Evaluating the cost-effectiveness of secukinumab in moderate-to-severe psoriasis: a Japanese perspective

Abstract

Aim: To evaluate the cost-effectiveness of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, compared to other clinically used biologics (adalimumab, infliximab, and ustekinumab) in Japan for the treatment of moderate-to-severe psoriasis from the healthcare system (total costs) and patient co-payment (using different frequencies of drug purchase) perspectives.

Methods: A decision-tree (first year)/Markov model (subsequent years), with an annual cycle, was developed. The model adopted a 5-year time horizon. Efficacy inputs were obtained from a mixed-treatment comparison analysis, and other model inputs were collected from published literature and local Japanese sources. Model outcomes included quality-adjusted life years (QALYs) and an incremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained. The annual discounting rate of 2% was applied to both costs and outcomes.

Results: Results for the healthcare system perspective showed that secukinumab had the highest number of quality-adjusted life years (QALYs) (4.07) vs other biologics, dominated ustekinumab and infliximab, and the ICER of secukinumab compared to adalimumab was ¥8,418,222/QALY gained. In the patient co-payment perspective with the monthly purchase of drugs, ustekinumab had the lowest co-payment cost, followed by infliximab, adalimumab, and secukinumab. In the patient co-payment perspective with a once every 3 months purchase of secukinumab and adalimumab, the co-payment costs of secukinumab, adalimumab, and ustekinumab became comparable, and infliximab had the highest co-payment cost.

Limitations: Only short-term efficacy data was modeled, as there was a lack of data on long-term outcomes. Treatment sequencing was restricted to first-line biologic treatment. Drop-out rates for comparators were assumed to be equivalent to secukinumab in the absence of available data.

Conclusions: Secukinumab is a cost-efficient treatment for moderate-to-severe psoriasis, providing greater health outcomes to patients at lower total costs compared to infliximab and ustekinumab, as well as comparable patient co-payment relative to other biologic treatments.

Keywords:

• Cost-effectiveness
• interleukin-17a
• Japan
• psoriasis
• secukinumab

JEL Classification:

• I19
• I00

Introduction

Psoriasis is a chronic, relapsing, immune mediated, inflammatory disease of the skin^1,2. In Europe and North America, psoriasis prevalence is ∼2%². A nationwide study conducted using the Japanese national claims database reported 0.34% prevalence of psoriasis in Japan³. Psoriasis varies widely in the severity of disease, and ∼25–44% of patients have moderate-to-severe disease⁴. Psoriasis is associated with significant clinical and emotional morbidities, particularly impacting patients’ work and social lives, and leading to reduced quality-of-life⁵.

Current treatments for psoriasis include topical agents, ultraviolet phototherapy, and systemic therapies^2,6. For moderate-to-severe psoriasis patients, traditional systemic therapies such as immunosuppressive agents (methotrexate and cyclosporine), oral retinoids (acitretin), and fumaric acid esters can be used. Biologic agents have further improved outcomes in moderate-to-severe psoriasis patients with the availability of TNF-α inhibitors (etanercept, infliximab, and adalimumab), interleukin (IL)-12 and 23 inhibitor (ustekinumab), and IL-17 inhibitors (secukinumab and, more recently, ixekizumab, brodalumab, and guselkumab). The use of biologic agents is recommended for the patients who have not adequately responded to standard systemic therapy⁷.

Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL-17A, has been shown to have significant efficacy in the treatment of moderate-to-severe psoriasis, demonstrating a rapid onset of action and sustained responses with a favorable safety profile^6,8–10. In Japan, secukinumab was approved for plaque psoriasis and psoriatic arthritis in 2014, and for generalized pustular psoriasis in 2015 for patients who have an inadequate response to traditional non-biologic treatments¹¹.

Few studies are available in the literature that evaluated the cost-effectiveness of different biologic treatments in psoriasis patients^12–14, including that of secukinumab^15–18. Due to the limited historical use of economic evaluations in pricing and reimbursement decisions in Japan, evidence regarding the cost-effectiveness of different biologic treatments in psoriasis in Japanese settings is scarce^19,20. Recently two published studies evaluated the cost-effectiveness of secukinumab in psoriasis in Japanese settings^21,22. However, none of them included different medical costs other than drug acquisition costs and reported quality adjusted life years (QALYs) as an outcome measure to assess the cost-effectiveness of secukinumab.

