Cost-Effectiveness Analysis of Abrocitinib Compared with Dupilumab for Adolescents With Severe Atopic Dermatitis in Spain

Introduction

Atopic dermatitis (AD) is a common chronic inflammatory skin condition characterized by persistent pruritus and eczema [1]. In Spain, AD affects approximately 6.43% of adolescents (aged 12–17 years) [2] with 3.1% experiencing severe disease [3], often requiring systemic treatment. AD significantly impacts the quality of life of adolescents, affecting their physical comfort, emotional well-being, and daily functioning [4, 5].

Abrocitinib, a Janus kinase (JAK) inhibitor, has been approved and reimbursed for adolescents with severe AD in Spain in July 2024. Given the availability of new drugs for these patients, conducting economic evaluations will aid in the evidence-based decision-making process. In this context, dupilumab, a monoclonal antibody directed against IL-4 receptor α subunit, that blocks both IL-4 and IL-13 signaling [6], was the first biologic therapy approved for adolescents with severe AD in Spain [7]. Its early approval has led to broader clinical experience and a higher number of treated patients, making it the most relevant comparator when evaluating new therapeutic options for adolescents with severe AD.

We previously developed and published a cost-effectiveness model assessing abrocitinib in adults with AD [8]. Given the growing clinical and economic burden of AD in younger populations, the model was adapted to specifically assess the cost effectiveness of abrocitinib (100 mg and 200 mg) monotherapy versus dupilumab monotherapy in adolescents (12–17 years old) with severe AD, from the Spanish National Health System (NHS) perspective.

Methods

The adapted model consisted of a 52-week decision tree followed by a Markov approach, where patients remained for the rest of a 5-year time horizon. This time frame was selected to align with the age range of the target population (12 to < 18 years), as the analysis was specifically designed to assess clinical and economic outcomes within this adolescent subgroup. By focusing on this age-defined period, the model avoids the uncertainty associated with long-term extrapolations into adulthood and better supports healthcare decision making for this population. The treatments included in the analysis were abrocitinib 100 mg, abrocitinib 200 mg, and dupilumab. Both abrocitinib doses were considered since both are approved for adolescents aged ≥ 12 years, reflecting clinical practice and potential dose adjustments.

The Markov model was conducted on a 6-month cycle length (with half-cycle correction) and consisted of three health states: maintenance with active treatment, subsequent treatment (following discontinuation or loss of response) and death (see Fig. S1 from the electronic supplementary material [ESM]). Key parameters were refined to better reflect the unique characteristics of adolescents, including differences in treatment efficacy, discontinuation rates, and healthcare resource utilization. These parameters were adapted based on a NICE evaluation of different available systemic therapies for AD, which included data for abrocitinib and dupilumab [9–11].

The modelled population had a mean age of 14.9 years at the start of the model, consistent with the mean age of adolescents with AD in Spain [3]. Age-dependent mortality data were obtained from the National Institute of Statistics mortality tables [12], assuming that AD does not increase mortality risk.

Key efficacy inputs adapted for the adolescent population included response rates at 16 and 52 weeks (decision tree), and treatment waning and discontinuation rates (Markov model). In clinical practice, some patients may achieve response at week 16 but cannot tolerate long-term treatment due to adverse events or other reasons, leading to treatment discontinuation. To account for this, conditional discontinuation data were incorporated into the 52-week response assessment, reflecting both loss of efficacy and treatment discontinuation, as outlined in the NICE report [9–11]. Based on these rates, the probability of patients who responded at week 16 transitioning to long-term maintenance therapy at week 52 was estimated (Table 1).

Table 1.

