Non-steroidal Anti-inflammatory Drugs In Osteoarthritis Research Articles

Technology of magnetophoresis of topical nonsteroidal anti-inflammatory drugs in osteoarthritis (clinical and experimental study)

BACKGROUND: The high degree of evidence for the use of pharmacotherapy currently does not cause doctors to doubt, however, the use of non-pharmacological approaches in general and physical factors in particular is the subject of many years of discussion for them. One of the main places in the pharmacotherapy of osteoarthritis is occupied by nonsteroidal anti-inflammatory drugs, while our interest is associated with a group of so-called topical drugs.
 AIM: In order to methodically substantiate the application of the magnetophoresis technology of the topical form of nimesulide in an experimental study, the influence of the magnetic field on the spectroscopic and thixotropic characteristics of the drug was determined, and the clinical efficacy of the combined use of magnetotherapy and the transdermal form of nimesulide in comparison with the application of the drug and magnetic therapy with a pulsed low-frequency magnetic field was determined.
 MATERIAL AND METHODS: A randomized study involving 60 patients with osteoarthritis of the knee joints was performed. The experimental part of the study on the effect of the magnetic field on the structure and properties of the gel form of the preparation containing 1% nimesulide (chemical formula: 4'-nitro-2'-phenoxy-methane sulfonanilide) was carried out in laboratory conditions. The clinical part of the study included the use of local therapy (application of nimesulide gel in an amount of 24 g) to the skin in the knee joint area, followed by the placement of inductors of the ALMAG+ magnetic therapy apparatus on the medial and lateral surfaces of the knee joint. The impact was carried out according to the recommended "3+1" program.
 RESULTS: An analysis of the effectiveness of therapy conducted in a group of 60 patients with osteoarthritis of the knee joints showed high efficiency, expediency and safety of the use of the technology under study in the treatment of patients with joint diseases.
 CONCLUSION: Due to the synergistic effect on the pathogenesis of articular syndrome, the gel form of nimesulide and the magnetic field have a unidirectional effect: anti-inflammatory, decongestant, analgesic, microcirculatory. In addition, the magnetic field enhances the absorption and flow of the drug into the tissues, being a physical enhancer (amplifier), which significantly affects the result of treatment.

Long-term use of nonsteroidal anti-inflammatory drugs for pain control in patients with osteoarthritis: results of the 12-month observational study AELITA (Analgesia: Effective Treatment Using The Therapeutic Algorithm)

Non-steroidal anti-inflammatory drugs (NSAIDs) are the primary means of managing chronic osteoarthritis (OA) pain. The choice of NSAIDs is based on an analysis of the risk of adverse reactions (ARs). Objective: to evaluate the efficacy and safety of long-term use of NSAIDs for pain control in patients with OA in real clinical practice.Patients and methods. To assess the results of long-term use of NSAIDs in OA, a 12-month observational non-interventional study was conducted. It included 611 patients with knee, hip and generalized OA, and nonspecific back pain associated with OA of the facet joints. All patients were prescribed aceclofenac (Aertal®) 200 mg/day. The patients' condition was assessed 2 weeks, 3, 6, 9 and 12 months after the start of therapy. The following parameters were determined: the intensity of pain during movement and the general health assessment (GA) according to the visual analogue scale (VAS, 10 cm); pain intensity according to the Likert verbal rating scale (VRS) (0–4); the number of patients with a pain reduction of ≥50% from baseline; patients' assessment of the result of therapy according to Likert VRS (1–5). The development of ARs was recorded at each visit.Results and discussion. By month 12, 46.8% of patients had dropped out of observation. In patients who continued the study, the average severity of pain according to the VAS at baseline, after 2 weeks, 3, 6, 9 and 12 months was: 6.5±1.2; 4.8±1.4; 3.2±1.4; 2.6±1.4; 2.2±1.1; 1.4±1.1 cm, respectively (significant differences compared to the baseline for all points – p<0.05). The same differences were obtained in GA assessment.Within the indicated time frame, the number of patients with moderate / severe pain (on the Likert scale) decreased from 77.8 to 24.9; 2.9; 2.3; 0.9 and 0%, respectively. The number of patients with a pain reduction of ≥50% from baseline was 12.0; 65.1; 81.0; 88.5 and 84.0%, respectively. A good or excellent assessment of treatment results after 2 weeks was given by 63.3% of patients, and after 12 months – by 95.6%. ARs were observed in about 30% of patients, mainly mild or moderate dyspepsia (in 11.1–23.3%) and arterial hypertension (in 7.1–10.9%). No serious ARs were registered.Conclusion. Aceclofenac is an effective and relatively safe drug for the long-term management of chronic pain in OA.

