Budget impact model of secukinumab for the treatment of moderate-to-severe psoriasis, psoriatic arthritis, and ankylosing spondylitis in Italy: a cross-indication initiative

Introduction

Psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis (AS) are chronic, immune-mediated, inflammatory diseases associated with various comorbidities and worsening health-related quality of life (QoL).^1–6 They are all generally chronic lifelong diseases having alternating flare-ups and periods of remission, resulting in reduced patients’ physical and psychological well-being, reduced work productivity, and higher health care costs in the longer term.^7,8

Among these three diseases, psoriasis is the most common condition, which is estimated to affect between 0.7% and 2.9% of the population in Europe.⁹ It primarily manifests on the skin, resulting in plaques on the elbows, knees, or scalp, which may extend to other areas of the body.^5,10,11 PsA and AS are part of spondyloarthritis (SpA), which are enthesitis driven, lifelong, painful, and debilitating immune-mediated inflammatory diseases affecting the joints and/or spine that can lead to irreversible structural bone damage caused by years of inflammation.^6,12–15 The prevalence of PsA in the general population has been reported to range from 0.01% in Asia¹⁶ to 0.67% in Norway,¹⁷ while the prevalence of AS ranges from 0.1% to 1.4% globally.¹⁸

Psoriasis is associated with significant clinical and emotional morbidity, impacting patients’ work and social lives and reduces the QoL.¹⁹ Moreover, psoriasis is linked to other health conditions, such as diabetes, heart disease, and depression,²⁰ further impacting the QoL of patients. Patients with PsA and AS experience pain, loss of physical function, and difficulty in performing activities of daily living, including the ability to work.⁶ Different studies have reported significant economic burden of psoriasis, PsA, and AS in different countries,^21–26 including Italy.^27,28 The economic and humanistic burden of SpA is closely connected to the functional status in PsA and AS patients, and it is increased by the fact that SpA usually occurs in active young adults.^7,29–33 According to a survey performed in 17 out of the 20 regions in Italy, sponsored by the National Association of Rheumatic Patients, half of the patients with SpA reported disability and one third felt that their condition limited their career progression and personal development.³⁴

Early efficacious treatments targeting inflammation control, prevention of comorbidities and complications, and function and social participation normalization are important in psoriasis, PsA, and AS management.^35,36 The initial treatment for mild psoriasis includes topical steroids and phototherapy, whereas the initial treatment for moderate-to-severe psoriasis includes phototherapy and conventional systemic therapy, alone or in combination.³⁷ In the past decade, the development of several drugs, biologics, and non-biologics has substantially improved the outcomes of patients with moderate-to-severe psoriasis.³⁸ These include tumor necrosis factor (TNF)-α inhibitors (adalimumab, etanercept, certolizumab, golimumab, and infliximab), interleukin (IL)-12 and 23 inhibitor (ustekinumab), and IL-17A inhibitors (secukinumab and ixekizumab). In addition, among non-biologics, apremilast improves the outcomes (see Table 1 for a list of currently approved and reimbursed treatments in Italy for each indication).^37,39 Conventional pharmacologic treatment options for PsA and AS include nonsteroidal anti-inflammatory drugs as the first-line treatment.^40–43 For PsA, conventional synthetic disease-modifying antirheumatic drugs are also used.^40,41 Biologics are currently used for PsA and AS patients inadequately controlled by conventional treatments mentioned above/previously.

Table 1 Approved indications and currently approved and reimbursed treatments for secukinumab in Italy, along with their posology Notes: Posology was obtained from products SmPC; please refer to last approved SmPC for loading doses where applied. Last reimbursement status for each drug can be found on the Italian Official Journal website.72 aNot reimbursed in Pso, reimbursed in PsA for patients which are intolerant or inadequate to biologic therapies. Abbreviations: AS, ankylosing spondylitis; DMARD, disease-modifying antirheumatic drug; IR, inadequate responders; PsA, psoriatic arthritis; Pso, psoriasis; SmPC, summary of product characteristics; TNF, tumor necrosis factor.

