Short-Term Cost per Responder of Lebrikizumab versus Tralokinumab for Moderate-to-Severe Atopic Dermatitis in Saudi Arabia: A Model-Based Payer Analysis

Abstract

Purpose

Atopic dermatitis (AD) imposes a clinical and economic burden, and biologic acquisition costs influence payer decisions. This study compared the short-term cost per responder of lebrikizumab and tralokinumab for moderate-to-severe AD in Saudi Arabia.

Methods

A cost-per-responder model used a Saudi payer perspective and publicly available Saudi Food and Drug Authority (SFDA) list prices, which may differ from negotiated or tender prices. Lebrikizumab 250 mg every two weeks and tralokinumab 300 mg every two weeks were compared before week-16 response assessment. Response probabilities were obtained from the 2025 network meta-analysis by Silverberg et al. EASI probabilities were reported directly; IGA 0/1 and pruritus NRS ≥4 probabilities were reconstructed from NMA relative effects and placebo risks. The primary endpoint was EASI 75 at week 16. In addition to the 16-week framework, exploratory pruritus analyses aligned week-4 response with costs through weeks 0 and 2, separately assessed inclusion of the week-4 dose, and tested whole-pack acquisition. Deterministic sensitivity, price-scenario, threshold, and fixed-budget analyses were performed.

Result

Lebrikizumab had higher modelled response probabilities across endpoints, whereas tralokinumab had a lower administered-dose acquisition cost before week 16 (SAR 19,858.50 vs SAR 44,130). Tralokinumab had lower costs per responder for EASI 50 (SAR 41,632 vs SAR 69,169), EASI 75 (SAR 63,649 vs SAR 94,903), EASI 90 (SAR 113,477 vs SAR 148,087), and IGA 0/1 (SAR 71,346 vs SAR 96,876). After correction of the available-case placebo denominator, week-4 pruritus response probabilities were 29.6% for lebrikizumab and 13.5% for tralokinumab. Using 16-week administered-dose costs, cost per pruritus responder was similar but marginally lower with tralokinumab (SAR 147,214 vs SAR 149,128). In the time-aligned analysis before the week-4 assessment, fractional-pack costing favoured tralokinumab (SAR 49,071 vs SAR 59,651), whereas whole-pack costing favoured lebrikizumab (SAR 59,651 vs SAR 65,429).

Conclusion

Under the modelled public Saudi list prices, tralokinumab had a lower short-term cost per responder for the week-16 skin-response endpoints. The pruritus result was exploratory and changed according to the cost horizon and pack-purchasing convention; it does not establish a consistent economic advantage for either treatment. The findings are price dependent and should not be interpreted as overall clinical superiority or long-term cost-effectiveness.

Introduction

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease characterised by eczematous lesions, pruritus, sleep disturbance, and impaired health-related quality of life. Beyond its clinical manifestations, AD imposes a substantial humanistic and economic burden on patients, caregivers, and healthcare systems. A systematic review of adults and adolescents with AD highlighted the broad clinical, quality-of-life, productivity, and economic consequences of the disease.¹ In Saudi Arabia, AD has also been associated with considerable humanistic and economic burden, including direct healthcare costs, productivity losses, and impaired patient well-being.² These local and international data support the need for treatment strategies that improve disease control while remaining economically sustainable.

Moderate-to-severe AD often requires systemic therapy when topical treatment and supportive measures are insufficient. The Saudi consensus statement on AD management recommends structured assessment using validated clinical and patient-reported measures, including EASI, physician/global assessment tools, DLQI, and pruritus NRS, to guide treatment monitoring and response evaluation.³ Among targeted systemic therapies, interleukin-13 (IL-13) inhibition is clinically relevant because IL-13 contributes to type 2 inflammation, skin-barrier dysfunction, and itch pathways in AD. Lebrikizumab and tralokinumab are IL-13-targeting monoclonal antibodies with demonstrated efficacy in pivotal placebo-controlled Phase 3 trials. In ADvocate 1 and ADvocate 2, lebrikizumab improved week-16 clinical responses in adolescents and adults with moderate-to-severe AD.⁴ In ECZTRA 1 and ECZTRA 2, tralokinumab monotherapy was superior to placebo at week 16 and was generally well tolerated through longer follow-up.⁵

