Cost-effectiveness of topical pharmacological, oral pharmacological, physical and combined treatments for acne vulgaris.

BACKGROUND: Acne vulgaris is a common skin condition that may cause psychosocial distress. There is evidence that topical treatment combinations, chemical peels and photochemical therapy (combined blue/red light) are effective for mild-to-moderate acne, while topical treatment combinations, oral antibiotics combined with topical treatments, oral isotretinoin and photodynamic therapy are most effective for moderate-to-severe acne. Effective treatments have varying costs. The National Institute for Health and Care Excellence (NICE) in England considers cost-effectiveness when producing national clinical, public health and social care guidance. AIM: To assess the cost-effectiveness of treatments for mild-to-moderate and moderate-to-severe acne to inform relevant NICE guidance. METHODS: A decision-analytical model compared costs and quality-adjusted life-years (QALYs) of effective topical pharmacological, oral pharmacological, physical and combined treatments for mild-to-moderate and moderate-to-severe acne, from the perspective of the National Health Service in England. Effectiveness data were derived from a network meta-analysis. Other model input parameters were based on published sources, supplemented by expert opinion. RESULTS: All of the assessed treatments were more cost-effective than treatment with placebo (general practitioner visits without active treatment). For mild-to-moderate acne, topical treatment combinations and photochemical therapy (combined blue/red light) were most cost-effective. For moderate-to-severe acne, topical treatment combinations, oral antibiotics combined with topical treatments, and oral isotretinoin were the most cost-effective. Results showed uncertainty, as reflected in the wide confidence intervals around mean treatment rankings. CONCLUSION: A range of treatments are cost-effective for the management of acne. Well-conducted studies are needed to examine the long-term clinical efficacy and cost-effectiveness of the full range of acne treatments.

Poverty and Targeted Immunotherapy: Survival in Children's Oncology Group Clinical Trials for High-Risk Neuroblastoma.

BACKGROUND: Whether social determinants of health are associated with survival in the context of pediatric oncology-targeted immunotherapy trials is not known. We examined the association between poverty and event-free survival (EFS) and overall survival (OS) for children with high-risk neuroblastoma treated in targeted immunotherapy trials. METHODS: We conducted a retrospective cohort study of 371 children with high-risk neuroblastoma treated with GD2-targeted immunotherapy in the Children's Oncology Group trial ANBL0032 or ANBL0931 at a Pediatric Health Information System center from 2005 to 2014. Neighborhood poverty exposure was characterized a priori as living in a zip code with a median household income within the lowest quartile for the cohort. Household poverty exposure was characterized a priori as sole coverage by public insurance. Post hoc analyses examined the joint effect of neighborhood and household poverty using a common reference. All statistical tests were 2-sided. RESULTS: In multivariable Cox regressions adjusted for disease and treatment factors, household poverty-exposed children experienced statistically significantly inferior EFS (hazard ratio [HR] = 1.90, 95% confidence interval [CI] = 1.28 to 2.82, P = .001) and OS (HR = 2.79, 95% CI = 1.63 to 4.79, P < .001) compared with unexposed children. Neighborhood poverty was not independently associated with EFS or OS. In post hoc analyses exploring the joint effect of neighborhood and household poverty, children with dual-poverty exposure (neighborhood poverty and household poverty) experienced statistically significantly inferior EFS (HR = 2.21, 95% CI = 1.48 to 3.30, P < .001) and OS (HR = 3.70, 95% CI = 2.08 to 6.59, P < .001) compared with the unexposed group. CONCLUSIONS: Poverty is independently associated with increased risk of relapse and death among neuroblastoma patients treated with targeted immunotherapy. Incorporation of social and environmental factors in future trials as health-care delivery intervention targets may increase the benefit of targeted therapies.

Assessment of macular choroidal thickness, central macular thickness and retinal nerve fiber layer in patients receiving oral isotretinoin treatment.

