Biomedical subjects

Katherine A Lyseng-Williamson

Publications and source records attributed to Katherine A Lyseng-Williamson.

At least 19 recordsLinked to original sources

PubMed2006

Moxonidine: a review of its use in essential hypertension.

Moxonidine (Physiotens, Moxon, Cynt) is an orally administered imidazoline compound with selective agonist activity at imidazoline I1 receptors and only minor activity at alpha2-adrenoceptors. Moxonidine acts centrally to reduce peripheral sympathetic activity, thus decreasing peripheral vascular resistance. In patients with mild to moderate hypertension, moxonidine reduces blood pressure (BP) as effectively as most first-line antihypertensives when used as monotherapy and is also an effective adjunctive therapy in combination with other antihypertensive agents. It improves the metabolic profile in patients with hypertension and diabetes mellitus or impaired glucose tolerance, is well tolerated, has a low potential for drug interactions and may be administered once daily in most patients. Thus, moxonidine is a good option in the treatment of patients with mild to moderate hypertension, particularly as adjunctive therapy in patients with the metabolic syndrome.

Animals↗

PubMed2006

Rimonabant.

Rimonabant is the first of a new class of selective cannabinoid receptor-1 blockers. It reduces the overactivity of the endocannabinoid system, improving lipid and glucose metabolism and regulating food intake and energy balance. In four randomised, double-blind clinical trials in overweight or obese adults with or without type 2 diabetes and/or dyslipidaemia, oral rimonabant 20mg once daily reduced weight and waist circumference to a significantly greater extent than placebo. A significantly greater proportion of rimonabant than placebo recipients achieved the clinically significant weight-loss target of > or =5% or > or =10% of initial weight. Rimonabant was associated with significant improvements in glycaemic control relative to placebo, with approximately equal to 57% of the reduction in glycosylated haemoglobin being independent of the effects of weight loss in one trial. Improvements in other cardiometabolic risk factors (i.e. increases in high-density lipoprotein-cholesterol [HDL-C] and decreases in triglyceride [TG] levels) were significantly greater with rimonabant than with placebo. The improvement in lipid profile also demonstrated a weight-independent effect, with approximately equal to 47-58% of the improvement in HDL-C and TG being beyond that expected through weight loss alone. Rimonabant was generally well tolerated, with most adverse events considered mild to moderate in severity.

Adult↗

PubMed2006

Famciclovir: a review of its use in herpes zoster and genital and orolabial herpes.

Famciclovir (Famvir) is the oral prodrug of penciclovir, an agent that has demonstrated antiviral activity against herpes simplex viruses, type 1 (HSV-1) and 2 (HSV-2) [which cause orolabial and/or genital herpes simplex], and against varicella zoster virus (VZV) [a reactivation of which leads to herpes zoster]. Famciclovir has efficacy similar to that of aciclovir (in immunocompetent or immunocompromised patients) or valaciclovir (in immunocompetent patients) in the treatment of herpes zoster, and efficacy similar to aciclovir in the treatment of first or recurrent episodes of genital herpes (in immunocompetent or immunocompromised patients). Famciclovir also has efficacy in the suppression of recurrent episodes of genital herpes, and in the treatment of orolabial herpes, in immunocompetent patients. As such, famciclovir is a well tolerated first-line option for the treatment of herpes zoster and the treatment and suppression of genital herpes, and is approved for the treatment of recurrent orolabial herpes. Convenient patient-initiated single-day (for recurrent genital herpes) and single-dose (for orolabial herpes) dosage regimens may contribute to treatment compliance, patient acceptability and subsequent treatment outcomes.

2-Aminopurine↗

PubMed2006

Clopidogrel: a pharmacoeconomic review of its use in patients with non-ST elevation acute coronary syndromes.