The present analysis assessed the cost-effectiveness of secukinumab compared to other clinically used biological treatments (adalimumab, infliximab, and ustekinumab) in moderate-to-severe psoriasis patients having inadequate response to current non-biologic systemic treatments in Japan. The analysis was conducted over a 5-year time horizon. Two different perspectives were considered: (i) a healthcare system perspective, under which total costs are included regardless of co-payment amounts; and (ii) patient co-payment perspectives. The patient co-payment perspective is critical in Japan, because patients are usually required to pay 30% of their drug and other medical costs (co-pay). The patient co-payment based on a unique high cost medical treatment system is often the reason to select one treatment over the other in Japan, which is even more important for a chronic disease including psoriasis.

Methods

Patient population, response definitions, and interventions

The target population for the analysis was Japanese patients, aged <70 years, and having a fiscal year salary between 3.7mJPY–7.7mJPY, who had failed to reach adequate control of their psoriasis symptoms when prescribed with current non-biologic systemic treatments in alignment with the Japanese label requirements.

At key treatment decision stages in the model, the following response definitions based on relative psoriasis area and severity index (PASI) were considered:

• PASI ≥75 (responder);

• PASI =50–74 (partial responder); and

• PASI <50 (non-responder).

Here different PASI levels represent the corresponding percentage reduction in the PASI score from the baseline. For example, PASI ≥75 indicates a 75% or more reduction in the PASI score from the baseline.

The following treatments and their respective dose strengths were considered for the cost effectiveness analysis:

• Adalimumab: 40 mg;

• Infliximab: 5 mg/kg (cost was estimated based on body weight of 60–80 kg);

• Ustekinumab: 45 mg. In Japan, up-titration of ustekinumab from 45 mg to 90 mg in partial responders is allowed, hence considered accordingly in this analysis²³; and

• Secukinumab: 300 mg.

In Japan, up-titration of adalimumab from 40 mg to 80 mg and infliximab from 5 mg/kg to 10 mg/kg are allowed in the case of partial response to treatments²⁴. However, in this analysis the dose strength of adalimumab 40 mg and infliximab 5 mg/kg were selected because there were not enough data published to enable the analysis of adalimumab 80 mg and infliximab 10 mg/kg. Ixekizumab, brodalumab, and guselkumab have been recently approved in Japan. However, they were yet not available in Japan at the time of analysis and were not included in this analysis.

Model structure

A decision-tree (first year)/Markov model (subsequent years), with an annual cycle, was developed in Microsoft Excel 2010 to compare secukinumab with other biologic treatments currently in clinical practice in Japan (adalimumab, infliximab, and ustekinumab) (Supplementary Figures S1 and S2). The model structure followed the same general approach in assessing the treatment response as seen in previous health technology assessment-focused economic evaluations of biologic drugs for treating psoriasis²⁵; namely, using the likelihood of achieving a pre-defined PASI response to separate the cohort into responders and non-responders. The model allows for treatment sequencing with different lines of treatment and calculation of QALYs from the PASI assessments.

The model incorporated efficacies from 4 weeks, 8 weeks, and 12 weeks, as patients’ skin clearance could improve during the first 3 months, with a response assessment at 16 weeks (Supplementary Figure S1). At week 16, the decision to continue treatment was assessed based on responses to treatments defined by PASI. Responding patients (PASI ≥75) continued with the same biologic treatment. Patients who did not respond (PASI <50) to first-line biologic treatment at the 16-week assessment were switched to standard of care (SoC) (included methotrexate and cyclosporin). Switching to the second-line biologic treatments was not considered in the present analysis. Partial responders (PASI 50–74) at the 16-week assessment who were treated with secukinumab, adalimumab, or infliximab were allowed to extend the current treatment, whereas those using ustekinumab 45 mg were up-titrated to ustekinumab 90 mg. Partial responders were again evaluated at week 28; patients who achieved PASI75 or more continued the same treatment, and those who did not were switched to SoC.

