Disease-free Days Research Articles

Evaluation of a paraffin-based moisturizer compared to a ceramide-based moisturizer in children with atopic dermatitis: A double-blind, randomized controlled trial.

Moisturizers are first-line therapy for treatment of atopic dermatitis (AD). Although there are multiple types of moisturizers available, head-to-head trials between different moisturizers are limited. To evaluate if a paraffin-based moisturizer is as effective as ceramide-based moisturizer in children with AD. In this double-blind, randomized comparative trial of pediatric patients with mild to moderate AD, subjects applied either a paraffin-based or ceramide-based moisturizer twice daily. Clinical disease activity using SCOring Atopic Dermatitis (SCORAD), quality of life using Children/Infants Dermatology Life Quality Index (CDLQI/IDLQI), and transepidermal water loss (TEWL) were measured at baseline and at follow-up at 1, 3, and 6 months. Fifty-three patients were recruited (27 ceramide group and 26 paraffin group) with a mean age of 8.2 years and mean disease duration of 60 months. The mean change in SCORAD at 3 months in the ceramide-based and paraffin-based moisturizer groups was 22.1 and 21.4, respectively (p = .37). The change in CDLQI/IDLQI, TEWL over forearm and back, amount and days of topical corticosteroid required, median time to remission and disease-free days at 3 months were similar in both groups. As the 95% confidence interval (CI) of mean change in SCORAD at 3 months in both groups (0.78, 95% CI: -7.21 to 7.52) was not within the predefined margin of equivalence (-4 to +4), the conclusion of equivalence could not be proven. Both the paraffin-based and ceramide-based moisturizers were comparable in improving the disease activity in children with mild to moderate AD.

Occupational and Non-occupational Injuries Can Result in Prolonged Augmentation of Psychiatric Disorders.

BackgroundThe long-term effects of occupational injury (OI) on psychiatric diseases are unclear. This study assessed and compared the effects of OI, no injury (control), and non-OI (NOI) on the development of psychiatric diseases.MethodsWe used Taiwan’s National Health Insurance Research Database to investigate the incidence of psychiatric disorders in OI, NOI, and control groups. The subjects were aged 20–50 years, actively employed in 2000, and did not have history of injury or psychiatric disorders. All subjects were followed from 2000 and were classified into OI, NOI, and control groups according to occurrence of target injury later on. Individuals in each group were matched by age, sex, insurance premium before the index date, and year of the index date. Psychiatric disease-free days were compared among the groups using survival analysis and Cox regression.ResultsWe included a total of 12,528 patients for final analysis, with 4,176 in each group. Compared with the control group, the OI group had an increased occurrence of trauma and stress-related disorder, depressive disorders, anxiety disorders, and alcohol and other substance dependence. These increases were similar to those in the NOI group. Elevated cumulative incidence rate of any psychiatric disorders was observed among those with OI or NOI up to 10 years after injury.ConclusionWe confirmed that OI and NOI induced psychiatric disorders. These findings highlight the need for workers’ compensation mechanisms to consider long-term psychological care among injured workers.

Anesthesia in Combination with Propofol Increases Disease-Free Survival in Bladder Cancer Patients Who Undergo Radical Tumor Cystectomy as Compared to Inhalational Anesthetics and Opiate-Based Analgesia

Background:The effect of anesthetic techniques on cancer recurrence has been the subject of intensive research in the past years, as it affects a large proportion of the population. The use of opioids and halogenated agents in cancer patients during the perioperative period may be related to higher rates of cancer recurrence and reduced disease-free survival. Methods:This was a prospective study. The sample was composed of 100 patients who underwent a radical cystectomy for infiltrating bladder cancer in a reference center. We compared disease-free survival associated with combined anesthesia versus opiate-based analgesia. The relationship between the administered hypnotic and disease-free survival was also investigated. Results:The median disease-free survival of the patients who received combined anesthesia was 585 (240–1,005) days versus 210 (90–645) days in the other group. A significant difference was observed between the two groups (p = 0.01). Combined analysis of all groups revealed significant differences in disease-free survival between patients who received combined anesthesia with propofol (510 [315–1,545] disease-free days) and those who received sevoflurane and opioids (150 [90–450] disease-free days) (p = 0.02). Conclusions:Anesthesia may play a crucial role in tumor relapse, as it is administered at the moment of the greatest risk of dissemination: surgical handling of the tumor. Opioids and volatile agents have been related to an increased risk for cancer recurrence. We compared the use of propofol + local anesthesia versus sevoflurane + opioids and also found that disease-free survival was longer among patients who received propofol + local anesthesia. Disease-free survival increases with the use of propofol in combination with epidural anesthesia in patients who undergo surgery for infiltrating bladder cancer.

