Effectiveness comparison and incremental cost-per-responder analysis of calcipotriene 0.005%/betamethasone dipropionate 0.064% foam vs. halobetasol 0.01%/tazarotene 0.045% lotion for plaque psoriasis: a matching-adjusted indirect comparative analysis.

Background: The fixed-dose combination foam formulation of calcipotriene 0.005% plus betamethasone dipropionate 0.064% (Cal/BD) has demonstrated efficacy and a favorable safety profile for the treatment of plaque psoriasis. Recently, a topical lotion of the combination of halobetasol 0.01% plus tazarotene 0.045% (HP/TAZ) was approved for treating adult plaque psoriasis. Currently, no head-to-head studies have compared Cal/BD foam with HP/TAZ lotion.Objective: Compare the effectiveness and drug incremental cost per responder (ICPR) of Cal/BD foam vs. HP/TAZ lotion in moderate-to-severe plaque psoriasis.Methods: An anchor-based, matching-adjusted indirect comparison was conducted for PGA treatment success (Physician's Global Assessment of "clear" or "almost clear," [PGA 0/1] with at least a 2-point improvement) using individual patient data from 3 randomized clinical studies of Cal/BD foam and published data from 2 randomized, Phase 3 clinical studies of HP/TAZ lotion. The number needed to treat and ICPR were also calculated.Results: After reweighting of patients in the Cal/BD foam studies to match summary baseline characteristics of the HP/TAZ lotion study patients and anchoring to vehicle effect, 4 weeks of Cal/BD foam produced a significantly greater rate of treatment success than 8 weeks of HP/TAZ lotion treatment (51.4 vs. 30.7%; treatment difference = 20.7%, p < .001). The number needed to treat with Cal/BD foam was also less than HP/TAZ lotion (1.9 vs. 3.3). Using US wholesale acquisition costs and equal weekly consumption rates, the incremental cost per PGA 0/1 responder relative to vehicle for Cal/BD foam was $3,988 and was 37% lower compared with HP/TAZ lotion ($6,294).Conclusions: The indirect comparison analyses showed that Cal/BD foam was associated with a greater rate of treatment success, lower ICPR, and quicker treatment response than HP/TAZ lotion in adult patients with moderate-to-severe plaque psoriasis.

A systematic review and economic evaluation of cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate for the treatment of intermittent claudication in people with peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is a condition in which there is blockage or narrowing of the arteries that carry blood to the legs and arms. It is estimated to affect around 4.5% of people aged between 55 and 74 years within the UK. The most common symptom of PAD is intermittent claudication (IC), characterised by pain in the legs on walking that is relieved with rest. OBJECTIVE: To assess the effectiveness and cost-effectiveness of cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate, compared with no vasoactive drugs, for IC due to PAD in adults whose symptoms continue despite a period of conventional management. DATA SOURCE: Electronic bibliographic databases were searched during April to June 2010 (MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Conference Proceedings Citation Index, BIOSIS Previews). REVIEW METHODS: Effectiveness outcomes sought were maximal walking distance (MWD), pain-free walking distance (PFWD), ankle-brachial pressure index, cardiovascular events, mortality, adverse events (AEs) and health-related quality of life (HRQoL). A narrative synthesis was provided for all outcomes and a network meta-analysis was undertaken for the walking distance outcomes. A Markov model was developed to assess the relative cost-effectiveness of the interventions from a NHS perspective over a lifetime. The model has three states: vasoactive drug treatment, no vasoactive drug treatment and death. Each 1-week cycle, patients may continue with the drug, discontinue the drug or die. Regression analysis was undertaken to model the relationship between MWD and utility so that a cost per quality-adjusted life-year (QALY) outcome measure could be presented. Univariate and probabilistic sensitivity analyses were undertaken. All costs and outcomes were discounted at 3.5%. RESULTS: Twenty-six randomised controlled trials were identified that met the inclusion criteria for the clinical effectiveness review. There was evidence that walking distance outcomes were significantly improved by both cilostazol and naftidrofuryl oxalate; the 95% credible intervals for the difference from placebo in the logarithm mean change MWD from baseline were 0.108 to 0.337 and 0.181 to 0.762, respectively. It was not possible to include inositol nicotinate within the meta-analysis of MWD and PFWD owing to the lack of 24-month data; however, the shorter-term data did not suggest a significant effect. AEs were minor for all drugs and included headaches and gastrointestinal difficulties. The incidence of serious adverse events (SAEs), including cardiovascular events and mortality, was not increased by the vasoactive drugs compared with placebo; however, most studies had a relatively short follow-up time to address this outcome. HRQoL data were limited. Two studies of limited quality were identified within the review of cost-effectiveness. The de novo model developed suggests that naftidrofuryl oxalate dominates cilostazol and pentoxifylline and has a cost per QALY gained of around £6070 compared with no vasoactive drug. This result is reasonably robust to changes within the key model assumptions. Inositol nicotinate was not included within the main analysis owing to lack of data. However, it is unlikely to be considered to be cost-effective due to its high acquisition cost (£900 vs £100-500 per year for the other drugs). CONCLUSIONS: Naftidrofuryl oxalate and cilostazol both appear to be effective treatments for this patient population, with minimal SAEs. However, naftidrofuryl oxalate is the only treatment that is likely to be considered cost-effective. The long-term effectiveness is uncertain and hence a trial comparing cilostazol, naftidrofuryl oxalate and placebo beyond 24 weeks would be beneficial. Outcomes associated with naftidrofuryl oxalate could also be compared with those associated with supervised exercise programmes and angioplasty.

