A single center, pilot, double-blinded, randomized, comparative, prospective clinical study to evaluate improvements in the structure and function of facial skin with tazarotene 0.1% cream alone and in combination with GliSODin(®) Skin Nutrients Advanced Anti-Aging Formula.

BACKGROUND: Superoxide dismutase (SOD) reduces the reactive oxygen species formation associated with oxidative stress. An imbalance between free radicals and antioxidants can lead to accelerated aging. GliSODin(®) Skin Nutrients Advanced Anti-Aging Formula (GAAF) is an SOD-containing dietary nutricosmetic formulated with other nutraceuticals that promote improvements in the structure and function of the skin, including hydration, elasticity, structural integrity, and photoaging caused by oxidative stress. Tazarotene cream 0.1% (TAZ) is a United States Food and Drug Administration-approved drug indicated for use in the mitigation of facial fine wrinkling, facial mottled hyper- and hypopigmentation, and benign facial lentigines when taken in conjunction with a comprehensive skin care and sun avoidance program. OBJECTIVE: To determine if the antioxidant, anti-aging, hydrating and skin-rejuvenating properties of GAAF complement the retinoic actions of TAZ to improve the structure and function of facial skin. METHOD: A 90-day comparative study of ten subjects with facial photodamage; daily topical application of TAZ was used in combination with three capsules of GAAF (780 mg each) or placebo orally, with food, per the randomization allocation. RESULTS: After 90 days of treatment, TAZ alone and in combination with GAAF improved fine wrinkles (↓1.2 versus 2.0), mottled hyperpigmentation (↓2.2 versus 2.8) and overall photodamage (↓1.0 versus 1.8), as well as patient-reported response to treatment (↓2.0 versus 1.6). At week 12, TAZ/GAAF combination treatment (Group A) versus TAZ treatment alone (Group C) was of significant clinical benefit, with respect to fine wrinkling (14.7%/41.7%), overall photodamage (15.6%/53.0%), skin moisture (19.1%/103.2%), skin elasticity (12.8%/87.7%), and response to treatment (8.8%/21.4%). CONCLUSION: The study suggests GAAF in combination with TAZ is safe and provides significant clinical benefit with relative improvement in facial fine wrinkling, overall photodamage, skin moisture and elasticity.

