Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new arthrotec research articles will be listed here shortly after becoming available to us.
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Medical research on arthrotec
Health Technol Assess. 2008 Apr; 12(11): 1-178
Chen YF, Jobanputra P, Barton P, Bryan S, Fry-Smith A, Harris G, Taylor RS
OBJECTIVES: To review the clinical effectiveness and cost-effectiveness of cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drugs (NSAIDs) (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis (OA) and rheumatoid arthritis (RA). DATA SOURCES: Electronic databases were searched up to November 2003. Industry submissions to the National Institute for Health and Clinical Excellence (NICE) in 2003 were also reviewed. REVIEW METHODS: Systematic reviews of randomised controlled trials (RCTs) and a model-based economic evaluation were undertaken. Meta-analyses were undertaken for each COX-2 selective NSAID compared with placebo and non-selective NSAIDs. The model was designed to run in two forms: the 'full Assessment Group Model (AGM)', which includes an initial drug switching cycle, and the 'simpler AGM', where there is no initial cycle and no opportunity for the patient to switch NSAID. RESULTS: Compared with non-selective NSAIDs, the COX-2 selective NSAIDs were found to be equally as efficacious as the non-selective NSAIDs (although meloxicam was found to be of inferior or equivalent efficacy) and also to be associated with significantly fewer clinical upper gastrointestinal (UGI) events (although relatively small numbers of clinical gastrointestinal (GI) and myocardial infarction (MI) events were reported across trials). Subgroup analyses of clinical and complicated UGI events and MI events in relation to aspirin use, steroid use, prior GI history and Helicobacter pylori status were based on relatively small numbers and were inconclusive. In the RCTs that included direct COX-2 comparisons, the drugs were equally tolerated and of equal efficacy. Trials were of insufficient size and duration to allow comparison of risk of clinical UGI events, complicated UGI events and MIs. One RCT compared COX-2 (celecoxib) with a non-selective NSAID combined with a gastroprotective agent (diclofenac combined with omeprazole); this included arthritis patients who had recently suffered a GI haemorrhage. Although no significant difference in clinical GI events was reported, the number of events was small and more such studies, where patients genuinely need NSAIDs, are required to confirm these data. A second trial showed that rofecoxib was associated with fewer diarrhoea events than a combination of diclofenac and misoprostol (Arthrotec). Previously published cost-effectiveness analyses indicated a wide of range of possible incremental cost per quality-adjusted life-year (QALY) gained estimates. Using the simpler AGM, with ibuprofen or diclofenac alone as the comparator, all of the COX-2 products are associated with higher costs (i.e. positive incremental costs) and small increases in effectiveness (i.e. positive incremental effectiveness), measured in terms of QALYs. The magnitude of the incremental costs and the incremental effects, and therefore the incremental cost-effectiveness ratios, vary considerably across all COX-2 selective NSAIDs. The base-case incremental cost per QALY results for COX-2 selective NSAIDs compared with diclofenac for the simpler model are: celecoxib (low dose) 68,400 pounds; celecoxib (high dose) 151,000 pounds; etodolac (branded) 42,400 pounds; etodolac (generic) 17,700 pounds; etoricoxib 31,300 pounds; lumiracoxib 70,400 pounds; meloxicam (low dose) 10,300 pounds; meloxicam (high dose) 17,800 pounds; rofecoxib 97,400 pounds; and valdecoxib 35,500 pounds. When the