2018 update of French Society for Rheumatology (SFR) recommendations about the everyday management of patients with spondyloarthritis

Objective

To update French Society for Rheumatology recommendations about the management in clinical practice of patients with spondyloarthritis (SpA). SpA is considered across the range of clinical phenotypes (axial, peripheral, and entheseal) and concomitant manifestations. Psoriatic arthritis is included among the SpA phenotypes.

Ketoprofen, acetaminophen, and placebo in the treatment of tension headache

Seven hundred three subjects completed a randomized, double-blind, parallel-group, single-center study comparing the single-dose efficacy of ketoprofen 12.5 mg, ketoprofen 25 mg, acetaminophen 1000 mg, and placebo in the treatment of tension headache. For the primary efficacy variable, 4-hour sum of pain relief intensity differences, ketoprofen 25 mg was significantly superior to placebo. Ketoprofen 25 mg also demonstrated superior pain relief in the first hour after dosing, and the time to meaningful pain relief was significantly shorter for the ketoprofen 25-mg group. Ketoprofen 12.5 mg proved to be significantly superior to placebo for pain relief intensity difference and pain relief at 3 hours, global assessment of medication at 4 hours, and for time to onset of meaningful pain relief. The data suggest a dose response for ketoprofen 12.5 mg and 25 mg. Acetaminophen 1000 mg proved to be numerically more favorable than placebo in most variables, but could not be separated from placebo with statistical significance. In spite of possible inflation of the placebo response due to sensitivity limits of the study, ketoprofen 25 mg demonstrated a more rapid onset of analgesia compared to acetaminophen 1000 mg, and patients' global assessment rated ketoprofen 25 mg higher than acetaminophen 1000 mg.     

Oral Versus Topical Diclofenac Sodium in the Treatment of Osteoarthritis

Osteoarthritis (OA) is one of the most common causes of joint pain in the United States and non-steroidal anti-inflammatories (NSAIDs), such as Diclofenac sodium, which is currently available in two main routes of administration; oral and topical distribution have been established as one of the standard treatments for OA. Generally, oral NSAIDs are well tolerated; however our narrative review suggests that the topical solution had a better tolerability property than oral Diclofenac sodium, especially due to side effects of gastrointestinal bleeding with the utilization of the oral format. In addition, the topical route may be considered a reasonable selection by clinicians for management of musculoskeletal pain in those patients with a history of potential risk and adverse side effects. Most studies reviewed comparing oral versus topical solution of Diclofenac sodium revealed comparable efficacy, with minimal side effects utilizing the topical route. The key point of this narrative review is to help clinicians that currently must decide between very inexpensive diclofenac oral presentations and expensive topical presentations especially in the elderly population and the pros and cons of such decision-making process.     

Effects of dipyrone on inflammatory infiltration and oxidative metabolism in gastric mucosa: comparison with acetaminophen and diclofenac

In the last several years, it has been proposed that neutrophil- and oxygen-dependent microvascular injuries may be important factors in the gastrointestinal toxicity of nonsteroidal antiinflammatory drugs (NSAIDs). In addition, after oral administration, reduced levels of gastric mucosal adenosine triphosphate in response to mitochondrial damage constitute the earliest event on topical mucosal erosions. In these experiments, we compared the implication of active oxygen, lipid peroxidation levels and neutrophil infiltration in gastric mucosal injury induced by the analgesic–antipyretic drugs, dipyrone (pyrazolone derivative) and acetaminophen (nonacidic drug), both with relatively weak antiinflammatory effects, with diclofenac (an acidic NSAID). After 6 hr of oral administration, dipyrone (120 and 500 mg/kg) did not provoke macroscopic lesions on rat gastric mucosa. Only the highest dose (1000 mg/kg) induced slight erosions similar to the same dose of acetaminophen without modifications in lipid peroxidation levels or myeloperoxidase activity. The area of mucosa with lesions, the increase in neutrophil infiltration, and concentration of TBA-reactive substances was significantly higher with diclofenac (50 mg/kg). By contrast, inhibition in superoxide dismutase activity was observed. In a dose-dependent manner, dipyrone and diclofenac decreased the levels of endogenous gluthatione, and the highest dose (1000 mg/kg) also inhibited glutathione peroxidase activity. None of treatments induced changes in xanthine oxidase activity, an index of ischemic condition. These findings confirm the favorable gastric tolerability of dipyrone, since only the highest dose produced weak mucosal lesions similar to that obtained with acetaminophen, and this effect only could be related to a diminished glutathione metabolism. In contrast, diclofenac induced significant erosions, and the data obtained indicate that the enhancement of oxidative stress plays an important role in the pathogenesis of damage.     