Safety and efficacy of intravenous Colchicine in children with Familial Mediterranean Fever.

Familial Mediterranean Fever (FMF), the most common monogenic inflammatory disease, is mainly treated by oral Colchicine. However, 5% of patients are considered non-responders and, therefore, candidates for biologic therapy. Intravenous (IV) Colchicine treatment has been shown to be effective and safe in adult patients. The objective of this study was to evaluate the safety of IV Colchicine for pediatric FMF patients in our hospital, refractory to oral Colchicine, by reviewing their medical records. Inclusion criteria were all patients with FMF who commenced treatment with IV Colchicine before the age of 18years, and received at least 6months of IV therapy. The patients completed questionnaires to assess the efficacy of the treatment. Between 2004 and 2017, 7 pediatric FMF patients receiving maximal oral Colchicine doses and deemed non-responders were treated with weekly IV Colchicine, including 38 cumulative patient years of follow-up data (a full blood count, renal and liver function tests). All patients were homozygous for the M694V genotype. Long-term follow-up showed normal laboratory results with no Colchicine-related hospital admissions or toxicity. Global health assessment and the number of disease-free days have significantly improved (P < 0.05). Prolonged IV Colchicine use is described in pediatric FMF patients for the first time, with an excellent safety profile in our population, and decrease in intensity and frequency of attacks. In the biological era, IV Colchicine, although not leading to complete remission, may be considered a second-line option in countries where anti-interleukin 1 blockers are not available, or as a third-line option in case of failure to respond to biologics.

Study of the Atopic March: Development of Atopic Comorbidities.

Atopic dermatitis (AD) is often the first step in the atopic march leading to the development of asthma or allergic rhinitis. The goal of this study was to determine whether early intervention with pimecrolimus limits the atopic march in infants with AD and to evaluate its efficacy and safety. This was a 3-year double-blind study in which patients were randomized to pimecrolimus or vehicle and then open-label pimecrolimus for a planned further 3 years. Rescue topical corticosteroid was permitted if 3 days of study medication led to no improvement; investigators made decisions on rescue medication until week 14 and caregivers thereafter. Efficacy assessments included disease-free days, Eczema Area and Severity Index, and body surface area affected. Infants ages 3 to 18 months with recent-onset AD (≤3 months) were observed for a mean of 2.8 years (N = 1,091). No significant differences between pimecrolimus- and placebo-treated groups were found in the percentage of patients with AD who developed asthma (10.7%) or other allergic conditions (allergic rhinitis, 22.4%; food allergy, 15.9%; allergic conjunctivitis, 14.1%; one or more atopic comorbidities, 37.0%) by study end. Allergic rhinitis, food allergy, and having one or more atopic comorbidities (but not asthma or allergic conjunctivitis alone) developed significantly more often in infants with greater AD severity at baseline. Pimecrolimus was significantly more effective than vehicle for AD treatment at week 14. Adverse event incidences were similar. This longitudinal observation of infants with AD provides evidence of the atopic march. Pimecrolimus was safe and effective in infants with mild to moderate AD.

Cost-Effectiveness of Ivermectin 1% Cream in Adults with Papulopustular Rosacea in the United States.

