Efficacy, safety, and cost-effectiveness of all-trans retinoic acid/Clobetasol Propionate Compound Ointment in the treatment of mild to moderate psoriasis vulgaris: A randomized, single-blind, multicenter clinical trial.

To assess the efficacy, safety, and cost-effectiveness of all-trans retinoic acid/Clobetasol Propionate Compound Ointment and calcipotriol/betamethasone dipropionate ointment in the treatment of mild-to-moderate patients with psoriasis vulgaris. This was a randomized, single-blind, multicenter clinical trial. A total of 240 patients were randomized to receive twice-daily all-trans retinoic acid/Clobetasol Propionate Compound Ointment (treatment group) or once-daily calcipotriol/betamethasone dipropionate ointment (control group) for 4 weeks. The efficacy, safety, and cost-effectiveness were assessed at Weeks 2 and 4. After 4 weeks, both groups showed a significant clinical improvement compared to baseline (88.33% vs. 89.83%, respectively, p = .7112). But PASI 75 response in the treatment group was superior to the control group (44.12% vs. 28.57%, respectively, p = .0200), at Week 4. SSRI improvement rate in the treatment group was also superior to control group (67.11% vs. 59.43%, respectively, p = .0119) at Week 4. All-trans retinoic acid/Clobetasol Propionate Compound Ointment showed a significant clinical improvement in erythema, infiltration, and scales of skin lesions and PASI score compared to baseline. 1.67% of patients (treatment group) reported adverse reactions compared to 2.50% (control group) with no statistical significance. In addition, the cost-effectiveness assessment showed a higher cost-effectiveness of the treatment group compared to the control group in 4 weeks (199.25 vs. 801.51). All-trans retinoic acid/Clobetasol Propionate Compound Ointment was effective and safe in the treatment of psoriasis vulgaris with similar efficacy as calcipotriol/betamethasone dipropionate ointment and lower treatment costs.

The cost-effectiveness of 5-FU-SA in the treatment of actinic keratoses of the face and scalp in the UK secondary care setting.

OBJECTIVE: The objective of this analysis was to estimate the relative cost-effectiveness of Actikerall 1 (5-FU-SA) vs cryotherapy in a secondary care setting in the UK, for lesion-directed treatment in patients with actinic keratoses (AK) of the face and scalp. METHODS: The model was a simple decision tree, with a 6-month time horizon. The perspective was that of the UK National Health Service (NHS). Modeled treatment effects included reported per-patient histological clearance and recurrence rates. Cost inputs comprised professional consultation time and cost of medication. Health-related utility estimation followed previously published methodology. Adverse events were not modeled. The key data and model structural assumptions followed expected UK practice. One-way and probabilistic sensitivity analyses were conducted to assess structural and parameter uncertainty. RESULTS: 5-FU-SA was found to be less costly (-£204) and more effective (+0.001 QALY) in base case and sensitivity analyses. In the probabilistic analysis there was 100% probability of being cost-effective over cryotherapy at £20,000 willingness to pay. Cost of professional time was a key driver of the model outcome. 5-FU-SA remained dominant across a range of scenario analyses, including exploration of assumptions around setting of care. LIMITATIONS: The time horizon of the analysis was short and data were not extrapolated beyond the duration of the clinical trial; however, this approach is consistent with likely follow-up of an AK patient. The clinical outcomes observed in the trial were based on a large proportion of cryotherapy patients undergoing an additional cycle of treatment; this may not occur or be required in an experienced secondary care setting. CONCLUSION: 5-FU-SA could be considered as a cost-effective choice for treatment of AK lesions of the face and scalp in secondary and mixed care settings in the UK. Use of 5-FU-SA in patients who would otherwise be managed with cryotherapy has the potential to result in cost savings.

A cost-utility analysis of ingenol mebutate gel for the treatment of actinic keratosis: a Scottish perspective.