Although the decision to stop or continue treatment was firmly based on PASI ≥75, the ability to achieve higher thresholds of PASI response implies a better quality of response, and ultimately this could be reflected as better quality-of-life. Therefore, the model was based on treatment-specific weighted average utility scores for achieving PASI ≥75, based on the proportion of these patients who also achieved the higher PASI 90 threshold.

The model also considered a drop-out rate for patients that continue the treatment in the first year. After the completion of 52 weeks, patients can enter the Markov in the “Active Tx” (Tx: treatment) or “Standard of Care” (SoC) health state (Supplementary Figure S2). Those in “Active Tx” were receiving one of the biologic therapies, and these patients can remain on the same treatment, drop out to SoC, or die. Once on SoC, patients remained on it until death or the end of the model time horizon.

Model assumptions

Patients not responding to initial treatment (PASI <50) were assumed to remain in that disease state with SoC until natural death. For patients with a sustained response in year 1, the PASI response profile at week 16 was assumed to continue to week 52. Clinical trials for secukinumab in psoriasis have demonstrated that patients on secukinumab have a sustained PASI response from week 16 to week 52²⁶, and very long-term data up to 5 years have also demonstrated a sustained PASI response^27,28. For patients that responded at week 16, but did not sustain their response for year 1, the PASI profile at week 16 was assumed to continue until the drop-out at midpoint between week 16 and 52. It was assumed that psoriasis has no effect on natural mortality. Treatment dosing was assumed to be in line with the label dose.

Model inputs

Various model inputs are described below, and the respective data and relevant sources are presented in tables.

Efficacy inputs

The PASI distribution data at weeks 4, 8, 12, and 16 for each model comparator were obtained from a mixed-treatment comparison analysis (fixed-effects ordinal analysis)²⁹, and are presented in Table 1. The 16-week PASI distribution was used to inform the 16-week treatment decision point in the model. The efficacy from extended treatment for partial responders was used for those patients who exhibit a partial response at week 16 and extend the same treatment (in the case of ustekinumab up-titrated from 45 mg to 90 mg).

Table 1. Efficacy inputs for the model.

PASI response rate	Secukinumab 300 mg	Adalimumab	Infliximab	Ustekinumab 45 mg
4-week response
PASI <50	25.7%	51.3%	36.8%	49.5%
PASI 50–74	35.2%	31.9%	35.5%	32.5%
PASI 75–89	26.1%	13.3%	20.2%	14.1%
PASI 90–100	12.9%	3.5%	7.4%	3.8%
8-week response
PASI <50	7.6%	24.9%	7.6%	17.1%
PASI 50–74	18.0%	28.9%	18.0%	25.9%
PASI 75–89	35.2%	30.9%	35.2%	34.4%
PASI 90–100	39.2%	15.3%	39.2%	22.6%
12-week response
PASI <50	7.3%	20.4%	5.9%	11.7%
PASI 50–74	13.8%	22.6%	12.2%	17.8%
PASI 75–89	31.7%	32.7%	30.4%	33.6%
PASI 90–100	47.3%	24.3%	51.4%	37.0%
16-week response
PASI <50	4.5%	17.8%	7.4%	8.2%
PASI 50–74	9.2%	19.6%	12.5%	13.2%
PASI 75–89	19.4%	25.8%	22.7%	23.3%
PASI 90–100	66.9%	36.8%	57.5%	55.3%
Efficacy from extended treatment in partial responders
PASI ≥75	77.0%	17.0%	77.0%	84.0%^a

PASI response rate at a particular level (PASI <50, PASI =50–74, etc.) represents the percentage of patients achieving a corresponding reduction in their PASI score from the baseline. For example, PASI <50 indicates the percentage (or number) of patients who have achieved less than 50% reduction in their PASI score from baseline given a particular therapy.

Efficacy data obtained from the mixed-treatment comparison (fixed-effects ordinal analysis)⁵¹. Extended treatment data for secukinumab 300 mg obtained from Langley et al.⁹; adalimumab data from Gordon et al.⁵²; infliximab was assumed similar to secukinumab 300 mg; ustekinumab data from Papp et al.⁵³.

