Clinical pharmacology of etoricoxib: a novel selective COX2 inhibitor

The development of COX2 inhibitors with improved biochemical selectivity (such as etoricoxib and valdecoxib) over that of commercially available coxibs has been driven by the potential advantage of safety using higher coxib doses for increased efficacy. Etoricoxib has been approved in the UK as a once-daily medicine for symptomatic relief in the treatment of osteoarthritis (OA), rheumatoid arthritis (RA) and acute gouty arthritis. It is currently approved with additional indications (i.e., for relief of acute pain associated with dental surgery, for primary dysmenorrhoea and for chronic musculo-skeletal pain, including chronic lower-back pain) in Mexico, Brazil and Peru. Etoricoxib has an in vitro COX1/COX2 IC(50) ratio of 344, the highest of any coxib. The administration of therapeutic doses of etoricoxib to healthy subjects does not affect COX1 activity in circulating platelets and gastric biopsies. The profound inhibition of monocyte COX2 activity at 24 h after dosing, as predicted by a pharmacological half-life of approximately 22 h, supports a once-daily dosing regimen of etoricoxib. In randomised, well-controlled clinical trials, etoricoxib has been shown to have a comparable clinical efficacy with traditional NSAIDs. Combined analysis of efficacy trials with etoricoxib versus non-selective NSAIDs has shown that the drug halves both investigator-reported upper gastrointestinal perforation, ulcers and bleeds (PUBs) and confirmed PUBs, and reduces the need for gastroprotective agents and gastrointestinal comedications by approximately 40%. The risk of lower extremity oedema and hypertension adverse experiences with etoricoxib was low and generally similar to comparator NSAIDs in a combined analysis of eight Phase III studies in OA, RA, chronic low-back pain and surveillance endoscopy. Large, randomised clinical trials have been planned to confirm the renal, gastrointestinal and cardiovascular safety of etoricoxib.     

Clinical pharmacology of etoricoxib: a novel selectiveCOX2 inhibitor

The development of COX2 inhibitors with improved biochemical selectivity (such as etoricoxib and valdecoxib) over that of commercially available coxibs has been driven by the potential advantage of safety using higher coxib doses for increased efficacy. Etoricoxib has been approved in the UK as a once-daily medicine for symptomatic relief in the treatment of osteoarthritis (OA), rheumatoid arthritis (RA) and acute gouty arthritis. It is currently approved with additional indications (i.e., for relief of acute pain associated with dental surgery, for primary dysmenorrhoea and for chronic musculo-skeletal pain, including chronic lower-back pain) in Mexico, Brazil and Peru. Etoricoxib has an in vitro COX1/COX2 IC₅₀ ratio of 344, the highest of any coxib. The administration of therapeutic doses of etoricoxib to healthy subjects does not affect COX1 activity in circulating platelets and gastric biopsies. The profound inhibition of monocyte COX2 activity at 24 h after dosing, as predicted by a pharmacological half-life of ~ 22 h, supports a once-daily dosing regimen of etoricoxib. In randomised, well-controlled clinical trials, etoricoxib has been shown to have a comparable clinical efficacy with traditional NSAIDs. Combined analysis of efficacy trials with etoricoxib versus non-selective NSAIDs has shown that the drug halves both investigator-reported upper gastrointestinal perforation, ulcers and bleeds (PUBs) and confirmed PUBs, and reduces the need for gastroprotective agents and gastrointestinal comedications by ~ 40%. The risk of lower extremity oedema and hypertension adverse experiences with etoricoxib was low and generally similar to comparator NSAIDs in a combined analysis of eight Phase III studies in OA, RA, chronic low-back pain and surveillance endoscopy. Large, randomised clinical trials have been planned to confirm the renal, gastrointestinal and cardiovascular safety of etoricoxib.     

