Review of Efficacy, Cost, and Adherence of Field Therapies for Actinic Keratosis

Nathaniel Lampley III
University of Cincinnati College of Medicine

Cincinnati, OH 

Rachel Rigo MD
Department of Dermatology

Weill Cornell Medicine
New York, NY

Todd Schlesinger MD
Clinical Research Center of the Carolinas 
Charleston, SC

Anthony M. Rossi MD 
Department of Dermatology Dermatology Service
Weill Cornell Medicine Department of Medicine
New York, NY Memorial Sloan Kettering Cancer Center
 New York, NY

SYNPOSIS
Field therapy for actinic keratosis (AK) offers the benefit of treating both 
visible clinical lesions and subclinical atypia. The primary goal is to reduce 
the risk of progression to keratinocyte carcinoma. When choosing a field 
therapy for AK, physicians should consider both the effective cost (EC)—de-
fined as the approximated cost to achieve 100% AK clearance in a single 
patient—and patient adherence to treatment. A literature search revealed 
that the effective cost of 5-fluorouracil (5-FU) and in-office photodynam-
ic therapy (PDT) are similar. However, the effect of patient adherence on 
real-world efficacy and long-term AK clearance favors in-office PDT and 
shorter-term topical regimens.

OBJECTIVE
To compare efficacy, cost, and adherence of topical therapies and in-of-
fice PDT for AK. 

METHODS
The authors searched PubMed, Embase, Web of Science, and Google Scholar 
databases for articles on AK field therapy published between October 2020 
and March 2021. The estimated cost of a given regimen was calculated as 
a projection of the per-unit cost multiplied by the number of units needed 
to complete the regimen. To calculate the total cost for PDT, the procedural 
cost was estimated from the average national Medicare reimbursement rate 
(as of May 23rd, 2021) and was added to the cost of the photosensitizer per 
treatment.  Effective cost (EC) was calculated by dividing total cost (TC) by 
the clearance rate (CR), EC=TC/CR.

RESULTS
Commonly prescribed and studied FDA-approved topical field treatments 
are shown in Table 1.  Only BF-200 ALA 10% gel has been approved by 
the FDA for field treatment and is thus included in this analysis. Effective 
cost of 5-FU 4% cream ($541.16 – $801.72) is similar to that of PDT 
with aminolevulinic acid (ALA) 10% gel ($593.14 – $870.58). However, 
total cost of 5-FU ranges from $433 (4% cream) to $1503 (0.5% cream), 
whereas total cost for a single round of PDT with 10% ALA gel is $540. 
In addition, at-home topical therapies present significant barriers to com-
pliance due to expected local skin reactions and long treatment regimens 
for many of these therapies, leading to potentially lower efficacy than is 
reported in clinical trials. This favors in-office PDT and shorter-term topi-
cal treatments.

CONCLUSION
In-office 10% gel ALA-PDT is a cost-effective alternative to topical therapies 
and offers comparable efficacy in field-directed treatment of AK.  

This study was investigator-initiated and funded by Biofrontera Inc.

Cost/regimen estimated using wholesale acqui-
sition cost (WAC) package prices and Medicare 
coverage rates for May 2021.
*Average wholesale price. 
5-FU = 5-fluorouracil; ALA = 5-aminolevulinic 
acid; CPT – Current Procedural Terminology; to-
tal cost = cost/regimen + CPT cost; effective cost 
= total cost/AK clearance rate.

1 Tolak, Hill Dermaceuticals, Stanford, FL
2 Ameluz, Biofrontera, Woburn, MA
3 Efudex, Bausch Health US, Bridgewater, NJ 
4 Aldara,Valeant Pharmaceuticals  
   North America, Bridgewater, NJ
5 Klisyri, Almirall LLC, Malvern, PA
6 Carac, Bausch Health US, Bridgewater, NJ
7 Solaraze, PharmDerm, Melville, NY
8 Zyclara, Valeant Pharmaceuticals  
   North America, Bridgewater, NJ