Dataset Information

Cost-utility of first-line actinic keratosis treatments in Finland.

ABSTRACT:

Introduction

Cost-utility assessment of first-line actinic keratosis (AK) treatments for max 25 cm2 AK field.

Methods

A probabilistic, 2-year decision tree model was used to assess costs, quality-adjusted life-years (QALY), incremental cost-effectiveness ratio (ICER), cost-effectiveness efficiency frontier, cost-effectiveness acceptability frontier (CEAF), and expected value of perfect information (EVPI) of AK treatments from the Finnish health care payer perspective with 3% discounting per annum. In the model, the first-line AK treatment resulted in complete clearance (CC) or non-CC with or without local skin responses (LSR), or AK recurrence. Non-CC AK was treated with methyl aminolevulinate+photodynamic therapy (MAL+PDT), and AK recurrence was retreated with the previous effective treatment. Costs included primary and secondary health care, outpatient drugs, and LSR management. QALYs were assessed with the EuroQol (EQ-5D-3L). Result robustness was assessed with sensitivity analyses.

Results

The mean simulated per patient QALYs (costs) were 1.526 (€982) for MAL+PDT, 1.524 (€794) for ingenol mebutate gel (IngMeb) 0.015% (3 days), 1.522 (€869) for IngMeb 0.05% (2 days), 1.520 (€1062) for diclofenac 3% (12 weeks), 1.518 (€885) for imiquimod 3.75% (6 weeks), 1.517 (€781) for imiquimod 5% (4/8 weeks), and 1.514 (€1114) for cryosurgery when treating AK affecting any body part. IngMeb 0.015% was less costly and more effective (dominating) than other AK treatments indicated for face and scalp area with the exception of imiquimod 5% for which the ICER was estimated at €1933/QALY gained and MAL+PDT, which had an ICER of €82,607/QALY gained against IngMeb 0.015%. With willingness-to-pay €2526-18,809/QALY gained, IngMeb 0.015% had >50% probability for cost-effectiveness on the CEAF. IngMeb 0.05% dominated AK treatments indicated for trunk and extremities. EVPIs for face and scalp (trunk and extremities) analyses were €26 (€0), €86 (€58), and €250 (€169) per patient with the willingness-to-pay of €0, €15,000, and €30,000 per QALY gained, respectively.

Conclusion

IngMebs were cost-effective AK treatments in Finland.

Funding

LEO Pharma.

SUBMITTER: Soini EJ

PROVIDER: S-EPMC4449383 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceActinic keratosis (AK), a skin growth induced by ultraviolet light exposure, requires chronic management because a small proportion can progress into squamous cell skin cancer. Spending for AK management was more than $1 billion in 2004. Investigating geographic variation in AK spending presents an opportunity to decrease waste or recoup excess spending.ObjectiveTo evaluate geographic variation in health care cost for management of AKs and the association with patient-related and health-related factors.Design, setting, and participantsThis retrospective cohort study was performed using data from the MarketScan medical claims database of 488 324 continuously enrolled members with 2 or more claims for AK. Data from January 1, 2008, to December 31, 2012, was used.Main outcomes and measuresAnnual costs of care were calculated for outpatient visits, AK destruction, and medications for AKs, and the total of these components. Costs were adjusted for inflation to 2014 US dollars. To display cost variation, we calculated the ratio of mean cost in the highest quintile (Q5) relative to the mean in the lowest quintile (Q1), or the Q5:Q1 ratio; Q5:Q1 ratios were adjusted based on age, sex, history of nonmelanoma skin cancer, US geographic region, and population density (metropolitan statistical area).ResultsOverall, data from 488 324 continuously enrolled members (mean [SD] age, 53.1 [7.5] years; 243 662 women) with 2 or more claims for AK were included. Overall, patients had 1 085 985 claims related to AK, and dermatologists accounted for 71.0% of claims. The 2-year total cost was $111.5 million, with $52.4 million in 2011 and $59.1 million in 2012. The unadjusted Q5:Q1 ratios for total annual cost per patient ranged from 9.49 to 15.10. Adjusted ratios ranged from 1.72 to 1.80.Conclusions and relevanceThere is variation in AK management cost within and between regions. This is not fully explained by differences in patient characteristics such as age, sex, or comorbidities. The annual cost for 10 common conditions from Medicare had lower Q5:Q1 ratios that ranged from 1.33 (joint degeneration of back/neck) to 1.69 (chronic sinusitis) when compared with 1.72 to 1.80 for AKs. This suggests an opportunity to investigate and improve the value of health care delivery in the management of AKs.