Papulopustular rosacea is a chronic skin disease involving central facial erythema in combination with papules and pustules. Papulopustular rosacea is treated with topical, systemic, or a combination of topical and systemic therapies. Currently approved topical therapies include azelaic acid gel/cream/foam twice daily (BID) and metronidazole cream/gel/lotion BID. Ivermectin 1% cream once daily (QD) is a new topical agent for the treatment of papulopustular rosacea that has been approved for the management of inflammatory lesions of rosacea and offers an alternative to current treatments. To evaluate the cost-effectiveness of ivermectin 1% cream QD compared with current topical treatments in order to understand the cost of adding ivermectin as a treatment option that would bring additional clinical benefit for adults with papulopustular rosacea in the United States. The cost-effectiveness of ivermectin 1% cream QD was compared with metronidazole 0.75% cream BID and azelaic acid 15% gel BID for adults in the United States with moderate-to-severe papulopustular rosacea using a Markov cohort state transition structure with 2 mutually exclusive health states (rosacea and no rosacea) and 5 phases. Patients could succeed or fail to respond to treatment and experience a relapse after treatment success. The model took a health care payer perspective (direct medical costs of topical and/or systemic therapy plus health care costs for physician and specialist visits) and used a 3-year time horizon. The model was run for a cohort of 1,000 patients. Costs (2014 U.S. dollars) and benefits (disease-free days and quality-adjusted life-years [QALYs]) were discounted at a rate of 3% per annum. Cost-effectiveness was determined by the incremental cost-effectiveness ratio (ICER) and measured in terms of incremental cost per QALY gained (estimated from health state utilities for patients with and without rosacea). Univariate and probabilistic sensitivity analyses (PSA) were conducted to assess the robustness of model outcomes. Compared with metronidazole 0.75% cream BID, ivermectin 1% cream QD was associated with higher costs but provided greater clinical benefit, with an ICER of $13,211 per QALY gained. For a cohort of 1,000 patients, ivermectin 1% cream QD provided an additional 72,922 disease-free days (200 years) over a 3-year period compared with metronidazole 0.75% cream BID, leading to a lower cost per disease-free day for ivermectin 1% cream QD ($4.54) compared with metronidazole 0.75% cream BID ($4.85). Ivermectin 1% cream QD was associated with lower total costs and greater clinical benefit compared with azelaic acid 15% gel BID at year 3 and dominated this treatment. After 3 years, ivermectin 1% cream QD was associated with the lowest health care costs ($62,767 compared with $73,284 for metronidazole 0.75% cream BID and $77,208 for azelaic acid 15% gel BID), reflecting a 15% reduction in physician visit costs, when compared with metronidazole 0.75% cream BID, and almost a 20% reduction, when compared with azelaic acid 15% gel BID. The univariate sensitivity analyses indicated that the results are sensitive to the time horizon selected: the longer the time horizon, the more beneficial the results for ivermectin 1% cream QD relative to the comparators, although even at 1 year, ivermectin 1% cream QD dominated azelaic acid 15% gel BID. The PSA suggested that ivermectin 1% cream QD was the most likely treatment to be cost-effective at a willingness-to-pay threshold of $15,000 and above. Ivermectin 1% cream QD had favorable incremental cost-effectiveness when compared with metronidazole 0.75% cream BID and dominated azelaic acid 15% gel BID in the treatment of papulopustular rosacea in the United States. Therefore, ivermectin 1% cream QD may be a good first-line treatment for papulopustular rosacea, providing additional clinical benefit at no or low additional cost. This study was sponsored by Galderma Laboratories. The sponsor was involved in the design of the model structure but not in the collection of the data used to populate the model. Manuscript preparation was also funded by Galderma. Taieb is an investigator and advisor for Galderma. Gold is an investigator for Galderma. Feldman is a consultant and speaker for Galderma and has received grants from Galderma. Dansk and Bertranou received a research grant from Galderma to conduct this study. Dansk and Bertranou contributed to the design of the model structure, the sourcing and inputting of the data, and the interpretation of the results. Taieb, Feldman, and Gold contributed to the interpretation of the results. All authors reviewed draft versions of the manuscript and gave permission for the submission of the final version.

Increased Tumor Ascorbate is Associated with Extended Disease-Free Survival and Decreased Hypoxia-Inducible Factor-1 Activation in Human Colorectal Cancer

Ascorbate is a co-factor for the hydroxylases that regulate the transcription factor hypoxia-inducible factor (HIF)-1, which provides cancer cells with a metabolic and survival advantage in the hypoxic environment of solid tumors. However, whether ascorbate affects tumor development is a highly debated issue. We aimed to determine whether tumor ascorbate was associated with HIF-1 activation and patient disease-free survival. In this study, we undertook a retrospective observational analysis of tissue-banked tumor and paired normal tissue from 49 colorectal cancer patients, measuring ascorbate levels, HIF-1α and its downstream gene products BNIP3, and vascular endothelial cell growth factor (VEGF). Patient survival was monitored for the first 6 years after surgery. We found that ascorbate levels were lower in tumor tissue compared to normal tissue (p < 0.001) but overall levels varied considerably. HIF-1α, VEGF, and BNIP3 were elevated in tumor samples (p < 0.01). There was an inverse relationship between tumor ascorbate content and HIF-1 pathway activation (p = 0.002) and tumor size (p = 0.018). Higher tumor ascorbate content was associated with significantly improved disease-free survival in the first 6 years after surgery (p = 0.006), with 141–1,094 additional disease-free days. This was independent of tumor grade and stage. Survival advantage was associated with the amount of ascorbate in the tumor, but not with the amount in adjacent normal tissue. Our results demonstrate that higher tumor ascorbate content is associated with decreased HIF-1 activation, most likely due to the co-factor activity of ascorbate for the regulatory HIF hydroxylases. Our findings support the need for future studies to determine whether raising tumor ascorbate is possible with clinical intervention and whether this results in modification of hydroxylase-dependent pathways in the tumor.