Cost-utility analysis of treatment with olanzapine compared with other antipsychotic treatments in patients with schizophrenia in the pan-European SOHO study

OBJECTIVE: To determine the cost utility of treating schizophrenic patients with olanzapine compared with other antipsychotics in a naturalistic outpatient setting. METHODS: The pan-European SOHO study is a 3-year, prospective, outpatient, observational study of outcomes associated with antipsychotic treatment, focusing on olanzapine, in ten European countries. For the cost-utility analysis, healthcare resource use (inpatient care, day care, outpatient psychiatric consultations and antipsychotic and concomitant medication use) and EQ-5D data were collected at baseline and at 3, 6 and 12 months. The perspective was that of the health service payer. UK healthcare unit costs (year 2004 values) were applied to the resource use data for the ten countries. UK population tariffs were applied to the EQ-5D data to determine utility values.An Epoch analysis was used to analyze the longitudinal data. Multivariate regression analyses that adjusted for baseline covariates were used to estimate the incremental cost and utility gains for patients treated with olanzapine compared with each of the other antipsychotics (risperidone, quetiapine, amisulpride, clozapine and oral or depot typical antipsychotics). RESULTS: A total of 10 972 patients were enrolled at baseline, of which 9107 completed the 12-month study period. Treatment with olanzapine was more effective in terms of QALYs gained than all of the other antipsychotic treatments. Treatment with olanzapine dominated quetiapine and amisulpride. The incremental cost for olanzapine compared with risperidone was pound sterling 226 per patient over 12 months and the incremental cost per QALY gained was pound 5156, with bootstrap analyses showing 100% of the replications falling below a pound sterling 30 000 per QALY gained threshold. Compared with treatment with clozapine, olanzapine was found to be marginally more effective, at an additional cost of pound sterling 13 per patient over 12 months and to have an incremental cost per QALY gained of pound sterling 775. Bootstrap analyses showed that 81% of replications fell below a pound sterling 30 000 per QALY gained threshold. Comparing olanzapine with oral and depot typical antipsychotics, the incremental cost was pound sterling 849 and pound sterling 1106 per patient over 12 months and the incremental cost per QALY gained was pound sterling 15 696 and pound sterling 23 331, respectively. Bootstrap analyses showed that 98% of the replications fell below a pound sterling 30 000 per QALY gained threshold for the comparison with oral typical antipsychotics, and 79% of replications for the comparison with depot preparations. CONCLUSIONS: Among SOHO patients, if a funding threshold of pound sterling 30 000 per QALY gained is assumed, this analysis suggests that olanzapine has a high probability of being the most cost-effective treatment compared with other antipsychotic treatments. However, comparison of olanzapine with clozapine and typical depot antipsychotics should be viewed with caution because clozapine is a second-line treatment and depot treatment is used for patients who do not adhere to their oral medication.     

Economic evaluation of etoricoxib versus non-selective NSAIDs in the treatment of ankylosing spondylitis in the UK

ABSTRACT

Objectives: To evaluate the cost-effectiveness of etoricoxib, a cyclooxygenase (COX)‐2 selective inhibitor, versus non-selective nonsteroidal anti-inflammatory drugs (nsNSAIDs) in the treatment of ankylosing spondylitis (AS).

Methods: The cost-effectiveness of etoricoxib versus nsNSAIDs was evaluated from the UK National Health Service (NHS) and society perspective with a decision-analytic model. Patients stayed on initial therapy throughout 52 weeks unless they experienced an adverse event (AE) or lacked efficacy, in which case they switched to another nsNSAID or a tumor necrosis factor alpha antagonist. Efficacy data were obtained from a 1‐year etoricoxib clinical trial in AS. Bath AS Functional Index (BASFI) data were translated into Quality Adjusted Life Year (QALY) weights using a published data on the relation between BASFI and Short-form (SF) 36 Quality of life scores, as well as the relation between SF‐36 and utility. Safety data were based on meta-analyses of etoricoxib trials. Information on treatment pathways, resource consumption, and absenteeism from work was obtained from literature and experts. Model outcomes included QALYs, perforations, ulcers, or bleeds, cardiovascular events, and costs.

