A cross-sectional retrospective assessment of anti-arthritic drugs in patients with arthritis in Korea

BACKGROUND: Selective cyclo-oxygenase-2 (COX-2) inhibitors were recently introduced for the treatment of arthritis because of their lower rates of gastrointestinal adverse events compared with traditional non-steroidal anti-inflammatory drugs (NSAIDs). OBJECTIVE: To examine the medication usage patterns for both osteoarthritis (OA) and rheumatoid arthritis (RA) in Korea. METHODS: The medical charts of a convenience sample of 402 patients with OA or RA were reviewed by the Arthritis Study Group in 14 hospitals and ten clinics in Korea. RESULTS: Traditional oral NSAIDs were the most commonly prescribed drugs for OA (68.3%) and RA (65.1%) patients. Two-thirds (66.7%) of the RA patients taking COX-2 inhibitors were prescribed other arthritis medications concurrently and 85.1% of RA patients taking NSAIDs were prescribed other arthritis medications concurrently. Patients on NSAIDs were almost twice as likely to have a gastroprotective agent (GPA) concurrently compared to COX-2 inhibitor users (OA patients 38.1% vs 21.2%; RA patients 57.9% vs 30.6%). Overall, patients taking COX-2 inhibitors were less likely to take GPAs concurrently compared to patients not taking COX-2 inhibitors (unadjusted OR 0.36; adjusted OR 0.39). CONCLUSIONS: Traditional oral NSAIDs were commonly prescribed to arthritis patients in Korea. In this study, patients taking COX-2 inhibitors were prescribed less adjunctive arthritis treatments and less gastroprotective agents than traditional oral NSAID users.     

Concomitant use of gastroprotective drugs among elderly NSAID/COX-2 selective inhibitor users: a nationwide register-based study

BACKGROUND AND OBJECTIVES: NSAIDs and cyclo-oxgenase (COX)-2-selective inhibitors have been associated with gastrointestinal (GI) complications among the elderly. It is recommended that gastroprotective drugs (i.e. misoprostol, proton pump inhibitors or high doses of histamine H2 receptor antagonists) be taken concomitantly to prevent NSAID-induced GI complications among older people. However, there are concerns that the rate of concomitant use of gastroprotective drugs in elderly NSAID users is too low. This study aimed to investigate the extent to which elderly users of NSAIDs/COX-2-selective inhibitors are concurrently taking gastroprotective drugs, and to determine the factors associated with concomitant use of gastroprotective drugs and NSAIDs/COX-2-selective inhibitors in a nationwide population of older people. METHODS: We analysed data on age, sex and dispensed drugs for people>or=75 years of age registered in the Swedish Prescribed Drug Register from October to December 2005 (n=732,230) and located 41,626 NSAID/COX-2-selective inhibitor users. Logistic regression analysis was used for analysing the association between the use of different NSAIDs/COX-2-selective inhibitors and gastroprotective drugs, and between individual characteristics and use of gastroprotective drugs. RESULTS: Gastroprotective drugs were used by 22% of NSAID/COX-2-selective inhibitor users. Celecoxib, ketoprofen, meloxicam and etoricoxib were most commonly used concomitantly with gastroprotective drugs. Meloxicam and celecoxib were most strongly associated with gastroprotective drugs, after adjustment for age, sex and number of other drugs. Furthermore, NSAID/COX-2-selective inhibitor+oral corticosteroid users, NSAID/COX-2-selective inhibitor+selective serotonin reuptake inhibitor users and users of two or more NSAIDs/COX-2-selective inhibitors were more likely to concomitantly use gastroprotective drugs compared with NSAID/COX-2-selective inhibitor only users, after adjustment for age, sex and number of other drugs. However, users of NSAIDs/COX-2-selective inhibitors+anticoagulants (both warfarin and low-dose aspirin [acetylsalicylic acid]) did not show an increased likelihood of concomitant use of gastroprotective drugs, after adjustment for age, sex and number of other drugs. CONCLUSION: Our results indicate that gastroprotective drugs are not prescribed to elderly NSAID users according to guidelines. Furthermore, COX-2-selective inhibitors were used with gastroprotective drugs more often than were traditional NSAIDs. Greater awareness of factors contributing to NSAID/COX-2-selective inhibitor-induced GI complications is warranted, particularly with respect to advanced age and concurrent use of anticoagulants.     