Network Meta-analysis on efficacy and safety of non-steroidal anti-inflammatory drugs for osteoarthritis in middle aged and old people

Objective To systematically evaluate the efficacy and safety of different non-steroidal anti-inflammatory drugs (NSAIDs) in middle-aged and old Chinese patients with osteoarthritis(OA). Methods A systematic literature search was conducted through PubMed, Cochrane Library, CNKI, Wan Fang Data and VIP databases to collect randomized controlled trials with non-steroidal anti-inflammatory drugs in middle-aged to old Chinese OA patients. The search time was from the establishment of the database to November 17, 2020. Two researchers independently carried out literature screening, data extraction and literature quality evaluation. Bayesian network meta-analysis was conducted with R3.6.0 software. Results 28 RCTs were included with 2531 patients. Based on the last follow-up pain visual analogue scale (VAS) score, the ranking chart showed that Etoricoxib had the highest probability of having the lowest pain VAS score (88.55%). In terms of total effective rate, the ranking chart showed that the probability of Etoricoxib as first choice was the highest (92.49%). As far as safety, diclofenac sodium patch had the lowest adverse effects rate (59.10%). Conclusion The results of this study indicated that Etoricoxib was the most effective treatment for middle-aged and old Chinese OA patients. It can significantly reduce the OA pain. Diclofenac sodium patch had the least adverse effects.

Predicting response to topical non-steroidal anti-inflammatory drugs in osteoarthritis: an individual patient data meta-analysis of randomized controlled trials.

ObjectivesTo identify predictors of the specific (difference between treatment and placebo) and overall (change from baseline in treatment arm) treatment effects of topical NSAIDs in OA.MethodsRandomized controlled trials (RCTs) of topical NSAIDs in OA were identified through systematic literature searching and inquiry to pharmaceutical companies. The raw, de-identified data were analysed in one-stage individual patient data meta-analysis (IPD-MA). Negative values for treatment effects (0–100 scale) indicate pain reduction.ResultsOf 63 eligible RCTs, 15 provided IPD (n = 1951 on topical NSAID), including 11 placebo-controlled RCTs (n = 1587 on topical NSAIDs, 1553 on placebo). Seven potential predictors of response were examined. Topical NSAIDs were superior to placebo [−6 (95% CI −9, −4)], with a small, but statistically significant greater effect in women than men [difference −4 (95% CI −8, −1)]. The overall treatment effect was 4-fold larger than the specific effect [−25 (95% CI −31, −19)] and increased with greater baseline pain severity (P < 0.001). No differences in efficacy were observed for age, BMI, features of inflammation, duration of complaints or radiographic OA severity.ConclusionTopical NSAIDs are effective for OA pain relief. Greater overall pain relief in individuals with more baseline pain might be due to contextual and non-specific effects, including regression to the mean. Additional factors that have been linked either mechanistically or through empirical evidence to outcomes should be selected for inclusion across future RCTs in order to facilitate the identification of response predictors through IPD-MA.

Topical Diclofenac, an Efficacious Treatment for Osteoarthritis: A Narrative Review.