^aEfficacy data for ustekinumab 90 mg as partial responders were up-titrated to ustekinumab 90 mg from ustekinumab 45 mg. The efficacy data for the up-titrated ustekinumab 90 mg for extended treatment was assumed equivalent to efficacy data for ustekinumab 90 mg at week 16 in the mixed-treatment comparison.

Unit costs inputs

The model considered direct costs which included drug treatment cost, cost per visit or assessment, cost per inpatient episode, and cost for SoC (see Table 2).

Table 2. Cost inputs.

Treatment	Costs
Cost for biologic systemic treatments
Secukinumab 300 mg	¥146,264 per dose
Adalimumab 40 mg: pre-filled syringe	¥65,144 per dose
Infliximab (per average weight person)	¥332,972 per dose
Ustekinumab 45 mg: pre-filled syringe	¥438,739 per dose
Cost per visit or assessment
Pre-treatment assessment	¥34,320
Monitoring	¥8,110
Regular physician visit	¥730
Instruction for self-injection^b	¥6,500
Specialist care	¥2,500
Physician visit for IV^a	¥4,500
Cost per inpatient episode
Psoriasis	¥382,560
Sepsis	¥438,350
Lymphoma	¥248,190
Melanoma	¥264,820
NMSC	¥183,200
Tuberculosis^c	¥1,100,000
Pneumonia	¥239,260
Skin and soft tissue infection	¥250,960
Bone and joint infection	¥457,500
Urinary tract infection	¥264,960
Standard of care unit cost
Physician visits	¥730
Monitoring lab work: methotrexate	¥1,600
Monitoring lab work: cyclosporin treatment	¥1,600
UVB phototherapy	¥3,400

Co-payments for biologic systemic treatments can be calculated based on the details given under the subsection “Patient co-payment”. For costs regarding assessment or visit, inpatient episode, and standard of care, co-payment by patients can be calculated as 30% of total costs.

^aApplicable for infliximab only.

^bApplicable for secukinumab and adalimumab.

^cPaid completely by publicly funded healthcare, hence no patient co-pay cost applicable.

Cost inputs data were obtained from the Ministry of Health, Labour and Welfare⁵⁴.

Resource use inputs

The drug treatment resource use pattern for each of the treatment pathways represented in the model is available in Supplementary Table S1.

Drop-out rate inputs

Drop-out rates for year 1 and years 2+ are available in Supplementary Table S2. The drop-out rates were applied at the end of each year. The drop-out rate of secukinumab from a long-term phase 3 study³⁰ was substituted for all treatments, as there was no comparable long-term study data available.

Utility inputs

Utility weights classified by PASI scores were calculated via a mixed model of pooled data from phase 3 trials using the UK tariff of EQ-5D, as no Japanese utility data for different PASI score groups were available (Supplementary Table S2).

Disutilities associated with the SoC treatments methotrexate and cyclosporin and the percentage of patients utilizing each therapy are available in Supplementary Table S2.

Mortality inputs

The general annual mortality rates considered in the model, based on gender and different age groups, are available in Supplementary Table S2.

Adverse events inputs

Only serious adverse events (SAEs) due to malignancies and severe infections requiring hospitalization were included in the analysis (Table 3). Severe infections included sepsis, tuberculosis, skin and soft tissue infections, bone and joint infections, pneumonia, and urinary tract infections.

Table 3. Probability of serious adverse events.

Adverse event	Secukinumab 300 mg	Adalimumab	Infliximab	Ustekinumab^a
Malignancies other than NMSC	0.004	0.006	0.077	0.006
NMSC	0.004	0.007	0.004	0.006
Severe infections	0.011	0.052	0.055	0.010

NMSC, non-melanoma skin cancer.

^aRepresents pooled ustekinumab 45 mg and 90 mg data.

Secukinumab data obtained from analysis of pooled data from clinical trials⁹; adalimumab, infliximab, and etanercept data obtained from product information and Dixon et al.⁵⁵; ustekinumab data obtained from product information.