Results: Etoricoxib was cost-effective compared to nsNSAIDs in terms of cost per QALY saved (£5611). Probabilistic sensitivity analysis found a 77% probability of the incremental cost per QALY saved being within a threshold for cost-effectiveness of £20?000. The expected direct costs over the 52-week period were £1.23 (95% uncertainty distribution £1.10; £1.39) and £1.13 per day (£0.78; £1.55) for patients starting with etoricoxib and nsNSAIDs, respectively. When costs related to absenteeism were taken into account, the cost per QALY saved was £281.

Conclusions: Given the underlying assumptions and data used, this economic evaluation demonstrated that, compared to nsNSAIDs, etoricoxib is a cost-effective therapy for AS patients in the UK.     

Carmustine implants for the treatment of newly diagnosed high-grade gliomas: a cost-utility analysis

BACKGROUND: High-grade gliomas are aggressive brain tumours that are extremely challenging to treat effectively. The intracranial implantation of carmustine wafers (BCNU-W), which delivers chemotherapy directly to the affected area, may prolong survival in this population. However, no attention has yet been paid to the economic implications of BCNU-W in this setting. OBJECTIVE: To investigate the cost effectiveness of BCNU-W as an adjunct to surgery followed by radiotherapy, compared with surgery plus radiotherapy alone. Newly diagnosed, operable grade III and IV gliomas in a population with a mean age of 55 years were considered. METHODS: A Markov cost-utility model was developed in Microsoft Excel, adopting a UK NHS perspective. Transition probabilities and cost data (year 2004 values) were obtained from published literature or expert opinion. The model incorporated utility values, obtained from members of the public, reflecting the quality of life associated with high-grade glioma. The effects of uncertainty were explored through extensive one-way and probabilistic sensitivity analysis. RESULTS: Surgery with the implantation of BCNU-W followed by radiotherapy costs pound sterling 54 500 per additional QALY gained when compared with surgery plus radiotherapy alone. Probabilistic sensitivity analysis shows a <10% probability that BCNU-W would be considered cost effective at a willingness-to-pay threshold of pound sterling 30 000 per QALY. Although model outputs were sensitive to alterations in several key parameters, the incremental cost effectiveness of the intervention remained above pound sterling 30 000 per QALY in all analyses. CONCLUSION: Compared with usual care for the treatment of newly diagnosed high-grade gliomas, BCNU-W is unlikely to be considered a cost-effective use of healthcare resources when judged by the standards commonly adopted in England and Wales. However, the dreadful prognosis of the condition and the paucity of alternative therapies are additional issues that healthcare commissioners may choose to take into account when considering an adoption decision.     

Cost effectiveness of imatinib compared with interferon-alpha or hydroxycarbamide for first-line treatment of chronic myeloid leukaemia

OBJECTIVE: To evaluate the cost utility of imatinib compared with interferon (IFN)-alpha or hydroxycarbamide (hydroxyurea) for first-line treatment of chronic myeloid leukaemia. DESIGN AND SETTING: A cost-utility (Markov) model within the setting of the UK NHS and viewed from a health system perspective was adopted. Transition probabilities and relative risks were estimated from published literature. Costs of drug treatment, outpatient care, bone marrow biopsies, radiography, blood transfusions and inpatient care were obtained from the British National Formulary and local hospital databases. Costs (pound, year 2001-03 values) were discounted at 6%. Quality-of-life (QOL) data were obtained from the published literature and discounted at 1.5%. The main outcome measure was cost per QALY gained. Extensive one-way sensitivity analyses were performed along with probabilistic (stochastic) analysis. RESULTS: The incremental cost-effectiveness ratio (ICER) of imatinib, compared with IFNalpha, was pound26,180 per QALY gained (one-way sensitivity analyses ranged from pound19,449 to pound51,870) and compared with hydroxycarbamide was pound86,934 per QALY (one-way sensitivity analyses ranged from pound69,701 to pound147,095) [ pound1=$US1.691=euro1.535 as at 31 December 2002].Based on the probabilistic sensitivity analysis, 50% of the ICERs for imatinib, compared with IFNalpha, fell below a threshold of approximately pound31,000 per QALY gained. Fifty percent of ICERs for imatinib, compared with hydroxycarbamide, fell below approximately pound95,000 per QALY gained. CONCLUSIONS: This model suggests, given its underlying data and assumptions, that imatinib may be moderately cost effective when compared with IFNalpha but considerably less cost effective when compared with hydroxycarbamide. There are, however, many uncertainties due to the lack of long-term data.     