simpler AGM was run using ibuprofen or diclofenac combined with proton pump inhibitor (PPI) as the comparator, the results change substantially, with the COX-2 selective NSAIDs looking generally unattractive from a cost-effectiveness point of view (COX-2 selective NSAIDs were dominated by ibuprofen or diclofenac combined with PPI in most cases). This applies both to 'standard' and 'high-risk' arthritis patients defined in terms of previous GI ulcers. The full AGM produced results broadly in line with the simpler model. CONCLUSIONS: The COX-2 selective NSAIDs examined were found to be similar to non-selective NSAIDs for the symptomatic relief of RA and OA and to provide superior GI tolerability (the majority of evidence is in patients with OA). Although COX-2 selective NSAIDs offer protection against serious GI events, the amount of evidence for this protective effect varied considerably across individual drugs. The volume of trial evidence with regard to cardiovascular safety also varied substantially between COX-2 selective NSAIDs. Increased risk of MI compared to non-selective NSAIDs was observed among those drugs with greater volume of evidence in terms of exposure in patient-years. Economic modelling shows a wide range of possible costs per QALY gained in patients with OA and RA. Costs per QALY also varied if individual drugs were used in 'standard' or 'high'-risk patients, the choice of non-selective NSAID comparator and whether that NSAID was combined with a PPI. With reduced costs of PPIs, future primary research needs to compare the effectiveness and cost-effectiveness of COX-2 selective NSAIDs relative to non-selective NSAIDs with a PPI. Direct comparisons of different COX-2 selective NSAIDs, using equivalent doses, that compare GI and MI risk are needed. Pragmatic studies that include a wider range of people, including the older age groups with a greater burden of arthritis, are also necessary to inform clinical practice.
Value Health. 2008 Jan 8;
Al MJ, Maniadakis N, Grijseels EW, Janssen M
Objective: To assess the balance between costs and upper gastrointestinal (GI) side effects of treatment with celecoxib, nonsteroidal antiinflammatory drugs (NSAIDs) alone, NSAID plus misoprostol, NSAID plus histamine-2 receptor antagonist (H(2)RA), NSAID plus proton pump inhibitor (PPI), and Arthrotec in The Netherlands. Methods: A model was used to convene data from various sources on the probability of GI side effects and resource use. The probabilities of GI side effects for celecoxib and NSAIDs alone were derived from trial data. Calculations were based on 6 months of treatment, and were from a societal perspective. Distinction was made between low-, medium-, and high-risk patients. An extensive probabilistic sensitivity analysis was performed to address uncertainty. Results: Assuming an average patient, the total costs per 6 months of therapy were: celecoxib euro255, NSAIDs alone euro166, NSAID plus misoprostol euro285, NSAID plus H(2)RA euro284, NSAID plus PPI euro243, and Arthrotec euro187. Treatment with celecoxib was associated with the lowest number of GI side effects and related deaths. Incremental costs per life-year saved for Arthrotec compared to NSAIDs alone were euro5676 for all patients and euro526 for medium-to-high-risk patients, whereas for high-risk patients, Arthrotec dominated NSAID alone. For celecoxib compared to Arthrotec, the incremental cost-effectiveness ratios (ICERs) were euro56,667, euro33,684, and euro15,429, respectively. Conclusion: Assuming a limit of euro20,000 per life-year gained, from an economic point of view, Arthrotec is the preferred treatment when all patients or medium-to-high-risk patients are considered. In high-risk patients, celecoxib is the preferred treatment strategy.