PURPOSE: To investigate the impact of oral isotretinoin therapy in choroidal thickness, central macular thickness (CMT), and retinal nerve fibre layer (RNFL) thickness using optical coherence tomography (OCT). PATIENTS AND METHODS: Choroidal thicknesses, CMT, and RNFL thickness of 64 eyes were evaluated at baseline and the end of the third month of isotretinoin therapy by spectral-domain OCT. For assessment of choroidal thickness, OCT measurements were obtained at the fovea with 6 additional measurements at adjacent locations (at 500-1000-1500 µm temporal to the fovea and 500-1000-1500 µm nasal to the fovea). RESULTS: There was not a statistically significant difference between the baseline and third-month follow-up measurements of choroidal thicknesses at seven distinct locations (p > 0.05). Similarly, RNFL thickness and CMT did not change with a mean dose of 30 (±6) mg per day isotretinoin therapy during follow-up (101.82 vs 102.24, p = 0.079; 217.77 vs 217.25, p = 0.731, respectively). CONCLUSION: After the use of oral isotretinoin for 3 months, no significant side effects have been observed in choroidal thickness, CMT, and RNFL thickness by OCT.

Simplifying contraception requirements for iPLEDGE: A decision analysis.

BACKGROUND: For persons of childbearing potential prescribed isotretinoin, the iPLEDGE program requires use of 2 simultaneous methods of contraception or commitment to abstinence. OBJECTIVE: To model the relative effectiveness of a variety of contraception strategies for patients taking isotretinoin, including those that are acceptable according to iPLEDGE. METHODS: We performed a decision analysis modeling the estimated rate of pregnancy with various contraception strategies during a typical 6-month course of isotretinoin. RESULTS: Tier 1 contraception options (eg, subdermal hormonal implant, intrauterine devices) each had effectiveness of >99.5% alone. When combined with a secondary form of contraception, tier 2 contraception options (eg, depot medroxyprogesterone injections, combined oral contraceptives) each had effectiveness >99%. LIMITATIONS: Sensitivity analyses were conducted to evaluate the impact of uncertain parameters on the results. CONCLUSION: There may be opportunities to simplify iPLEDGE by recognizing the high effectiveness of tier 1 contraception options and increasing use of secondary forms of contraception among those using tier 2 contraception options as their primary form of contraception. Future studies are needed to understand the most effective strategies in clinical practice to prevent unintended pregnancy for patients taking isotretinoin to improve outcomes and provide patient-centered care.

Bilateral Sacroiliitis Confirmed with Magnetic Resonance Imaging during Isotretinoin Treatment: Assessment of 11 Patients and a Review of the Literature.

In recent years, several cases pointing at sacroiliitis due to isotretinoin treatment have been reported, but a causal association remains unproven. The aim of this study was to assess the characteristics of patients in whom bilateral sacroiliitis was detected while using isotretinoin treatment for acne and to review previous sacroiliitis cases treated with isotretinoin. In total, 11 patients who were diagnosed with sacroiliitis during isotretinoin treatment were identified, and patient characteristics were noted. Patients were classified according to magnetic resonance imaging (MRI) findings. The 11 patients (3 men and 8 women) ranged in age from 16 to 37 years (mean age 24.27 years). All the 11 (100.00%) patients presented with hip pain, which in 3 (27.27%) patients started in the first month, in 3 (27.27%) in the second, in 2 (18.18%) in the third, in 2 (18.18%) in the fourth, and in 1 (9%) in the fifth. HLA-B27 (human leucocyte antigen) was negative in all cases. MRI findings confirmed mild bilateral sacroiliitis in 5 (45.45%) patients, moderate in 3 (27.27%), and severe in 2 (18.18%). Although our study included a small number of cases, it indicates a strong association between isotretinoin and sacroiliitis.

Canadian Clinical Practice Guidelines for Rosacea.

Rosacea is a chronic facial inflammatory dermatosis characterized by background facial erythema and flushing and may be accompanied by inflammatory papules and pustules, cutaneous fibrosis and hyperplasia known as phyma, and ocular involvement. These features can have adverse impact on quality of life, and ocular involvement can lead to visual dysfunction. The past decade has witnessed increased research into pathogenic pathways involved in rosacea and the introduction of novel treatment innovations. The objective of these guidelines is to offer evidence-based recommendations to assist Canadian health care providers in the diagnosis and management of rosacea. These guidelines were developed by an expert panel of Canadian dermatologists taking into consideration the balance of desirable and undesirable outcomes, the quality of supporting evidence, the values and preferences of patients, and the costs of treatment. The 2015 Cochrane review "Interventions in Rosacea" was used as a source of clinical trial evidence on which to base the recommendations.