Economic evaluation of gemcitabine alone and in combination with cisplatin in the treatment of nonsmall cell lung cancer

OBJECTIVE: To evaluate the cost effectiveness of gemcitabine in the treatment of nonsmall cell lung cancer (NSCLC). METHODS: Gemcitabine was compared with best supportive care and gemcitabine/cisplatin was compared with three standard chemotherapies and four other novel chemotherapy combinations. Costs and effectiveness measures were based on resource and outcome data from previously reported clinical trials. All direct costs associated with NSCLC treatment were included and adjusted to year 2000 values. PERSPECTIVE: UK National Health Service. RESULTS: Gemcitabine plus best supportive care was associated with an incremental cost per progression-free life year gained of pound sterling5228 compared with best supportive care alone. In comparison with standard chemotherapies, gemcitabine/cisplatin was associated with an incremental cost per progression-free life year gained of pound sterling1751 versus etoposide/cisplatin and cost per 1-year survival gain of pound sterling5681 versus mitomycin/vinblastine/platinum. Incremental cost per tumour response was pound sterling2032 relative to etoposide/cisplatin, pound sterling5169 relative to mitomycin/ifosfamide/cisplatin and pound sterling6240 relative to mitomycin/vinblastine/platinum. Compared with four novel (newer) combination chemotherapies gemcitabine/ cisplatin showed cost savings in each case, with the same or better outcome. Thus, gemcitabine/cisplatin showed improved cost effectiveness and dominance. Sensitivity analyses showed the results were robust to variations to the values of key parameters. CONCLUSION: Gemcitabine alone or in combination with cisplatin was assessed to be a cost-effective or cost-saving therapy when compared with best supportive care, standard chemotherapy regimens and novel chemotherapy combinations. Chemotherapy regimens containing gemcitabine therefore represent good value for money and efficient use of healthcare resources in the treatment of advanced NSCLC.     

Modelling the economic and health consequences of cardiac resynchronization therapy in the UK

OBJECTIVE: Clinical evidence supports the use of cardiac resynchronization therapy (CRT) in advanced heart failure, but its cost-effectiveness is still unclear. This analysis assessed the economic and health consequences in the UK of implanting a CRT in patients with NYHA class III-IV heart failure. METHODS: A discrete event simulation of heart failure was used to compare the course over 5 years of 1000 identical pairs of patients -- one receiving both CRT and optimum pharmacologic treatment (OPT), the other OPT alone. All inputs were obtained from the data collected in the CArdiac REsynchronization in Heart Failure (CARE-HF) trial and a hospital in the UK. Direct medical costs (in 2004 pound) from the perspective of the National Health Service were considered. Both costs and benefits were discounted at 3.5%. Sensitivity analyses addressed all model inputs and multivariate analyses were performed by varying key parameters simultaneously. RESULTS: The model predicted 471 deaths and 2263 hospitalizations over 5 years with OPT alone and 348 deaths and 1764 hospitalizations with CRT, equivalent to a 26% reduction in mortality and 22% in hospitalizations, at a discounted cost of pound 11,423 per patient with CRT vs. pound 4,900 with OPT alone. CRT was predicted to increase quality-adjusted survival by 0.43 QALYs per patient, resulting in an incremental cost-effectiveness ratio of pound 15,247 per QALY gained (range: pound 12,531- pound 23,184). Sensitivity analyses revealed that this outcome was most sensitive to time horizon and cost of implantation. CONCLUSION: Based on these 5-year analyses, CRT is expected to yield substantial health benefits at a reasonable cost.     