Clopidogrel (Plavix) is a selective inhibitor of adenosine diphosphate-induced platelet aggregation. In patients with acute coronary syndromes (ACS) [unstable angina or non-ST-segment elevation myocardial infarction], clopidogrel plus aspirin (acetylsalicylic acid) for up to 1 year significantly reduced the risk of cardiovascular events relative to placebo plus aspirin in the well designed clinical trial CURE (Clopidogrel in Unstable angina to prevent Recurrent Events) and its substudy in patients undergoing percutaneous coronary intervention (PCI) [PCI-CURE]. In pharmacoeconomic evaluations based on data from these trials conducted in a number of countries that used a variety of models, methods and/or type of costs, clopidogrel plus aspirin was consistently predicted to be cost effective relative to aspirin alone in the management of patients with ACS, including those undergoing PCI. Clopidogrel plus aspirin in patients with ACS reduced the incremental cost per cardiovascular event prevented and/or life-year gained (LYG) relative to aspirin alone in analyses using within-trial data (including longer-term analyses incorporating life-expectancy estimates) from the CURE or PCI-CURE studies. In Markov models of cost effectiveness with a lifetime horizon from a healthcare payer perspective based on the CURE trial, relative to aspirin alone, clopidogrel plus aspirin for 1 year was predicted to have incremental costs per LYG of 8132Euro in Spain (2003 values) and 1365Euro in Sweden (2000 values). In similar Swedish analyses from a healthcare payer perspective, clopidogrel plus aspirin for 1 year was predicted to have incremental costs per LYG of 10,993Euro (2004 values) relative to aspirin alone based on data from the PCI-CURE substudy. Broadly similar results have also been reported in modelled analyses from other countries. Cost-utility analyses based on the CURE trial suggest that, relative to lifelong aspirin alone, clopidogrel plus aspirin for 1 year followed by aspirin alone is associated with incremental costs per QALY gained that are below the traditional threshold of cost utility in Spain, the UK and the US. In patients with ACS, including those undergoing PCI, the addition of clopidogrel to standard therapy with aspirin is clinically effective in preventing cardiovascular events. Available pharmacoeconomic data from several countries, despite some inherent limitations, support the use of clopidogrel plus aspirin for up to 1 year as a cost-effective treatment relative to aspirin alone in this patient population.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2006

Ziconotide.

Ziconotide, an intrathecal analgesic for the management of chronic intractable pain, binds with high affinity to N-type calcium channels in neuronal tissue and obstructs neurotransmission. In three pivotal, well designed trials of 5-6 or 21 days' duration, titrated ziconotide was significantly more effective than placebo in treating chronic malignant or nonmalignant pain as assessed by mean percentage improvements from baseline in Visual Analogue Scale Pain Intensity scores. Improvements in secondary endpoints (e.g. proportion of patients who responded or achieved pain relief and the change in opioid use) generally support the efficacy of ziconotide over placebo. Ziconotide maintains its analgesic efficacy in preliminary results from long-term, open-label trials (data available for up to 12 months). Most ziconotide-related adverse events are neurological, mild to moderate in severity, resolve over time and reverse without sequelae on drug discontinuation. Low initial doses of ziconotide and gradual titration to onset of analgesia reduces the incidence and severity of adverse events. No evidence of respiratory depression has been reported with intrathecal ziconotide.

Animals↗

PubMed2006

Oral paricalcitol.

black triangle An oral formulation of paricalcitol has been developed for the prevention and treatment of secondary hyperparathyroidism in patients with stage 3 or 4 chronic kidney disease.black triangle Paricalcitol is a synthetic vitamin D analog that binds to the vitamin D receptor inducing suppression of parathyroid hormone (PTH) secretion.black triangle Oral paricalcitol was significantly more effective than placebo in treating secondary hyperparathyroidism in patients with stage 3 or 4 chronic kidney disease. In a pooled analysis of three well designed, 24-week trials, two consecutive reductions from baseline in intact PTH levels of >/=30% were achieved by significantly more paricalcitol than placebo recipients (91% vs 13%).black triangle In addition, mean levels of the biochemical bone markers serum bone-specific alkaline phosphatase, serum osteocalcin, and urinary pyridinoline were reduced from baseline to a significantly greater extent with paricalcitol than with placebo, indicating a reduction in bone turnover.black triangle Oral paricalcitol was well tolerated; there was no significant difference between paricalcitol and placebo recipients in the incidence of hypercalcemia, hyperphosphatemia, or elevated calcium-phosphorus product.

Calcium↗

PubMed2006

Spotlight on bevacizumab in advanced colorectal cancer, breast cancer, and non-small cell lung cancer.