BACKGROUND: Actinic keratosis (AK) is a UV-induced, pre-malignant skin condition that is common in adults over 60 years of age with fair skin in Scotland. The most commonly prescribed first-line treatment for AK in Scotland is currently diclofenac gel (3 %). Ingenol mebutate gel is a recently developed topical therapy available in two strengths for the treatment of AK lesions on the face and scalp (150 mcg/g once daily for 3 consecutive days) or trunk and extremities (500 mcg/g once daily for 2 consecutive days). OBJECTIVE: To compare the cost-effectiveness of two strengths of ingenol mebutate gel developed to treat AK lesions on the face and scalp (150 mcg/g once daily for 3 consecutive days) or trunk and extremities (500 mcg/g once daily for 2 consecutive days) with other first-line AK therapies including diclofenac gel, 5-FU, 5-FU/salicylic acid, and cryotherapy for the first-line treatment of AK in adult patients, from the perspective of the National Health Service (NHS) in Scotland. METHODS: A cost-utility analysis was conducted using a decision-tree approach to calculate the costs and benefits of different treatment strategies for AK on the face and scalp or trunk and limbs over a 12-month time horizon. Data on the relative efficacy of treatments were obtained from a systematic literature review and meta-analysis. Utility scores and resource-use data were obtained from published sources. RESULTS: Over 12 months, ingenol mebutate 150 mcg/g gel and 500 mcg/g gel were cost-effective compared with the most commonly used topical therapy in Scotland, diclofenac (3 %) gel, at a willingness-to-pay threshold of £20,000 per QALY, with a minimal additional cost of £43 and £105, respectively per QALY gained. CONCLUSIONS: Ingenol mebutate gel is a cost-effective therapy for the first-line treatment of AK from a Scottish NHS perspective.

Cost-effectiveness analysis of 5-fluorouracil 0.5%/salicylic acid 10% in the treatment of actinic keratosis in Spain.

OBJECTIVE: The aim of this study is to conduct a cost-effectiveness analysis of 5-fluorouracil 0.5%/salicylic acid 10% (5-FU/SA) in the treatment of isolated hyperkeratotic actinic keratosis lesions in Spain. METHODS: An analytical decision-making model was constructed to compare whether 5-FU/SA was a cost-effective option compared with cryotherapy from the perspective of the Spanish National Health System with a time horizon of 6 months. Costs were expressed in 2014 euros. RESULTS: The cost of patients with hyperkeratotic actinic keratosis treated with 5-FU/SA or cryotherapy was €266 and €285, respectively. 5-FU/SA was associated with higher rates of treatment success and, consequently, more quality-adjusted life years, than cryotherapy. Therefore, 5-FU/SA was the dominant treatment, as it was associated with a lower treatment cost and greater effectiveness than cryotherapy. CONCLUSIONS: Economically, 5-FU/SA was a dominant option compared with cryotherapy in the treatment of isolated hyperkeratotic actinic keratosis lesions in Spain.

Unattractive consequences: litigation from facial dermabrasion and chemical peels.

BACKGROUND: Facial dermabrasion and chemical peel are common cosmetic procedures that are generally safe yet do possess inherent risks. The patient's expectations, formed well in advance of treatment, strongly correlate with overall satisfaction. OBJECTIVES: The authors reviewed and analyzed litigation related to the performance of facial dermabrasion and chemical peel. METHODS: The authors searched the WestlawNext legal database for relevant litigation and examined factors such as allegations raised, patient demographics, defendant specialties, final outcomes, and payments. RESULTS: Proceedings from 25 cases were analyzed, involving 22 female and 2 male plaintiffs; in 1 case, sex was not specified. Sixteen cases (64%) resulted in a decision for the defendant and 9 (36%) were resolved with payments. The median difference between out-of-court settlements (median, $940 000) and jury-awarded damages (median, $535 000) was not statistically significant. Factors raised in litigation included poor cosmetic outcome (80%), alleged intratreatment negligence (68%), permanent injury (64%), informed-consent deficits (60%), emotional/psychological injury (44%), posttreatment negligence (32%), and the need for additional treatment/surgery (32%). CONCLUSIONS: Out-of-court settlements and jury-awarded damages were considerable in cases where physicians practicing various (or multiple) specialties were named as defendants. These findings emphasize the need for physicians to thoroughly document potential complications prior to treatment, during the informed-consent process. Additionally, general considerations should be taken into account, such as patient expectations and the potential need for other procedures, which may enhance pretreatment communication and ultimately minimize liability. Finally, it is important to stress that physicians may be held liable for procedures performed by nonphysician ancillary staff.

