Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inducible cyclooxygenase-2 (COX-2), but not constitutive COX-1, can be upregulated in rheumatoid synovial tissue by interleukin-1 beta and phorbol esters and is inhibited by dexamethasone. This supports the role of COX-2 in acute inflammation in arthritis. Selective inhibition of COX-2 by non-steroidal anti-inflammatory drugs (NSAIDs) has been proposed as an approach to reduce their associated side effects while maintaining efficacy. The improved safety profile of selective COX-2 inhibitors will allow more widespread and sustained use than is currently possible with standard NSAIDs. In rheumatoid arthritis they may be used as effective symptomatic relief, in combination with disease modifying therapy at an early stage of disease. In osteoarthritis, and, more particularly, soft tissue rheumatism, pain contributes to the development of chronic disease, therefore the main benefit of selective COX-2 inhibition will be to provide safe, effective pain relief to maintain mobility and reduce disability.
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PMID:Clinical implications of selective cyclooxygenase-2 inhibition. 862 78

Meloxicam is a new preferential cyclooxygenase-2 (COX-2) inhibitor currently for the treatment of osteoarthritis and rheumatoid arthritis. Its pharmacokinetic profile is characterized by a prolonged and almost complete absorption and the drug is > 99.5% bound to plasma proteins. Meloxicam is metabolized to four biologically inactive main metabolites, which are excreted in both urine and faeces. The elimination half-life (t1/2) of meloxicam is approximately 20 h. This is reflected in a total plasma clearance (CL) of 0.42-0.48 1/h. Steady-state plasma concentrations are achieved within 3-5 days. The pharmacokinetic parameters of meloxicam are linear over the dose range 7.5-30 mg and bioequivalence has been shown for a number of different formulations. No interactions were observed following the concomitant administration of food, cimetidine, antacid, aspirin, beta-acetyldigoxin, methotrexate, warfarin or furosemide. Neither hepatic insufficiency nor moderate renal dysfunction have any relevant effects on the pharmacokinetics of meloxicam and dosage adjustments in the elderly are not required.
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PMID:A review of the clinical pharmacokinetics of meloxicam. 863 Jun 30

A multicentre, double-blind, randomized study was conducted in patients with rheumatoid arthritis (RA) in order to compare the efficacy and safety of two different doses of meloxicam, a new preferential cyclooxygenase-2 (COX-2) inhibitor. Four hundred and twenty-three patients were randomized to receive once-daily oral meloxicam 7.5 mg (n = 216) or meloxicam 15 mg (n = 207) for 3 weeks. The Ritchie joint index and pain in the morning were significantly improved versus baseline (P < 0.001) in both groups. There were no significant differences between the effects of each dose with respect to these measures nor with respect to final assessment of global efficacy by the patients. However, the 15 mg dose was associated with a significantly (P < 0.05) better effect on morning stiffness and grip strength. No differences between the doses were observed with regard to the other secondary efficacy parameter (pain at night, body weight and erythrocyte sedimentation rate). Both doses of meloxicam were well tolerated. There were no differences between the doses with respect to global tolerance as assessed by the patient and the patients, 'general condition'. In conclusion, meloxicam at a once-daily dose of either 7.5 or 15 mg is well tolerated and effective in the treatment of patients with RA.
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PMID:A double-blind, three-week study to compare the efficacy and safety of meloxicam 7.5 mg and meloxicam 15 mg in patients with rheumatoid arthritis. 863 Jun 31

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) which preferentially inhibits cyclooxygenase-2 over cyclooxygenase-1. A double-blind parallel-group trial compared meloxicam 7.5 mg once daily (n = 199) with naproxen 750 mg (n = 180) in rheumatoid arthritis. There was no significant difference between the groups regarding the primary efficacy variables (global efficacy assessment by patient and investigator, number of painful/tender and swollen joints) and eight of the ten secondary efficacy endpoints. Only the swollen joint severity index and the number of discontinuations due to lack of efficacy favoured naproxen 750 mg significantly over meloxicam 7.5 mg. Meloxicam was better tolerated in the gastrointestinal (GI) tract, with fewer GI adverse events in the meloxicam-treated group (30.3%) than in the naproxen-treated group (44.7%), where two patients developed ulcers. No ulcers were seen in meloxicam patients. Significantly more patients discontinued due to GI adverse events in the naproxen group. Additionally, there was a significant decrease in haemoglobin and a significant increase in serum creatinine and urea in the naproxen group compared with the meloxicam group. In conclusion, meloxicam 7.5 mg once daily is a promising treatment in rheumatoid arthritis, with efficacy comparable to naproxen 750 mg. Meloxicam has the advantage of a significantly lower incidence of GI and renal side effects.
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PMID:A six-month double-blind trial to compare the efficacy and safety of meloxicam 7.5 mg daily and naproxen 750 mg daily in patients with rheumatoid arthritis. 863 Jun 32