Pro-apoptotic effect of nonsteroidal anti-inflammatory drugs on synovial fibroblasts

Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the articular synovial tissues. Although the etiology of RA has not yet been elucidated, physical and biochemical inhibition of synovial hyperplasia, which is the origin of articular destruction, may be an effective treatment for RA. Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used for the treatment of RA. The mechanism of action of NSAIDs generally involves the inhibition of cyclooxygenase (COX) at sites of inflammation. Thus, NSAIDs were not generally considered to have a so-called anti-rheumatic effect, including inhibition of progressive joint destruction and induction of remission. However, certain conventional NSAIDs and celecoxib, a selective COX-2 inhibitor, have been reported to inhibit synovial hyperplasia by inducing the apoptosis of human synovial fibroblasts. Therefore, it has been suggested that such NSAIDs may not only have an anti-inflammatory effect but also an anti-rheumatic effect. In this review, we summarize findings about the pro-apoptotic effect, in other words, anti-proliferative effect of NSAIDs on synovial fibroblasts from patients with RA.     

5-ASA and colorectal cancer chemoprevention in inflammatory bowel disease: Can we afford to wait for ‘best evidence’?

Patients with inflammatory bowel disease have a higher risk of developing colorectal cancer. The main risk factors for colorectal cancer are not suitable targets for therapeutic intervention, and primary chemoprevention is an intriguing therapeutic option. The analogies between acetyl-salicylic acid and 5-amino-salicylic acid, and the results obtained by using acetyl-salicylic acid as a chemopreventive agent in patients with sporadic colorectal cancer have prompted the study of potential chemopreventive effects of 5-amino-salicylic acid in inflammatory bowel disease. The results of both epidemiological and experimental studies have shown that long-term 5-amino-salicylic acid treatments appear to have a chemopreventive effect. The evidence for this effect is provided by retrospective and case-control studies whose results, however, do not reach the highest grades for evidence-based recommendations. Nevertheless, these results are supported by a series of experimental studies demonstrating the multiplicity of actions of 5-amino-salicylic acid. Although data regarding the chemopreventive effect of 5-amino-salicylic acid may not be rigorous enough to meet the criteria for the highest evidence-based medicine recommendations, we feel that the argument to wait until we have Grade A evidence is not necessarily rational in this case, because discontinuation of 5-amino-salicylic acid treatment to perform a randomised controlled trial would be unethical secondary to their proven efficacy for maintenance treatment.     

