Abstract
To the Editor:
Biological therapies such as tralokinumab and dupilumab have revolutionized treatment for moderate-to-severe atopic dermatitis (AD). However, their high costs challenge universal healthcare systems aiming to balance efficacy, access, and affordability. We conducted a cost-per-responder (CPR) analysis comparing these biologics across select high-income universal healthcare systems: Germany, France, Italy, Spain, the United Kingdom, Australia, and Canada. CPR is the product of the number needed to treat (NNT) and the cost of the medication, measured over 16 weeks in this study.1,2
We analyzed efficacy data from pivotal trials—ECZTRA-3 (tralokinumab) and LIBERTY AD CHRONOS (dupilumab)—using unanchored matching-adjusted indirect comparisons, focusing on Eczema Area and Severity Index 75% improvement. 3 NNT is estimated at 4 for tralokinumab and 3 for dupilumab. 4 Drug costs were extracted from pharmacoeconomic studies, government formularies, and price lists and converted to USD based on 2023 exchange rates, as most studies were conducted in this time period.1-3 Costs accounted for dosing schedules over 16 weeks (tralokinumab Q4W, dupilumab Q2W).
Dupilumab consistently demonstrated a lower NNT (higher efficacy) compared to tralokinumab (3 vs 4). CPR estimates for tralokinumab ranged from $17,000 to $49,000, while dupilumab ranged from $17,000 to $39,000 (Table 1). Despite dupilumab’s higher per-dose cost and biweekly administration, its superior efficacy generally resulted in better cost-effectiveness across countries. In Australia and Canada, where negotiated pricing and reimbursement policies influence costs, dupilumab’s CPR was approximately 20–30% lower than tralokinumab’s. European data echoed this trend, with local pricing and dosing frequency narrowing differences in Italy and the UK. The United States, included as a reference, showed the highest CPR values overall. 5
Cost-per-Responder (CPR) Estimates for Tralokinumab and Dupilumab (16 Weeks, USD), Alphabetically Ordered (USA Listed First for Reference)
Costs are estimated from 2023 exchange rates for USD. 2023 USD (EUR→USD 1.1, GBP→USD 1.3, AUD→USD 0.65).
CPR, Cost per responder (the cost of drug treatment per patient achieving clinical response in pivotal trials); FDA, U.S. Food and Drug Administration (United States regulatory authority); EMA, European Medicines Agency (European Union regulatory authority); MHRA, Medicines and Healthcare products Regulatory Agency (United Kingdom regulatory authority, post-Brexit); TGA, Therapeutic Goods Administration (Australia’s regulatory authority); HAS, Haute Autorité de Santé (French National Authority for Health, responsible for clinical benefit evaluation); CEPS, Comité économique des produits de santé (French Economic Committee for Health Products, negotiates drug prices); AMNOG, Arzneimittelmarkt-Neuordnungsgesetz (“Pharmaceutical Market Restructuring Act”), the German framework for early benefit assessment and pricing of new drugs; G-BA, Gemeinsamer Bundesausschuss (Federal Joint Committee of Germany, conducts HTA and benefit assessments); AEMPS, Agencia Española de Medicamentos y Productos Sanitarios (Spanish Agency of Medicines and Medical Devices); P&R, Pricing and reimbursement (term used to indicate formal drug price and reimbursement negotiations in many European countries); HTA, Health technology assessment (formal evaluation of the medical, economic, social, and ethical implications of a health intervention).
Our findings highlight that dupilumab’s greater efficacy outweighs its dosing and cost disadvantages in most universal healthcare contexts, resulting in a more favorable CPR. Many clinicians extend the dosing interval for dupilumab in patients with stable disease control, often to every 4 weeks or even less frequent dosing, reducing overall treatment costs while maintaining efficacy. This practice is increasingly supported by real-world evidence. 6
Tralokinumab’s label permits every-4-week dosing in selected patients after week 16, but large real-world datasets confirming the effectiveness of interval extension beyond this point remain limited. Tralokinumab’s less frequent dosing schedule and competitive pricing in certain markets provide partial cost offsets compared to dupilumab; however, earlier approval of dupilumab (2017 vs 2021 for tralokinumab) may have allowed more time for payers and HTA bodies to negotiate pricing and establish managed-entry agreements, contributing to lower CPR in some countries.
CPR is also influenced by list prices, confidential discounts, reference pricing, and local HTA decisions, so approval timing is likely one of several factors. Tralokinumab CPR is lower in France, Germany, and Spain, likely reflecting pricing frameworks such as value-based pricing, external reference pricing, and managed-entry agreements that are unique to these nations. These systems often secure lower acquisition prices through negotiation, confidential discounts, or hospital tenders. Local HTA decisions may also influence reimbursement levels. While our analysis is based on public list prices, these policy mechanisms likely explain the lower CPRs observed and provide strategies for other health systems.
Policymakers should consider both clinical outcomes and budget impact when deciding formulary placement and negotiate pricing accordingly. Expanding dermatology services, especially in rural areas, is critical to improving access and maximizing biologics’ benefits.
Limitations include reliance on indirect trial comparisons and publicly available pricing data, which may not capture confidential discounts or patient assistance programs. Variability in local healthcare delivery and patient populations could influence applicability. Future research should prioritize designing CPR models that incorporate drug survival curves, interval extension practices, and country-specific confidential discounts or managed-entry agreements to better reflect the real-world economic impact of biological therapies in AD.
Dupilumab offers superior cost-effectiveness in moderate-to-severe AD across multiple universal healthcare systems, with tralokinumab providing a competitive alternative depending on local pricing and dosing considerations. These insights can guide policy decisions and individualized treatment strategies.