Patient co-payment in Japan

As per the National Health Insurance (NHI) system of Japan in 2017, co-payment by NHI members, aged <70 years and with a fiscal year salary of 3.7 mJPY–7.7 mJPY, was calculated based on the monthly drug cost as mentioned below³¹:

1. For the monthly drug cost ≤ ¥267,000, NHI covers 70% of the drug price, and the remaining 30% comes under the co-payment (maximum co-payment of ¥80,100).

2. For the monthly drug cost > ¥267,000, co-payment is decided based on the following formula, where, in addition to 30% (¥80,100), patients have to pay an extra 1% for the cost that goes beyond ¥267,000: $$\text{Co}-\text{pay}=\yen 80,100+\left(\text{drug} \text{cost}-\yen 267,000\right)\times 1\%$$

From the 4th benefits onwards, the flat co-payment of ¥44,400 is applicable.

Perspectives considered and analysis

The base case analysis estimated the cost-effectiveness of secukinumab compared with other biologics (adalimumab, infliximab, and ustekinumab) from the Japanese healthcare system perspective (which considered total costs, regardless of co-payment amounts). Furthermore, we conducted a secondary analysis using a patient co-payment perspective.

Within the Japanese patient co-payment perspective, two distinct analyses were performed and compared: one analysis using a monthly purchase of biologic treatments, and the other analysis using a 3-month purchase of biologic treatments. The 3-month purchases are allowed in Japan for subcutaneous treatments of adalimumab and secukinumab that can be self-administered by patients. It is anticipated that the 3-month purchase of secukinumab or adalimumab could result in lower patient co-payment burden compared to the monthly purchase of the same drugs.

The base-case analysis and secondary analyses were conducted over a 5-year time horizon considering the chronic characteristics of the disease. The annual discounting rate of 2% was applied to both costs and outcomes, in alignment with the guideline of the economic evaluation of drugs in Japan³².

Costs and QALYs are reported for each biologic treatment and for each perspective. For the base case analysis (healthcare system perspective with total costs), incremental cost effectiveness ratios (ICERs) were calculated, reflecting the incremental costs associated with an additional QALY gained. A treatment is considered “dominant” if associated with greater QALYs at lower costs compared to the other treatments. For the perspective of patient co-payment, total costs were compared between the monthly purchase and the 3-month purchase analyses.

Sensitivity analyses were conducted for the healthcare system perspective in the form of one-way sensitivity analysis and probabilistic sensitivity analysis (PSA) to assess the robustness of the study findings. The model input parameters such as efficacy inputs, drop-out rates, discount rates, utility weight inputs, and costs were varied as part of a one-way sensitivity analysis to identify parameters having the greatest effect on results (see Supplementary Table S3 for a detailed list of parameters varied and their ranges). The results of the PSA were summarized using cost-effectiveness acceptability curves calculated from the net monetary benefit (NMB) statistic across a wide range of willingness-to-pay (WTP) thresholds for each biologic treatment for the healthcare system perspective.

Results

Base-case analysis with healthcare system perspective (considering total costs)

From the healthcare system base case analysis, secukinumab generated the highest number of QALYs (4.07) for a total cost of ¥7,951,434 over the 5-year time horizon (Table 4). Moreover, secukinumab had the highest percentage of PASI ≥90 responders at week 16 (67%) and week 52 (65%) compared to other biologic treatments. Also, secukinumab had the longest maintenance of PASI ≥90 (2.66 years out of 5-year time frame) (see Supplementary Table S4 for more details).

Table 4. Costs, QALYs, and ICER values from the healthcare system perspective (considering total costs).

Treatment	Total costs	QALYs	ICER (secukinumab 300 mg vs comparator)
Secukinumab 300 mg	¥7,951,434	4.07
Adalimumab	¥6,289,767	3.87	¥8,418,222/QALY
Infliximab	¥8,961,400	4.04	Secukinumab dominates Infliximab
Ustekinumab 45 mg^a	¥8,466,420	4.03	Secukinumab dominates Ustekinumab

^aPartial responders at week 16 were up-titrated to ustekinumab 90 mg.

Infliximab and ustekinumab generated 4.04 and 4.03 QALYs at a cost of ¥8,961,400 and ¥8,466,420, respectively (Table 4). Secukinumab dominated both infliximab and ustekinumab. Adalimumab generated lower QALYs (3.87) at a lower cost of ¥6,289,767 compared to secukinumab (Table 4). This resulted in an ICER of ¥8,418,222/QALY gained for secukinumab compared to adalimumab.

