European journal of rheumatology and inflammation最新文献

This double-blind clinical trial compares droxicam, a new non-steroidal anti-inflammatory agent and the reference compound diclofenac sodium. After a 7 day placebo run-in period, 80 patients with gonarthrosis and coxarthrosis were randomized to receive 20mg/day of droxicam and 150mg/day of diclofenac for 6 weeks. Evaluations were carried out at weeks 0 (placebo run-in), 2,3, and 6. Both drugs showed statistically significant improvements in all clinical measurements (index of severity, pain intensity, morning stiffness, maximal forced flexion and extension of the knee) after 6 weeks of treatment. Investigator's and patient's opinions were consistent with these results. The consumption of paracetamol was significantly lower amongst patients treated with droxicam. Withdrawals due to lack of therapeutic efficacy did not occur. A lower incidence of side effects, mostly upper gastrointestinal symptoms, was noticed amongst droxicam-treated patients. However, two patients in the droxicam group were withdrawn at week 3 and two days after week 6 because of epigastric pain and nausea, and cutaneous rash, respectively. Both study drugs are of benefit in reducing pain and improving joint motion and function in patients with coxarthrosis and gonarthrosis.

This double-blind randomized controlled trial compares the efficacy of droxicam (20mg/day) and that of indomethacin (100mg/day) administered to 20 patients (7 men, 13 women; aged 54.7 +/- 13.2 years) with active classical or definite rheumatoid arthritis during 9 weeks, after a 7-day single-blind run-in paracetamol (1,500mg/day) period. Evaluations were carried out at weeks 0 (washout), 1,2,4,6 and 9. After 9 weeks of treatment, both drugs showed a statistically significant improvement of joint pain intensity, articular index (number of swollen or painful joints and degree of involvement), duration of morning stiffness, functional capacity, and level of fatigue. Inter-treatment differences at all study intervals were not observed. Grip strength improved only in indomethacin-treated patients. Withdrawals due to lack of therapeutic efficacy did not occur. Side effects occurred in four patients from each group. One patient in the indomethacin group withdrew at the week 1 due to epigastric pain and heartburn. In conclusion, droxicam (20mg/day) seems to be as effective as indomethacin (100mg/day) in the alleviation of symptoms in patients with rheumatoid arthritis.

A novel in vitro microassay is described which allows the direct effects of short-lived cells or transient cell processes on cartilage matrix to be investigated. The method involves layering cells onto 2 microns cryostat sections of cartilage and assessing matrix integrity with quantitative histochemistry. Rat polymorphonuclear neutrophils (PMNs) caused glycosaminoglycan (GAG) loss from sections of bovine nasal cartilage. This loss of GAG was greatly enhanced by the presence of zymosan, phorbol ester or calcium ionophore. Similar results were obtained using human articular cartilage with human PMNs. This technique may be useful in the detection of novel chondroprotective agents.

Components of the kallikrein-kininogen-kinin are activated in response to noxious stimuli (chemical, physical or bacterial), which may lead to excessive release of kinins in the synovial joints that may produce inflammatory joint disease. The inflammatory changes observed in synovial tissue may be due to activation of B2 receptors. Kinins also stimulate the synthesis of other pro-inflammatory agents (PGs, LTs, histamine, EDRF, PGI2 and PAF) in the inflamed joint. B2 receptor antagonists may provide valuable agents as new analgesic drugs. Further, it is suggested that substances directed to reduce the activation of KKS may provide a pharmacological basis for the synthesis of novel anti-rheumatic or anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs have been implicated in renal impairment. The purpose of this report is to review the effect of etodolac, a new anti-inflammatory agent, on renal function and the effect of renal impairment on etodolac pharmacokinetics. Pharmacokinetic and renal function studies were conducted in normal and in renally impaired volunteers. Additionally, the renal safety of etodolac was assessed in 2,629 arthritic patients who were treated in clinical trials. The results suggest that etodolac does not affect renal function in normal individuals, nor does it exacerbate underlying renal insufficiency when administered to patients with mild to moderate renal impairment. The pharmacokinetics of etodolac are unchanged in patients on hemodialysis and in elderly patients. Furthermore, no patient was withdrawn from clinical trials for significantly abnormal renal function test values resulting from etodolac therapy alone.