Cost‐effectiveness evaluation of clobetasol propionate shampoo (CPS) maintenance in patients with moderate scalp psoriasis: a Pan‐European analysis

Scalp psoriasis is a difficult to treat and usually chronic manifestation of psoriasis. The CalePso study showed that CPS (Clobex(®) Shampoo) in maintenance therapy of scalp psoriasis (twice weekly) significantly increases the probability of keeping patient under remission during 6 months, compared with vehicle (40.3% relapses vs. 11.6% relapses, ITT). The objective of the study was to assess the cost-effectiveness of a maintenance therapy with CPS vs. its vehicle in nine European countries. A 24-week decision tree model was developed with 4-weekly time steps. The considered population has moderate scalp psoriasis successfully treated with a daily application of CPS up to 4 weeks. Data were taken from the CalePso study and from national experts' recommendations for alternative treatment choices, with their probabilities of success taken from literature to develop country-specific models. Health benefits are measured in disease-free days (DFD). The economic analysis includes drug and physician costs. A probabilistic sensitivity analysis (PrSA) assesses the uncertainty of the model. Depending on the country, the mean total number of DFDs per patient is 21-42% higher with CPS compared with vehicle, and the mean total cost is 11-31% lower. The mean costs per DFD are 30-46% lower with CPS compared with the vehicle. The PrSA showed in 1000 simulations that CPS is more effective vs. vehicle in 100% of the cases and less expensive than its vehicle in 80-99% of the cases. This model suggests that CPS is cost-effective in maintaining the success achieved in moderate scalp psoriasis patients.

Prognostic Influences of Cardiac Rehabilitation in Korean Acute Myocardial Infarction Patients

ObjectiveTo observe the prognostic influences of the cardiac rehabilitation (CR) program in Korean acute myocardial infarction (AMI) patients during the first year after an occurrence of the disease.MethodA total of 141 AMI patients who underwent percutaneous coronary intervention (PCI) were recruited consecutively for this study and divided into the CR group and the control group. The CR group completed the phase 2 CR program in the hospital for a period of 6-8 weeks and maintained self-exercise in their community by exercise prescription for a year after AMI. We performed a prospective comparison of the patients' demographic data, high sensitive C-reactive protein (hs-CRP) level after the 4-month CR program, and the rate of recurrence (AMI, re-hospitalization, positive coronary angiogram, needed revascularization procedure, or death) between the two groups.ResultsCompared to the control group (0.33±0.48 mg/dl), the hs-CRP level was lower in the CR group (0.18±0.32 mg/dl) after 4 months of exercise. The recurrence rate was lower (10%, 7/69) in the CR group, compared to the control group (24%, 17/72, p<0.05). The number of disease-free days was larger in the CR group (354±38.34), compared to the control group (316±99.96, p<0.05). In a comparison of statistical methods used for testing the equality of two survivor distributions, the CR group showed a lower recurrence rate than the control group (p<0.05).ConclusionParticipation in the CR program designed for AMI patients who underwent PCI-induced normalization of the serum hs-CRP level and lowering of the recurrence rate by 14% during the first year.