Bevacizumab (Avastin) is a humanized recombinant antibody that prevents vascular endothelial growth factor (VEGF) receptor binding, and inhibits angiogenesis and tumor growth. In patients receiving an irinotecan plus fluorouracil/leucovorin (IFL) regimen for first-line treatment of metastatic colorectal cancer, the addition of bevacizumab significantly increased overall survival by 4.7 months relative to IFL plus placebo. In the second-line treatment of advanced colorectal cancer, patients who received bevacizumab in combination with a fluorouracil/leucovorin plus oxaliplatin (FOLFOX4) regimen had an overall survival time that was 2 months longer than that in patients receiving FOLFOX4. Preliminary results indicated that bevacizumab significantly extended progression-free survival by 4.9 months in patients receiving paclitaxel for the first-line treatment of locally recurrent or metastatic breast cancer. The addition of bevacizumab to paclitaxel plus carboplatin in the first-line treatment of advanced non-small cell lung cancer (NSCLC) significantly prolonged overall survival by >2 months. Bevacizumab has acceptable tolerability in patients with advanced colorectal cancer, breast cancer, or NSCLC, with the majority of adverse events being generally mild and clinically manageable. Thus, bevacizumab provides a highly effective addition to standard chemotherapeutic regimens for advanced colorectal cancer, breast cancer, and NSCLC.

Angiogenesis Inhibitors↗

PubMed2006

Bosentan: a review of its use in pulmonary arterial hypertension and systemic sclerosis.

Bosentan (Tracleer), an orally administered dual endothelin (ET)(A) and ET(B) receptor antagonist, is indicated in the treatment of pulmonary arterial hypertension (PAH). The efficacy of oral bosentan 125 mg twice daily in improving exercise capacity has been demonstrated in well designed trials in adult patients with idiopathic PAH or PAH associated with connective tissue disease or congenital systemic-to-pulmonary shunts, and in other trials in patients with idiopathic PAH or PAH associated with congenital heart disease or HIV infection. The beneficial effects of first-line bosentan treatment may be maintained for up to 1 year in patients with idiopathic PAH or PAH associated with connective tissue disease. Despite the potential for treatment-related teratogenicity and hepatotoxicity, long-term data indicate that bosentan is generally well tolerated at the approved dosages. Although well designed trials are required to establish the efficacy of bosentan versus or in combination with other specific PAH therapies, especially sildenafil, the convenient oral administration and lack of serious injection-related adverse effects may render bosentan preferable to other PAH therapies. Preliminary data indicate that bosentan may be effective in pediatric PAH patients, although randomized trials are required. Furthermore, bosentan may be a useful option for the prevention of digital ulcer development in patients with systemic sclerosis. Thus, in accordance with current clinical guidelines, bosentan is a convenient, effective, and generally well tolerated agent for use in the first-line treatment of class III PAH or second-line treatment of class IV PAH.

Antihypertensive Agents↗

PubMed2005

Tenofovir disoproxil fumarate: a review of its use in the management of HIV infection.

Tenofovir disoproxil fumarate (tenofovir DF; Viread), an ester prodrug of the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir, is indicated in combination with other antiretroviral agents in the treatment of HIV infection. As a component of an antiretroviral regimen, oral tenofovir DF 300 mg once daily effectively reduces viral load in patients with HIV infection who are treatment-experienced with baseline NRTI resistance mutations or treatment-naive. Tenofovir DF provides a simple and convenient once-daily dosage regimen, and is generally well tolerated and able to produce sustained suppression of viral replication.

Adenine↗

PubMed2005

Subcutaneous recombinant interferon-beta-1a (Rebif): a review of its use in relapsing-remitting multiple sclerosis.

Subcutaneous recombinant interferon-beta-1a (Rebif) 22 or 44 microg three times weekly is a valuable option in the first-line treatment in patients with relapsing-remitting multiple sclerosis (RRMS). It has shown benefits on outcome measures related to relapses, progression of disability and magnetic resonance imaging (MRI) in clinical trials. A significant efficacy advantage for subcutaneous interferon-beta-1a three times weekly over intramuscular interferon-beta-1a 30 microg once weekly was shown at 24 and 48 weeks. The most common adverse events are generally mild and clinically manageable. Considering both direct and indirect comparative clinical trial data, an assessment suggests that subcutaneous interferon-beta-1a 44 microg three times weekly has the best benefit-to-risk values of the available disease-modifying drugs used to treat RRMS.