Multiple head-to-head trials have demonstrated that topical nonsteroidal anti-inflammatory drugs (NSAIDs), including topical diclofenac, provide at least equivalent analgesia, improvement in physical function, and reduction of stiffness compared with oral NSAIDs in osteoarthritis and have fewer systemic adverse events. While efficacy of topical diclofenac in osteoarthritis is well established, understanding of the time to onset of action, duration of effect, and the minimum effective concentration is limited. Factors likely to influence these parameters include drug penetration and localization. Diclofenac concentrations in the joint tissues are likely to be more relevant than plasma concentrations. However, although diclofenac penetrates and is retained in these “effect compartments” at the site of inflammation and drug activity, no specific minimum effective concentration of diclofenac in plasma or synovial tissue has been identified. Recent evidence suggests that a reduction in inflammatory markers may be a better predictor of efficacy than plasma concentrations. This narrative review explores existing evidence in these areas and identifies the gaps where further research is needed. Based on our findings, topical NSAIDs such as diclofenac should be considered as a guideline-supported, generally well-tolerated, and effective first-line treatment option for knee and hand OA, especially for older patients and those who have comorbid conditions and/or risk factors for various systemic (gastrointestinal, hepatic, renal, or cardiovascular) adverse events associated with oral NSAIDs, particularly at high doses and with long-term use.Electronic supplementary materialThe online version of this article (10.1007/s40744-020-00196-6) contains supplementary material, which is available to authorized users.

Safety of Oral Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: What Does the Literature Say?

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely recommended and prescribed to treat pain in osteoarthritis. While measured to have a moderate effect on pain in osteoarthritis, NSAIDs have been associated with wide-ranging adverse events affecting the gastrointestinal, cardiovascular, and renal systems. Gastrointestinal toxicity is found with all NSAIDs, which may be of particular concern when treating older patients with osteoarthritis, and gastric adverse events may be reduced by taking a concomitant gastroprotective agent, although intestinal adverse events are not ameliorated. Cardiovascular toxicity is associated with all NSAIDs to some extent and the degree of risk appears to be pharmacotherapy specific. An increased risk of acute myocardial infarction and heart failure is observed with all NSAIDs, while an elevated risk of hemorrhagic stroke appears to be restricted to the use of diclofenac and meloxicam. All NSAIDs have the potential to induce acute kidney injury, and patients with osteoarthritis with co-morbid conditions including hypertension, heart failure, and diabetes mellitus are at increased risk. Osteoarthritis is associated with excess mortality, which may be explained by reduced levels of physical activity owing to lower limb pain, presence of comorbid conditions, and the adverse effects of anti-osteoarthritis medications especially NSAIDs. This narrative review of recent literature identifies data on the safety of non-selective NSAIDs to better understand the risk:benefit of using NSAIDs to manage pain in osteoarthritis.

Safety of Topical Non-steroidal Anti-Inflammatory Drugs in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

ObjectiveWe aimed to assess the safety of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials.MethodsA comprehensive literature search was undertaken in the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus electronic databases. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with topical NSAIDs in patients with OA were eligible for inclusion. Authors and/or study sponsors were contacted to obtain the full report of AEs. The primary outcomes were overall severe and serious AEs, as well as the following MedDRA System Organ Class (SOC)-related AEs: gastrointestinal, vascular, cardiac, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue.ResultsThe search strategy identified 1209 records, from which 25 papers were included in the qualitative synthesis and 19 were included in the meta-analysis, after exclusions. Overall, more total AEs (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.04–1.29; I2 = 0.0%) and more withdrawals due to AEs (OR 1.49, 95% CI 1.15–1.92; I2 = 0.0%) were observed with topical NSAIDs compared with placebo. The same results were achieved with topical diclofenac, largely driven by an increase in skin and subcutaneous tissue disorders (OR 1.73, 95% CI 0.96–3.10), although the difference was not statistically significant compared with placebo. No significant difference in the odds for gastrointestinal disorders was observed between topical NSAIDs and placebo (OR 0.96, 95% CI 0.73–1.27).ConclusionsTopical NSAIDs may be considered safe in the management of OA, especially with regard to low gastrointestinal toxicity. The use of topical NSAIDs in OA should be considered, taking into account their risk: benefit profile in comparison with other anti-OA treatments.Electronic supplementary materialThe online version of this article (10.1007/s40266-019-00661-0) contains supplementary material, which is available to authorized users.

A sound approach to choosing nonsteroidal anti-inflammatory drugs for osteoarthritis

The current guidelines for prescribing analgesic therapy for osteoarthritis (OA) are based on the latest knowledge about the pathogenesis of this disease and the mechanism of action of analgesics. The leading principle of choosing analgesics is to assess the nature of pain and the patient's condition, adverse drug reactions. This is directly related to nonsteroidal anti-inflammatory drugs (NSAIDs) that are now the most important class of painkillers used in OA. Among the drugs of this class, meloxicam, a representative of the oxicam group, which relatively equally inhibits cyclooxygenase 1 and 2 and also affects the activity of microsomal prostaglandin E2 synthase 1, should be identified. This drug is characterized by a proven efficacy and a favorable safety profile. Nevertheless, the need for multifactorial evaluation of treatment-associated complications should be recognized as a priority when using any NSAIDs.