Secondary analyses with patients’ co-payment perspective (monthly and 3-month drug purchase scenarios)

In the patient co-payment perspective, the QALYs generated by each of the biologic treatments were equivalent to those generated in the healthcare system perspective.

In the monthly purchase of drugs scenario, ustekinumab had the lowest co-payment cost (¥1,135,257), followed by infliximab (¥1,498,207), adalimumab (¥1,881,173), and secukinumab (¥2,266,541) during 5-year time horizon (Table 5). Lower co-payment costs of ustekinumab and infliximab could be attributed to the co-payment system in Japan, based on whether drug purchasing cost exceeds the specified amount for the month, i.e. ¥267,000 for patients under 70 years of age. The purchasing costs of ustekinumab and infliximab, which can be administered at more than a 1-month interval, exceeded the above threshold amount, resulting in a significant reduction in the patient co-payment. In contrast, for secukinumab and adalimumab, which are administered either every 2 or 4 weeks, the purchasing cost did not exceed the threshold amount with the monthly purchase of drugs.

Table 5. Costs from the perspective of patient co-payment

Treatment	Co-payment costs
Monthly drug purchase
Secukinumab 300 mg	¥2,266,541
Adalimumab	¥1,881,873
Infliximab	¥1,498,207
Ustekinumab 45 mg^a	¥1,135,257
3-month drug purchase
Secukinumab 300 mg	¥1,158,705
Adalimumab	¥1,156,008
Infliximab	¥1,498,207
Ustekinumab 45 mg^a	¥1,135,257

^aPartial responders at week 16 were up-titrated to UST 90 (ustekinumab 90 mg).

In the 3-month purchase for subcutaneous and self-injected secukinumab and adalimumab scenario, co-payment costs were significantly reduced compared to monthly purchases for both secukinumab (¥2,266,541 with monthly purchase vs ¥1,158,705 with 3-month purchase; 49% reduction) and adalimumab (¥1,881,173 with monthly purchase vs ¥1,156,008 with 3-month purchase; 39% reduction) during 5-year time horizon (Table 5). As a result, co-payment of secukinumab, adalimumab, and ustekinumab became comparable, and infliximab had the highest co-payment cost.

Sensitivity analysis

The NMB results were mainly sensitive to Year 2+ drop-out rates, weeks 4, 16, and 24 efficacy data, discount rates, probability of severe infections, and costs associated with psoriasis inpatient episode for a healthcare system perspective (Supplementary Figure S3). The probability of secukinumab being cost-effective compared to the other three treatments was higher at thresholds of ¥8,500,000 and above per QALY gained (Supplementary Figure S4).

Discussion

The present analysis assessed the cost-effectiveness of secukinumab compared with other currently used biologic treatments of moderate-to-severe psoriasis in clinical practice in Japan (i.e. ustekinumab, adalimumab, and infliximab) with two different perspectives: healthcare system perspective, and patient co-payment perspective using monthly and 3-month drug purchase. To our knowledge, this is the first study which assessed the cost-effectiveness of secukinumab compared to other biologics in Japanese settings using a cost-utility (cost per QALY) analysis and incorporating different medical costs in addition to drug acquisition costs. The indirect cost in terms of productivity loss due to the disease burden was not included in the present analysis, as a societal perspective was not considered.

Historically, there has been very limited use of economic evaluations in pricing and reimbursement decisions of drugs in Japan^19,20. Although pharmaceutical companies could submit cost-effectiveness data when applying through the National Health Insurance (NHI) drug price listing system since 1992, there has been no formal structure to evaluate the cost-effectiveness of the drug within the pricing system. Nevertheless, cost-effectiveness evaluation was implemented on a trial basis from fiscal year 2016 and is believed to play a significant role in future drug pricing and reimbursement decisions in Japan³².