The upper gastrointestinal safety of rofecoxib vs. NSAIDs: an updated combined analysis*

SUMMARY

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are nonspecific cyclo-oxygenase (COX-1/COX-2) inhibitors and are associated with gastrointestinal (GI) toxicity attributable to COX-1 inhibition. Rofecoxib, a COX-2 specific inhibitor, was developed to provide similar efficacy and less GI toxicity than NSAIDs.

Objective: To update the results of a previously performed analysis of the incidence of upper GI perforations, symptomatic gastroduodenal ulcers, and upper GI bleeding (PUBs) with rofecoxib compared with non-selective NSAIDs.

Research design and methods: We compared the incidence of PUBs in a combined analysis of 20 randomized, double-blind, clinical trials of rofecoxib versus NSAIDs. Men and women (N = 17?072) from multinational trial sites with osteoarthritis or rheumatoid arthritis were studied. There was no upper age limit in any of the trials. Investigator-reported PUBs were reviewed by a blinded, external adjudication committee using pre-specified criteria. The incidence of confirmed PUBs, the main outcome measure, among patients treated with rofecoxib 12.5?mg, 25?mg, or 50?mg (combined, N = 10?026) was compared to that among patients treated with ibuprofen, diclofenac, nabumetone, or naproxen (combined, N = 7046).

Results: The incidence of PUBs over 24.8?months was significantly lower with rofecoxib vs. NSAIDs (cumulative incidence 1.6% vs. 3.1%, p < 0.001; rate/100 patient-years 0.74 vs. 1.87; relative risk 0.36, 95% CI 0.24, 0.54). Results of subgroup analyses and comparisons of rofecoxib with individual NSAID comparators were consistent with the primary result, as was an analysis in patients with no PUB risk factors.

Discussion: The analysis demonstrated a consistently lower incidence of confirmed PUBs with rofecoxib than with NSAIDs over 24.8?months. These results confirm those of a previous smaller combined analysis of clinical trials with rofecoxib vs. non-selective NSAIDs in OA patients only, in which the risk reduction for confirmed PUBs was approximately 50%. In addition, this analysis demonstrated risk reductions with rofecoxib vs. NSAIDs in risk subgroups and in patients who did not have any known risk factors for PUBs consistent with the primary result. Some of the studies in this analysis required scheduled endoscopies. Asymptomatic upper GI ulcers or bleeding diagnosed during scheduled procedures were not included in the primary endpoint, which may have caused a bias against rofecoxib.

Conclusions: Treatment with rofecoxib was associated with a statistically significantly (p < 0.001) lower incidence of PUBs than was treatment with NSAIDs. The difference was maintained in subgroups of patients with risk factors, as well as in those with no risk factors, for PUBs.     

180例类风湿关节炎非甾体抗炎药物应用合理性和安全性评价

抽取2017年1月至9月我院使用非甾体类抗炎药（NSAIDs）的类风湿性关节炎（RA）住院患者用药医嘱,统计患者基本信息、胃肠道（GI）和心血管（CV）危险因素以及用药情况,在共计180例RA患者中,只有1.1%的患者使用了NsNSAIDs,绝大多数患者使用选择性环氧合酶-2（COX-2）抑制剂。本院医生应用NSAIDs治疗RA存在用药不合理、不安全的情况,很可能导致不良反应发生率升高,需要探讨改进,以期为临床合理应用NSAIDs提供参考。     

A Comparison of Adverse Renovascular Experiences Among Osteoarthritis Patients Treated with Rofecoxib and Comparator Non-selective Non-steroidal Anti-inflammatory Agents