Secukinumab, a recombinant fully human monoclonal IgG1 antibody that selectively neutralizes the proinflammatory cytokine IL-17A constitutes an alternative and efficacious mechanism of action for the treatment of these immune-mediated inflammatory diseases.⁴⁴ In 2015, secukinumab received market authorization in Europe for the treatment of adult patients with moderate-to-severe plaque psoriasis (300 mg), active PsA (150/300 mg), and active AS (150 mg), offering a new treatment option for these diseases and being the first non-TNF biologic for AS.⁴⁴ Indeed, secukinumab is currently the only non-TNF biologic that is approved in all three indications. Ixekizumab, an IgG4 monoclonal antibody L-17A inhibitor, has been recently authorized for use in adults with active PsA in addition to moderate-to-severe plaque psoriasis patients.⁴⁵

Secukinumab has been shown to have significant efficacy in the treatment of moderate-to-severe psoriasis,⁴⁶ PsA,⁴⁷ and AS,⁴⁸ demonstrating a rapid onset of action and sustained responses with a consistent safety profile, according to the results of several phase three clinical trials both vs placebo and comparators.^46–54 In addition to its clinical value, secukinumab has been reported as a dominant or cost-effective treatment option compared to other biologics in multiple economic evaluations for the three indications.^55–59 However secukinumab, being a biologic drug, is a costly treatment option and, in a context of limited resources, it is necessary to evaluate sustainability of its use.

This analysis aimed to estimate the budget impact of the introduction of secukinumab to the Italian market for the three indications (psoriasis, PsA and AS) over a 3-year time horizon from the perspective of Italian National Health Service (INHS).

Materials and methods

A cross-indication budget impact analysis (BIA) was developed by means of a dynamic simulation model in Microsoft Excel^®. The model evaluated the budgetary impact of introducing secukinumab into the current approved and reimbursed treatments for moderate-to-severe psoriasis, active PsA, and active AS in Italy. The analysis was carried out from the perspective of the INHS over a 3-year timeframe. The model was populated with data available from literature and market research; therefore, no institutional review board or ethics committee approval was required. Model inputs included epidemiology data, current and future market share projections for treatments, data on resource use and on the following cost items (expressed in 2017 euros): drug therapy costs, administration costs, disease-related costs (resource use and associated costs), and adverse event (AE)-related costs.

Modeling framework

The budget impact model compared two different scenarios: 1) without secukinumab introduction (where secukinumab is not available as an alternative biologic treatment for psoriasis, PsA, and AS patients and 2) with the introduction of secukinumab (where secukinumab is available as an alternative biologic treatment for psoriasis, PsA, and AS patients, and secukinumab market share changes over time. The model compares the costs of the current and expected psoriasis, PsA, and AS treatment options over 3 years. The treatment regimens that were modeled included market shares of approved treatments including biosimilars (etanercept and infliximab biosimilars) and expected market shares after introduction of secukinumab to the market. For each licensed treatment, the indication-specific posology was taken from the summary of product characteristics from the European Medicines Agency (see Table 1).

For each disease, BIA was conducted for the first 3 years after secukinumab introduction. The total annual cost was obtained for each scenario, and the budget impact was estimated as the difference between the two scenarios, without and with secukinumab introduction into the Italian market, for the eligible population. Results are presented for all three indications combined and for each of the indications taken individually. The modeling framework and methods are consistent with the recommendations made by the International Society for Pharmacoeconomics and Outcomes Research’s Task Force on Good Research Practices and are presented in Figure 1.^60,61

Figure 1 Model structure. Notes: Initial population without secukinumab was based on national epidemiological data derived from ISTAT. Adult patients (aged ≥18 years) diagnosed with psoriasis, PsA, and AS and currently treated with a biologic treatment were included in the BIA. The number of current psoriasis, PsA, and AS patients treated with different biologic drugs was obtained from the market share data (IQVIA 2016, Novartis data-processing). In the BIA, a formulary without secukinumab was compared to one with secukinumab (new formulary). A 3-year time horizon was considered for the analysis: market share related to 2016 was used and projection for the following 3 years was adopted. *Market share could be different for indication. Abbreviations: AS, ankylosing spondylitis; BIA, budget impact analysis; ISTAT, Italian National Statistical Institute; PMPY, per Member per Year; PsA, psoriatic arthritis; PsO, psoriasis.