Medication choice and associated health care outcomes and costs for patients with acne and acne-related conditions in the United States.

BACKGROUND: Acne is a common condition for which multiple treatment options are available. The patterns of pharmacotherapy for acne and similar conditions, and the effect of those patterns on cost, are not well characterized. OBJECTIVE: This study examined the impacts of patient demographics and medication choices on patients' health status and associated medication costs. METHODS: A retrospective cross-sectional study was conducted using the 2007 Medical Expenditure Panel Survey (MEPS) database. Information on patient demographics, health status, medication utilization and medication costs was obtained from the database representing 3,784,816 patients with acne and similar conditions. RESULTS: Weighted multiple linear regression analyses indicated that the use of topical retinoids was preferred in combination with other treatments rather than as monotherapy. Oral antibiotics were widely prescribed and their use was associated with a significant decrease in total annual prescription spending. Use of oral retinoids and oral contraceptives increased the annual prescription costs significantly. Increase in annual drug refills was not associated with the improvement in health status. CONCLUSION: We observed an association with medication choice for acne and acne-related conditions on medication spending. Pharmacologic treatment of acne significantly adds to acne-related annual healthcare costs compared to non-pharmacologic treatment.

Positive effect of modified Goeckerman regimen on quality of life and psychosocial distress in moderate and severe psoriasis.

Psoriasis is a chronic inflammatory skin disease with a profound effect on quality of life and psychosocial stress. The relationship between clinical improvement and psycho-social impact after treatment is complex. The objective of this study was to compare changes in quality of life and psychosocial distress, and overall cost-effectiveness, in patients with psoriasis receiving the modified Goeckerman regimen (UV irradiation and coal tar) with those receiving conventional treatment. Patients with moderate/severe psoriasis receiving the Goeckerman regimen were followed from admission to discharge. Clinical severity, was evaluated weekly using the Psoriasis Area and Severity Index (PASI). Psoriasis Disability Index (PDI) and Hospital Anxiety and Depression Scale (HADS) questionnaires were applied at admission and one month after discharge. Thirty-six patients with psoriasis receiving conventional treatment and 48 patients receiving the Goeckerman regimen were recruited to the study. The mean PASI score in the Goeckerman group decreased from 27.1 to 6.9 and PDI scores decreased from 25.3 to 13.8. HADS scores for anxiety and depression decreased significantly from 9.8 to 6.3 and 9.1 to 6.8, respectively. In comparison with conventional therapy, the modified Goeckerman regime showed similar clinical efficacy, with additional benefits in improving overall quality of life and psychosocial distress in patients with moderate/severe psoriasis, and more cost-effectiveness.

The EVERT (effective verruca treatments) trial protocol: a randomised controlled trial to evaluate cryotherapy versus salicylic acid for the treatment of verrucae.

BACKGROUND: Verrucae are a common, infectious and sometimes painful problem. The optimal treatment for verrucae is unclear due to a lack of high quality randomised controlled trials. The primary objective of this study is to compare the clinical effectiveness of two common treatments for verrucae: cryotherapy using liquid nitrogen versus salicylic acid. Secondary objectives include a comparison of the cost-effectiveness of the treatments, and an investigation of time to clearance of verrucae, recurrence/clearance of verrucae at six months, patient satisfaction with treatment, pain associated with treatment, and use of painkillers for the treatments. METHODS/DESIGN: This is an open, pragmatic, multicentre, randomised controlled trial with two parallel groups: cryotherapy using liquid nitrogen delivered by a healthcare professional for a maximum of 4 treatments (treatments 2-3 weeks apart) or daily self-treatment with 50% salicylic acid for a maximum of 8 weeks. Two hundred and sixty-six patients aged 12 years and over with a verruca are being enrolled into the study. The primary outcome is complete clearance of all verrucae as observed on digital photographs taken at 12 weeks compared with baseline and assessed by an independent healthcare professional. Secondary outcomes include self-reported time to clearance of verrucae, self-reported clearance of verrucae at 6 months, cost-effectiveness of the treatments compared to one another, and patient acceptability of both treatments including possible side effects such as pain. The primary analysis will be intention to treat. It is planned that recruitment will be completed by December 2009 and results will be available by June 2010. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18994246.