Nicotinic acid: new/old drug. Immediate or sustained release: too risky for a drug with no proven benefit.

(1) For patients with hypercholesterolaemia requiring primary or secondary prevention, pravastatin, simvastatin and atorvastatin have a proven benefit in terms of mortality and/or morbidity. Gemfibrozil and cholestyramine have a proven impact on morbidity. (2) The lipid-lowering properties of immediate-release nicotinic acid have been known for about 50 years, as have its frequent and sometimes severe adverse effects. About 70% of patients experience cutaneous flushing, and 20-30% develop gastrointestinal adverse effects. Hepatotoxic effects occur in about 2% of patients, especially in those using high daily doses or sustained-release formulations. (3) The clinical evaluation of immediate-release nicotinic acid is mainly based on two comparative placebo-controlled trials. One, involving 5000 patients monitored on average for 15 years, showed no effect on survival. One trial suggested that immediate-release nicotinic acid reduced the risk of recurrent myocardial infarction. (4) Sustained-release nicotinic acid has not been evaluated in terms of its effect on morbidity or mortality. It has been shown to lower LDL cholesterol and triglyceride levels and to raise the HDL cholesterol level. (5) This new pharmaceutical formulation has a profile and frequency of known adverse effects similar to those of immediate-release nicotinic acid. (6) When hypercholesterolaemia persists despite an appropriate diet, it is best to use one drug with a proven preventive impact on mortality and/or morbidity. This is not the case for sustained-release nicotinic acid. (7) When statin therapy is inadequate, it remains to be shown whether adding another cholesterol-lowering drug is beneficial in terms of morbidity and mortality. If, in rare cases, combination with a statin is envisaged, it is best to use gemfibrozil or cholestyramine. Note that gemfibrozil should only be combined with a statin with the greatest caution.

Modern modified 'ultra' Goeckerman therapy: a PASI assessment of a very effective therapy for psoriasis resistant to both prebiologic and biologic therapies.

BACKGROUND: Compared with the original Goeckerman therapy devised by Dr Goeckerman in the 1930s, modern modified Goeckerman therapy in the second millennium shows significantly enhanced efficacy by improvements in technology (e.g. narrowband UVB) and the possibility of adding other relatively safe therapeutic options for more resistant cases to enhance efficacy without compromising the basic safety profile. METHODS: For approximately 6 months, psoriasis patients undergoing Goeckerman therapy at the UCSF Psoriasis Center were followed from admission to discharge. A total of 25 consecutive psoriasis patients were treated with the Goeckerman regimen until (near-) clearance or for a maximum period of 3 months, and their weekly improvements in terms of PASI (psoriasis area and severity index) were recorded. RESULTS: In all, 100% reached PASI 75 by 12 weeks of treatment. In fact, by 8 weeks, 95% reached PASI 75 and most of the patients were discharged within 2 months. CONCLUSIONS: The onset of treatment effect was rapid. Goeckerman therapy is still a valuable and important part of the psoriatic armamentarium.

Overview of pharmacologic therapy for the treatment of dyslipidemia.

Although the National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines stress the importance of nonpharmacologic lipid modification interventions such as diet and exercise, the guidelines also recognize that many patients will require drug therapy to achieve low-density lipoprotein cholesterol (LDL-C) target goals. Currently available lipid-modifying drugs include bile acid sequestrants (or resins), fibrates, nicotinic acid, and statins, with each class exerting different effects on the lipid profile. In addition, nonprescription agents such as plant stanols and sterols have been shown to be effective in modifying plasma lipids. Of these agents, the statins are the most effective, most widely prescribed, and best-tolerated form of lipid-lowering drug therapy. New formulations of other drugs, such as niacin and bile acid sequestrants, can also improve treatment regimes and reduce side effects, thereby improving patient compliance with these therapies. In patients who have high levels of LDL-C and triglycerides together with low concentrations of high-density lipoprotein cholesterol (HDL-C), combination therapy may be required. Ezetimibe, a selective cholesterol absorption inhibitor, is the first of a new class of lipid-lowering agents and provides a new agent for the management of patients with dyslipidemia. Data from the ezetimibe clinical development program suggests that this agent can be used alone or in combination with statins to reduce LDL-C, improve compliance, and bring more patients to ATP III target goal.