Rheumatology (Oxford). 2006 Jul; 45(7): 903-10
Rahme E, Toubouti Y, Hunsche E
OBJECTIVES: Lack of efficacy or tolerability of some non-steroidal anti-inflammatory drugs (NSAIDs) may lead to switching between non-selective NSAIDs (nsNSAIDs) and cyclooxygenase-2 (COX-2) selective inhibitors (coxibs), potentially increasing treatment costs due to additional physician visits and wastage of medication. This study assessed drug switching and associated costs among elderly chronic NSAID users. METHODS: Data for patients who filled their first prescription for a coxib or nsNSAID in 2001 were obtained from the Quebec Health Insurance Agency. Follow-up was terminated at the earliest of: 1 yr, the first day without NSAID exposure following the index filling date, or death. Patients could switch NSAIDs several times during follow-up. Person-days of exposure were categorized by the NSAID most recently dispensed: rofecoxib, celecoxib, Arthrotec(R) or non-Arthrotec (nA) nsNSAID. Cox regression models compared time to switch between groups, adjusting for patient baseline characteristics. Upon a switch, pills remaining from the previous prescription were considered wasted. The costs of wasted pills and switch-associated physician visits were estimated. RESULTS: Throughout follow-up, patients filled 38 267 prescriptions for rofecoxib, 31 282 for celecoxib, 1108 for Arthrotec and 4388 for nA-nsNSAIDs. Adjusted hazard ratios (95% confidence interval) for switching versus nA-nsNSAIDs were: rofecoxib, 0.39 (0.35-0.44); celecoxib, 0.43 (0.38-0.48). Compared with nA-nsNSAID prescriptions, adjusted switching-related healthcare costs were 53 and 47% lower on average for rofecoxib and celecoxib prescriptions, respectively. These costs were 34% higher for Arthrotec prescriptions than for nA-nsNSAIDs. CONCLUSIONS: Compared with recipients of nsNSAIDs, coxib recipients were less likely to switch medications and had approximately half the adjusted costs for switching-related wasted resources per prescription.
Acetaminophen for osteoarthritis.
Cochrane Database Syst Rev. 2006; CD004257
Towheed TE, Maxwell L, Judd MG, Catton M, Hochberg MC, Wells G
BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis. Published guidelines and expert opinion are divided over the relative role of acetaminophen (also called paracetamol or Tylenol) and non-steroidal anti-inflammatory drugs (NSAIDs) as first-line pharmacologic therapy. The comparative safety of acetaminophen and NSAIDs is also important to consider. This update to the original 2003 review includes nine additional RCTs. OBJECTIVES: To assess the efficacy and safety of acetaminophen versus placebo and versus NSAIDs (ibuprofen, diclofenac, arthrotec, celecoxib, naproxen, rofecoxib) for treating OA. SEARCH STRATEGY: We searched MEDLINE (up to July 2005), EMBASE (2002-July 2005), Cochrane Central Register of Controlled Trials (CENTRAL), ACP Journal Club, DARE, Cochrane Database of Systematic Reviews (all from 1994 to July 2005). Reference lists of identified RCTs and pertinent review articles were also hand searched. SELECTION CRITERIA: Published randomized controlled trials (RCTs) evaluating the efficacy and safety of acetaminophen alone in OA were considered for inclusion. DATA COLLECTION AND ANALYSIS: Pain, physical function and global assessment outcomes were reported. Results for continuous outcome measures were expressed as standardized mean differences (SMD). Dichotomous outcome measures were pooled using relative risk (RR) and the number needed to treat (NNT) was calculated. MAIN RESULTS: Fifteen RCTs involving 5986 participants were included in this review. Seven RCTs compared acetaminophen to placebo and ten RCTs compared acetaminophen to NSAIDs. In the placebo-controlled RCTs, acetaminophen was superior to placebo in five of the seven RCTs and had a similar safety profile. Compared to placebo, a pooled analysis of five trials of overall pain using multiple methods demonstrated a statistically significant reduction in pain (SMD -0.13, 95% CI -0.22 to -0.04), which is of questionable clinical significance. The relative percent improvement from baseline was 5% with an absolute change of 4 points on a 0 to 100 scale. The NNT to achieve an improvement in pain ranged from 4 to 16. In the comparator-controlled RCTs, acetaminophen was less effective overall than NSAIDs in terms of pain reduction, global assessments and in terms of improvements in functional status. No significant difference was found overall between the safety of acetaminophen and NSAIDs, although patients taking traditional NSAIDS were more likely to experience an adverse GI event (RR 1.47, (95% CI 1.08 to 2.00). 19% of patients in the traditional NSAID group versus 13% in the acetaminophen group experienced an adverse GI event. However, the median trial duration was only 6 weeks and it is difficult to assess adverse outcomes in a relatively short time period. AUTHORS' CONCLUSIONS: The evidence to date suggests that NSAIDs are superior to acetaminophen for improving knee and hip pain in people with OA. The size of the treatment effect was modest, and the median trial duration was only six weeks, therefore, additional considerations need to be factored in when making the decision between using acetaminophen or NSAIDs. In OA subjects with moderate-to-severe levels of pain, NSAIDs appear to be more effective than acetaminophen.