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID), which has a higher activity against cyclooxygenase-2 (COX-2) than against cyclooxygenase-1 (COX-1), with potentially high anti-inflammatory and analgesic action. This study was designed to assess the long-term safety and efficacy of meloxicam 15 mg daily. Three hundred and fifty-seven patients (aged 19-84 yr, mean 56 yr) with rheumatoid arthritis (RA) received meloxicam 15 mg orally once daily, for up to 18 months. Sixty-six per cent of patients remained on therapy for 18 months. Mean global efficacy, assessed by each patient on a visual analogue scale (0 cm = excellent, 10 cm = useless), was 3.32 +/- 3.1 cm at the last study visit (all patients included) and 2.33 +/- 2.25 cm after 18 months. Health status, general condition, morning stiffness, grip strength of right hand, Ritchie joint index, pain in the morning and pain at night all improved significantly. Efficacy was maintained through the study. Only 11.4% of patients discontinued prematurely due to lack of efficacy. Mean global tolerance was good. Twenty-eight per cent of patients experienced gastrointestinal (GI) adverse events, 21% musculoskeletal system disorders, 18% skin disorders and 15% respiratory disorders. Only 13.7% of patients discontinued due to adverse events. Severe GI effects, such as perforation, ulcer and bleeding, occurred in only three patients (0.8%). Withdrawals due to GI adverse events occurred in 3.9% of patients. Meloxicam 15 mg once daily was effective and compared favourably with standard NSAIDs regarding tolerance when administered to patients with RA over an 18 month period.
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PMID:A long-term study to evaluate the safety and efficacy of meloxicam therapy in patients with rheumatoid arthritis. 863 Jun 33

Meloxicam is a new preferential cyclooxygenase-2 (COX-2) inhibitor for the treatment of rheumatic disease. This paper presents a global safety analysis of data from meloxicam clinical studies, focusing on gastrointestinal (GI) adverse events. Meloxicam 7.5 and 15 mg (n = 893 and 3282) were compared with piroxicam 20 mg (n = 906), diclofenac 100 mg slow release (n = 324) and naproxen 750-1000 mg (n = 243). With respect to all GI adverse events, meloxicam 7.5 and 15 mg were significantly better than all comparators in a pooled analysis of double-blind studies in rheumatoid arthritis (RA) and osteoarthritis (OA). When examining non-serious GI events, severe GI events, discontinuous due to GI events, dyspepsia, abdominal pain and upper GI events, both meloxicam doses were significantly better than comparator non-steroidal anti-inflammatory drugs (NSAIDs) in most cases. Where statistical significance was not demonstrated, there was generally a trend in favour of meloxicam. With respect to upper GI perforations, ulcerations and bleedings, the most serious of NSAID-associated side-effects, meloxicam was better tolerated than the comparators, reaching statistical significance for piroxicam and naproxen. Meloxicam's improved GI safety profile is likely to be due to its preferential inhibition of inducible COX-2 relative to constitutive COX-1.
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PMID:Safety of meloxicam: a global analysis of clinical trials. 863 Jun 41