Factors affecting the results of analgesic therapy. Results of the Russian multicentre study of NOTE (NSAID: Open-label Trial of Efficacy).

To identify factors affecting the effectiveness of NSAIDs in patients with OA and LBP. An observational study was conducted to evaluate the effectiveness of a 2-week course of NSAIDs in OA and LBP in real clinical practice. The study group consisted of 3604 patients with OA and LBP (60.6% women and 39.4% men, mean age 55.0±13.4 years). According to the study design, aceclofenac (Airtal) and other NSAIDs used in the ratio 1:1. The main criterion of effectiveness was the frequency of complete pain relief after 2 weeks of therapy. In addition, the decrease of pain and general health were determined on a 10-point numerical rating scale (NRS). We compared the frequency of complete pain relief in patients who had and did not have the studied factors. The value of the studied factors was determined using OR (95% CI). Most patients received aceclofenac (54.9%), as well as diclofenac (2.0%), ketoprofen (1.9%), lornoxicam (2.2%), meloxicam (13.7%), naproxen (2.1%), nimesulide (5.8%), celecoxib (5.9%), ethicoxib (7.1%) and other NSAIDs (4.4%); 56.2% of patients received muscle relaxants, mainly tolperisone (74.7%), vitamin B (10.4%), and proton pump inhibitors (42.8%). Complete pain relief was achieved in 54.8% of patients. The pain decrease and general health improvement were (for NRS) 63.9±13.4% and 61.7±14.8%, respectively. The efficacy of aceclofenac was slightly higher than in the whole group: complete pain relief was in 59.9% of patients. Adverse events in aceclofenac use were observed in 2.3% of patients, other NSAIDs-from 2.4 to 14.1%. The frequency of complete pain relief was higher in men: OR 1,239 (95% CI 1.08-1.418; p=0.002), who had the first episode of pain - OR 3.341 (95% CI 2.873-3.875; p=0.000), a good&quot; response &quot; to NSAIDs in history - OR 1.656 (95% CI 1.385-1.980; p=0.000) and received NSAIDs in combination with muscle relaxants - OR 1.218 (95% CI 1.067-1.390; p=0.004). The effect of therapy is lower in patients 65 years and older-OR 0,378 (95% CI 0.324-0.442; p=0,000), with body mass index &gt;30 kg/m² - OR 0.619 (95% CI 0.529-0.723; p=0.000), with severe pain (≥7 points NRS) - OR 0.662 (95% CI 0.580-0.756; p=0.002), with pain at rest, - OR 0.515 (95% CI 0.450-0,589; p=0.000), pain at night - OR 0.581 (95% CI 0.501-0.672; p=0.000) and the presence of stiffness - OR 0.501 (95% CI 0.438-0,573; p=0.000). Treatment results are significantly worse in the cases of combination of LBP and joint pain, as well as pain in the trochanter major and pes anserinus area (p&lt;0.001). NSAIDs are the first-line medications for the pain treatment in LBP and OA. Aceclofenac is effective and safe in this conditions. When carrying out analgesic therapy should take into account factors that affect the effectiveness of treatment: old age, overweight, insufficient effect of NSAIDs in history, severe pain, signs of &quot;inflammatory&quot; pain, multiple sources of pain.

Differential chemoreactome analysis of glucosamine sulfate and non-steroidal anti-inflammatory drugs: promising synergistic drug combinations