Objective assessment of isotretinoin-associated cheilitis: Isotretinoin Cheilitis Grading Scale.

IMPORTANCE: Isotretinoin remains an effective treatment for severe acne. Despite its effectiveness, it includes many side effects, of which cheilitis is the most common. OBJECTIVE: To develop an objective grading scale for assessment of isotretinoin-associated cheilitis. DESIGN: Cross-sectional clinical grading study. SETTING: UC Davis Dermatology clinic. PARTICIPANTS: Subjects were older than 18 years old and actively treated with oral isotretinoin. EXPOSURES: Oral Isotretinoin. MAIN OUTCOMES AND MEASURES: We developed an Isotretinoin Cheilitis Grading Scale (ICGS) incorporating the following four characteristics: erythema, scale/crust, fissures and inflammation of the commissures. Three board-certified dermatologists independently graded photographs of the subjects. RESULTS: The Kendall's coefficient of concordance (KCC) for the ICGS was 0.88 (p < 0.0001). The Kendall's coefficient was ≥0.72 (p < 0.0001) for each of the four characteristics included in the grading scale. An image-based measurement for lip roughness statistically significantly correlated with the lip scale/crusting assessment (r = 0.52, p < 0.05). CONCLUSION AND RELEVANCE: The ICGS is reproducible and relatively simple to use. It can be incorporated as an objective tool to aid in the assessment of isotretinoin associated cheilitis.

A novel patient support program to address isotretinoin adherence: proof-of-concept analysis.

The iPLEDGE protocol for isotretinoin treatment requires multiple steps to be completed within strict timing windows, resulting in many interruptions or discontinuations of treatment. The US Food and Drug Administration has indicated that approximately 40% of isotretinoin prescriptions written over the course of one year of the iPLEDGE program were denied due to failure to comply with iPLEDGE. Insurance restrictions add to the likelihood of prescriptions not being filled. Here, we describe a novel program implemented specifically to assist patients and providers with improving isotretinoin therapy adherence. This innovative isotretinoin support program provides assistance with insurance questions and hurdles, an uninterrupted treatment supply, educational support, reminder communications, and an indigent patient assistance program. Proof-of-concept analysis shows that 17 months after implementation of the program, 93% of prescriptions received have been filled. Utilization of the program appears to improve adherence to an isotretinoin treatment regimen, with fewer interruptions due directly to unfilled prescriptions.

Concomitant use of isotretinoin and contraceptives before and after iPledge in the United States.

PURPOSE: The major concern associated with isotretinoin treatment is its high teratogenic potential. Therefore, ensuring use of contraception while on therapy is an important strategy for at-risk patients and has been emphasized in all risk management programs. iPledge, the latest and most rigorous isotretinoin program, requires, among other stipulations, monthly assessments of contraceptive use for patients undergoing isotretinoin treatment. The purpose of this study is to evaluate isotretinoin usage patterns and assess concomitant use of isotretinoin and contraceptives before and after iPledge. METHODS: Female patients aged 13-45 years with a new prescription for isotretinoin products during 2004-2008 were identified in the IMS Health longitudinal prescription claims database. Monthly concomitant use of isotretinoin and contraceptives was estimated. Segmented regression analysis of interrupted time series data was used to assess changes in monthly proportion of concomitant use in the 24 months preceding versus following iPledge implementation. RESULTS: The number of isotretinoin prescriptions decreased after iPledge implementation. A small but significant increase in monthly proportion of patients concomitantly using isotretinoin and contraceptive therapies was observed immediately after iPledge implementation (1.3%, p-value = 0.02), particularly among younger patients (2.5%, p-value < 0.01). No changes in the proportion of concomitancy over time (i.e. slope) between the periods before and after iPledge implementation were observed. CONCLUSION: The findings of this pharmacy prescription claims-based study suggest a small increase in concomitant use of isotretinoin and contraceptives coincident with the time of implementation of iPledge, particularly among younger women. Published 2013. This article is a U. S. Government work and is in the public domain in the USA.

Ocular adverse effects of systemic treatment with isotretinoin.