An economic evaluation of fluvastatin used for the prevention of cardiac events following successful first percutaneous coronary intervention in the UK

AIMS: To estimate the costs, benefits and cost effectiveness, from the UK NHS perspective, of fluvastatin (relative to no HMG-CoA reductase inhibitor [statin]) for the secondary prevention of major adverse cardiac events following a successful first percutaneous coronary intervention (PCI). METHODS: A cost-effectiveness analysis was undertaken using efficacy data from the Lescol Intervention Prevention Study (LIPS). LIPS was a randomised, double-blind, placebo-controlled trial undertaken in 77 centres (predominantly in Europe). Patients included in the trial had moderate hypercholesterolaemia and had successfully undergone their first PCI. Fluvastatin (Lescol) 40 mg twice daily plus dietary counselling was given to the intervention group for up to 4 years; the control group received dietary counselling only. A Markov model was used to estimate the incremental costs per QALY gained over a 10-year period, with cost data drawn from the UK NHS (2002 values). Monte Carlo simulations and multivariate analysis were used to assess uncertainty. Costs were discounted at 6% per annum, and health outcomes at 1.5% per annum. RESULTS: On average, treatment with fluvastatin cost an additional pound 300 (SD pound 303) [euro 423; SD euro 428] per patient and resulted in an additional 0.092 (SD 0.06) QALYs per patient over 10 years compared with controls. The incremental cost per QALY gained with fluvastatin versus the control group was pound 3207 (SD pound 5,497) [euro 4,527; SD euro 7,759]. Fluvastatin was dominant (better outcomes and lower costs) in 15.9% of the simulations and was dominated in 2.9%. The key determinants of cost effectiveness were: the effectiveness of fluvastatin in reducing acute myocardial infarction, subsequent PCI, coronary artery bypass graft and cardiac deaths; the utility weight associated with a subsequent post-PCI state; the cost of fluvastatin; and the time horizon evaluated. CONCLUSIONS: Fluvastatin is the only statin which has proven effective in preventing major coronary adverse events in new PCI patients; other statins lack this evidence. This Markov model, with its underlying assumptions and data, suggests that fluvastatin is a viable and economically efficient pharmaceutical (relative to no statin) to reduce heart disease in the UK when given routinely to all patients following PCI.     

Potential costs and effects of the National Service Framework for Coronary Heart Disease in the UK

OBJECTIVE: To estimate the costs and effect of implementing the National Service Framework for Coronary Heart Disease (CHD) in the UK. DESIGN: Decision trees were built on the results from randomised controlled trials on improving coronary revascularisation. All costs were presented in UK pounds (1997 values). PATIENTS: Each year 6600 new patients with CHD are expected to require revascularisation in the UK. INTERVENTIONS: The new patients would be equally divided into those undergoing coronary artery bypass grafting (CABG) and those undergoing a percutaneous coronary intervention (PCI) i.e., percutaneous transluminal angioplasty (PCTA). PTCA could be administered with or without abciximab (a glycoprotein IIb/IIIa receptor antagonist), stent, or stent plus abciximab (stent+). RESULTS: CABG/stent alone has an incremental cost of more than 115,489 pounds per additional quality-adjusted life-year (QALY) gained compared with CABG/ PTCA+. This high incremental cost is not attractive because if CABG/ stent would be added to abciximab (CABG/stent+) its incremental cost-effectiveness ratio would be 2529 pounds per extra QALY compared with CABG/stent. Therefore, the debate should not be limited to the issue of stents but it should focus on the need for administering abciximab in addition to stent. The 5-year direct costs of implementing such a strategy in the UK is expected to be 50.6 million pounds (1997 values). CONCLUSIONS: Abciximab and probably any glycoprotein IIb/IIIa receptor antagonists should be added to any PCI, especially if stents are used.     