From the perspective of the healthcare system (total costs), secukinumab dominated infliximab and ustekinumab, providing higher QALYs at a lower cost compared to these two treatments. The ICER for secukinumab compared to adalimumab was ¥8,418,222/QALY gained. Currently no particular ICER threshold or WTP threshold is available in Japan to interpret cost-effectiveness results. Although ¥5,000,000–¥6,000,000 per QALY gained is frequently referred to as a threshold in Japan³³, the threshold value could go up to ¥8,000,000 per QALY gained for severe disease conditions with worse health states³⁴. Moderate-to-severe psoriasis dramatically impacts the patients with reductions in physical functioning and mental health comparable to that seen in patients with cancer, arthritis, hypertension, heart disease, and diabetes^35,36. Moreover, psoriasis is associated with multiple comorbidities including psoriatic arthritis (PsA), obesity, hypertension, malignancies, metabolic syndrome, and cardiovascular diseases^37,38. Patients with psoriasis also have an increased risk of depression/anxiety and suicidality^39,40. The presence of these comorbidities further increases the burden of the disease, and considerably impacts quality-of-life of patients^41–43. Considering all these facts, the threshold of up to ¥8,000,000 per QALY gained could be considered for psoriasis treatments. The ICER for secukinumab compared to adalimumab was above the ¥5,000,000–¥6,000,000 per QALY gained, and slightly higher than the WTP threshold of ¥8,000,000 per QALY gained.

Two scenarios based on a different drug purchase schedule (monthly and 3-month purchase of drugs) were considered and compared for the patient co-payment perspective analysis. The patient co-payment perspective is very important in Japanese settings, as patients have to bear a significant part of total costs (usually 30% of their total costs). The patient co-payment could be a critical parameter to select one treatment over others, particularly considering high costs of biologic treatments. For example, despite secukinumab showing superior clinical efficacy compared to ustekinumab in the CLEAR study⁴⁴, ustekinumab could be a more preferred option in clinical practice in Japan due to the lower patient co-payment vs secukinumab. Our analysis showed that, in the case of a 3-month drug purchase, the co-payment cost for secukinumab could be significantly reduced vs a monthly drug purchase, becoming comparable to the co-payment cost of ustekinumab. In other terms, in a 3-month drug purchase scenario, secukinumab provides a higher clinical response to patients based on PASI at similar patient co-pay.

In the literature, there are few published studies available that assessed the cost-effectiveness of secukinumab in psoriasis in different countries. In these published studies, secukinumab was found to be a cost-effective option compared to ustekinumab and other assessed biologic treatments, as also demonstrated in the current analysis. D’Ausilio et al.¹⁶ assessed the cost-effectiveness of secukinumab 300 mg compared with other systemic biologic drugs and standard of care for plaque psoriasis in the Italian National Health System (NHS) setting. At 10 years, secukinumab was a dominant option compared with ustekinumab, and cost-effective vs adalimumab, infliximab, etanercept, and SoC. Lee et al.¹⁸ evaluated the cost-effectiveness of secukinumab vs biologic therapies for plaque psoriasis in adults from the Canadian healthcare perspective. In this study, etanercept was strongly dominated, while adalimumab, ustekinumab 45 mg, secukinumab 150 mg, and ustekinumab 90 mg were weakly dominated by secukinumab 300 mg. The ICER for infliximab vs secukinumab 300 mg was very high ($1,039,403/QALY gained)¹⁸. Costa-Scharplatz et al.¹⁵ conducted a cost-minimization analysis between secukinumab and ustekinumab in patients with moderate-to-severe plaque psoriasis from a Swedish societal perspective. Considering a 2-year time horizon, secukinumab was estimated to be a cost-saving option, with the average total cost per patient reaching PASI75 of 363,020 SEK vs 410,647 SEK for ustekinumab¹⁵. Augustin et al.⁴⁵ assessed the cost per responder of secukinumab as first biologic treatment of moderate-to-severe psoriasis, with adalimumab, infliximab, etanercept, and ustekinumab in Germany. Secukinumab had the lowest cost per PASI 90 responder over 16 weeks, as well as 52 weeks compared to other biologics. Secukinumab was also found to be cost-effective compared to other biologic treatments in patient with PsA in different country settings^46,47.