Summary

Background: Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) inhibit both cyclo-oxygenase (COX) isoenzymes, i.e. COX-1 and COX-2. Rofecoxib, an agent that selectively inhibits COX-2, has been shown to provide equivalent anti-inflammatory and analgesic efficacy to comparator non-selective NSAIDs in osteoarthritis (OA) and other pain models with a significant improvement in gastrointestinal (GI) safety and tolerability. Based on renal physiology studies, it was predicted that rofecoxib would have renovascular effects similar to those observed with non-selective NSAIDs -specifically edema, blood pressure elevation, attenuation of the effects of ACE inhibitors, and (in rare circumstances), acute renal failure might be manifest in a small percentage of patients.

Objective: To assess the renovascular safety profile of rofecoxib in OA patients compared to that of non-selective NSAID comparators.

Methods: Renovascular adverse experiences (AEs) in over 5000 participants in Phase IIb/III OA clinical trials were reviewed and compared between rofecoxib and non-selective NSAID comparators (ibuprofen 800mg tid, diclofenac 50mg tid, nabumetone 1500mg qd).

Results: The incidence of lower extremity edema (LEE) AEs was generally similar between rofecoxib 12.5mg/day, rofecoxib 25mg/day, and non-selective comparator NSAIDs. Treatment discontinuations due to LEE AEs and clinically significant weight gain (> 2 kg) associated with LEE AEs were infrequent and generally similar in all active treatment groups. Congestive heart failure (CHF) was rare in all treatment groups. The incidence of hypertension AEs was low in all active treatment groups. Discontinuations due to hypertension AEs and hypertension AEs requiring a change or adjustment in blood pressure medications were similar and uncommon in all treatment groups. There was only a single report of acute renal failure (in the ibuprofen treatment group).

Conclusions: In the rofecoxib phase IIb/III OA database, the renal safety profile for rofecoxib, a selective inhibitor of COX-2, was generally similar to that of the comparator, non-selective NSAIDs which were studied.     

GP and Patient Perspectives on Treatment with Non-steroidal Anti-inflammatory Drugs for the Treatment of Pain in Osteoarthritis

Summary

Two nationwide surveys were carried out using an electronic poll of 2000 GPs and postal questionnaires were sent to 30000 patients with osteoarthritis (OA).

Both surveys found a high level of gastrointestinal (GI) side-effects in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). Almost every GP (97%) reported experience of patients suffering GI symptoms while on an NSAID, 38% reported patients who had been hospitalised and 4% reported patients who had died owing to NSAID-induced side-effects. Most GPs (92%) said they were concerned about GI safety when prescribing an NSAID and almost a third (32%) said they were concerned about litigation from patients who had experienced a bleed.

Use of NSAIDs in OA remained high, with 44% of GPs prescribing conventional NSAIDs to at least three quarters of their patients, 57% of GPs using simple analgesia and just 12% using a cyclo-oxygenase-2 (COX-2) selective inhibitor in over 74% of patients.

Some 45% of patients reported receiving NSAIDs compared with 43% on simple analgesia and 4% on COX-2 selective inhibitors.

Most GPs (69%) stated that their main therapeutic objective in using an NSAID to treat OA was to control pain without GI side-effects. Almost a quarter (24%) said they used low-dose NSAIDs in the hope that this would control pain without GI side-effects.

Dissatisfaction with treatment was the most common reason reported by GPs for patients on an NSAID to re-present, with 73% citing either breakthrough pain or incomplete pain relief as the most common reason for patient dissatisfaction. This mirrored the patients' perception, with 63% citing inadequate pain relief as their main reason for dissatisfaction with current painkillers compared to 17% who cited stomach upsets or irritation.

Patient and GP appear to be united in their concern at the GI risks of NSAID treatment. In the light of this and recent data on the efficacy, safety profile and cost-effectiveness of COX-2 selective inhibitors, GPs should re-examine their medical management of OA.     

Safety and efficacy of paracetamol and NSAIDs in osteoarthritis: which drug to recommend?