Lebrikizumab and tralokinumab were selected because both are monoclonal antibodies directed at IL-13 and can therefore be compared as two targeted options within the same biologic mechanism. The study does not attempt to compare the full systemic-treatment landscape, which also includes other biologics and oral targeted therapies. Their comparative value for payers depends not only on response probabilities but also on local acquisition prices, dosing schedules, and the endpoint used to define response. Indirect evidence from the 2025 network meta-analysis by Silverberg et al suggested higher short-term response probabilities with lebrikizumab than with tralokinumab for several outcomes; however, these are indirect estimates and not randomized head-to-head evidence.⁶ Cost-per-responder analysis provides a pragmatic short-term metric by estimating acquisition cost per defined response. A recent US-based analysis showed that the economic ranking can differ under country-specific price assumptions.⁷

Saudi-specific evidence comparing the short-term cost per responder of these two IL-13-targeted biologics using local public list prices remains limited. This gap matters because public Saudi prices, institutional procurement prices, confidential rebates, and national tender prices may differ substantially. This study therefore compared lebrikizumab with tralokinumab for moderate-to-severe AD from a Saudi payer perspective using public SFDA list prices and NMA-derived response probabilities. EASI 50, EASI 75, EASI 90, IGA 0/1, and pruritus NRS response were evaluated together with deterministic, price-scenario, threshold, fixed-budget, week-4 time-aligned, and whole-pack sensitivity analyses.

Materials and Methods

Study Design and Perspective

This study was conducted as a short-term model-based cost-per-responder analysis comparing lebrikizumab 250 mg every two weeks with tralokinumab 300 mg every two weeks for moderate-to-severe AD in Saudi Arabia. The model combined clinical-effectiveness estimates from the 2025 NMA by Silverberg et al with publicly available SFDA list prices to estimate drug-acquisition cost per predefined clinical response.

The analysis was performed from a Saudi payer perspective using public SFDA list-price inputs. These are not confidential rebates, reimbursement net prices, institutional purchase prices, or national tender prices. Only direct drug-acquisition costs were included. Administration costs were assumed to be zero because both biologics are administered subcutaneously and can be self-administered. Monitoring, visits, switching, discontinuation, rescue therapy, adverse events, and indirect costs were excluded because this was not a cost-utility, full cost-effectiveness, or budget-impact analysis.

Target Population

The model population reflected the NMA evidence base: adolescents and adults with moderate-to-severe AD who were candidates for systemic therapy. The NMA included randomized, double-blind, placebo-controlled monotherapy trials at approved doses. The source assessment considered variation in potential treatment-effect modifiers to be limited overall, but heterogeneity was reported for mean age in adolescent-only trials, baseline EASI, the proportion with baseline IGA 4, and placebo EASI response; prior systemic-treatment exposure was not consistently detailed across every contributing dataset.⁶

Accordingly, the analysis assumes sufficient comparability and transitivity across the contributing trials but does not assume that the populations were identical. Differences in age distribution, baseline severity, previous systemic treatment, and other trial characteristics may affect indirect relative effects and reconstructed absolute responses. These international trial populations may also differ from patients treated in routine Saudi practice.

Comparators and Dosing Regimens

Two IL-13 inhibitor monotherapy regimens were compared. Lebrikizumab was modelled as 500 mg administered subcutaneously at weeks 0 and 2, followed by 250 mg every two weeks. Tralokinumab was modelled as a 600 mg subcutaneous loading dose at week 0, followed by 300 mg every two weeks. These dosing schedules were selected to reflect the regimens used in the clinical evidence base and labelled dosing schedules for moderate-to-severe AD.

For the week-16 response assessment, drug exposure was calculated using all doses administered before the week-16 outcome assessment, including doses given from treatment initiation through week 14. Under this approach, the cumulative dose before week-16 assessment was 2500 mg for lebrikizumab and 2700 mg for tralokinumab. A dose administered at week 16 was not included because the model estimated the treatment cost incurred up to the clinical response assessment point.

Clinical Effectiveness Inputs

Clinical-effectiveness inputs were obtained from the 2025 NMA by Silverberg et al, which compared approved systemic monotherapies for moderate-to-severe AD, including lebrikizumab and tralokinumab.⁶ The selected endpoints represent clinically meaningful response thresholds used in trials and treat-to-target decision-making.

The primary effectiveness endpoint was the proportion of patients achieving EASI 75 at week 16. Secondary endpoints were EASI 50 at week 16, EASI 90 at week 16, IGA 0/1 at week 16, and a ≥4-point improvement in pruritus NRS at week 4. The week-4 pruritus endpoint was included because early itch relief is clinically meaningful and may influence patient satisfaction, adherence, and continuation decisions during the initial treatment period.