Montelukast does not prevent reactive airway disease in young children hospitalized for RSV bronchiolitis

To evaluate the long-term effect of montelukast on symptoms of cough and wheeze following RSV bronchiolitis. Fifty eight patients (aged < or = 24 months) hospitalized with a first episode of RSV bronchiolitis were enrolled in this double blind prospective randomized trial comparing montelukast (n = 31) vs placebo (n = 27). During the 3-month treatment period, there were no statistical significant differences between the two groups for symptom-free days and nights (48.5 [interquartile range 33.0.0-66.0] for montelukast vs 57.0 [29.0-71.0] for placebo p = 0.415) nor disease-free days and nights (44.5 days [26.0-54.0] vs 53.0 [22.3-71.0]; p = 0.266). During the 1 year follow-up, there were 41 exacerbations in the montelukast group vs 54 exacerbations in the placebo group (p = 0.57). Time to first exacerbation was not different. Number of unscheduled visits and need to start inhaled steroids were comparable in the two groups. Treatment with montelukast after hospital admission for RSV bronchiolitis in children younger than 2 years of age did not reduce symptoms of cough and wheeze. We cannot exclude that a subgroup of children may, however, benefit from this treatment.

Three Times Weekly Tacrolimus Ointment Reduces Relapse in Stabilized Atopic Dermatitis: A New Paradigm for Use

Long-term, safe and effective therapeutic options for managing the chronic relapsing nature of atopic dermatitis are essential for improving patient quality of life. To minimize the risks of continued topical corticosteroid usage and potentially reduce the incidence of flares, we tested the efficacy and safety of a rotational paradigm of initial brief application of topical corticosteroid followed by long-term intermittent application of non-steroidal tacrolimus ointment to previously inflamed sites of dermatitis. In this 2-phase study, patients who were 2 to 15 years of age and had moderate to severe atopic dermatitis were randomly assigned to 4 days of twice-daily double-blind therapy with either alclometasone ointment 0.05% or tacrolimus ointment 0.03% (Phase I acute), followed by up to 16 weeks of twice-daily open-label tacrolimus ointment 0.03% (Phase I short-term). Patients whose disease stabilized underwent new randomization to double-blind tacrolimus ointment 0.03% or vehicle applied once daily, 3 times per week to clinically normal-appearing skin for up to 40 weeks (Phase II). Corticosteroid use was prohibited. Of 206 randomly assigned patients, 152 completed Phase I; 105 of 152 were randomly assigned into Phase II (68 tacrolimus ointment and 37 vehicle). There were no differences in adverse events between alclometasone and tacrolimus (Phase I) or between tacrolimus and vehicle (Phase II). In the acute period, alclometasone-treated patients showed greater improvement in atopic dermatitis signs and symptoms; thereafter, when all patients applied tacrolimus ointment (short-term), there were no differences. In Phase II, tacrolimus-treated patients had significantly more disease-free days compared with vehicle, significantly longer time to first relapse, and significantly fewer disease relapse days. For patients with stabilized moderate to severe atopic dermatitis, long-term intermittent application of tacrolimus ointment to normal-appearing but previously affected skin was significantly more effective than vehicle at maintaining disease stabilization, with a safety profile similar to vehicle.

Evaluation of the cost-effectiveness of Helicobacter pylori eradication triple therapy vs. conventional therapy for ulcers in Japan.

Helicobacter pylori eradication triple therapy with a combination of lansoprazole, amoxicillin and clarithromycin was approved in Japan in September 2000. To compare the cost-effectiveness of this eradication therapy with conventional histamine-2 receptor antagonist therapy in Japan. We established two Markov models for gastric and duodenal ulcers. The model design was based on the Japanese H. pylori eradication guideline and a specialist's opinions, and the model inputs were obtained from a literature review. The models predict the direct medical costs, number of disease-free days and cost per disease-free day for 5 years. In the gastric ulcer model, the expected total costs of eradication and conventional therapies per patient were yen169 719 and yen390 921, respectively; the expected numbers of disease-free days were 1454 days and 1313 days, respectively. In the duodenal ulcer model, the expected total costs were yen134 786 and yen324 689, respectively; the expected numbers of disease-free days were 1503 days and 1387 days, respectively. The sensitivity analyses showed that the results of the base case analysis were robust. This eradication therapy is less costly and more effective than conventional therapy for the treatment of gastric and duodenal ulcers in a Japanese medical setting.