A review of acitretin for the treatment of psoriasis.

BACKGROUND: Acitretin is an oral retinoid that is approved for the treatment of psoriasis. It is unique compared to other systemic therapies for psoriasis such as methotrexate and cyclosporine in that it is not immunosuppressive. It is, therefore, safe for use in psoriasis patients with a history of chronic infection such as HIV, hepatitis B, hepatitis C or malignancy who have a contraindication to systemic immunosuppressive therapy and require systemic therapy because topical therapy is inadequate and they are unable to commit to phototherapy. Acitretin is one of the treatments of choice for pustular psoriasis. Even though acitretin is less effective as a monotherapy for chronic plaque psoriasis, combination therapy with other agents, especially UVB or psoralen plus UVA phototherapy, can enhance efficacy. OBJECTIVE: To provide an updated review of the safety and efficacy of acitretin in the treatment for psoriasis. METHODS: Literature review of journal articles from 2008 to 2009 since the last review of acitretin evaluated medical literature from 2005 to 2008. RESULTS/CONCLUSION: Acitretin is an effective systemic therapy for psoriasis and is generally well tolerated at low doses for long-term use. If monotherapy with acitretin is inadequate, it can be used in combination with other treatments, particularly UVB phototherapy, to increase efficacy.

Randomised controlled trial and economic evaluation of podophyllotoxin solution, podophyllotoxin cream, and podophyllin in the treatment of genital warts.

OBJECTIVES: To evaluate the efficacy and cost effectiveness of self applied podophyllotoxin 0.5% solution and podophyllotoxin 0.15% cream, compared to clinic applied 25% podophyllin in the treatment of genital warts over 4 weeks. METHODS: We conducted a randomised controlled trial in 358 immunocompetent men and women with genital warts of 3 months' duration or less. RESULTS: In the principal analysis both podophyllotoxin solution (OR 2.93, 95% CI 1.56 to 5.50) and podophyllotoxin cream (OR 1.97, 95% CI 1.04 to 3.70) were associated with significantly increased odds of remission of all warts compared to podophyllin. We performed two further analyses. When subjects defaulting from follow up were assumed to have been cured odds of remission of all warts were also significantly increased both for podophyllotoxin solution (OR 3.04, 95% CI 1.68 to 5.49) and for podophyllotoxin cream (OR 2.46, 95% CI 1.38 to 4.40). When subjects defaulting from follow up were assumed not to have been cured odds of remission of all warts were significantly increased for podophyllotoxin solution (OR 1.92, 95% CI 1.13 to 3.27), but not for podophyllotoxin cream (OR 1.17, 95% CI 0.69 to 2.00). Local side effects were seen in 24% of subjects, and recurrence of warts within 12 weeks of study entry in 43% of all initially cleared subjects, without statistically significant differences between the treatment groups. Direct, indirect, and total costs were similar across the three treatment groups. Podophyllotoxin solution was the most cost effective treatment, followed by podophyllotoxin cream, with podophyllin treatment being the least cost effective. CONCLUSIONS: Self treatment of anogenital warts with podophyllotoxin showed greater efficacy and cost effectiveness than clinic based treatment with podophyllin.

The epidemiology and treatment of anogenital warts in Singapore: a retrospective evaluation.