Introduction: Osteoarthritis (OA) is the most common form of arthritis and is a major cause of disability, especially in people ≥ 45 years old. Several international societies recommend the use of both acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) to alleviate OA pain. However, patients with OA often have comorbidities, notably cardiovascular risk factors, which may hamper the use of these analgesics.

Areas covered: This paper reviews the safety of both acetaminophen and NSAIDs in OA. Recent data have pointed to a gastrointestinal and cardiovascular toxicity of acetaminophen, which has been neglected for a long time. In addition, several meta-analyses revealed that acetaminophen is a poor analgesic in OA. Traditional NSAIDs and cyclooxygenase 2 inhibitors (coxibs) have similar analgesic effects but vary greatly in their potential gastrointestinal and cardiovascular toxicity.

Expert opinion: Given the putative gastrointestinal and cardiovascular toxicity and poor analgesic properties of acetaminophen in OA, its use in patients with risk factors is questionable. Acetaminophen should be used at the lowest effective dosage and for the shortest time in all OA patients. Given the different safety profiles, the choice of NSAIDs, traditional or coxibs, should be based on individual patient risk factors. A good knowledge of the different strategies to decrease the gastrointestinal and cardiovascular toxic effects of NSAIDs is key to the management of OA.     

The search for new COX-2 inhibitors: a review of 2002 – 2008 patents

Background: Two COX isoenzymes are known, COX-1 and COX-2, for which the main inhibitors are the NSAIDs. The common anti-inflammatory drugs (such as aspirin, ibuprofen and naproxen) all act by blocking the action of both the COX-1 and COX-2 enzymes. The COX-2 inhibitors represent a new class of drugs that do not affect COX-1 but selectively block COX-2. This selective action provides the benefits of reducing inflammation without irritating the stomach and cardiovascular effects. Objective: This review focuses on patents published in the field during 2002 – 2008, paying particular attention to promising COX-2 inhibitors. Conclusion: Structural analogues of the COX-2 inhibitors celecoxib and valdecoxib, and novel potential pyridazine, triazole, indole and thione derivatives emerge as promising leads for the treatment of inflammation, pain and other diseases.     

Characteristics of children and adolescents first prescribed proton pump inhibitors or histamine-2-receptor antagonists: an observational cohort study

Objective: To describe the characteristics of pediatric patients prescribed proton pump inhibitors (PPIs) vs those of pediatric patients prescribed histamine-2-receptor antagonists (H₂RAs).

Methods: Observational studies were conducted using The Health Improvement Network (THIN) and the PHARMO Database Network. Patients aged 0–18 years who were first prescribed a PPI or H₂RA between October 1, 2009 and September 30, 2012 (THIN) or between September 1, 2008 and August 31, 2011 (PHARMO) were included. Patient characteristics were identified and compared between the PPI and H₂RA cohorts using odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age and sex.

Results: The mean age (years) was higher in the PPI than in the H₂RA cohorts (THIN 12.3 [n?=?8204] vs 5.4 [n?=?7937], PHARMO 11.0 [n?=?15 362] vs 7.1 [n?=?6168]). Previous respiratory disease was more common in the PPI than in the H₂RA cohort in THIN (OR?=?1.19, 95% CI?=?1.08–1.30), as were asthma and respiratory medication use in PHARMO (OR?=?1.27, 95% CI?=?1.12–1.45 and OR?=?1.23, 95% CI?=?1.10–1.38, respectively) and oral corticosteroid use in both databases (OR?=?1.45, 95% CI?=?1.10–1.92 [THIN]; OR?=?2.80, 95% CI?=?2.11–3.71 [PHARMO]). Non-steroidal anti-inflammatory drugs, antibiotics, and oral contraceptives were also more common in PPI than in H₂RA cohorts in both databases.

Conclusions: Pediatric patients receiving PPIs and those receiving H₂RAs may represent different patient populations. PPIs may be more commonly prescribed than H₂RAs among patients with respiratory diseases.