Comparing the cost-effectiveness of disease-modifying drugs for the first-line treatment of relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system that primarily afflicts young adults. Approximately 400,000 people in the United States are affected by MS. Although several forms of MS exist, the most common course is known as relapsing-remitting MS (RRMS), which affects about 85% of MS patients. This form of MS is characterized by relapses of neurologic symptoms followed by periods of recovery. Progression of disease can lead to increasingly severe disability. Since the introduction of immunomodulatory biologic agents, such as interferon betas and glatiramer acetate, treatment has helped to change the course of the disease. Under budgetary constraints, health services payers are challenged to differentiate the economic value of these agents for formulary selection and/or placement. OBJECTIVE: The primary objective of this analysis was to evaluate the 2-year cost-effectiveness of 4 disease modifying drugs (DMDs) used as first-line treatment of RRMS: glatiramer acetate, interferon (IFN) Beta-1a IM injection, IFN Beta-1a SC injection, and IFN Beta-1b SC injection. METHODS: An Excel-based model was developed to compare the relative effectiveness and cost components of relapses, disability progression, and DMDs in the treatment of RRMS over a 2-year time horizon. The relative risk reduction (RRR) method was used to compare reduction in relapse rates and disease progression data from pivotal randomized double-blind placebo-controlled clinical trials of the DMDs. RRRs for relapses and disability progression, respectively, were calculated as the relative difference (treatment vs. placebo) in relapse rates and disease progression rates from placebo-controlled clinical trials. These RRRs were applied to the weighted average rates of relapse and number of disability progression steps seen in the placebo arms of the pivotal studies. The evaluation was conducted from the perspective of a U.S. health care payer (only direct medical costs considered). Medical savings were calculated as costs saved due to relapses avoided and prevention in disability progression steps. In the base case analysis, we assumed 89.4% persistence, a cost per relapse of $4,682, and a cost per disability progression step of $1,788. Monthly cost of therapy was defined as wholesale acquisition cost ($0 contractual discounts and $25 patient copayment assumed in the base case analysis) plus routine monitoring costs as assessed by an expert panel. The primary economic endpoint was cost per relapse avoided. Costs and outcomes occurring in the second year were discounted 3% to bring to 2008 present values. Oneway and multiway probabilistic (Monte Carlo) sensitivity analyses were conducted on key input variables to assess their impact on cost per relapse avoided. RESULTS: Without DMD treatment, patients were predicted to experience 2.55 relapses and 0.44 disability progression steps over a 2-year period (discounted values). The 2-year reductions in clinical relapses for treatment with glatiramer acetate, IFN Beta-1a IM injection, IFN Beta-1a SC injection, and IFN Beta-1b were 0.66, 0.42, 0.74, and 0.70, respectively. The 2-year reductions in disability progression steps for treatment with glatiramer acetate, IFN Beta-1a IM injection, IFN Beta-1a SC injection, and IFN Beta-1b were 0.05, 0.15, 0.12, and 0.11, respectively. In the base case analysis, IFN Beta-1a SC injection, IFN Beta-1b SC injection, and glatiramer acetate had the most favorable costs per relapse avoided ($80,589; $87,061; and $88,310; respectively) and IFN Beta-1a IM injection had the least favorable cost-effectiveness ratio ($141,721 per relapse avoided). Sensitivity analyses showed that these results were robust to changes in key input parameters, such as the number of relapses and disease progression steps in untreated patients, the RRR in clinical relapse and progression rates, the rate of persistence, the average cost of relapse, and the average cost of a disease progression step. CONCLUSION: This evaluation suggests that IFN Beta-1a SC injection, IFN Beta-1b SC injection, and glatiramer acetate represent the most cost-effective DMDs for the treatment of RRMS, where cost-effectiveness is defined as cost per relapse avoided, assuming that (a) the RRR in relapses and disease progression steps calculated from multiple DMD placebo-controlled clinical trials reflect real differences among DMDs over 2 years; and (b) resource unit costs derived from published sources reflect economic consequences of relapses and disease progression.

Current management of glaucoma and the need for complete therapy.

Glaucoma is a long-term ocular neuropathy defined by optic disc or retinal nerve fiber structural abnormalities and visual field abnormality. Primary open-angle glaucoma is the most common type of glaucoma. Currently available treatments, initiated in a stepwise process, focus on intraocular pressure (IOP) reduction, and initially include topical drug therapy (single then multidrug combinations), followed by laser then surgical treatment. Topical prostaglandin analogues or beta-adrenergic receptor blockers are first used, followed by alpha-agonists or topical carbonic anhydrase inhibitors, and infrequently, cholinergic agonists and oral therapy. Limitations to existing topical IOP-reducing medications include continued disease progression in glaucoma patients with normal IOP, treatment failure, and low rates of compliance and persistence. Therapeutic agents under investigation include neuroprotectants, which target the disease process manifested by death of retinal ganglion cells, axonal loss, and irreversible loss of vision. Neuroprotectants may be used alone or in combination with IOPreducing therapy (a treatment strategy called complete therapy). Memantine, an N-methyl-D-aspartate receptor blocker currently approved for dementia, is the neuroprotectant farthest along in the process seeking regulatory approval for glaucoma treatment and has a favorable safety profile because of its selective mechanism of action. Several other neuroprotectants are in early stage investigation. Complete therapy provides hope for improved outcomes by reducing the significant morbidity and economic consequences that occur as a result of neurodegeneration and disease progression.

Cost considerations in the medical management of glaucoma in the US: estimated yearly costs and cost effectiveness of bimatoprost compared with other medications.