Management of acne.

Precise classification methods are used to define acne according to type (comedonal, papulopustular, or nodular) and severity. The relative effectiveness of several topical and systemic agents has been established in clinical trials, making possible an algorithm of specific treatment decisions based on acne classification.

Once-daily tazarotene 0.1 % gel versus once-daily tretinoin 0.1 % microsponge gel for the treatment of facial acne vulgaris: a double-blind randomized trial.

The efficacy and tolerability of tazarotene 0.1% gel and tretinoin 0.1% microsponge gel were evaluated in a multicenter, double-blind, randomized, parallel-group study in patients with mild-to-moderate inflammatory facial acne vulgaris. A total of 169 patients were randomized to once-daily applications of one of these topical retinoids for 12 weeks. Both agents were associated with significant reductions from baseline in the noninflammatory and inflammatory lesion counts. Tazarotene treatment was associated with a significantly greater incidence of treatment success (defined as > or = 50% global improvement [67% vs 49%; P=.03]) and significantly greater reductions in overall disease severity (36% vs 26%; P=.02) and noninflammatory lesion count (60% vs 38% at week 12; P=.02) than tretinoin microsponge treatment. Both drugs were well tolerated, with mean levels of dryness, burning, pruritus, erythema, and peeling generally being no more than trace throughout the study. There were no clinically significant between-group differences in these measures of tolerability. Two patients in each group (2%) discontinued because of treatment-related adverse events. The mean amount of medication applied by the patients was 0.28 g per application with tazarotene and 0.41 g per application with tretinoin microsponge, resulting in cost-effectiveness ratios of $81.45 per treatment success with tazarotene and $108.24 per treatment success with tretinoin microsponge. Tazarotene was observed to have greater efficacy and comparable tolerability and to be a cost-effective alternative to tretinoin 0.1% microsponge gel.

A multicenter, double-blind, randomized comparison study of the efficacy and tolerability of once-daily tazarotene 0.1% gel and adapalene 0.1% gel for the treatment of facial acne vulgaris.

The efficacy and tolerability of tazarotene 0.1% gel and adapalene 0.1% gel were compared in a multicenter, double-blind, randomized, parallel-group study in 145 patients with mild-to-moderate facial acne vulgaris. Both treatments were applied once daily in the evenings for up to 12 weeks. Compared with adapalene, treatment with tazarotene was associated with a significantly greater incidence of treatment success (> or = 50% global improvement) (78% vs 52%; P=.002) and significantly greater reductions in overall disease severity (P<.0001), noninflammatory lesion count (P<.0001), and inflammatory lesion count (P=.0002). In the early weeks of treatment, tazarotene was associated with transiently greater levels of burning, pruritus, erythema, and peeling compared with adapalene (P<.01). However, mean levels of these parameters were consistently less than mild in both treatment groups and, at the end of treatment, patients considered both treatments to be comparably well tolerated (the proportion of patients in each group who rated the comfort of their treated skin as comfortable or very comfortable was 76% with tazarotene and 69% with adapalene). Mean usage of study medication was 0.32 g per application of tazarotene and 0.42 g per application of adapalene, which resulted in cost-effectiveness ratios of $79.95 per treatment success for tazarotene and $107.88 per treatment success for adapalene. Sensitivity analyses suggest that these cost-effectiveness results are robust across a range of cost and efficacy assumptions. In conclusion, tazarotene 0.1% gel was more effective than adapalene 0.1% gel and was also a more cost-effective treatment option.

Psoriasis: current perspectives with an emphasis on treatment.

An individualized treatment regimen is necessary for each patient with psoriasis because of the diverse nature of the disease. The manifestation of psoriasis, the severity and extent of the lesions, and the medical history and lifestyle of the patient are important factors that determine the selection of treatment, but in general therapies with the fewest side effects are preferred. First-line topical treatments are corticosteroids, calcipotriene, and tazarotene. If topical treatments are unsuccessful, phototherapy with ultraviolet B or photochemotherapy with psoralens plus ultraviolet A (PUVA) are the next choices. If psoriasis fails to respond to an adequate trial of topical therapy or phototherapy, systemic therapies including methotrexate, acitretin, or cyclosporin should be initiated. Because the regimens involved in systemic and phototherapy are complex and require frequent dose adjustments and specialized equipment, the patient should be referred to a dermatologist when topical therapy is not effective.

A pharmacoeconomic analysis of topical therapies for patients with mild-to-moderate stable plaque psoriasis: a US study.