EASI 50, EASI 75, and EASI 90 absolute response probabilities were taken directly from the NMA. Absolute probabilities for IGA 0/1 and week-4 pruritus NRS ≥4 were reconstructed because the NMA reported comparative odds ratios rather than all absolute treatment probabilities for these outcomes. Reconstruction combined the NMA relative effects with pooled placebo risks from relevant source trials. For pruritus, only studies with numeric placebo-response data contributed to the available-case placebo denominator; studies reporting the response as unavailable were excluded rather than treated as zero-response observations. Reconstructed estimates remain indirect and were therefore designated exploratory where appropriate.

Cost Inputs

Drug-acquisition costs were obtained from the publicly available SFDA Drugs List and expressed in 2025 Saudi Riyals (SAR). They represent public list prices and may differ from actual negotiated, institutional, reimbursement, or tender prices.

The public list price entered for lebrikizumab was SAR 4413 per 250 mg pre-filled syringe, and the price entered for tralokinumab was SAR 4413 per pack of four 150 mg pre-filled syringes (600 mg per pack). The administered-dose base case prorated the tralokinumab pack price to the modelled milligrams and therefore assumed fractional-pack equivalence with no drug wastage. Through week 14, the modelled base-case acquisition cost was SAR 44,130 for lebrikizumab and SAR 19,858.50 for tralokinumab; the latter corresponds to 4.5 tralokinumab pack equivalents. A whole-pack sensitivity analysis used five tralokinumab packs (SAR 22,065).

No administration cost was applied. Rebates, confidential discounts, value-based agreements, tender prices, and future procurement changes were not modelled. Because public list prices can differ materially from actual payer expenditure, all results should be interpreted as price-scenario estimates rather than observed procurement costs.

Cost-per-Responder Analysis

For each endpoint and treatment, cost per responder was calculated using the following formula:

Cost per responder = total drug acquisition cost per patient ÷ response probability

For week-16 EASI and IGA outcomes, the numerator was the modelled administered-dose acquisition cost through week 14 and the denominator was the relevant NMA-derived or reconstructed response probability.

The manuscript base framework paired the week-4 pruritus response with 16-week administered-dose cost to represent continuation through an initial payer reassessment period. Because this pairing does not align the clinical and cost time points, it was treated as exploratory. Time-aligned analyses used costs incurred before the week-4 assessment (weeks 0 and 2) and, separately, costs including the week-4 dose. A further whole-pack analysis tested acquisition without credit for unused tralokinumab syringes.

Fixed-Budget Analysis

A fixed-budget analysis was conducted to estimate the number of responders achievable under a hypothetical budget of SAR 1,000,000. For each treatment and endpoint, the number of responders covered by the fixed budget was calculated as:

Number of responders covered = fixed budget ÷ cost per responder

The fixed-budget analysis was retained as a concise translation of the cost-per-responder results and was not interpreted as a separate measure of clinical superiority.

Deterministic Sensitivity Analysis

Deterministic sensitivity analysis was performed to assess the effect of uncertainty in clinical response probabilities on cost-per-responder results. For each endpoint and treatment, the base-case response probability was replaced with the corresponding lower and upper bounds of the 95% credible interval from the NMA or reconstructed response estimate. Drug acquisition costs, dosing schedules, administration costs, and all other model assumptions were held constant.

For each scenario, cost per responder was recalculated. The difference in cost per responder between lebrikizumab and tralokinumab was then estimated by subtracting the tralokinumab cost per responder from the lebrikizumab cost per responder. Positive values indicated a higher cost per responder for lebrikizumab, whereas negative values indicated a higher cost per responder for tralokinumab.

Price Scenario Analysis

A price scenario analysis was conducted to assess the robustness of the base-case findings to changes in drug acquisition prices. Separate scenarios were modelled in which the acquisition price of lebrikizumab was reduced by 10%, 20%, 30%, and 40% while the tralokinumab price was held constant. Additional scenarios evaluated changes in the tralokinumab acquisition price, including 10% and 20% reductions and 10% and 20% increases, while the lebrikizumab price was held constant. Selected combined scenarios were also examined, including proportional price reductions for both agents and scenarios in which lebrikizumab price reductions were evaluated against increased tralokinumab prices.