J Rheumatol. 2005 Nov; 32(11): 2212-7
Ashworth NL, Peloso PM, Muhajarine N, Stang M
OBJECTIVE: To identify the unbiased differences in the risk of hospitalization with peptic ulcer disease (PUD) or gastrointestinal (GI) hemorrhage among populations using 4 nonsteroidal antiinflammatory drugs (NSAID): nabumetone, Arthrotec, diclofenac plus a cytoprotective agent dispensed separately (diclo+coRx), and naproxen. METHODS: A population based historical cohort study using linked data from provincial healthcare databases. The population of the province of Saskatchewan, Canada, entitled to drug plan benefits in 1995 was eligible (roughly 91% of 1 million people). Participants were identified if they filled a prescription for one of the 4 study NSAID (18,424 individuals). They were then followed for 6 months to determine outcomes. Logistic regression was used to produce estimates of the risk of admission to hospital with a primary diagnosis of PUD or GI hemorrhage associated with the study drugs unbiased by known confounders. RESULTS: Compared to Arthrotec the adjusted odds of hospitalization for PUD for participants taking nabumetone was 2.6 (95% CI 1.0-6.6), diclo+coRx 6.8 (95% CI 3.5-13.4), and naproxen 7.9 (95% CI 3.9-15.9). Compared to nabumetone the adjusted odds of hospitalization for PUD for participants taking diclo+coRx was 2.7 (95% CI 1.2-6.0) and naproxen 3.1 (95% CI 1.3-7.1). No significant differences were noted in terms of admissions for GI hemorrhage. CONCLUSION: Participants taking nabumetone and Arthrotec had significantly lower risk of hospitalization for PUD than those taking the other study drugs. Arthrotec was superior to nabumetone in a head to head comparison and especially when compared with the diclo+coRx and naproxen groups. No short term differences were seen in the rates of admission for GI hemorrhage. It appears that inherent gastroprotective strategies with Arthrotec and to a lesser extent with nabumetone do translate into decreased serious GI side effects at the population level in the short term.
Cochrane Database Syst Rev. 2005; CD005115
Garner SE, Fidan DD, Frankish R, Maxwell L
BACKGROUND: Editor's note: The anti-inflammatory drug rofecoxib (Vioxx) was withdrawn from the market at the end of September 2004 after it was shown that long-term use (greater than 18 months) could increase the risk of heart attack and stroke. Further information is available at www.vioxx.com.Osteoarthritis is a chronic disease of the joints, characterised by joint pain, stiffness and loss of physical function. Its onset is age-related and occurs usually between the ages of 50 and 60. It is the commonest cause of disability in those aged over 65, with OA of the knee and/or hip affecting over 20 per cent of the elderly population. OBJECTIVES: To establish the efficacy and safety of rofecoxib in the management of OA by systematic review of available evidence. SEARCH STRATEGY: We searched the following databases up to August 2004: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment Database. The bibliographies of retrieved papers and content experts were consulted for additional references. SELECTION CRITERIA: All eligible randomised controlled trials (RCTs) were included. No unpublished RCTs were included in this edition of the review. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers. A validated checklist was used to score the quality of the RCTs. Comparable trials were pooled using fixed effects model. MAIN RESULTS: Twenty-six RCTs were included. The comparators were placebo, diclofenac, ibuprofen, naproxen, nimesulide, nabumetone, paracetamol, celecoxib and Arthrotec. The evidence reviewed indicated that rofecoxib was more effective than placebo (patient global response RR 1.75 95% CI: 1.35, 2.26) but was associated with more adverse events (RR 1.32 95% CI 1.11, 1.56). There were no consistent differences in efficacy between rofecoxib and any of the active comparators at equivalent doses. Endoscopic studies