A multicenter, randomized, controlled trial to evaluate the safety profile, tolerability, and efficacy of rofecoxib in advanced elderly patients with osteoarthritis

Truitt, K. E.; Sperling, Rhoda; Ettinger, W. H.; Greenwald, Maria; DeTora, Lisa; Zeng, Qi; Bolognese, James A.; Ehrich, Elliot W.

doi:10.1007/bf03351533

Cited by 55 publications

(38 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…147 The study was performed in 22 centres in Europe (not including the UK). No additional outcome data were provided by the authors of this study.…”

Section: Characteristics Of Studiesmentioning

confidence: 99%

A comparison of the cost-effectiveness of five strategies for the prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: a systematic review with economic modelling

Brown¹,

Hooper²,

Elliott³

et al. 2006

Health Technol Assess

135

View full text Add to dashboard Cite

Non-UK purchasers will have to pay a small fee for post and packing. For European countries the cost is £2 per monograph and for the rest of the world £3 per monograph.You can order HTA monographs from our Despatch Agents:-fax (with credit card or official purchase order) -post (with credit card or official purchase order or cheque) -phone during office hours (credit card only).Additionally the HTA website allows you either to pay securely by credit card or to print out your order and then post or fax it. NHS libraries can subscribe free of charge. Public libraries can subscribe at a very reduced cost of £100 for each volume (normally comprising 30-40 titles). The commercial subscription rate is £300 per volume. Please see our website for details. Subscriptions can only be purchased for the current or forthcoming volume. Contact details are as follows: Payment methods Paying by chequeIf you pay by cheque, the cheque must be in pounds sterling, made payable to Direct Mail Works Ltd and drawn on a bank with a UK address. Paying by credit cardThe following cards are accepted by phone, fax, post or via the website ordering pages: Delta, Eurocard, Mastercard, Solo, Switch and Visa. We advise against sending credit card details in a plain email. Paying by official purchase orderYou can post or fax these, but they must be from public bodies (i.e. NHS or universities) within the UK. We cannot at present accept purchase orders from commercial companies or from outside the UK. How do I get a copy of HTA on CD?Please use the form on the HTA website (www.hta.ac.uk/htacd.htm). Or contact Direct Mail Works (see contact details above) by email, post, fax or phone. HTA on CD is currently free of charge worldwide.The website also provides information about the HTA Programme and lists the membership of the various committees. HTA Health Technology Assessment is indexed and abstracted in Index Medicus/MEDLINE, Excerpta Medica/EMBASE and Science Citation Index Expanded (SciSearch ® ) and Current Contents® /Clinical Medicine. NHS R&D HTA ProgrammeT he research findings from the NHS R&D Health Technology Assessment (HTA) Programme directly influence key decision-making bodies such as the National Institute for Health and Clinical Excellence (NICE) and the National Screening Committee (NSC) who rely on HTA outputs to help raise standards of care. HTA findings also help to improve the quality of the service in the NHS indirectly in that they form a key component of the 'National Knowledge Service' that is being developed to improve the evidence of clinical practice throughout the NHS.The HTA Programme was set up in 1993. Its role is to ensure that high-quality research information on the costs, effectiveness and broader impact of health technologies is produced in the most efficient way for those who use, manage and provide care in the NHS. 'Health technologies' are broadly defined to include all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care, rather than settings of car...

show abstract

“…147 The study was performed in 22 centres in Europe (not including the UK). No additional outcome data were provided by the authors of this study.…”

Section: Characteristics Of Studiesmentioning

confidence: 99%

A comparison of the cost-effectiveness of five strategies for the prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: a systematic review with economic modelling

Brown¹,

Hooper²,

Elliott³

et al. 2006

Health Technol Assess

135

View full text Add to dashboard Cite

show abstract

“…This may be the reason for the occurrence of side effects such as salt and water retention and the lack of a linear dose dependence of the analgesic and anti-inflammatory effects of rofecoxib Truitt et al, 2001). …”

Section: Ap-1 Activation and Nf-b Inhibition Through Rofecoxib 1157mentioning

confidence: 99%

“…Hence, the COX-2 selectivity of rofecoxib might at least partly contribute to the increase of the cardiovascular risk. Another feature with rofecoxib is the lack of a clear dose-effect relationship concerning its clinical analgesic and also its anti-inflammatory efficacy Truitt et al, 2001). Thus, there is no reliable information about which dose will probably work for an individual patient.…”

mentioning

confidence: 99%

Opposite Effects of Rofecoxib on Nuclear Factor-κB and Activating Protein-1 Activation