For each price scenario, the adjusted drug acquisition cost was recalculated by applying the scenario-specific percentage change to the base-case unit acquisition price. The adjusted total drug acquisition cost was then divided by the endpoint-specific response probability to estimate the revised cost per responder. Clinical response probabilities, dosing schedules, administration costs, treatment duration, and all other model assumptions were held constant across price scenarios. This analysis was intended to examine the extent to which the base-case cost-per-responder findings were dependent on the acquisition-price assumptions.

Threshold Analysis

A threshold price analysis was performed to estimate the price reduction required for the treatment with the higher base-case cost per responder to reach parity with the treatment with the lower base-case cost per responder. For each endpoint, the treatment with the lower base-case cost per responder was used as the reference option. The unit price of the alternative treatment was reduced until its cost per responder equalled that of the reference treatment, while clinical response probabilities, dosing schedules, administration costs, treatment duration, and the reference treatment price were held constant.

For the week-16 EASI and IGA endpoints, tralokinumab had the lower base-case cost per responder and lebrikizumab was therefore varied to estimate parity. For pruritus, the treatment requiring a price change depended on the selected cost horizon and pack convention; the threshold table reports the 16-week administered-dose base case only.

Model Assumptions

The analysis assumed monotherapy at the modelled doses, persistence through the response assessment, no switching or non-adherence, zero administration cost, and exclusion of broader medical and indirect costs. International NMA response estimates were assumed transferable to Saudi practice despite possible differences in age, baseline severity, previous systemic treatment, adherence, persistence, and patient mix. The 16-week horizon captures initial response but cannot represent long-term value in a chronic relapsing disease. Public SFDA list prices were assumed relevant to the modelled payer perspective, although actual institutional, reimbursement, and tender prices may differ. The administered-dose base case assumed fractional-pack equivalence and no wastage; whole-pack analyses tested this assumption.

Ethics and Data Availability

This study used aggregated published clinical evidence and publicly available SFDA price data. No individual patient data were collected, accessed, or analysed; therefore, additional ethics approval was not required.

Results

Model Inputs

The model compared lebrikizumab 250 mg every two weeks with tralokinumab 300 mg every two weeks before the week-16 assessment. Doses through week 14 totalled 2500 mg and SAR 44,130 for lebrikizumab and 2700 mg and SAR 19,858.50 for tralokinumab under administered-dose/fractional-pack costing (Table 1). The tralokinumab base case represents 4.5 pack equivalents and assumes no wastage.

Table 1.

Modelled Dosing Schedules and 16-Week Drug-Acquisition Costs

Parameter	Lebrikizumab	Tralokinumab
Modelled regimen	500 mg at weeks 0 and 2, then 250 mg every 2 weeks	600 mg at week 0, then 300 mg every 2 weeks
Route	Subcutaneous	Subcutaneous
Unit/pack definition	250 mg pre-filled syringe	Pack of four 150 mg pre-filled syringes
Unit/pack price	SAR 4413 per 250 mg syringe	SAR 4413 per 600 mg pack
Doses included in cost calculation	Weeks 0, 2, 4, 6, 8, 10, 12, and 14	Weeks 0, 2, 4, 6, 8, 10, 12, and 14
Cumulative dose before week-16 assessment	2500 mg	2700 mg
Unit cost per mg	SAR 17.65	SAR 7.36
Total drug acquisition cost before week-16 assessment	SAR 44,130.00	SAR 19,858.50
Administration cost	SAR 0.00	SAR 0.00

Notes: Costs use public SFDA list prices. The base case uses administered-dose/fractional-pack equivalents and assumes no wastage; whole-pack sensitivity is shown in Table 3.

Base-Case Cost per Responder

Lebrikizumab had higher modelled response probabilities than tralokinumab for all endpoints, while tralokinumab had lower cost per responder for EASI 50, EASI 75, EASI 90, and IGA 0/1. For EASI 75, cost per responder was SAR 94,903 with lebrikizumab and SAR 63,649 with tralokinumab. After correction of the available-case placebo denominator, week-4 pruritus response probabilities were 29.6% and 13.5%, respectively. When paired with 16-week administered-dose costs, cost per pruritus responder was SAR 149,128 with lebrikizumab and SAR 147,214 with tralokinumab, a small difference of SAR 1914 favouring tralokinumab (Table 2).

Table 2.