INTRODUCTION: The aim of this study was to evaluate the cost effectiveness of glaucoma treatment with bimatoprost compared with other intraocular pressure (IOP)-lowering medications in adult patients with chronic glaucoma or ocular hypertension (IOP of between 22 mm Hg and 34 mm Hg), from a US healthcare payers' perspective. METHODS: Estimated yearly costs and cost per treatment success for 0.03% bimatoprost once daily (Lumigan) were compared with 0.5% timolol twice daily (generic), 0.005% latanoprost once daily (Xalatan) and the fixed combination of 0.5% timolol and 2.0% dorzolamide twice daily (Cosopt). The model was based on year 2003 medical resource costs (physician visits and drug acquisition costs) and treatment success rates from published clinical trials. The clinical measure utilised was the percentage of patients achieving target IOPs. RESULTS: A higher percentage of patients achieved target IOPs with bimatoprost than with each of the other medications. At most target pressures, the cost per treatment success for patients starting treatment on bimatoprost was less than that for patients started on other drugs. This was true despite that, when looking at costs alone, the estimated yearly costs for bimatoprost (averaged over both patient success and patient failures) were similar to or greater than those for the other drugs. The greatest differences in cost per treatment success were seen at target pressures < or =15 mm Hg. For example, at a target pressure of 13 mm Hg, the cost per treatment success based on the model was 9238-10,229 US dollars for bimatoprost, 23,218 US dollars for timolol, 21,943 US dollars for latanoprost and 16,034 US dollars for timolol/dorzolamide. The incremental cost of achieving additional clinical success for bimatoprost ranged from 800 US dollars to 1,700 US dollars versus generic timolol, and from 300 US dollars to 3,100 US dollars versus timolol/dorzolamide. Bimatoprost was more effective and less costly than latanoprost. CONCLUSION: In our simplified model of cost per treatment success based on responder rates at varying IOPs, the greater efficacy of bimatoprost resulted in a cost per treatment success that was generally lower for bimatoprost than for timolol, latanoprost or timolol/dorzolamide. This was most pronounced at target pressures <15 mm Hg.

The cost of migraine and its treatment.

Migraine headache incurs estimated annual costs totaling as much as 17 billion dollars in the United States. Most of the direct costs are for outpatient services: medications, office or clinic visits, emergency department visits, laboratory and diagnostic services, and management of treatment side effects. Indirect costs from lost productivity in the workplace add substantially to the total. The triptan class of drugs, used for abortive treatment, account for the greatest portion of medication costs. Because these agents are expensive, optimal use is critical. Research suggests that a stratified care strategy, with initial therapy based on the patient's score on the Migraine Disability Assessment Scale, is both clinically advantageous and more cost-effective than stepped-care strategies. Also, the triptans are not interchangeable, and costs as well as clinical outcomes may vary with different agents in this class. Migraine prophylaxis is aimed at preventing frequent attacks and the development of a long-term condition that often incurs heavy costs for abortive treatment, diagnostic services, and medical care. Agents approved for migraine prophylaxis include the antiepileptics divalproex and topiramate and the beta blockers propranolol and timolol. As with abortive therapy, costs vary widely among these prophylactic agents. A novel approach to migraine prophylaxis is injection of botulinum toxin. A cost-analysis model is presented to show the impact of utilizing botulinum toxin in a large managed care system.

Clinical guidelines for the treatment of glaucoma.

Several documents guide screening and detection of glaucoma. The AAO guidelines are considered the current standard. The VA has established the need for regular screening based on identified factors. Finally, a task force working with NCQA to develop a glaucoma-related HEDIS measure may provide future direction in populationwide care.

Constructing disease management programs for glaucoma.

Glaucoma, which is associated with diabetes, hypertension, and hypothyroidism, is considered to be a good candidate for disease management. This article explains to clinicians and administrators who are interested in the identification and treatment of glaucoma what they should know about disease management and how they might benefit from establishing a DM program for glaucoma.