Glucosamine sulfate (GS) is essential for the regeneration of cartilaginous tissue and, in addition, it has anti-inflammatory properties comparable to those of nonsteroidal anti-inflammatory drugs (NSAIDs). Clinical trials indicate the synergism between GS and NSAIDs in osteoarthritis (OA) and other joint diseases. Objective : to estimate the degree of synergism between different combinations of GS and NSAIDs. Material and methods . A differential chemoreactome analysis was employed to evaluate the effects of GS and seven agents from the class of NSAIDs, such as ketorolac, nimesulide, diclofenac, meloxicam, dexketoprofen, celecoxib, and etoricoxib, for estimating the degree of synergism between different combinations of GS and NSAIDs. Results and discussion . Dexketoprofen is shown to enhance most effectively the anti-inflammatory properties of GS as compared to ketorolac that does this to a lesser extent. The drug should be practically used as follows: the most effective combination (GS + dexketoprofen (or GS + ketorolak) is taken at week 1 of treatment for rapid pain elimination; thereafter there may be a combination of GS and NSAIDs, the intake of which is associated with minimal adverse reactions for a longer time. Conclusion . The investigation has shown that the coadministration of GS and NSAIDs is promising in treating joint diseases.

Biologic drugs as analgesics for the management of osteoarthritis.

Biologic drugs are novel therapeutic agents with demonstrated effectiveness in the management of a variety of chronic inflammatory disorders. Unmet needs in the treatment of chronic pain have led physicians to utilize a similar approach to patients suffering from conditions not characterized by systemic inflammation such as osteoarthritis (OA). The aim of this review is to discuss the current knowledge on the use of commonly used biologic agents [i.e., anti-tumor necrosis factor alpha (anti-TNF alpha) and anti-nerve growth factor (anti-NGF)] for the management of OA. A narrative literature review of studies investigating the use of biologic agents for the management of osteoarthritis was conducted. We searched MEDLINE and EMBASE for English language publications. A hand-search of reference lists of relevant studies was also performed. Current evidence does not support TNF-alpha inhibition for the management of OA, although a selected subgroup of these patients with a marked inflammatory profile may benefit from this therapy. Anti-NGF therapy has been shown to reduce pain and improve function compared to placebo and non-steroidal anti-inflammatory drugs in OA but concerns remain regarding the safety of such treatment. The discrepant results observed in RCTs of biologic agents may be related to heterogeneity, small sample sizes, and differences in the mode of administration of these drugs. Anti-NGF therapy is efficacious for pain in patients with hip and knee OA. Despite the fact that current data suggests that anti-cytokine treatments have limited efficacy in patients with chronic osteoarthritic pain, larger and better designed studies in more selected populations are justified to determine whether such therapeutic approaches can improve outcomes in this disabling condition where our medical treatment armamentarium is relatively poor.

Osteoarthritis of the knee and hip. Part II: therapy with ibuprofen and a review of clinical trials

We review the pharmacological properties and clinical evidence pertaining to the efficacy of ibuprofen as a first-line treatment in hip and knee osteoarthritis (OA). In the context of our previous paper's exploration of the aetiology and pathogenesis of OA as a basis for pharmacotherapy, we discuss the pharmacokinetics (PK) and clinical pharmacodynamics (PD) of ibuprofen relevant to OA. Although widely used, the benefits and risks of ibuprofen, especially compared with other non-steroidal anti-inflammatory drugs (NSAIDs) and placebo, have only recently been evaluated in OA of the hip and knee in randomized-controlled clinical trials (RCT). The efficacy and occurrence of adverse reactions from ibuprofen was compared with placebo in a structural review of the literature and systematic review of RCTs in large-scale clinical trials. Ibuprofen has been found to result in approximately 50-60% improvement over placebo in WOMAC scores, including those reflecting inflammatory joint pain in knee and hip OA or other indices of pain, disability and impaired function. Mega-trials performed in comparison with the newer NSAIDs, the coxibs, have shown that ibuprofen has comparable therapeutic benefits and although serious gastrointestinal conditions are sometimes more frequent after short-term treatment, longer-term (several months) therapy in OA reduces the advantages of the coxibs over other NSAIDs including ibuprofen. Cardiovascular risk, though present with coxibs and some NSAIDs in OA, is lower or slightly so with ibuprofen compared with coxibs. Ibuprofen is effective and relatively safe (especially at low over-the-counter doses and in the short term) for mild-to-moderate OA of the knee and hip. The PK properties of ibuprofen in OA (short plasma t½) confer advantages of this drug for OA, while evidence for clinically relevant PD benefits in joints of patients with OA, though limited, is suggestive of local anti-inflammatory activity.