In Japanese settings, two studies reported the cost-effectiveness of secukinumab in psoriasis. Takahashi et al.²² reported that, although the cost for the reduction of 1 PASI score was highest for secukinumab among all the treatments, the number of days required for reducing 1 PASI score was lowest for secukinumab. Imafuku et al.²¹ reported that secukinumab and adalimumab had the lower cost-per-responder compared to ustekinumab and infliximab and, hence, could be considered cost-efficacious treatment options. These two published Japanese studies considered only the drug acquisition costs, whereas in our analysis all different medical costs were explicitly considered for the total cost calculation. Also our analysis used QALYs as an outcome measure to assess the cost-effectiveness of secukinumab (cost-utility analysis) in psoriasis patients. The use of QALY as an outcome measure in our analysis is in alignment with Japanese economic evaluation guidelines³², and QALY is also the most preferred outcome measure as per the guidelines of countries such as England/Wales⁴⁸, and Sweden⁴⁹, among others.

Our analysis has few limitations. Only short-term efficacy data was modeled, as there was a lack of data on long-term outcomes and a meta-analysis was restricted to short time points due to crossover of the treatment arms beyond week 12 or week 16. The other limitation was treatment sequencing, which was restricted to first-line biologic treatment only in the present analysis. In clinical practice, non-responders to the first-line biologic treatment could switch to another biologic treatment. However, efficacy data associated with treatment sequencing are not readily available in the current literature, and, hence, a treatment sequence approach is not without limitations, and results may be sensitive to treatment sequencing assumptions⁵⁰. In this analysis, we calculated the QALYs with applying the drop-out rate of secukinumab for all treatments, as there was no report to input other treatments’ drop-out rates for a 5-year time frame. Ixekizumab, brodalumab, and guselkumab were not included in the analysis, as they are recently approved, and were not available in Japan at the time of analysis. In future, further analysis could be done with these new agents, when meta-analysis including all psoriasis treatments becomes available for implementation in the model. Also, it could be considered to rerun this analysis with drop-out rates from registry studies, comparing all available treatments, and with inclusion of a switch to second-line biologic treatment as new relevant data become available.

Conclusions

Our analysis has demonstrated that secukinumab is an efficient treatment option in moderate-to-severe psoriasis patients in Japan from a healthcare system perspective, as well as from a patient co-payment perspective, assuming less burdensome drug purchase options such as a 3-month drug purchase.

Transparency

Declaration of funding

The study was funded by Novartis Pharma K.K., Tokyo, Japan.

Declaration of financial/other interests

IG, HF, and YT are employees of Novartis. Atsuyuki I received honorariums from Novartis. Atsuyuki I and Ataru I received consultancy fee from Novartis. JME peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors would like to thank Niraj Modi, Novartis Healthcare Pvt. Ltd., Hyderabad, India, for providing writing/editorial assistance.

Additional information

Notes on contributors

Atsuyuki Igarashi

Atsuyuki I, Ataru I, YT created concept for the study; CNG, IG and YT designed the study; IG helped with acquisition of data; CNG analyzed data; Atsuyuki I. and Ataru I. interpreted the data; IG and YT drafted the manuscript.

Ataru Igarashi

Atsuyuki I, Ataru I, YT created concept for the study; CNG, IG and YT designed the study; IG helped with acquisition of data; CNG analyzed data; Atsuyuki I. and Ataru I. interpreted the data; IG and YT drafted the manuscript.

Christopher N. Graham

Atsuyuki I, Ataru I, YT created concept for the study; CNG, IG and YT designed the study; IG helped with acquisition of data; CNG analyzed data; Atsuyuki I. and Ataru I. interpreted the data; IG and YT drafted the manuscript.

Isabelle Gilloteau

Atsuyuki I, Ataru I, YT created concept for the study; CNG, IG and YT designed the study; IG helped with acquisition of data; CNG analyzed data; Atsuyuki I. and Ataru I. interpreted the data; IG and YT drafted the manuscript.

Yumiko Tani

Atsuyuki I, Ataru I, YT created concept for the study; CNG, IG and YT designed the study; IG helped with acquisition of data; CNG analyzed data; Atsuyuki I. and Ataru I. interpreted the data; IG and YT drafted the manuscript.