prophylaxis with PPIs in chronic NSAID users was inadequately employed. It was not prescribed in the majority of patients (69.2%) and it was used with no justification in others (15%).

Non-steroidal anti-inflammatory drug (NSAID) use increases the risk of gastrointestinal complications such as ulcers or bleeding. The presence of factors like advanced age, history of peptic ulcer, Helicobacter pylori infection and the use of anticoagulants or antiplatelet agents increase this risk further. COX-2 inhibitors and antisecretory drugs, particularly proton pump inhibitors, help to minimize the risk of gastrointestinal complications in high-risk patients. This review presents a practical approach to the prevention and treatment of NSAID-associated peptic ulcer disease and examines the new advances in the rational use of NSAIDs.