5-Lipoxygenase Metabolic Contributions to NSAID-Induced Organ Toxicity

Cyclooxygenase (COX)-1, COX-2, and 5-lipoxygenase (5-LOX) enzymes produce effectors of pain and inflammation in osteoarthritis (OA) and many other diseases. All three enzymes play a key role in the metabolism of arachidonic acid (AA) to inflammatory fatty acids, which contribute to the deterioration of cartilage. AA is derived from both phospholipase A(2) (PLA(2)) conversion of cell membrane phospholipids and dietary consumption of omega-6 fatty acids. Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit the COX enzymes, but show no anti-5-LOX activity to prevent the formation of leukotrienes (LTs). Cysteinyl LTs, such as LTC(4), LTD(4), LTE(4), and leukoattractive LTB(4) accumulate in several organs of mammals in response to NSAID consumption. Elevated 5-LOX-mediated AA metabolism may contribute to the side-effect profile observed for NSAIDs in OA. Current therapeutics under development, so-called "dual inhibitors" of COX and 5-LOX, show improved side-effect profiles and may represent a new option in the management of OA.

Conflicts of interest, authorship, and disclosures in industry-related scientific publications: the tort bar and editorial oversight of medical journals.

Conflicts of interest, authorship, and disclosures in industry-related scientific publications: the tort bar and editorial oversight of medical journals.

An alternative topical treatment of osteoarthritis of the knee with cutaneous diclofenac solution

Background: Osteoarthritis (OA) is the most common chronic degenerative disease, which is characterised by the destruction of the articular cartilage and subchondral bone. The current treatment of OA is based primarily on the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics. There are disadvantages to routinely using NSAIDs in OA. Topical NSAIDs represent a potentially important advance in this regard as they may be significantly safer than oral NSAIDs. Cutaneous diclofenac solution (Pennsaid®) was developed for the treatment of symptomatic OA of the knee and contains diclofenac sodium as an active ingredient and dimethyl sulfoxide (DMSO), a penetration enhancer. Objective: To review: i) dermal drug application; ii) the treatment of OA with systemic and topical NSAID therapies; and iii) the clinical efficiency of Pennsaid on the topical treatment of OA of the knee. Methods: A literature search was carried out on skin, topical drug delivery, treatment of OA and assessment of published clinical studies with Pennsaid. Results and discussion: The clinical studies showed that applying the topical diclofenac solution (Pennsaid) to a painful knee with primary OA could provide symptom relief equivalent to oral diclofenac with minimal systemic side effects; however, studies are needed that compare the effectiveness of Pennsaid with different topical forms of diclofenac.

Celecoxib Plus Aspirin Versus Naproxen and Lansoprazole Plus Aspirin: A Randomized, Double-Blind, Endoscopic Trial

Patients requiring low-dose aspirin along with nonsteroidal anti-inflammatory drugs are at increased risk for gastrointestinal injury. This study compared the incidence of gastroduodenal ulcers in patients treated with low-dose aspirin and a cyclooxygenase-2 selective nonsteroidal anti-inflammatory drug or a nonselective nonsteroidal anti-inflammatory drug plus the proton pump inhibitor lansoprazole. Subjects 18 years or older with osteoarthritis, without gastroduodenal ulcer or erosive esophagitis at baseline endoscopy, and a cardiovascular indication for prophylaxis low-dose (81 or 325 mg) aspirin were prescribed open-label aspirin and blindly randomized to celecoxib 200 mg/day or naproxen 500 mg twice daily plus lansoprazole 30 mg once daily. Endoscopy was performed at 12 weeks or early termination. One thousand forty-five subjects were randomized and received at least 1 dose of study medication, and 854 (n = 426 celecoxib, n = 428 naproxen plus lansoprazole) subjects with both baseline and final visit endoscopies were evaluable for the primary efficacy analysis. Among these subjects, the rate of endoscopically confirmed gastroduodenal ulcers was not different in the celecoxib (9.9%) and naproxen plus lansoprazole (8.9%; treatment difference [95% confidence interval], 1.0% [-2.9% to 4.9%]) groups. In patients with osteoarthritis taking low-dose aspirin, the use of celecoxib or naproxen plus lansoprazole resulted in similar rates of gastroduodenal ulceration.