INTRODUCTION: A retrospective study in the referral centre for sexually transmitted infections (STIs) in Singapore to describe the epidemiology and treatment outcome of patients with anogenital warts. SUBJECTS AND METHODS: We reviewed the case records of 301 patients with anogenital warts who were seen over a 1-year period (1999). We also attempted to interview every patient by telephone to find out if they had any clinical recurrences for which treatment was sought elsewhere. RESULTS: There were 255 males and 46 females with a mean age of 34 years. Two hundred and nineteen (72.8%) presented with symptoms lasting 12 weeks or less. In males, warts occurred most frequently in the preputial cavity (52.5%) and on the penile shaft (40.8%). In females, they occurred most frequently on the external genitalia (91.3%). Two hundred and thirty-five males were treated with cryotherapy and 69% (95% CI, 62.6% to 74.8%) achieved clinical resolution after a mean of 6 treatment cycles. Seven males were treated with podophyllin 0.25% in ethanol and 71% (95% CI, 29.0% to 96.3%) were clinically cured after a mean of 4 treatment cycles. Thirty-nine females were treated with cryotherapy and 67% (95% CI, 49.8% to 80.9%) achieved clinical cure after a mean of 4 treatment cycles. Of the 290 patients treated at the centre, 212 (73%; 95% CI, 67.3% to 77.8%) patients (184 males, 28 females) achieved clinical cure after a mean of 7 weeks (range, 1 to 34 weeks); 90% (95% CI, 86.0% to 93.2%) of them by 15 weeks. Seven-two patients defaulted follow-up and 6 responded partially to treatment. Of the 212 patients who achieved clinical cure, 195 were interviewed by telephone, on an average, 17.7 months after clinical resolution. Thirty-seven (19%; 95% CI, 13.7% to 25.2%), all males, relapsed clinically after a mean of 100 days (range, 5 to 329 days); 90% (95% CI, 84.6% to 93.6%) relapsed by 228 days. CONCLUSIONS: Podophyllin 0.25% in ethanol was the most cost-effective treatment for males. One in 5 patients had a recurrence of their warts and most had their recurrence within 8 months of initial resolution.

The cost-effectiveness of isotretinoin in the treatment of acne. Part 1. A meta-analysis of effectiveness literature.

OBJECTIVES: This paper reports the results of a meta-analysis of isotretinoin treatment in moderate to severe acne. It forms part of a comprehensive investigation into the cost-effective treatment of acne in South Africa and as such establishes the clinical foundation for an economic model of acne management. This foundation includes an evaluation of the daily dosages, treatment durations, success rates, clinical effectiveness and relapse rates reported in published trials since 1981. METHODOLOGY: A predetermined protocol for the study established the scope, appropriate inclusion and exclusion criteria for peer-reviewed data, and the statistical rigour that would be applied to the selected data. Following an extensive literature search, data reflecting the effectiveness of isotretinoin were extracted, statistically assessed, described and reported. The combinability of the data was confirmed using analyses of variance and chi-square tests, as applicable. RESULTS: Isotretinoin consistently proved to be a highly effective agent in the treatment of moderate to severe acne vulgaris. The response rate determined by the meta-analysis indicated a clinical cure in 84.22% to 86.71% of patients treated. From the data considered, the average treatment duration was calculated to be 17.9 weeks (4 months). The relapse rate was low (21.45%) and dose-dependent. Optimal results were achieved by treating patients with a daily dose of 1 mg/kg and treating to a target cumulative dose of 120 mg/kg over the treatment duration. CONCLUSION: The results of this meta-analysis support the continued use of isotretinoin in the treatment of acne. The results are important in the field of pharmaceutical benefit management where they will assist in the optimal management of this health condition. The results will be used to develop a pharmaco-economic model to evaluate the various treatment regimens used for acne in South Africa.

The cost-effectiveness of isotretinoin in the treatment of acne. Part 2. A chronic medication plan profiling study.