indicated that compared to ibuprofen 800 mg three times a day, rofecoxib caused fewer erosions and gastric ulcers at doses of 25mg and 50mg; the difference in duodenal ulcers was evident only at a dose of 25mg. Rofecoxib 50mg also caused more endoscopically observed ulcers greater than rofecoxib 25mg (RR 2.48 CI: 1.21, 5.11). Very few of the trials reported overall rates of GI adverse events although rofecoxib was found to cause fewer GI events than naproxen. Only one of the nine trials comparing rofecoxib to celecoxib reported on the overall rates of GI events and this was a comparison of the higher recommended dose of rofecoxib with the lower recommended dose of celecoxib. Similarly, the three trials in older hypertensive patients that examined the cardiovascular safety of rofecoxib and celecoxib used non-comparable doses; the results of these studies indicated that rofecoxib caused more patients to have oedema and a clinically significant increase in systolic blood pressure. This difference between rofecoxib and celecoxib was not evident in studies conducted in more general populations. AUTHORS' CONCLUSIONS: Rofecoxib was voluntarily withdrawn from global markets in October 2004 therefore there are no implications for practice concerning its use. There remains a number of questions over both the benefits and risks associated with Cox II selective agents and further work is ongoing.
Klin Med (Mosk). 2004; 82(10): 56-61
Lazebnik LB, Kotsiubinskaia OB, Konev IuV, Drozdov VN
The prohypertensive effect of non-steroidal anti-inflammatory drugs (NSAIDs) can be manifested by the decreased efficiency of antihypertensive therapy. The tactics of their differential use in relation to the its effect on blood pressure (BP) in patients with osteoarthrosis (OA) and arterial hypertension (AH) has not been developed for the most effective and safe therapy. In this connection, it is extremely urgent to study the comparative safety of used NSAIDs as to their prohypertensive effect and to work out the management of patients with AH and OA. Ninety-eight patients with second-third degree OA of the knee and hip joints concurrent with the pain syndrome and first-second grade AH were followed up. Diclofenac, ketoprofen, arthrotec, nimesulide, and meloxicam were used. In a control group, the analgesic tramadol was supplemented to the therapy. AH was controlled by enalapril monotherapy. In groups of patients receiving diclofenac, arthrotec, meloxicam, and ketoprofen, there was a trend for the number of cases of an adequate nocturnal BP lowering (Dipper) to reduce and for those of an inadequate nocturnal BP decrease (Non-dipper), which may be accounted for by the prohypertensive effect of these drugs; this trend was most pronounced in the diclofenac and arthrotec groups. Despite its marked prohypertensive effect, nimesulide did not impair circadian BP variations. The central-acting analgesic tramadol exerted no prohypertensive effect and it did not increase BP values. The prohypertensive effect of the tested NSAIDs and tramadol increases in the following order: tramadol, ketoprofen, meloxicam, nimesulide, arthrotec, diclofenac.
Reumatismo. 2004 Apr-Jun; 56(2): 89-93
Rothschild BM
This study was conducted to assess the feasibility of COX1 NSAID substitution for aspirin for preventative therapy related to circulating anticoagulants, as manifest by inhibition of platelet aggregation. There was no difference in platelet aggregation inhibition between aspirin, naproxen, ketoprofen or diclofenac and misoprostol (in combination in the form of Arthrotec). As COX1 NSAIDs appear equivalent in platelet inhibition efficacy to aspirin, therapeutic regimens can be simplified in those individuals who require an NSAID for other problems. Further, despite its short serum halflife, Arthrotec appears as effective as an antiplatelet agent. Controlled, double blind studies of efficacy in blocking clinical events (both cardiovascular and gastrointestinal) are recommended.