Risk of Cardiovascular Events in Patients Receiving Celecoxib: A Meta-Analysis of Randomized Clinical Trials

Some nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 selective inhibitors, have been associated with increased cardiovascular (CV) events in recent clinical trials or observational studies. To determine whether the cyclooxygenase-2 selective inhibitor celecoxib affects CV risk, the incidence of CV events was analyzed in patients treated with celecoxib, placebo, or nonselective NSAIDs in the clinical trial database for celecoxib using defined Antiplatelet Trialists' Collaboration end points of nonfatal myocardial infarction, nonfatal stroke, and CV death. Patient data were derived from studies in osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, low back pain, and Alzheimer's disease. This meta-analysis included (1) 7,462 patients exposed to celecoxib 200 to 800 mg/day for 1,268 patient-years compared with 4,057 patients treated with placebo for 585 patient-years, and (2) 19,773 patients treated with celecoxib 200 to 800 mg/day for 5,651 patient-years compared with 13,990 patients treated with nonselective NSAIDs (diclofenac, ibuprofen, naproxen, ketoprofen, and loxoprofen) for 4,386 patient-years. CV events were adjudicated by a 3-member expert end point committee (WBW, JSB, PBG) blinded to treatment group and study. The incidence rates of the combined CV events were not significantly different between patients treated with celecoxib and placebo or between those treated with celecoxib and nonselective NSAIDs. Event rates were similar for adjudicated and nonadjudicated data. Dose of celecoxib, the use of aspirin, or the presence of CV risk factors did not alter these results. In conclusion, these analyses failed to demonstrate an increased CV risk with celecoxib relative to placebo and demonstrated a comparable rate of CV events with celecoxib treatment compared with nonselective NSAIDs.

Consensus Development Conference on the Use of Nonsteroidal Anti-Inflammatory Agents, Including Cyclooxygenase-2 Enzyme Inhibitors and Aspirin

Consensus Development Conference on the Use of Nonsteroidal Anti-Inflammatory Agents, Including Cyclooxygenase-2 Enzyme Inhibitors and Aspirin

Less Use of NSAIDs in Long-Term than in Recent Chondroitin Sulphate Users in Osteoarthritis: a Pharmacy-based Observational Study in France

In clinical trials, long-term use of a specific chondroitin sulphate, Chondrosulf® 400 (CS400) has demonstrated symptomatic efficacy in osteoarthritis comparable to that of nonsteroidal anti-inflammatory drugs (NSAIDs) with significantly fewer side-effects. CS400 could therefore reduce the use of and risks associated with NSAIDs. A cross-sectional observational study was therefore devised in 199 randomly selected pharmacies in France to verify the concomitant use of analgesic and NSAIDs medication in patients prescribed CS400.Consecutive patients filling a prescription for CS400 were prospectively recruited and classified into recent users (3 months or less of continuous use) and long-term users (more than 3 months of continuous use) of CS400. The main outcome measure was current and long-term use of analgesics and NSAIDs.The 844 participating patients included 623 (73.8%) women and 221 (26.2%) men. Mean age was 65.9 years. Ninety eight (11.6%) patients did not use any analgesic or NSAIDs for osteoarthritis; 746 (88.4%) reported the use of at least one of these drugs. Compared to recent users, long-term users of CS400 had a significantly lower current (44.4 versus 52.5%, p < 0.05) and long-term use of NSAIDs (11.8% versus 18.5%, p < 0.05), and of analgesics (70.3 versus 79.3%, p < 0.01).

Why and How to Use NSAIDs in Osteoarthritis

There is an increasing body of evidence that an inflammatory process can be involved in the development and the progression of osteoarthritis. Such inflammation can be observed at both the cartilage, subchondral bone, and synovial tissue level. Of the 2 main categories of anti-inflammatory drugs [corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs)], NSAIDs are the most commonly used oral drugs in osteoarthritis. The symptomatic short-term effect of coxibs is similar to the conventional NSAIDs one and of greater magnitude than the one of analgesics such as paracetamol (acetaminophen). On the basis of current knowledge of potential gastrointestinal and, more importantly, cardiovascular side-effects, the still remaining important question is related to the efficacy-toxicity balance of a chronic systematic daily intake of NSAIDs versus an "at request" (PRN) intake.