Pharmacoeconomic analysis of ciclopirox nail lacquer solution 8% and the new oral antifungal agents used to treat dermatophyte toe onychomycosis in the United States

Background: Recently a novel topical nail lacquer, ciclopirox solution 8%, has been approved for the treatment of onychomycosis. Objective: This was undertaken to determine the most cost-effective treatment for the treatment of dermatophyte onychomycosis of the toes in the United States in 2000. Methods: The nature of the problem was defined. The drug comparators were ciclopirox nail lacquer, terbinafine, itraconazole (pulse), itraconazole (continuous), fluconazole, and griseofulvin. A decision analytic model that reflected the manner in which pedal tinea unguium is managed was produced. Studies that have evaluated the efficacy of the nail lacquer and the oral antifungal agents for this indication were identified. Appropriate studies were used in a meta-analysis to determine the mycologic and clinical response rates when the drug comparators are used for the treatment for toe dermatophyte onychomycosis. For each drug comparator a cost of regimen analysis was carried out. This is the sum of the drug acquisition cost, the cost of medical management, and the cost of managing adverse effects. Next, the expected cost of management was calculated, disease free days were determined, and a sensitivity analysis was conducted. Results: For each comparator the meta-analytic average mycologic cure (MC) rate and clinical response (CR) rates were: ciclopirox nail lacquer (MC: 52.6 ± 4.2%, CR: 52.4 ± 9.0%), griseofulvin (MC: 41.1 ± 20.4%, CR: 33.7 ± 14.1%), itraconazole (continuous) (MC: 66.3 ± 4.2%, CR: 70.3 ± 4.2%), itraconazole (pulse) (MC: 70.8 ± 5.7%, CR: 73.6 ± 4.6%), terbinafine (MC: 77.2 ± 4.0%, CR: 75.3 ± 2.9%), and fluconazole (MC: 65.6 ± 7.1%, CR: 66.5 ± 11.7%). The cost of regimen for the drug comparators was: ciclopirox nail lacquer $325.2, griseofulvin $1413.1, itraconazole (continuous) $1410.2, itraconazole (pulse) $811.7, terbinafine $890.1, and fluconazole $966.8. The cost/mycologic cure rate and expected cost/expected symptom free day were, ciclopirox nail lacquer ($618.2, 1.69), griseofulvin ($3438.2, 5.3), itraconazole (continuous) ($2126.9, 3.52), itraconazole (pulse) ($1146.4, 2.01), terbinafine ($1153.0, 2.14), and fluconazole ($1473.7, 2.10). The relative cost-effectiveness was ciclopirox nail lacquer 1.00, itraconazole (pulse) 1.19, fluconazole 1.24, terbinafine 1.27, itraconazole (continuous) 2.08, and griseofulvin 3.13. Sensitivity analysis indicated that ciclopirox nail lacquer was a cost effective alternative compared with the oral regimens of terbinafine, itraconazole (continuous), and griseofulvin when clinical response rate was used as the primary efficacy parameter. Conclusion: Ciclopirox nail lacquer solution 8% is a recent addition to the armamentarium of therapies available to the physician and patient for the treatment of onychomycosis. The nail lacquer is a cost effective agent compared with the oral antifungal therapies, terbinafine, itraconazole, fluconazole, and griseofulvin. (J Am Acad Dermatol 2000;43:S81-95.)

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.

Cost-effectiveness of two new treatments for onychomycosis: An analysis of two comparative clinical trials

Background: Pharmacoeconomic analyses are becoming an increasingly integral component of the overall profile of new drugs. This is particularly true for terbinafine and itraconazole, because both agents have been shown to be clinically effective and relatively safe. Objective: This study examined the cost-effectiveness of terbinafine and itraconazole in two recent comparative clinical trials of these new agents for onychomycosis of the toenails. Methods: Data as reported in the two clinical trials were used as the basis for an analytic decision-tree model that included cost of drug, medical management of the disease and any adverse reactions, and clinical efficacy data into calculations that estimated the relative cost effectiveness ratio for each drug on the basis of cost per disease-free day. Results: The total cost of terbinafine therapy ranged from $697.55 to $699.11, and the total cost of itraconazole therapy ranged from $1216.40 to $1218.80. The expected cost per disease-free day of itraconazole was $2.05 and $2.37, in the Bräutigam and De Backer trials, respectively; similar costs for terbinafine were $1.27 and $1.50. Relative to terbinafine, which was assigned a value of 1.0, the cost-effectiveness ratio of itraconazole was 1.62 and 1.58 in each trial, indicating a lower cost-effectiveness than terbinafine. Conclusion: Terbinafine is more cost-effective than itraconazole in the treatment of toenail onychomycosis. (J Am Acad Dermatol 1998;38:S69-72.)

Pharmacoeconomic analysis of topical treatments for tinea infections.