Base-Case Response Probabilities and Cost per Responder

Endpoint	Time Point	Lebrikizumab Response	Tralokinumab Response	Lebrikizumab Cost per Responder	Tralokinumab Cost per Responder	Difference, LEB - TRALO	Lower Cost-per-Responder Option
EASI 50 (direct NMA)	Week 16	63.8%	47.7%	SAR 69,169	SAR 41,632	SAR 27,537	Tralokinumab
EASI 75 (direct NMA)	Week 16	46.5%	31.2%	SAR 94,903	SAR 63,649	SAR 31,254	Tralokinumab
EASI 90 (direct NMA)	Week 16	29.8%	17.5%	SAR 148,087	SAR 113,477	SAR 34,610	Tralokinumab
IGA 0/1 (reconstructed)	Week 16	45.6%	27.8%	SAR 96,876	SAR 71,346	SAR 25,530	Tralokinumab
Pruritus NRS ≥4 (reconstructed)	Week 4	29.6%	13.5%	SAR 149,128	SAR 147,214	SAR 1914	Tralokinumab

Notes: EASI absolute responses were reported directly in the 2025 NMA. IGA 0/1 and WPNRS4 absolute responses were reconstructed. The pruritus outcome is measured at week 4, whereas the base table uses 16-week administered-dose cost. WPNRS4 reconstruction uses only studies with numeric placebo-response data; studies reporting NA are excluded from the denominator.

Exploratory Week-4 Pruritus Cost Sensitivity Analysis

Table 3 presents an exploratory sensitivity analysis examining how alternative dosing horizons and drug-acquisition conventions affect the cost per pruritus responder (CPR) at week 4. Under the administered-dose/fractional-pack scenarios, tralokinumab consistently had a lower CPR than lebrikizumab, including the 16-week base case (SAR 147,214 vs SAR 149,128). However, when whole-pack acquisition was assumed, the ranking reversed, with lebrikizumab showing a lower CPR both before the week-4 assessment (SAR 59,651 vs SAR 65,429) and over the 16-week pack-sensitivity scenario (SAR 149,128 vs SAR 163,572). These findings indicate that the relative cost ranking is sensitive to assumptions regarding pack acquisition and the costing horizon.

Table 3.

Exploratory Week-4 Pruritus Cost Sensitivity

Scenario	Clinical Horizon	Cost Convention	LEB Cost	TRALO Cost	LEB CPR	TRALO CPR	Lower CPR Option
16-week base case	Weeks 0-14	Administered dose/fractional packs	SAR 44,130	SAR 19,858.50	SAR 149,128	SAR 147,214	Tralokinumab
Before week-4 assessment	Weeks 0 and 2	Administered dose/fractional packs	SAR 17,652	SAR 6,619.50	SAR 59,651	SAR 49,071	Tralokinumab
Including week-4 dose	Weeks 0, 2, and 4	Administered dose/fractional packs	SAR 22,065	SAR 8826	SAR 74,564	SAR 65,429	Tralokinumab
Before week-4 assessment	Weeks 0 and 2	Whole packs purchased	SAR 17,652	SAR 8826	SAR 59,651	SAR 65,429	Lebrikizumab
16-week pack sensitivity	Weeks 0-14	Whole packs purchased	SAR 44,130	SAR 22,065	SAR 149,128	SAR 163,572	Lebrikizumab

Notes: All scenarios use the corrected week-4 response probabilities (29.6% for lebrikizumab and 13.5% for tralokinumab). “Before assessment” includes doses at weeks 0 and 2. The ranking reverses under whole-pack acquisition; the endpoint is therefore exploratory and assumption-sensitive.

Deterministic Sensitivity Analysis

Deterministic sensitivity analysis showed that tralokinumab retained a lower cost per responder across the low- and high-response scenarios for all week-16 EASI and IGA endpoints. For pruritus, the low-response scenario favoured lebrikizumab (SAR 206,220 vs SAR 265,947), whereas the high-response scenario favoured tralokinumab (SAR 86,594 vs SAR 107,129), confirming that this reconstructed endpoint is unstable (Table 4).

Table 4.