Etoricoxib

Etoricoxib is a cyclo-oxygenase (COX)-2-selective NSAID with a higher COX-1 to COX-2 selectivity ratio than the other COX-2-selective NSAIDs rofecoxib, valdecoxib or celecoxib. In patients with rheumatoid arthritis, improvements in tender and swollen joint counts and patient and investigator global assessment of disease activity were significantly greater in etoricoxib than in placebo recipients in two studies. Etoricoxib was also significantly more effective than naproxen in one of these studies. In patients with osteoarthritis of the hip or knee, etoricoxib was significantly more effective than placebo and had similar efficacy to naproxen with regards to improvements in pain and physical function scores and patient global assessment of disease status scores in two studies. Etoricoxib had similar efficacy to diclofenac in patients with osteoarthritis of the knee. Single-dose etoricoxib relieved pain in patients with postoperative dental pain in two studies. Similar scores assessing total pain relief over 8 hours (TOPAR8) were reported in etoricoxib and naproxen sodium or ibuprofen recipients, and higher TOPAR8 scores were reported with etoricoxib than with paracetamol (acetaminophen)/codeine. Pain relief was significantly better with etoricoxib than placebo in two studies in patients with chronic low back pain. Etoricoxib had similar efficacy to indomethacin in a study in patients with acute gout, and single-dose etoricoxib had similar efficacy to naproxen sodium in a study in women with primary dysmenorrhoea. Compared with non-COX-selective NSAIDs, etoricoxib was associated with significantly fewer upper gastrointestinal (GI) perforations, ulcers or bleeds, and was significantly less likely to result in treatment discontinuation because of NSAID-type GI symptoms or any GI symptoms.     

Modelling the long term cost effectiveness of clopidogrel for the secondary prevention of occlusive vascular events in the UK

OBJECTIVE: To assess the long term cost effectiveness of clopidogrel monotherapy compared with acetylsalicylic acid (aspirin; ASA) monotherapy in patients at risk of secondary occlusive vascular events (OVEs) in the UK. DESIGN: Cost utility analysis based on clinical data from CAPRIE (a multicentre randomised controlled trial, involving 19185 patients); long-term effects were extrapolated beyond the trial period using a Markov model populated with data from UK observational studies. Health economic evaluation carried out from the perspective of the UK National Health Service. PARTICIPANTS: A representative cohort of 1000 UK patients aged 60 years (approximate mean age of the CAPRIE population), with the qualifying diagnoses of myocardial infarction, ischaemic stroke and peripheral arterial disease, who are at risk of secondary OVEs (non-fatal myocardial infarction, non-fatal stroke or vascular death). INTERVENTIONS: Patients were assumed to receive treatment with either clopidogrel (75 mg/day) for 2 years followed by ASA (325 mg/day, average) for their remaining lifetime, or ASA alone (325 mg/day, average) for life. MAIN OUTCOME MEASURES: Incremental cost per life year gained and incremental cost per quality-adjusted life year (QALY) gained. RESULTS: In the base case, the incremental cost effectiveness of clopidogrel versus ASA in this population is estimated at 18888 pounds per life year gained and 21 489 pounds per QALY gained. Multiple deterministic and probabilistic sensitivity analyses suggest the model is robust to variations in a wide range of input parameters. CONCLUSION: Two years of treatment with clopidogrel can be considered a cost effective intervention in patients at risk of secondary OVEs in the UK.     

Home-based medication review in older people: is it cost effective?