NSAIDs在幽门螺杆菌相关性胃黏膜病变中的作用

目的 了解NSAIDs与Hellicobecter pylori感染在胃黏膜病变中的作用。方法 患者190例，①病例选择：连续服用NSAIDs治疗2周-12周190例。男性121例，女性69例。平均年龄55岁。②均经胃镜检查和病理组织学检查。对糜烂性胃炎的胃镜诊断和病理诊断胃黏膜炎症分级。③进行H．pylori感染的检测。分为H．pylori感染组与H．prlori阴性组。分析两组的病理组织学改变的特点，了解是否有显著性差异。结果 ①胃镜检查，轻度糜烂106例（55．8％，106／190）。中．重度糜烂84例（44．2％，84／190）。糜烂性胃炎的轻重程度与服药的剂量时间无明显的相关性。②H．pylori感染组46例（24．2％）。H．prlori阴性组144例（75．8％）。③两组病人胃镜诊断的糜烂性胃炎程度无显著性差异（P〉0．05）。④病理情况：H．prlori感染组黏膜中．重度胃炎明显多于H．prlori阴性组（P〈0．01）。⑤病理改变中有淋巴组织增生56例。其中H．prlori感染组有淋巴组织增生22例（47．8％），H．prlori阴性组34例（23．6％）。134例未见淋巴组织增生，其中H．pylori感染组24例（52．2％），H．pylori阴性组110例（76．4％）。两组相比，有显著性差异（P〈0．01）。结论 服用NSAIDs2周以上对胃黏膜有不同程度的损伤。服用NSMDs同时合并H．pylori感染的患者的胃黏膜损伤的严重程度远远高于非感染组。NSAIDs与H．pylori感染是导致胃黏膜损伤的独立危险因子，它们对胃黏膜的损伤作用是叠加的。NSAIDs相关性胃病合并H．pylori感染，根除H．prlori治疗是必要的。     

Nonsteroidal Anti-Inflammatory Drugs Versus Corticosteroid for Treatment of Shoulder Pain: A Systematic Review and Meta-Analysis

Objective

To compare the treatment efficacy between corticosteroid injection and nonsteroidal anti-inflammatory drugs (NSAIDs) for patients with shoulder pain.

Data Sources

PubMed and EMBASE databases were searched from inception to January 2014. Reference lists of the retrieved studies were additionally scrutinized.

Study Selection

Randomized controlled trials (RCTs) comparing corticosteroid injection with NSAIDs for treatment of shoulder pain were included. The primary outcome was remission, and the secondary outcomes were pain relief and improvement of range of active abduction. Study selection was conducted by 2 researchers independently. Any disagreements were solved by discussion and confirmed by the third reviewer.

Data Extraction

Two reviewers independently conducted data extraction and the quality assessment. Data regarding patients, intervention, control, and outcomes were extracted from the included trials.

Data Synthesis

Six high-quality RCTs of 267 patients meeting the inclusion criteria were included. For an outcome of remission, NSAIDs were less effective than corticosteroid in 4 or 6 weeks (relative risk, .64; 95% confidence interval, .45–.92). NSAIDs did not significantly differ with corticosteroid in pain relief and improvement of range of active abduction.

Conclusions

Current meta-analysis suggests that NSAIDs are less effective than corticosteroid in achieving remission in patients with shoulder pain at 4 or 6 weeks after treatment. Considering the limited number of studies and small size of each trial, the results should be interpreted with caution, and more high-quality RCTs are encouraged.     

Nonsteroidal anti-inflammatory drugs (NSAIDs) in older people: Prescribing patterns according to pain prevalence and adherence to clinical guidelines

The evidence on the patterns of nonsteroidal anti-inflammatory drug (NSAID) use according to pain prevalence and clinical guidelines in older people is sparse. This cross-sectional study examined the patterns of NSAID use according to pain prevalence and concordance with clinical guideline recommendations for safe NSAID use in older people, in relation to duration of use, patterns of use, concomitant use of proton pump inhibitors (PPIs), and prevalence of specific drug interactions. Community-dwelling men (n = 1696) age ?70 years living in Sydney were studied. 8.2% (n = 139) of participants reported regular NSAID use compared with 2.9% (n = 50) reporting as-needed use. The mean treatment duration for regular NSAID use was 4.9 years, suggesting long-term rather than short-term use as recommended by the guidelines. Although guidelines recommend use of PPIs together with an NSAID, only 25.2% of regular NSAID users reported PPI use. Regular NSAID users were significantly more likely to report use of opioid analgesics (P < .0001) compared with nonregular users. In relation to pain prevalence, regular NSAID users were significantly more likely to report chronic pain (P < .0001), recent pain (P = .0001), and chronic intrusive pain (P < .0001) compared with nonregular users. The findings of this study indicate that NSAID prescribing practices do not align with clinical guidelines for safe use in older people. This difference between the guideline recommendations and what is happening in the real world should be explored further.