Response and discontinuation rates

Parameter	Abrocitinib 100 mg [9]	Abrocitinib 200 mg [9]	Dupilumab 200/300 mg [9–11]
Decision tree
Response at week 16	67.4%	78.6%	58.5%
Response at week 52a	86.7%	88.9%	94.9%
Markov model
Discontinuation rateb	13.3%	11.1%	5.1%

^aResponse rate at week 52 for week 16 responders

^bTreatment discontinuation rates assumed equal to observed conditional discontinuation rates between weeks 16–52

In the Markov model, response was reassessed every cycle. Given the limited long-term data on treatment maintenance with abrocitinib and dupilumab, treatment benefit was assumed to decline progressively, in line with the NICE report approach (2% in year 2, 5% in year 3, 7% in year 4, and 8% in year 5) [9–11]. Adverse events (AEs) occurring in at least 5% of clinical trial participants for any treatment were considered [13, 14].

Utility values were assigned based on treatment response. All patients began with a baseline utility of 0.55, based on values reported for adolescents with AD [9], which remained unchanged until week 16, when treatment response was evaluated. Responders were assigned a utility of 0.88, assuming equivalent values for JAK inhibitors and biologics [9]. Non-responders and those who discontinued treatment transitioned to a subsequent treatment state, where a weighted utility of 0.71 was applied, reflecting the utility of responders and non-responders to standard of care, as outlined in the NICE report [9].

Direct costs (€, 2025) were obtained from local sources [15, 16] and included drug acquisition and administration, adverse events (AE) management, monitoring laboratory tests, medical visits and hospitalizations, and cost of subsequent treatment. Medical resource utilization data was extracted from the NICE report, specifically for the adolescent population [9–11] (see Table S1 in the ESM). Both costs and outcomes were discounted at 3% per year.

The analysis was expressed as an incremental cost-effectiveness ratio (ICER), calculated as incremental cost per quality-adjusted life year (QALY) gained (willingness-to-pay threshold [WTP]: €27,000/QALY [17]). One-way sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA) with 1000 iterations were carried out to test the robustness of the results. OWSA was performed by varying all base-case model parameters by ± 20% to evaluate their impact on model outcomes.

We also conducted a scenario-based sensitivity analysis to explore the impact of potential confidential price agreements. To this end, we constructed a two-dimensional matrix simulating varying discount levels for each of the two treatments under evaluation, ranging from 0 to 70% in 10% increments. Furthermore, a scenario analysis was performed for a 3-year time horizon.

Results

Abrocitinib 100 mg and 200 mg were found to be dominant versus dupilumab, generating a gain of 0.02 and 0.10 QALYs with cost savings of €8579.2, and €9460.5, respectively (Table 2).

Table 2.

Deterministic results

Results	Abrocitinib 100 mg	Abrocitinib 200 mg	Dupilumab 200/300 mg
Costs
Drug acquisitiona	€57,496	€56,775	€65,988
Drug administration			€60
Adverse events	€293	€345	€303
Testing costs	€1063	€1276	€1120
Medical visits and hospitalization	€5677	€5252	€5638
Total costs	€64,529	€63,648	€73,108
Total QALYs	3.71	3.80	3.70
Abrocitinib 100 mg vs dupilumab
∆Cost			− €8579.2
∆QALYs			0.02
ICER			Dominant
Abrocitinib 200 mg vs dupilumab
∆Cost			− €9460.5
∆QALYs			0.10
ICER			Dominant

^aThe reported drug acquisition cost accounts for both the cost of the evaluated treatment and the subsequent treatment initiated after discontinuation. This approach explains the observed cost differences between abrocitinib 100 mg and 200 mg

ICER incremental cost-effectiveness ratio, QALY quality-adjusted life years

Sensitivity analyses confirmed the robustness of the results. OWSA demonstrated that variations in key parameters did not affect the dominance of abrocitinib. PSA showed that abrocitinib was dominant in 70.7% and 80.7% of simulations for the 100-mg and 200-mg doses, respectively, compared with dupilumab, considering the WTP threshold of €27,000 per QALY gained (Fig. 1).

Fig. 1.