BACKGROUND: Medication review by pharmacists is increasingly being implemented in the primary care setting and has been incorporated into the new pharmacy contract in the UK. This study aims to determine the cost effectiveness of home-based medication review in older people. METHODS: This economic evaluation was based on a randomised controlled trial (the HOMER [HOME-based medication Review] trial). Patients aged >80 years (n = 872) were recruited if admitted as an emergency to an acute or community hospital in Norfolk or Suffolk (any cause), returning to their own home or warden-controlled accommodation, and taking two or more drugs daily on discharge. Patients randomised to the intervention group received two home visits by a pharmacist within 2 and 8 weeks of discharge to educate patients and carers about their drugs, remove out-of-date drugs, inform GPs of drug reactions or interactions and inform the local pharmacist if an adherence aid was needed. The control arm received usual care. Economic evaluation was performed from the UK NHS perspective, with follow-up for 6 months and cost data from 2000. Resource use data were collected from hospital episode statistics and from a sample of GP records of trial participants. Intervention, hospital, ambulance and general practice costs were considered to determine average costs and incremental cost-effectiveness ratios. Use of the EQ-5D questionnaire permitted outcomes to be expressed as QALYs. Probabilistic sensitivity analysis was employed to calculate cost-effectiveness acceptability curves. RESULTS: Mortality and admission data were available for 829 of 855 patients included in the study (415 intervention and 414 control patients). Of those patients randomised to the intervention group, 358 had a medication review at a total intervention cost of 51,622 pound (or 124 pound per randomised patient). The intervention did not reduce hospital admissions. The average cost per intervention group patient was 1695 pound compared with 1424 pound for control patients. The incremental cost per life year gained through the intervention was 33,541 pound. The incremental cost per QALY gained in the intervention was 54,454 pound. Sensitivity analysis suggested a 25% probability that home-based medication review is cost effective using a threshold of 30,000 pound per QALY. CONCLUSION: The current policy imperative for implementing medicines review needs to be reconsidered in the light of the findings of this study: a small, non significant gain in quality of life, no reduction in hospital admissions and a low probability of cost effectiveness.     

Clinical pharmacology of etoricoxib

Etoricoxib is a highly selective COX-2 inhibitor (coxib) approved in Europe for the treatment of osteoarthritis (OA), rheumatoid arthritis and acute gouty arthritis. Etoricoxib is an effective analgesic drug that has shown some improved efficacy versus traditional NSAIDs and it is the only coxib approved for the treatment of acute gouty arthritis. Moreover, recent studies evidence its efficacy in patients with ankylosing spondylitis. In the Etoricoxib Diclofenac Gastrointestinal Evaluation study performed in patients with OA, etoricoxib significantly reduced the rate of discontinuation by 50% due to gastrointestinal adverse events versus diclofenac. Comparable rates of thrombotic cardiovascular events were detected. Rates of discontinuation due to hypertension-related adverse effects were higher on etoricoxib than diclofenac. Similarly to other selective COX-2 inhibitors, etoricoxib is contraindicated in patients with ischaemic heart disease or stroke and it should be used with caution in patients with risk factors for heart disease. The European Medicines Agency has contraindicated the use of etoricoxib in patients with uncontrolled hypertension. Selective COX-2 inhibitors remain an appropriate choice in patients at low cardiovascular risk, but with increased risk of gastrointestinal complications.     