OBJECTIVES: Aspects of current clinical practice, needed for a pharmaco-economic model of isotretinoin, were determined from an acne-profiling study on chronic medication plan data. The patient sample was analysed as a whole and as two subgroups, representing isotretinoin and oral antibiotic patients. The study focused on the prevalence of the condition, patient age and gender distributions, and pharmacotherapeutic patterns and costs. METHODOLOGY: Anonymous patient records from the Pharmaceutical Benefit Management (Pty) Ltd, Cape Town, chronic medication plan were screened and analysed using descriptive and inferential statistical methods. For all hypothesis tests, the significance level (alpha) was set a priori at 5% (0.05). In order to determine the distribution of costs among patient groups, cost-concentration curves were constructed. RESULTS: A total of 5,198 patient records were analysed, representing 3,546 acne patients (2.7% of applicants to the plan). The majority of patients were female (72.2%, median age 23 years), with male patients treated at a younger age (median age 19 years). The cyproterone/oestrogen combination was found to be the most frequently prescribed agent (25.2% of script items), followed by isotretinoin (15.6%). The oral antibiotics as a group accounted for 24.9% of script items, the leading agents being minocycline (10.1%) and doxycycline (7.1%). Isotretinoin (44.1%) represented the greatest expense, followed by hormonal therapies (24.7%) and oral antibiotics (16.7%). Female isotretinoin patients (55.1%) were older (median age 25 years), while the male patients were of an equivalent age to the collective sample. Patients treated with oral antibiotics represented the youngest group of patients (median age 20 years), with 57.8% being female. The annual pharmacotherapy expense per patient on oral antibiotics was R1 971.81 compared with R2 670.20 for all patients, and R6 140.81 for the isotretinoin group. For each of these groups there was an uneven cost distribution among patients. CONCLUSION: The treatment of acne represents a significant burden to funders, estimated at R7.2 million per 100,000 beneficiaries. The distinct age and gender distribution patterns, together with the uneven distribution of costs among patients, provide valuable information for the treatment and management of the condition. This information indicates that the introduction of clinically based, focused management principles supported by sound pharmaco-economic arguments will be required to manage acne effectively.

The cost-effectiveness of isotretinoin in the treatment of acne. Part 3. A cost-minimisation pharmaco-economic model.

OBJECTIVES: The cost-effectiveness of systemic isotretinoin therapy in the treatment of moderate to severe acne was assessed in a comparative cost-minimisation analysis. Systemic isotretinoin at the recommended daily dose of 1 mg/kg (cumulative dose of 120 mg/kg) was compared with: (i) oral antibiotics taken as chronic medication; (ii) a combination of chronic oral antibiotics and anti-androgen therapy; and (iii) isotretinoin prescribed only after two failed courses of oral antibiotics, as per South African guidelines. The perspective taken was that of the funder of health care, and the resources used were funder charges as a proxy for costs. METHODOLOGY: Statistical and epidemiological data as well as relevant costs from the previously reported meta-analysis and profiling study for acne therapy were used as the clinical basis for the construction of a cost-minimisation model. Additional costs were sourced from published pharmaceutical retail prices and professional rates. The South African treatment guidelines were used to define the frequencies associated with physician visits and pathology testing. Standard statistical methods were applied, as appropriate. From the above, a modified Markov process was used to model the costs associated with the four comparator treatment regimens over a period of 120 months. Suitable clinical and economic endpoints were defined so that comparison could be made between regimens. RESULTS: Assuming a relapse rate of 21.45%, it was found that isotretinoin therapy compares favourably with the other regimens. After 50 and 35 months, systemic isotretinoin cumulative costs were less than those incurred in oral antibiotic and oral antibiotic/anti-androgen therapy, respectively. For the stepped therapy of oral antibiotics followed by systemic isotretinoin, these break-even periods were 56 and 39 months, respectively. The cost per successfully treated patient receiving isotretinoin was R8941. This compares well with the cost for those patients receiving chronic oral antibiotics, which after 5 years amounted to R10 428 per patient. Sensitivity analyses proved these findings to be robust to variations in the isotretinoin relapse rate, and the cost of oral antibiotic therapy and the concomitant use of topical therapies. CONCLUSION: From the cost-minimisation model it is clear that where systemic isotretinoin is clinically indicated, the sooner such therapy is initiated the more cost-effective the outcome will be. If isotretinoin is prescribed on diagnosis of moderate to severe acne, then the cost of treatment is significantly reduced in the long term when compared with standard chronic oral antibiotic therapy.