Adjuvants, Immunologic↗

PubMed2005

Inhaled salmeterol/fluticasone propionate: a review of its use in asthma.

Salmeterol/fluticasone propionate, administered twice daily via a multidose dry powder inhaler (Seretide/Advair Diskus), Seretide Accuhaler or metered-dose hydrofluoroalkane (chlorofluorocarbon-free) inhaler (Seretide Evohaler), is a combination of the long-acting beta(2)-adrenoceptor agonist (beta(2)-agonist) [LABA] salmeterol and the corticosteroid fluticasone propionate. Maintenance therapy with combined salmeterol/fluticasone propionate is at least as effective in improving lung function and symptoms and is as well tolerated in patients with asthma as concurrent salmeterol plus fluticasone propionate. In patients previously receiving as-required short-acting beta(2)-agonists (SABAs) or inhaled corticosteroids, salmeterol/fluticasone propionate was significantly more effective in providing asthma control than fluticasone propionate and in improving lung function and asthma symptoms than inhaled corticosteroids (at equivalent or higher dosages), salmeterol or montelukast (as monotherapy or in combination with fluticasone propionate). Salmeterol/fluticasone propionate was more effective in improving asthma symptoms than adjusted-dose budesonide/formoterol in patients with uncontrolled asthma despite treatment with inhaled corticosteroids with or without a LABA in a well designed 1-year study. In pharmacoeconomic analyses, salmeterol/fluticasone propionate compared favourably with inhaled corticosteroids and mono- or combination therapy with oral montelukast. Salmeterol/fluticasone propionate is, therefore, an effective, well tolerated and cost-effective option for the maintenance treatment of patients with asthma.

Acetates↗

PubMed2005

Docetaxel: a review of its use in metastatic breast cancer.

Docetaxel (Taxotere), a cytotoxic taxane, is an antimicrotubule agent effective in the treatment of patients with breast cancer. The clinical profile of docetaxel as an effective cytotoxic agent in the treatment of metastatic breast cancer is well established. As yet, no single standard regimen has been identified as optimal for the treatment of patients with metastatic breast cancer after failure of prior chemotherapy. However, the efficacy of docetaxel monotherapy administered every 3 weeks as a 1-hour infusion is similar to or better than that of doxorubicin, paclitaxel and fluorouracil plus vinorelbine, and better than that of methotrexate plus fluorouracil or mitomycin plus vinblastine. Although docetaxel is associated with neutropenia and other adverse events, its overall tolerability profile is generally acceptable in the majority of patients. Docetaxel, therefore, is an effective option in the treatment of patients with metastatic breast cancer after failure of prior chemotherapy.

Animals↗

PubMed2005

Memantine: a pharmacoeconomic review of its use in moderate-to-severe Alzheimer's disease.

Memantine (Ebixa, Namenda, Axura) is an uncompetitive NMDA receptor antagonist used in the management of patients with moderate-to-severe Alzheimer's disease. It is currently the only drug approved for use in these more advanced stages of the disease. Significant reductions in functional and cognitive decline have been demonstrated with memantine relative to placebo in randomised, double-blind trials in this patient population. Clinical trial and postmarketing surveillance data indicate that the drug is generally well tolerated. Two fully published modelled cost-effectiveness analyses of memantine in moderate-to-severe Alzheimer's disease have been conducted in the UK and Finland, in which patient progression was simulated through health states related to dependency, residential setting and cognitive function. Although the specific costs included in the analyses varied, as did the study perspective and geographical location, results of the base-case analyses consistently showed that memantine was dominant over no pharmacological treatment. In the UK and Finnish analyses, memantine increased the duration of independence by 1.3 and 4.1 months, respectively, and the time to institutionalisation by 0.8 and 1 month. Mean total per-patient costs were reduced by 1963 pounds over 2 years (2003 costs) in the UK analysis and by 1687 eurossover 5 years (2001 costs) in the Finnish analysis. Memantine was also associated with a small gain in quality-adjusted life expectancy in the UK model. In sensitivity analyses, memantine remained dominant for almost all plausible changes to key variables. Memantine reduced total societal costs by $1090 per patient per month (1999 costs) compared with no pharmacological treatment over 28 weeks in a resource utilisation and cost analysis conducted alongside a pivotal US trial in patients with moderate-to-severe Alzheimer's disease. Results were primarily driven by reductions in total caregiver costs, which included the opportunity cost of time spent in caregiving tasks, and in direct nonmedical costs, which included the cost of care in a nursing home or similar institution.In conclusion, in patients with moderate-to-severe Alzheimer's disease, memantine is associated with significant reductions in functional and cognitive decline compared with no pharmacological treatment. Available pharmacoeconomic data from Europe and the US, despite some inherent limitations, support the use of memantine as a cost-effective treatment in this patient population, although definitive conclusions are not feasible because of limited data.