Cost-utility analysis of primary prophylaxis versus treatment on-demand for individuals with severe haemophilia

OBJECTIVE: To assess the cost effectiveness of primary prophylaxis with clotting factor instead of treatment following a bleed (on-demand) for individuals with severe haemophilia. DESIGN: Different data sources on the clinical effects and costs of treatments were combined using a Markov model. SETTING: English treatment centres. PERSPECTIVE: UK societal. PARTICIPANTS: Hypothetical cohorts of 100 individuals with severe haemophilia A or B or severe von Willebrands disease. INTERVENTIONS: Primary prophylaxis treatment on-demand with clotting factor. OUTCOME MEASURES: Costs, quality-adjusted life-years (QALYs) and incremental cost per QALY in UK pounds ( pound, 1999/2000 values). RESULTS: The baseline results showed that treating individuals with severe haemophilia A/severe von Willebrands disease or severe haemophilia B with primary prophylaxis instead of treatment on-demand cost an additional pound 46500 and pound 8600 per QALY gained, respectively. However, the results were extremely sensitive to a number of factors including the clotting factor unit cost, the time between prophylactic doses and the discount rate. CONCLUSIONS: Despite the high costs of treatment, primary prophylaxis was cost effective compared with treatment on-demand in some scenarios. Primary prophylaxis is more likely to be cost effective for individuals with severe haemophilia B compared with individuals with severe haemophilia A/severe von Willebrands disease. Further research is required to assess the relationship between methods of clotting factor infusion and health-related quality-of-life.     

Cost-effectiveness analyses of natalizumab (Tysabri) compared with other disease-modifying therapies for people with highly active relapsing-remitting multiple sclerosis in the UK

BACKGROUND: Natalizumab (Tysabri) is a new disease-modifying therapy that has been shown to be clinically effective in patients with relapsing-remitting multiple sclerosis (RRMS) and has been licensed for use in patients with highly active RRMS (HARRMS). These patients are those who experience higher relapse rates and faster disability progression than the general RRMS population. OBJECTIVES: To estimate the cost effectiveness of natalizumab compared with interferon-beta, glatiramer acetate and best supportive care from various UK cost perspectives. METHODS: A 30-year Markov model was developed, based on previously published models for multiple sclerosis, to estimate transition between disability states and the probability of relapse within disability states. The model was parameterized with data from the UK Multiple Sclerosis (MS) Survey 2005 and data from the AFFIRM study, a 2-year multicentre, randomized, double-blind, placebo-controlled trial of natalizumab in RRMS patients. Additional data were sourced from the literature. A UK societal cost perspective was used in the base case, with additional cost perspectives considered in the sensitivity analysis. The baseline characteristics for the patient group were taken from the patient population in the AFFIRM study (mean age 36 years, mean time since diagnosis 5 years and a mean Kurtzke Extended Disability Status Scale [EDSS] score of 2.5). The model and its parameterization were designed and developed to support a reimbursement application for natalizumab submitted to the UK National Institute for Health and Clinical Excellence (NICE). Efficacies for natalizumab and glatiramer acetate were taken from clinical trial data, and for interferon-beta from a meta-analysis of clinical trial data. Disutilities from adverse events for each comparator were also included in the model. Outcomes and costs were discounted at 3.5% per anum.Costs for interferon-beta and glatiramer acetate were based on published prices (year 2006 values) under the UK Risk Sharing Scheme, and for natalizumab the UK NHS list price was used. Diagnostic, administration and adverse event costs were also included. The incremental cost-effectiveness ratios (ICERs) were calculated for the base case, and a probabilistic sensitivity analysis was performed to assess the probability of cost effectiveness at different willingness-to-pay thresholds. RESULTS: The ICER for natalizumab compared with interferon-beta was 2300 pound per QALY. Compared with glatiramer acetate, it was 2000 pound per QALY, and compared with best supportive care it was 8200 pound per QALY. From a health and social care cost perspective, the ICERs were 18,700 pound, 20,400 pound and 25,500 per QALY, respectively. At a willingness-to-pay threshold of 30,000 pound per QALY, the probability of natalizumab being cost effective against any comparator from a societal perspective was >89%. CONCLUSION: If UK society is willing to pay more than 8200 pound per QALY, or Health and Social Services are willing to pay more than 26,000 pound per QALY, this analysis suggests that natalizumab is likely to be a cost-effective treatment for all patients with HARRMS.