PSA cost-effectiveness plane. (A) abrocitinib 100 mg vs dupilumab; (B) abrocitinib 200 mg vs dupilumab. PSA probabilistic sensitivity analysis, QALYs quality-adjusted life years

Additionally, price sensitivity analysis demonstrated fairly consistent results across the plausible ranges of confidential price agreements (Fig. 2). Abrocitinib dominance was maintained across comparable price levels and under equal percentage reductions for both treatments. Abrocitinib only became not cost effective under conditions where dupilumab discounts were substantial and abrocitinib discounts were minimal. Since abrocitinib consistently yields a gain in QALYs, it cannot be dominated under any pricing scenario.

Fig. 2.

Price sensitivity analysis for all presentations. ICER incremental cost-effectiveness ratio, QALY quality-adjusted life year

When evaluating the cost effectiveness over a 3-year time horizon, abrocitinib 100 mg and 200 mg maintained dominance versus dupilumab, generating a QALYs gain of 0.04 and 0.10 with per-person cost savings of €6432 and €6962, respectively.

Discussion

Adequate control of moderate to severe AD in adolescence is important, in view of its negative impact in daily functioning, psychoemotional impact and the risk of disease persistence and cumulative burden on health and quality of life in adulthood. Our findings suggest that abrocitinib use is a viable and dominant strategy in adolescents with severe AD in Spain, supporting its inclusion in treatment guidelines. Furthermore, these results align with our prior analysis in the adult population [8], indicating that abrocitinib is a dominant alternative to dupilumab both in adults and adolescents with severe AD. In addition to its favorable cost effectiveness, abrocitinib offers dose flexibility, allowing treatment adjustments based on patient needs, which may further optimize long-term disease management.

To the best of our knowledge, this is the first study to evaluate the cost effectiveness of abrocitinib versus dupilumab for treating adolescents with severe AD. Previous economic evaluations have primarily focused on adult populations, with limited data available for younger patients. This study fills an important gap in the literature, providing valuable insights for healthcare decision makers regarding the economic value of abrocitinib in this population. Importantly, our findings are also consistent with recent health technology assessments, such as the NICE appraisal, which recommended abrocitinib as a treatment option for moderate-to-severe AD in adults and young people aged 12 years and over [10].

Nevertheless, some limitations should be acknowledged. Most inputs used in this analysis were derived from international adolescent populations rather than specifically from Spanish adolescents, which required assumptions about their applicability to the Spanish healthcare context. Additional considerations include uncertainties regarding long-term treatment discontinuation and treatment benefit. However, sensitivity analyses consistently demonstrated the robustness of the model, supporting the reliability of our conclusions.

Supplementary Information

Below is the link to the electronic supplementary material.

Funding

This study was sponsored by Pfizer, S.L.U., Spain. The authors have received consulting fees from Pfizer S.L.U. for the preparation of this scientific letter. Writing support for this scientific letter was provided by Alba Bellmunt at Outcomes’ 10 (a ProductLife Group Company) and was funded by Pfizer.

Declarations

Conflict of interest

Maria del Pilar Fortes Soto and Alfonso De Lossada Juste are employees of Pfizer (Spain). Alba Bellmunt and Neus Vidal-Vilar disclosed that they are paid consultants at Outcomes’10 (a ProductLife Group Company), a company paid by Pfizer to assist with the writing of this scientific letter. Pedro Herranz Pinto has served as investigator and/or speaker for Abbvie, Almirall, Bristol Myers Squibb, Janssen, Leopharma, Lilly, Novartis, Pfizer, Regeneron, Sandoz, Sanofi, and UCB Pharma. Minia Campos Domínguez has served as speaker for Sanofi, Almirall and Abbvie, as investigator for Abbvie, has participated in advisory boards for Pfizer, and has received funding for training activities from Galderma. Rosa María Romero Jiménez has served as speaker for Sanofi and Novartis.

Availability of data and material

Data are available from the corresponding author upon reasonable request.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Code availability

The data presented in this study are available within the article or in the Supporting Information Materials. The model used in this study is available from the corresponding author upon reasonable request.

Author contributions

All authors contributed to the conception of the study and AB performed the analysis. All authors drafted the original research letter and made substantial contributions to the original draft and the final version. All authors reviewed and approved the final version for submission. All authors agreed to be responsible for all aspects of the work.