An inducible form of cyclooxygenase-2 (COX-2) has been shown to be upregulated in vitro by various pro-inflammatory agents, such as lipopolysaccharide, IL-1 and TNF, COX-2 appears to be responsible for the increase in prostaglandin synthesis at the site of inflammation. To examine the involvement of COX-2 in inflammation, we analysed the expression of this gene in human rheumatoid arthritis (RA) and in rat adjuvant-induced arthritis. Immunocytochemical studies of synovial membrane biopsies from human RA, osteoarthritic (OA) and normal joints using a COX-2 specific antibody showed positive staining in RA, but not in normal synovial membranes. Specifically, expression of COX-2 was detected in synovial lining cells, lymphoid aggregates and endothelial cells of blood vessels. Although some positive staining was observed in the OA joints, the number of stained cells was dramatically lower and the staining of the cells was less intense than in the rheumatoid tissue. By reverse transcription and polymerase chain reaction analysis, COX-2 mRNA was detected in the rat adjuvant arthritic limb, whereas no COX-2 mRNA was detectable in the normal limb. These observations indicate that COX-2 expression is upregulated in inflammatory joint disease and that COX-2 is a potential therapeutic target for specific inhibition.
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PMID:Expression of cyclooxygenase-2 in human and an animal model of rheumatoid arthritis. 876 Nov 81

A series of sulfonamide-containing 1,5-diarylpyrazole derivatives were prepared and evaluated for their ability to block cyclooxygenase-2 (COX-2) in vitro and in vivo. Extensive structure-activity relationship (SAR) work was carried out within this series, and a number of potent and selective inhibitors of COX-2 were identified. Since an early structural lead (1f, SC-236) exhibited an unacceptably long plasma half-life, a number of pyrazole analogs containing potential metabolic sites were evaluated further in vivo in an effort to identify compounds with acceptable pharmacokinetic profiles. This work led to the identification of 1i (4-[5-(4-methylphenyl)-3-(trifluoromethyl)- H-pyrazol-1-yl]benzenesulfonamide, SC-58635, celecoxib), which is currently in phase III clinical trials for the treatment of rheumatoid arthritis and osteoarthritis.
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PMID:Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benze nesulfonamide (SC-58635, celecoxib). 913 32

This paper reviews clinical trials that have been published during the course of the past year on the rheumatologic diseases. The greatest number of clinical trials were done in rheumatoid arthritis. These trials show promising results for combination therapy with disease-modifying antirheumatic drugs, whereas results of studies with monoclonal antilymphocyte antibodies have been disappointing. The role of oral collagen remains to be defined. Nonsteroidal anti-inflammatory drugs with selective cyclooxygenase-2 (Cox-2) inhibition may have a more favorable toxicity profile and are likely to find wide use. As adjuvant therapy, trimethoprim-sulfamethoxazole appears to be useful in preventing relapses in Wegener's granulomatosis, and patients develop fewer infections. With the exception of juvenile rheumatoid arthritis, intravenous immunoglobulin therapy appeared ineffective in the diseases studied. The inclusion of more standardized and disease-specific outcome measures has enhanced the quality of clinical trials in rheumatology and their applicability to rheumatologic practice.
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PMID:Recent clinical trials in the rheumatic diseases. 913 9

Pain is the major symptom that leads patients to consult their physicians for the treatment of arthritis; therefore, effective pain control is an important goal in the management of this disorder. Pharmacologic therapy begins with simple analgesics and education. In many patients, simple analgesics do not adequately control moderate arthritis pain, and nonsteroidal antiinflammatory drugs (NSAID) are substituted for or added to the analgesic therapy. While NSAID are effective in controlling pain in mild to moderate osteoarthritis (OA), they are associated with significant toxicity (most frequently gastrointestinal) and may even cause complications that result in death. Patients who experience the pain associated with arthritis would therefore benefit from the antiinflammatory and analgesic actions of agents that are devoid of significant toxicities. Cyclooxygenase-2 (COX-2) inhibitors are being evaluated in clinical trials or are in development. These agents appear to inhibit only the COX-2 isoenzyme, which is produced largely during inflammation and is responsible for the biosynthesis of prostaglandins and other mediators of inflammation as well as sensitizers to pain. Because COX-2 inhibitors do not inhibit COX-1 isoenzyme activity at pharmacologic concentrations, they are devoid of many of the toxicities that are typical side effects of NSAID. Short term studies in dental pain, OA, and rheumatoid arthritis found that the COX-2 inhibitor celecoxib was an effective analgesic but did not cause gastroduodenal erosions. It has the potential to provide analgesia and antiinflammatory action in patients with arthritis without the side effects of NSAID. Further studies are required to substantiate these findings.
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PMID:Pain management in osteoarthritis: the role of COX-2 inhibitors. 924 47


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