Alzheimer Disease↗

PubMed2005

Tolcapone: a review of its use in the management of Parkinson's disease.

Tolcapone (Tasmar) is a selective, reversible inhibitor of peripheral and central catechol-O-methyltransferase (COMT). Results of well designed studies indicate that oral tolcapone is an effective adjunct to levodopa plus a peripheral dopa-decarboxylase inhibitor (DDCI) in patients with fluctuating Parkinson's disease. Tolcapone significantly improves levodopa-induced motor fluctuations and significantly reduces levodopa requirements. The drug is generally well tolerated, with the most commonly occurring adverse events being dopaminergic related. Thus, tolcapone is a useful option in patients with fluctuating Parkinson's disease who are receiving levodopa/DDCI and are not responding to, or are not candidates for, other adjunctive treatments.

Antiparkinson Agents↗

PubMed2005

Spotlight on subcutaneous recombinant interferon-beta-1a (Rebif) in relapsing-remitting multiple sclerosis.

Subcutaneous recombinant interferon-beta-1a (Rebif) 22 or 44 microg three times weekly is a valuable option in the first-line treatment in patients with relapsing-remitting multiple sclerosis. It has shown benefits on outcome measures related to relapses, progression of disability, and magnetic resonance imaging in clinical trials. A significant efficacy advantage for subcutaneous interferon-beta-1a three times weekly over intramuscular interferon-beta-1a 30 microg once weekly was shown at 24 and 48 weeks. The most common adverse events are generally mild and clinically manageable. Considering both direct and indirect comparative clinical trial data, an assessment suggests that subcutaneous interferon-beta-1a 44 microg three times weekly has the best benefit-to-risk values of the available disease-modifying drugs used to treat relapsing-remitting multiple sclerosis.

Humans↗

PubMed2004

Lumiracoxib.

Lumiracoxib is a highly selective and potent cyclo-oxygenase (COX)-2 inhibitor, with a novel structure that conveys weakly acidic properties and a unique pharmacological profile. It is rapidly absorbed, with a relatively short plasma half-life. In well designed clinical trials of 1-52 weeks' duration in patients with osteoarthritis (OA) or rheumatoid arthritis, the efficacy of oral lumiracoxib 100-400 mg/day in decreasing pain intensity and improving functional status was greater than that with placebo and similar to those with nonselective NSAIDs or celecoxib 200mg once daily. In single- and multiple-dose well designed trials in patients with acute pain associated with primary dysmenorrhoea, dental or orthopaedic surgery or tension-type headache, lumiracoxib 100-800 mg once daily was more effective in relieving acute pain than placebo or controlled-release oxycodone 20 mg, and was at least as effective as selective COX-2 inhibitors or nonselective NSAIDs. Lumiracoxib was generally well tolerated in clinical trials, with a similar overall tolerability profile to those of placebo and other COX-2-selective inhibitors. In a large 52-week safety trial in patients with OA, lumiracoxib 400mg once daily had a rate of gastrointestinal ulcer complications that was approximately one-third to one-quarter of that of ibuprofen 800 mg three times daily or naproxen 500 mg twice daily. Lumiracoxib was not associated with an increase in cardiovascular events.