J Rheumatol. 2004 May; 31(5): 951-6
Ashworth NL, Peloso PM, Muhajarine N, Stang M
OBJECTIVE: To identify the unbiased differences in all cause mortality among populations using 4 non-steroidal antiinflammatory drugs (NSAID): nabumetone, Arthrotec, diclofenac plus a cytoprotective agent dispensed separately (diclofenac+), and naproxen. METHODS: We performed a population based historical cohort study using linked data from several provincial health care databases. Logistic regression was used to produce estimates of the mortality associated with the study drugs unbiased by known confounders. The entire population of the province of Saskatchewan, Canada entitled to drug plan benefits in 1995 was eligible (approximately 91% of 1 million people). Participants were identified if they filled a prescription for one of the 4 study NSAID (18,424 individuals). They were then followed forward in time for 6 months to determine all cause mortality. RESULTS: Compared to nabumetone, the adjusted odds of death for participants taking Arthrotec was 1.4 (95% confidence interval, CI: 0.9-2.1), for diclofenac+ 2.0 (1.3-3.1), and naproxen 3.0 (1.9-4.6). CONCLUSION: The multivariate analysis showed patients taking nabumetone and Arthrotec had significantly lower mortality than those taking other study drugs. Nabumetone had 1/3 to 1/5 the mortality associated with the diclofenac+ and naproxen groups. It appears that inherent gastroprotective strategies in the study NSAID may translate into decreased mortality at the population level.
J Rheumatol. 2004 Jan; 31(1): 140-9
Pope JE, Prashker M, Anderson J
OBJECTIVE: To determine whether or not N of 1 trials with diclofenac/misoprostol (Arthrotec) are superior and cost-effective compared with standard treatment in osteoarthritis (OA). METHODS: We randomized subjects with OA who were "uncertain that nonsteroidal antiinflammatory drugs (NSAID) were helpful" to 2 different groups. One group received conventional treatment whereby they were told to stop their NSAID and to wait and see what happened. If necessary, treatment with other NSAID and all other usual OA treatment strategies were used. The other group received a series of crossover trials with diclofenac 50 mg and misoprostol 200 micro g twice a day or an identical placebo for 2 weeks each in a random double-blinded manner. Every 4 weeks they chose which treatment they preferred. By 3 months, if there was no clear preference, the N of 1 trials were discontinued. All trial participants were seen monthly for 3 months and at 6 months. All costs (direct and indirect) were collected for both groups. Costs of research-generated visits were not counted in the "conventional treatment" group. RESULTS: Fifty-one subjects were randomized (stratified by most symptomatic OA area): 25 with knee, 7 with hip, and 19 with hand OA. Twenty-four were randomized into the N of 1 group. There were no differences in the baseline and followup variables including age, income, education, past and current NSAID use, global assessment, Health Assessment Questionnaire (HAQ), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Medical Outcome Study Short Form-36 (SF-36) scores. In the N of 1 group, 11 patients preferred diclofenac in total (of whom 7 did only one round, 2 did 2 rounds, and 2 did 3 rounds). None of the N of 1 patients preferred placebo and 11 had no preference (2 dropped out at baseline). At 6 months, 15 of 19 in "conventional therapy" and 17 of 21 in N of 1 were taking NSAID. That is, NSAID appeared to be effective in 81% of N of 1 subjects and 79% of conventionally treated patients, even though subjects were initially uncertain that their NSAID were helpful. The total OA-related costs in Canadian dollars per patient (in 1996) for N of 1 treated patients at 6 months were: 551.66 dollars +/- 154.02 dollars (SD) versus 395.62 dollars +/- 226.87 dollars for controls, excluding 2 research visits for controls (p < 0.009). The HAQ pain and disability, WOMAC scales, and physician global assessments improved more in the N of 1 group (at greater cost), but no between-group differences in efficacy were seen, possibly due to small numbers. CONCLUSION: N of 1 trials were time-consuming in these patients and are more expensive, but with slightly better outcomes. In addition, NSAID seem to be effective in a majority of subjects with OA who have been uncertain of their benefit.