Deterministic Sensitivity Analysis Using Lower and Upper Credible-Interval Response Estimates

Endpoint	Scenario	Lebrikizumab Cost per Responder	Tralokinumab Cost per Responder	Difference, LEB - TRALO	Lower Cost-per-Responder Option
EASI 50	Low-response scenario	SAR 80,676	SAR 49,155	SAR 31,521	Tralokinumab
EASI 50	High-response scenario	SAR 61,377	SAR 35,910	SAR 25,467	Tralokinumab
EASI 75	Low-response scenario	SAR 117,367	SAR 79,118	SAR 38,249	Tralokinumab
EASI 75	High-response scenario	SAR 79,228	SAR 51,986	SAR 27,242	Tralokinumab
EASI 90	Low-response scenario	SAR 197,009	SAR 150,443	SAR 46,566	Tralokinumab
EASI 90	High-response scenario	SAR 115,222	SAR 87,099	SAR 28,123	Tralokinumab
IGA 0/1	Low-response scenario	SAR 116,192	SAR 95,692	SAR 20,500	Tralokinumab
IGA 0/1	High-response scenario	SAR 82,761	SAR 54,611	SAR 28,150	Tralokinumab
Pruritus NRS ≥4	Low-response scenario	SAR 206,220	SAR 265,947	-SAR 59,727	Lebrikizumab
Pruritus NRS ≥4	High-response scenario	SAR 107,129	SAR 86,594	SAR 20,535	Tralokinumab

Note: For pruritus, the low-response scenario favours lebrikizumab and the high-response scenario favours tralokinumab, further demonstrating instability.

Price Scenario Analysis

For EASI 75, tralokinumab remained lower cost per responder when lebrikizumab’s price decreased by 10%, 20%, or 30%. Lebrikizumab became lower cost per responder at a 40% reduction and in the mixed scenario combining a 30% lebrikizumab reduction with a 10% tralokinumab increase. The remaining scenarios are summarized in Table 5.

Table 5.

Price-Scenario Analysis for EASI 75 at Week 16

Price Scenario	LEB Price Change	TRALO Price Change	LEB Cost per EASI 75 Responder	TRALO Cost per EASI 75 Responder	Difference, LEB - TRALO	Lower Cost-per-Responder Option
Base case	0%	0%	SAR 94,903	SAR 63,649	SAR 31,254	Tralokinumab
Lebrikizumab −10%	−10%	0%	SAR 85,413	SAR 63,649	SAR 21,764	Tralokinumab
Lebrikizumab −20%	−20%	0%	SAR 75,923	SAR 63,649	SAR 12,274	Tralokinumab
Lebrikizumab −30%	−30%	0%	SAR 66,432	SAR 63,649	SAR 2783	Tralokinumab
Lebrikizumab −40%	−40%	0%	SAR 56,942	SAR 63,649	-SAR 6707	Lebrikizumab
Tralokinumab −10%	0%	−10%	SAR 94,903	SAR 57,284	SAR 37,619	Tralokinumab
Tralokinumab −20%	0%	−20%	SAR 94,903	SAR 50,919	SAR 43,984	Tralokinumab
Tralokinumab +10%	0%	+10%	SAR 94,903	SAR 70,014	SAR 24,889	Tralokinumab
Tralokinumab +20%	0%	+20%	SAR 94,903	SAR 76,379	SAR 18,524	Tralokinumab
Both −10%	−10%	−10%	SAR 85,413	SAR 57,284	SAR 28,129	Tralokinumab
Both −20%	−20%	−20%	SAR 75,923	SAR 50,919	SAR 25,004	Tralokinumab
Lebrikizumab −20%, tralokinumab +10%	−20%	+10%	SAR 75,923	SAR 70,014	SAR 5909	Tralokinumab
Lebrikizumab −30%, tralokinumab +10%	−30%	+10%	SAR 66,432	SAR 70,014	-SAR 3582	Lebrikizumab

Note: Price changes are applied to public list-price acquisition costs while clinical response probabilities remain fixed; confidential rebates and tender prices are not modelled.

Threshold Analysis

Threshold analysis showed that lebrikizumab price reductions of 39.8%, 32.9%, 23.4%, and 26.4% were required for parity with tralokinumab for EASI 50, EASI 75, EASI 90, and IGA 0/1, respectively. Under the 16-week administered-dose pruritus base case, the near-parity result required an approximately 1.3% lebrikizumab price reduction to match tralokinumab (Table 6).

Table 6.