OBJECTIVE: To examine whether isotretinoin therapy could result in deleterious ocular effects, as previously described in case report studies. DESIGN: Retrospective cohort study. SETTING: The study was conducted using the electronic medical databases of a large health maintenance organization in Israel. PATIENTS: The study population consisted of 14 682 adolescents and young adults who were new users of isotretinoin for acne and 2 age- and sex-matched comparison groups (isotretinoin-naive patients with acne and acne-free patients). MAIN OUTCOME MEASURES: Ocular adverse effects (AEs) or purchases of ophthalmic medications within 1 year after the first dispensed isotretinoin prescription. RESULTS: In total, 13.8% of the isotretinoin group experienced ocular AEs vs 9.6% of the isotretinoin-naive group and 7.1% of the acne-free group. During a 1-year follow-up period, the isotretinoin group had significantly higher risk for any ocular AEs (hazard ratio, 1.70; P.001) compared with the acne-free group. No such increased risk was observed for the isotretinoin-naive group. The isotretinoin group had higher relative risks for inflammatory and structural AEs. CONCLUSION: Isotretinoin use may be associated with short-term ocular events, especially conjunctivitis, underscoring the importance of educating patients and caregivers about these potentially important AEs of the therapy.

Usage and equity of access to isotretinoin in New Zealand by deprivation and ethnicity.

AIMS: Oral isotretinoin, for severe acne, was until March 2009 fully funded in New Zealand only if the prescription was written by a vocationally registered dermatologist. This funding restriction was argued on the basis of complexity of management and an appreciable risk of teratogenicity if given during pregnancy or within a month of conception. However, this funding restriction had the potential to create inequitable access barriers. This study was an audit examining the use of isotretinoin by deprivation level and ethnicity, in order to examine potential inequities in use. METHOD: Dispensed prescription data for funded isotretinoin, for the year ending June 2008, held in a national repository was analysed using simple descriptive methods based on ethnicity and deprivation level. The same analysis was carried out for cyproterone acetate with ethinyloestradiol, another acne pharmaceutical available on prescription with no funding restrictions. There was demographic data on 60% of prescriptions based on the health identification number NHI. RESULTS: People living in more deprived areas (as defined by NZDep Index) were less likely to use isotretinoin, as were Maori and Pacific people. The association with deprivation level was not present for cyproterone acetate with ethinyloestradiol, although disparities in use by ethnicity remained. CONCLUSIONS: Given there is no evidence for lower rates of acne for Maori and Pacific people, the reasons may include financial and other barriers.

Global assessment of genetic variation influencing response to retinoid chemoprevention in head and neck cancer patients.

Head and neck squamous cell carcinoma (HNSCC) patients are at an increased risk of developing a second primary tumor (SPT) or recurrence following curative treatment. 13-cis-retinoic acid (13-cRA) has been tested in chemoprevention clinical trials, but the results have been inconclusive. We genotyped 9,465 single nucleotide polymorphisms (SNP) in 450 patients from the Retinoid Head and Neck Second Primary Trial. SNPs were analyzed for associations with SPT/recurrence in patients receiving placebo to identify prognosis markers and further analyzed for effects of 13-cRA in patients with these prognostic loci. Thirteen loci identified a majority subgroup of patients at a high risk of SPT/recurrence and in whom 13-cRA was protective. Patients carrying the common genotype of rs3118570 in the retinoid X receptor (RXRA) were at a 3.33-fold increased risk (95% CI, 1.67-6.67) and represented more than 70% of the study population. This locus also identified individuals who received benefit from chemoprevention with a 38% reduced risk (95% CI, 0.43-0.90). Analyses of cumulative effect and potential gene-gene interactions also implicated CDC25C:rs6596428 and JAK2:rs1887427 as 2 other genetic loci with major roles in prognosis and 13-cRA response. Patients with all 3 common genotypes had a 76% reduction in SPT/recurrence (95% CI, 0.093-0.64) following 13-cRA chemoprevention. Carriers of these common genotypes constituted a substantial percentage of the study population, indicating that a pharmacogenetic approach could help select patients for 13-cRA chemoprevention. The lack of any alternatives for reducing risk in these patients highlights the need for future clinical trials to prospectively validate our findings.