Niederberger

Tegeder²,

Schäfer³

et al. 2002

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Rofecoxib is a selective cyclooxygenase (COX)-2 inhibitor approved for the treatment of pain and inflammation in rheumatoid and osteoarthritis. Daily doses between 12.5 and 50 mg were found to reduce pain and inflammation, however, without a clear dose-effect relationship. Interestingly, rofecoxib treatment is associated with an unexpected incidence of renal adverse events compared with other COX inhibitors. Here, the effects of rofecoxib on the transcription factors nuclear factor-B (NF-B) and activating protein-1 (AP-1) were analyzed to find out whether transcriptional changes might explain the lack of clear dose dependency and the occurrence of renal side effects. In vitro, rofecoxib dose dependently inhibited DNA binding capacity of NF-B at doses of 10 to 100 M, whereas the binding activity of AP-1 was considerably increased at 100 M. In vivo, the anti-inflammatory effect of rofecoxib was equal at 1 and 10 mg/kg, whereas 50 mg/kg caused a significant further reduction of a zymosan-induced paw edema. This was associated with a clear decrease of inducible nitric oxide synthase (iNOS) protein expression in the spinal cord at this dose. At 1 and 10 mg/kg, however, iNOS was increased but COX-2 was decreased. Thus, the expression of proinflammatory proteins was similarly inconsistent as transcription factor regulation. In conclusion, the opposite effects of rofecoxib on AP-1 and NF-B may explain the lack of clear dose dependency with rofecoxib in clinical studies or animal experiments. The effects on AP-1 may possibly affect renal sodium transport because certain renal sodium channels are regulated through AP-1. Transcription factor regulation might therefore influence both wanted and unwanted effects of rofecoxib.

show abstract

“…In the treatment of patients with OA, rofecoxib administration once daily has been compared with that of placebo (Ehrich et al 1999b(Ehrich et al , 2001 (Truitt et al 2001) with the duration of trials ranging from 1 to 52 weeks. The majority of the studies were conducted on patients with OA of the knee or hip in a randomized, placebo-controlled and double-blind manner.…”

Section: Rofecoxibmentioning

confidence: 99%

“…R ofecoxib 12.5-50 mg daily has been reported to be more effective than placebo in a 6-week double-blind study in patients with OA (nˆ672) (Ehrich et al 2001). In another study (Ehrich et al 1999b), rofecoxib (25 and 125 mg daily), when compared with placebo in 262 patients with OA of knee following varied periods of treatment (i.e., one, two and six weeks), exhibited significant improvement in the primary end points, the WOM AC pain subscale and patients' assessment of arthritic pain (P < 0.001 for both dosages).…”

Section: Rofecoxibmentioning

confidence: 99%

Rofecoxib: an update on physicochemical, pharmaceutical, pharmacodynamic and pharmacokinetic aspects

Ahuja

Singh

2003

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

Rofecoxib (MK-966) is a new generation non-steroidal anti-inflammatory agent (NSAID) that exhibits promising anti-inflammatory, analgesic and antipyretic activity. It selectively inhibits cyclooxygenase (COX)-2 isoenzyme in a dose-dependent manner in man. No significant inhibition of COX-1 is observed with rofecoxib up to doses of 1000 mg. The pharmacokinetics of rofecoxib has been found to be complex and variable. Mean oral bioavailability after single dose of rofecoxib (12.5, 25 or 50 mg) is 93% with t m a x varying widely between 2 and 9 h. It is highly plasma-protein bound and is metabolized primarily by cytosolic reductases to inactive metabolites. Rofecoxib is eliminated predominantly by hepatic metabolism with a terminal half-life of approximately 17 h during steady state. Various experimental models and clinical studies have demonstrated rofecoxib to be superior, or at least equivalent, in anti-inflammatory, analgesic and antipyretic efficacy to comparator nonselective NSAIDs in osteoarthritis, rheumatoid arthritis and other pain models. Emerging evidence suggests that rofecoxib may also find potential use as supportive therapy in various pathophysiologic conditions like Alzheimer's disease, and in various malignant tumours and polyps, where COX-2 is overly expressed. Rofecoxib is generally well-tolerated. Analysis of data pooled from several trials suggests that rofecoxib is associated with fewer incidences of clinically symptomatic gastrointestinal ulcers and ulcer complications vis-a Á -vis conventional NSAIDs. However, this gastropreserving effect may be negated by concurrent use of low-dose aspirin for cardiovascular risk reduction. Rofecoxib tends to show similar tolerability for renal and cardiothrombotic events as compared with nonnaproxen nonselective NSAIDs. No clinically significant drug interaction has been reported for rofecoxib except with diuretics, where it reverses their salt-wasting effect and thus can be clinically exploited in electrolyte-wasting disorders. There is only modest information about the physicochemical and pharmaceutical aspects of rofecoxib. Being poorly water soluble, its drug delivery has been improved using varied formulation approaches. Although it is stable in solid state, rofecoxib is photosensitive and base-sensitive in solution form with its degradation mechanistics elucidated. Analytical determinations of rofecoxib and its metabolites in biological fluids employing HPLC with varied types of detectors have been reported. Isolated studies have also been published on the chromatographic and spectrophotometric assay of rofecoxib and its degradants in bulk samples and pharmaceutical dosage forms. The current article provides an updated overview on the physicochemical, pharmaceutical, pharmacokinetic and pharmacodynamic vistas of rofecoxib.

show abstract

A multicenter, randomized, controlled trial to evaluate the safety profile, tolerability, and efficacy of rofecoxib in advanced elderly patients with osteoarthritis

Cited by 55 publications

References 30 publications

A comparison of the cost-effectiveness of five strategies for the prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: a systematic review with economic modelling

A comparison of the cost-effectiveness of five strategies for the prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: a systematic review with economic modelling

Opposite Effects of Rofecoxib on Nuclear Factor-κB and Activating Protein-1 Activation

Rofecoxib: an update on physicochemical, pharmaceutical, pharmacodynamic and pharmacokinetic aspects

Contact Info

Product

Resources

About