Threshold Price Reductions Required to Achieve Cost-per-Responder Parity

Endpoint	Base-Case Lower Cost-per-Responder Option	Treatment Requiring Price Reduction For Parity	Required Price Reduction
EASI 50	Tralokinumab	Lebrikizumab	39.8%
EASI 75	Tralokinumab	Lebrikizumab	32.9%
EASI 90	Tralokinumab	Lebrikizumab	23.4%
IGA 0/1	Tralokinumab	Lebrikizumab	26.4%
Pruritus NRS ≥4	Tralokinumab	Lebrikizumab	1.3%

Note: The pruritus threshold refers only to the 16-week administered-dose base case; the preferred option changes under whole-pack costing.

Fixed-Budget Analysis

Under a hypothetical SAR 1,000,000 acquisition budget, the EASI 75 result translated to 15.7 responders with tralokinumab and 10.5 with lebrikizumab. Results for the other endpoints are presented concisely in Table 7. For pruritus, the 16-week administered-dose base case yielded 6.8 and 6.7 responders, respectively, reinforcing near parity rather than a clinically meaningful budget advantage.

Table 7.

Responders Achievable Under a Fixed SAR 1,000,000 Acquisition Budget

Endpoint	Time Point	Lebrikizumab Responders	Tralokinumab Responders	Difference, TRALO - LEB	Greater Responder Yield
EASI 50	Week 16	14.5	24.0	9.6	Tralokinumab
EASI 75	Week 16	10.5	15.7	5.2	Tralokinumab
EASI 90	Week 16	6.8	8.8	2.1	Tralokinumab
IGA 0/1	Week 16	10.3	14.0	3.7	Tralokinumab
Pruritus NRS ≥4	Week 4	6.7	6.8	0.1	Tralokinumab

Notes: Values equal the hypothetical fixed budget divided by endpoint-specific cost per responder. This is a concise translation of the CPR results, not a separate clinical-effectiveness comparison.

Discussion

This short-term analysis found that tralokinumab had a lower 16-week cost per responder for EASI 50, EASI 75, EASI 90, and IGA 0/1 under the modelled public Saudi list prices, despite higher response probabilities with lebrikizumab. The corrected pruritus result was close to parity under 16-week administered-dose costing and reversed across time-aligned fractional-pack and whole-pack scenarios. It should therefore be regarded as exploratory and assumption-sensitive. These findings are endpoint-specific acquisition-cost estimates, not a full cost-utility analysis or evidence of clinical superiority.^7–9

The clinical component of the model is consistent with the broader evidence base for IL-13 inhibition in moderate-to-severe atopic dermatitis. In the ADvocate 1 and ADvocate 2 phase 3 trials, lebrikizumab 250 mg every two weeks improved week-16 IGA 0/1 and EASI 75 responses compared with placebo in adolescents and adults with moderate-to-severe disease.⁴ Similarly, the ECZTRA 1 and ECZTRA 2 trials showed that tralokinumab 300 mg every two weeks was superior to placebo at week 16 and was generally well tolerated through longer follow-up.⁵ Network meta-analytic evidence has generally favoured lebrikizumab over tralokinumab for short-term response probabilities across EASI, IGA, and pruritus outcomes, although these estimates remain indirect and should not be interpreted as randomized head-to-head evidence.^6,10 Therefore, the present economic findings do not imply that tralokinumab is clinically more effective; rather, they show that the lower acquisition cost of tralokinumab in the model outweighed lebrikizumab’s higher modelled response probabilities for several skin-clearance endpoints.

The primary endpoint, EASI 75 at week 16, is particularly important because it is widely used in trials and treat-to-target frameworks as a clinically meaningful response threshold in moderate-to-severe atopic dermatitis. International treat-to-target recommendations support EASI 75 or an equivalent low disease-activity state as an important systemic-treatment target, while also emphasizing that treatment decisions should include patient-reported symptoms, quality of life, and shared decision-making rather than relying on a single measure alone.^11,12 The Saudi consensus statement also highlights the importance of validated disease-severity and patient-reported measures, including EASI, physician/global assessment measures, DLQI, and pruritus NRS, for monitoring treatment response in local practice.³ In this context, the lower cost per EASI 75 responder with tralokinumab is relevant for short-term payer assessment, but it should be interpreted alongside broader clinical and patient-centered outcomes.

The EASI 90 and IGA 0/1 findings provide additional context. Tralokinumab retained lower cost per responder despite lower response probabilities, showing that the public list-price difference outweighed the modelled efficacy difference in this short horizon. This ranking is not evidence that tralokinumab is clinically superior and should not be generalized beyond the specified doses, public prices, response inputs, and Saudi payer scenario.