A payor-perspective economic analysis of the topical creams ciclopirox, clotrimazole, ketoconazole, miconazole, and terbinafine (TER) used to treat dermatophytosis has been made. This pharmacoeconomic evaluation was conducted in Austria, Germany, and Switzerland. A four-phase approach was used. Phase 1: experts were assembled to identify the standard approach for management of fungal infections and a decision tree was constructed to model the process. Phase 2: meta-analysis was used to determine success, failure, and relapse rates. Phase 3: economic analyses performed included cost of regimen, total expected cost, and cost-effectiveness. Phase 4: sensitivity analyses (robustness analysis) were also executed to determine the validity of the assumptions. In the total expected cost analysis, TER demonstrated the lowest overall cost of treating patients. Terbinafine also provided the highest number of disease-free days during the analytic time horizon and, consequently, the lowest cost per disease-free day. Sensitivity analyses suggest that TER is the most cost-effective topical product for treating dermatophytosis in Austria, Germany, and Switzerland. All analytic scenarios suggest that TER therapy demonstrates lower expected costs and generates more DFDs when compared with the fungistatic topical therapies included in this pharmacoeconomic analysis. Terbinafine is expected to be the most cost-effective choice in Austria, Germany, and Switzerland for treatment of dermatophytosis minor.

Terbinafine

Terbinafine is an orally and topically active allylamine antifungal drug which is an effective and well tolerated therapy for a wide range of superficial dermatophyte infections. In contrast to most other commonly prescribed antifungal agents, terbinafine is fungicidal in vitro and possesses improved pharmacokinetic properties with respect to drug penetration into nail tissue following oral administration. These properties enable terbinafine to achieve high success rates with shortened therapy regimens in the treatment of dermatophyte skin infections and onychomycosis. Pharmacoeconomic analyses have shown that oral terbinafine, with its higher rates of clinical efficacy and lower rates of relapse/reinfection, is less costly and more cost effective than oral griseofulvin, ketoconazole and itraconazole when used as initial therapy in the treatment of onychomycosis. However, some points regarding the clinical efficacy of itraconazole relative to terbinafine and the drug treatment regimens used in these studies need further clarification. In the management of tinea pedis, a cost analysis suggested that initial therapy with terbinafine 1% cream was more costly than initial therapy with miconazole, oxiconazole or clotrimazole. However, in cost-effectiveness studies, terbinafine had a lower cost per disease-free day than ciclopirox, clotrimazole, ketoconazole and miconazole in the treatment of dermatophyte skin infections. In conclusion, available clinical and pharmacoeconomic data support the use of topical terbinafine as first-line treatment of dermatophyte skin infections unless the acquisition cost of terbinafine is markedly greater than that of alternative topical antifungal agents. Oral terbinafine can be recommended as a cost-effective first-line treatment, preferable to oral griseofulvin, ketoconazole and itraconazole, in patients with dermatophyte onychomycosis.

Pharmacoeconomic analysis of topical treatments for tinea infections.

The purpose of this study was to perform a government-perspective economic analysis of the most widely used topical creams [namely, ciclopirox (CIC), clotrimazole (CLO), ketoconazole (KET), miconazole (MIC), and terbinafine (TER)], for the treatment of 2 types of dermatophyte skin infections: dermatophytosis major (excluding onychomycosis) and dermatophytosis minor. A 3-phase approach was used. In phase I, experts were assembled to identify the standard approach for management of fungal infections and a decision tree was constructed to model the process; in phase II, meta-analysis was used to determine success, failure, and relapse rates; and in phase III, economic analyses were performed including cost of regimen, total expected cost and cost-effectiveness analysis. Sensitivity analyses (robustness analyses) were also performed in phase III. It was found that while TER was successful following 1 week of administration for minor infections and after 2 weeks for major infections, duration of drug treatment was usually twice that time. Other comparators (CIC, CLO, KET and MIC) took 4 weeks to achieve a successful outcome. In addition, an extra 2 weeks were often needed to clear both types of infections because the comparators are fungistatic, whereas TER is fungicidal. In the total expected cost analysis, TER had the lowest overall cost of treating patients for both infection categories. It was also responsible for the highest number of disease-free days and, consequently, the lowest cost per disease-free day. Sensitivity analyses confirmed that TER was the most cost-effective topical agent for treating dermatophytosis major (excluding onychomycosis) and dermatophytosis minor.