We have shown that interleukin-1 (IL-1) suppresses expression of cartilage-specific types II and IX collagens by cultured human chondrocytes. This inhibition is potentiated by agents which block IL-1-stimulated PGE2 production (J. Clin. Invest. 82:2026, 1988). In contrast, expression of types I and III collagens and fibronectin, matrix components produced by chondrocytes that have lost cartilage-specific phenotype, is increased by IL-1, particularly when IL-1-stimulated synthesis of PGE2 is blocked by a prostaglandin synthetase inhibitor. Etodolac is a new NSAID which is an effective inhibitor of PGE2 synthesis. The enhanced potency of etodolac in chondrocytes (compared with macrophages) suggests that this drug may have selective effects on different target cell types. The present studies were undertaken to compare the effects of etodolac and other nonsteroidal anti-inflammatory drugs (NSAIDs) on IL-1-induced modulation of chondrocyte phenotype. Juvenile human costal chondrocytes or adult articular chondrocytes in primary culture were incubated with etodolac, indomethacin or ketoprofen in the absence or presence of IL-1 beta. After treatment the [3H] proline-labelled collagens were analyzed by SDS-PAGE and type I and type II collagen mRNAs were analyzed by Northern or dot hybridization. Indomethacin (0.3-300 nM) or ketoprofen (2-2000 nM) produced a dose-dependent suppression of type II collagen synthesis associated with decreased levels of type II collagen mRNA in the absence of IL-1, while they potentiated the inhibitory effects of IL-1. In contrast, etodolac (2-2000 nM) maintained expression of type II collagen protein and mRNA. Etodolac unmasked a stimulatory effect of IL-1 on synthesis of type I collagen and fibronectin and levels of type I collagen mRNA, but to a lesser extent than indomethacin. These results suggest that, despite equipotent inhibitory effects of etodolac (IC50 congruent to 10 nM) on PGE2 biosynthesis compared with indomethacin (IC50 congruent to 1.0 nM) or ketoprofen (IC50 congruent to 10 nM), etodolac may be capable of maintaining type II collagen expression by chondrocytes. In vivo this could help to prevent the detrimental effects of mediators such as IL-1 on cartilage matrix synthesis in inflammatory joint diseases.

Etodolac is a new nonsteroidal anti-inflammatory drug (NSAID). Published and unpublished data on etodolac in pain management are reviewed to assess the analgesic effectiveness of this drug. Data are presented from four representative studies that showed the analgesic activity of etodolac in postsurgical pain models. These results suggest that the drug would have analgesic utility in other painful conditions such as gout and musculoskeletal disorders. The efficacy of etodolac in such conditions is confirmed by the results from eight controlled clinical studies in patients with gouty arthritis, tendinitis and bursitis, and acute sports injuries. Etodolac 200 or 300 mg twice a day (b.i.d.) or 200 mg three times a day (t.i.d.) was compared with naproxen 500 mg b.i.d. and diclofenac 50 mg b.i.d. or 50 mg t.i.d. All three NSAIDs provided analgesia, and etodolac was comparable in efficacy to the comparators. The data presented in this review suggest a future role for etodolac as an analgesic as well as an anti-inflammatory agent.

Etodolac is a new nonsteroidal anti-inflammatory drug (NSAID) with potent analgesic and antiarthritic properties. The purpose of these randomized, double-blind, parallel-group studies was to compare etodolac with other standard NSAIDs or placebo for the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Results of rheumatoid arthritis and osteoarthritis studies showed etodolac (200 to 300 mg b.i.d. or 200 mg t.i.d.) to be comparable to naproxen (500 mg b.i.d.), piroxicam (20 mg once daily), and diclofenac (50 mg t.i.d.). Key efficacy variables improved significantly (p less than or equal to 0.05) in all treatment groups, and there were no significant between-group differences. Studies comparing etodolac (200 mg b.i.d.) with indomethacin (50 mg t.i.d.) for treatment of ankylosing spondylitis showed significant improvement from baseline in both the patient's and physician's global assessments for both treatments. Titrated-dose studies compared etodolac (50 to 200 mg b.i.d.) with naproxen (250 to 375 mg b.i.d.) and placebo for the treatment of ankylosing spondylitis. Both active drugs resulted in greater improvement than did placebo in the patient's and investigator's global assessments. These results indicate that etodolac is as effective as naproxen, piroxicam, and diclofenac for the treatment of rheumatoid arthritis and osteoarthritis. Moreover, it is comparable to naproxen and indomethacin and superior to placebo for the treatment of ankylosing spondylitis.

The safety of etodolac, a new nonsteroidal anti-inflammatory drug (NSAID), was reviewed by examining data from 3,302 patients enrolled in double-blind and open-label clinical trials and from 8,334 patients taking etodolac in post-marketing surveillance studies. The review determined that gastrointestinal disturbances are the most frequently reported side effects, followed by headache, dizziness, rash, and pruritus. The rate of abdominal pain and dyspepsia is similar to that observed with several other NSAIDs but is lower than that seen with aspirin. Gastrointestinal ulceration occurs in less than 0.3% of patients taking etodolac, and drug-related hepatic, renal, and hematologic dysfunctions are rare. The elderly appear to be no more at risk of experiencing adverse effects than the general population. Overall, the review confirmed the excellent safety profile of etodolac reported previously.