Pruritus is clinically important because it affects sleep, daily functioning, and quality of life.^1,13, However, the economic pruritus finding is exploratory: the outcome was measured at week 4, the original numerator covered 16 weeks, the absolute probabilities were reconstructed, and the preferred treatment changed with the cost horizon and pack-purchasing convention. The result should therefore remain secondary to the time-aligned week-16 EASI and IGA findings and should not be described as a robust lebrikizumab advantage.

The Saudi context is central, but the model uses public SFDA list prices rather than observed institutional procurement, confidential net, reimbursement, or national tender prices. Because acquisition-price differences drive much of the ranking, actual payer conclusions could change under different contracts. The analysis may inform local formulary discussion, but it is not a tender analysis or a substitute for formal reimbursement evaluation.

The price scenario and threshold analyses strengthen the interpretation of the base-case findings. In the primary EASI 75 analysis, tralokinumab remained the lower cost-per-responder option when the acquisition price of lebrikizumab was reduced by 10%, 20%, and 30%, whereas lebrikizumab became lower cost per responder only under larger price reductions or favourable mixed-price scenarios. This was consistent with the threshold analysis, which suggested that lebrikizumab would require substantial price reductions to achieve cost-per-responder parity with tralokinumab for EASI and IGA endpoints. These findings are compatible with the broader health-economic principle that economic conclusions are often setting-dependent and sensitive to local costs, payer rules, and price changes.^8,14,15 A recent US-based cost-per-responder analysis of the same two biologics reached a different ranking under US pricing assumptions, which further illustrates that cost-per-responder conclusions should be understood as price- and jurisdiction-dependent rather than universal.⁷

Several methodological limitations should be acknowledged. No randomized head-to-head trial directly compared lebrikizumab with tralokinumab. The NMA considered variation in potential effect modifiers to be limited overall, but reported heterogeneity in age for adolescent-only trials, baseline EASI, the proportion with baseline IGA 4, and placebo response.^6,16,17 Prior systemic-treatment exposure and other characteristics were not uniformly available across every contributing trial. IGA and pruritus absolute responses were reconstructed and depend on relative-effect, baseline-risk, similarity, and transitivity assumptions; the pruritus reconstruction additionally used an available-case placebo denominator. These inputs are modelled estimates rather than definitive direct comparative effects.

The clinical inputs were derived from international trials, whereas the economic inputs were Saudi-specific. Transferability to routine Saudi practice is therefore assumed rather than demonstrated. Saudi patients may differ in baseline characteristics, adherence, persistence, prior treatment, and care pathways, and local real-world comparative effectiveness data were unavailable.

The model was limited to short-term acquisition costs through the initial 16-week response period in a chronic relapsing disease. It excluded long-term disease control, itch and sleep trajectories, quality of life, safety, dosing convenience, adherence, persistence, discontinuation, switching, rescue therapy, monitoring, and adverse-event costs. It did not estimate QALYs, incremental cost-effectiveness ratios, net monetary benefit, or long-term budget impact. Consequently, the results do not establish lifetime value, affordability, or overall economic dominance.

The study may support Saudi payer and formulary discussions when interpreted together with clinical efficacy, patient-reported outcomes, safety, treatment convenience, persistence, and local procurement terms. Future studies should use Saudi real-world effectiveness and persistence data, longer horizons, and verified net-price scenarios. They should also evaluate multidimensional response definitions, such as EASI 75 combined with a clinically meaningful pruritus improvement, rather than treating skin clearance and symptom control as isolated outcomes.

Conclusion

In this short-term Saudi payer analysis, tralokinumab had a lower administered-dose acquisition cost per responder for EASI 50, EASI 75, EASI 90, and IGA 0/1 under the modelled public SFDA list prices, despite higher modelled response probabilities with lebrikizumab. The pruritus comparison was close to parity under the 16-week administered-dose base case and changed direction in the time-aligned fractional-pack and whole-pack analyses; it is therefore exploratory and does not support a consistent advantage for either treatment.

These findings are short-term, endpoint-specific, and strongly dependent on the Saudi public list prices and pack assumptions used. They do not establish overall clinical superiority, long-term cost-effectiveness, or transferability to other settings. Saudi real-world effectiveness studies and multidimensional outcomes combining objective skin response with patient-reported symptom improvement are needed.

Disclosure

The authors report no conflicts of interest in this work.