Project description:Actinic keratoses (AKs) are common skin lesions heralding an increased risk of developing squamous cell carcinoma (SCC) and other skin malignancies, arising principally due to excessive ultraviolet (UV) exposure. They are predominantly found in fair-skinned individuals, and increasingly, are a problem of the immunosuppressed. AKs may regress spontaneously, remain stable or transform to invasive SCC. The risk of SCC increases for those with more than 5 AKs, and the majority of SCCs arise from AKs. The main mechanisms of AK formation are inflammation, oxidative stress, immunosuppression, impaired apoptosis, mutagenesis, dysregulation of cell growth and proliferation, and tissue remodeling. Human papilloma virus has also been implicated in the formation of some AKs. Understanding these mechanisms guides the rationale behind the current available treatments for AKs. One of the main principles underpinning the management of AKs is that of field cancerization. Wide areas of skin are exposed to increasing amounts of UV light and other environmental insults as we age. This is especially true for the head, neck and forearms. These insults do not target only the skin where individual lesions develop, but also large areas where crops of AKs may appear. The skin between lesions is exposed to the same insults and is likely to contain as-yet undetectable preclinical lesions or areas of dysplastic cells. The whole affected area is known as the 'field'. Management is therefore divided into lesion-directed and field-directed therapies. Current therapies include lesion-directed cryotherapy and/or excision, and topical field-directed creams: 5-fluorouracil, imiquimod, diclofenac, photodynamic therapy and ingenol mebutate. Combining lesion- and field-directed therapies has yielded good results and several novel therapies are under investigation. Treatment is variable and tailored to the individual making a gold standard management algorithm difficult to design. This literature review article aims to describe the rationale behind the best available therapies for AKs in light of current understanding of pathophysiology and epidemiology. A PubMed and MEDLINE search of literature was performed between January 1, 2000 and September 18, 2013. Where appropriate, articles published prior to this have been referenced. This is not a systematic review or meta-analysis, but aims to highlight the most up to date understanding of AK disease and its management.

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Project description:OBJECTIVE:To compare the repetitive DNA patterns of human actinic keratoses and squamous cell carcinomas to determine the genetic alterations that are associated with malignant transformation. INTRODUCTION:Cancer cells are prone to genomic instability, which is often due to DNA polymerase slippage during the replication of repetitive DNA and to mutations in the DNA repair genes. The progression of benign actinic keratoses to malignant squamous cell carcinomas has been proposed by several authors. MATERIAL AND METHODS:Eight actinic keratoses and 24 squamous cell carcinomas (SCC), which were pair-matched to adjacent skin tissues and/or leucocytes, were studied. The presence of microsatellite instability (MSI) and the loss of heterozygosity (LOH) in chromosomes 6 and 9 were investigated using nine PCR primer pairs. Random Amplified Polymorphic DNA patterns were also evaluated using eight primers. RESULTS:MSI was detected in two (D6S251, D9S50) of the eight actinic keratosis patients. Among the 8 patients who had squamous cell carcinoma-I and provided informative results, a single patient exhibited two LOH (D6S251, D9S287) and two instances of MSI (D9S180, D9S280). Two LOH and one example of MSI (D6S251) were detected in three out of the 10 patients with squamous cell carcinoma-II. Among the four patients with squamous cell carcinoma-III, one patient displayed three MSIs (D6S251, D6S252, and D9S180) and another patient exhibited an MSI (D9S280). The altered random amplified polymorphic DNA ranged from 70% actinic keratoses, 76% squamous cell carcinoma-I, and 90% squamous cell carcinoma-II, to 100% squamous cell carcinoma-III. DISCUSSION:The increased levels of alterations in the microsatellites, particularly in D6S251, and the random amplified polymorphic DNA fingerprints were statistically significant in squamous cell carcinomas, compared with actinic keratoses. CONCLUSION:The overall alterations that were observed in the repetitive DNA of actinic keratoses and squamous cell carcinomas indicate the presence of a spectrum of malignant progression.

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