Psoriasis is a persistent skin disorder characterized by abnormal keratinocyte differentiation, keratinocyte hyperproliferation, and increased expression of inflammatory markers at the cellular level, leading to erythema, induration, and scaling of the skin. Depending on the severity of the disease, annual outpatient costs range from $1400 to $6600 per patient, totaling $3.2 billion each year in the United States. Because the disease is persistent and progressive, patients receiving a diagnosis of psoriasis early in life can expect to require lifelong care, which translates into lifelong expense. Treatments include topical formulations, systemic therapies, phototherapies, and combination therapies. Of these, topical agents are the first-line treatments, including fluocinonide and other steroids, calcipotriene, and tazarotene, a once-daily retinoid. To establish the relative cost-effectiveness of these drugs (fluocinonide, calcipotriene, and tazarotene), we conducted a pharmacoeconomic study from the perspective of a third-party payer, using a decision-analytic model validated by clinical experts. Data were drawn from a meta-analysis of the contemporary medical literature. Clinical success, clearing, and relapse rates determined the probabilities for therapeutic outcomes and the number of anticipated disease-free days for each study comparator. Costs for physician visits, drug acquisition, laboratory testing, and adverse-events management were added to each branch of the decision tree and multiplied by the appropriate probabilities to establish the expected cost of treatment, stratified by the primary treatment choice. Cost-effectiveness was expressed as the total expected cost of achieving a disease-free day. Tazarotene 0.1% was 16.74% more cost-effective than tazarotene 0.05%, 85.46% more cost-effective than fluocinonide, and 143.75% more cost-effective than calcipotriene. The expected cost of achieving a disease-free day was $49.46 for tazarotene 0.1%, $57.74 for tazarotene 0.05%, $91.73 for fluocinonide, and $120.56 for calcipotriene. Treatment with tazarotene offers an opportunity to reduce the cost of care for patients with mild-to-moderate psoriasis and enhance patient satisfaction by gaining more disease-free days.

Pharmacoeconomics of the therapy of diarrhoeal disease.

We review the pathophysiology of intestinal water and electrolyte transport leading to diarrhoea, the currently available pharmacological strategies for its treatment, and the economic implications of such treatments. Diarrhoea occurs most frequently and is associated with highest mortality in children under 5. Oral rehydration therapy (ORT) is the cornerstone of its management. The safety and efficacy of ORT in the prevention of death from dehydration, both in field and also in hospital settings, are now well established. Because it is also inexpensive, ORT is widely applicable worldwide. More recently, rice-based ORT has emerged, based on well known traditional remedies for diarrhoea in southeast Asia and the Far East. Rice-based ORT has the advantage of being more culturally acceptable, readily available even in rural homes in developing countries, and is more effective in reducing stool output and the duration of diarrhoea, compared with conventional glucose-electrolyte solutions such as World Health Organization ORT. For infants, the well known antidiarrhoeal properties of human milk needs emphasis for a variety of reasons including economic ones. Data concerning the economic benefits to a nations' health budget as a result of nationwide implementation of oral rehydration solution (ORS) use are limited. Available data from individual centres in developing countries, if projected to national level, would incur considerable economic advantage. Except for a few notable infections such as shigellosis, cholera, amoebiasis and giardiasis, the widespread use of antibiotics in acute diarrhoea, still a common practice in many developing countries, has no proven value and may be detrimental. The economic implications of antibiotic abuse in the treatment of diarrhoea in developing countries is enormous. Despite the availability of a wide spectrum of pharmacological agents for diarrhoea reviewed in this article, only a few such agents are of proven clinical efficacy: corticosteroids, aminosalicylates and immunosuppressants in the treatment of inflammatory bowel disease and opioid derivatives such as loperamide which may be useful in protracted diarrhoea in children and in disorders where rapid gastrointestinal transit is the main cause of diarrhoea. Opioids are not recommended for acute infective diarrhoea in childhood. Octreotide, a somatostatin analogue, is reported to be useful in the treatment of secretory diarrhoea due to noninfective causes and in the treatment of intractable diarrhoea associated with AIDS. Its high cost and need for parenteral administration prevent its wider application.(ABSTRACT TRUNCATED AT 400 WORDS)

Quantitative thermographic assessment of inositol nicotinate therapy in Raynaud's phenomena.

The basal temperature of the hands has been measured by quantitative thermography in a group of normal controls and rheumatoid patients exhibiting Raynaud's phenomenon. The thermographic index for both the dorsum of the hand and the fingers was significantly lower in the patients with Raynaud's. Oral treatment with inositol nicotinate (Hexopal) was followed by an initial rise in the thermographic index in both areas. After the initial increase the temperature fell again but then rose after two months treatment. At nine months two subjects on continuous therapy had higher indices than the four who had discontinued therapy. It is suggested that long-term treatment with nicotinate acid derivatives may produce improvement in the peripheral circulation by a different mechanism than the transient effect detected by short-term studies.