Administration, Oral↗

PubMed2004

Infliximab: a pharmacoeconomic review of its use in rheumatoid arthritis.

Infliximab (Remicade), a biological disease-modifying antirheumatic drug (DMARD), binds to and inhibits the activity of tumour necrosis factor-alpha, which is thought to play an important role in the pathophysiology of rheumatoid arthritis. Intravenous infliximab plus methotrexate is recommended in patients with rheumatoid arthritis who have not achieved satisfactory disease control with adequate courses of other DMARDs. Pharmacoeconomic analyses have been based on efficacy data from the pivotal placebo-controlled Anti-Tumour Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) trial in patients with active, refractory rheumatoid arthritis. Infliximab every 8 weeks plus methotrexate demonstrated rapid and sustainable improvements in clinical response, delayed radiographic progression, and/or improved functional status and health-related QOL compared with placebo plus methotrexate at weeks 30, 54 and 102. In cost-utility analyses of infliximab plus methotrexate conducted from a healthcare payer and/or societal perspective in the US, Europe, Portugal, Sweden and the UK, infliximab 3 mg/kg every 8 weeks plus methotrexate was associated with acceptable (<$US50,000 per discounted QALY gained) cost-utility ratios relative to methotrexate alone in patients with active, refractory rheumatoid arthritis. When only direct costs were considered, the lifetime incremental cost per discounted QALY gained with infliximab plus methotrexate relative to methotrexate alone was $US30,500-38,700 (year of costing 1998 or not reported; treatment duration 54 or 102 weeks or lifelong) in the US and Europe analyses, and euro39 500 (year of costing not reported; lifelong treatment) in the Portuguese analysis. The cost-utility ratios were more favourable when lost productivity costs or the additional benefit of infliximab on radiographic stabilisation were considered. In the Swedish and UK analyses with a 10-year time horizon, infliximab plus methotrexate for 1 or 2 years was associated with cost-utility ratios of euro28 600-56 100 (year of costing not reported) when direct costs were considered, and euro3440-48 200 when direct costs plus loss-of-productivity costs were considered. In conclusion, cost-utility analyses, which were based on modelling of data from the pivotal clinical trial of infliximab plus methotrexate, indicate that infliximab plus methotrexate is associated with acceptable cost-effectiveness ratios (<$US50,000 per discounted QALY gained) relative to methotrexate monotherapy in patients with active rheumatoid arthritis who have not responded to previous methotrexate or other DMARD therapy. The cost effectiveness of infliximab versus other DMARDs is at present unclear, but will be clarified when appropriate data from directly comparative clinical and/or pharmacoeconomic studies become available. In patients in whom adequate courses of other DMARDs have failed to achieve satisfactory disease control, infliximab plus methotrexate may prevent or delay disability, which may produce reductions in nondrug costs that can help offset its acquisition cost.

Antibodies, Monoclonal↗

PubMed2004

Etanercept: a pharmacoeconomic review of its use in rheumatoid arthritis.

Etanercept (Enbrel), which inhibits the activity of tumour necrosis factor-alpha, is indicated in the treatment of patients with active rheumatoid arthritis (RA). A lifetime cost-utility analysis in patients with severe disease-modifying antirheumatic drug (DMARD)-resistant RA in the UK suggested that etanercept is associated with acceptable cost-utility ratios relative to traditional nonbiological DMARDs. In a 12-month cost-utility study in Spain, etanercept was predicted to be dominant over infliximab plus methotrexate in patients with active, refractory RA with regards to the cost per QALY gained and cost per American College of Rheumatology (ACR) 20 response achieved. In short-term cost-effectiveness analyses conducted in the US, the cost effectiveness of etanercept relative to other treatments in patients with methotrexate-naive or -resistant RA depends on whether predicted incremental cost-effectiveness ratios of at least USD 41,900 per ACR 20 response or USD 34,800 per ACR 70 weighted response over a 6-month period are considered acceptable (1999 values). The relative efficacy and cost effectiveness of etanercept and other biological DMARDs will be clarified when appropriate data from directly comparative clinical and/or long-term pharmacoeconomic studies become available. Etanercept may prevent or delay disability, which may produce reductions in nondrug costs that could help offset its acquisition cost.

Antirheumatic Agents↗