Model input data

Patient population and market shares

The size of initial population was based on national epidemiological data derived from Italian National Statistical Institute. Adult patients (aged ≥18 years) diagnosed with psoriasis, PsA, and AS and currently treated with a biologic treatment were included in the BIA. The number of current psoriasis, PsA, and AS patients treated with different biologic drugs was obtained from the market share data.⁶² The model also accounted for the incidence and new treatment starters for each indication. In order to estimate the number of patients treated over 3 years, yearly future growth rates of 17%, 10%, and 12% for psoriasis, PsA, and AS, respectively, were used on the basis of market research findings. Table 2 shows the input data on eligible population and market growth. Based on dynamic market research, 30% of patients were assumed as biologic-naïve patients.⁶² Detailed psoriasis, PsA, and AS population projections for both scenarios (with and without secukinumab) over the 3 years and the respective changing market share for all treatments are shown in Tables S1-S3.

Table 2 Model input data on population Abbreviations: AS, ankylosing spondylitis; PsA, psoriatic arthritis.

Costs

Only direct costs of the treatments were considered, including drugs costs, administration costs associated with intravenous (IV) infusions, disease-related costs (resource use and associated costs: non-biologic drugs, physician visits, emergency room visits, phototherapy), and AE costs.

Drugs costs

Drug acquisition costs were derived from official national price lists, and ex-factory prices were used (with -5%, -5% mandatory rebates). Induction and maintenance periods for each drug were taken into account in calculating drug costs. For the doses and administration schedules, summary of product characteristics was used. Table 3 shows the doses and cost per dose for the biologic treatments as well as apremilast, and concomitant non-biologic treatments. For infliximab, the dose of drug to be administered is established on the basis of the patient’s weight, and in our analysis it was obtained by considering the mean patients’ weight in the three indications (88.54 kg for psoriasis, 87.11 kg for PsA, and 81.57 kg for AS)

Table 3 Doses and cost per dose for the biologic treatments as well as apremilast, and concomitant non-biologic treatments Note: Gazzetta Ufficiale Italiana, Farmadati Italia ex-factory list price (with -5%, -5% mandatory rebates). Abbreviations: AS, ankylosing spondylitis; DMARDs, disease-modifying antirheumatic drugs; NSAIDs, nonsteroidal anti-inflammatory drugs; PsA, psoriatic arthritis.

No additional administration costs were considered for subcutaneous treatments, while for IV treatment (infliximab and its biosimilar), estimated administration cost per infusion was about €291 (discounted in 2017).^63,64

Resource use and associated costs

To estimate the resource use impact for each indication, the proportion of patients requiring health care interventions along with the frequency were obtained. To estimate these costs, the unit costs were multiplied by the frequency and proportion of patients. Unit costs for each included item are available in Table S4.

AE costs

AEs such as serious infections, non-melanoma skin cancer (NMSC), and malignancies other than NMSC were considered by individual event rates (see Table S5). Costs per event, obtained from National Diagnosis-Related Group tariffs (DRG 89, 284, 414), were €3,185, €773, and €2,194 for serious infections, NMSC, and malignancy other than NMSC, respectively.⁶⁵

Sensitivity and scenario analyses

To assess the robustness of results, a one-way sensitivity analysis was performed by changing the following parameters by ±10%: secukinumab cost, secukinumab market share, IV administration costs, and AE costs. Moreover, in order to quantify the impact of a larger uptake of secukinumab in PsA and AS biologic-naïve patients, we carried out a scenario with twice as many PsA and AS biologic-naïve patients starting with secukinumab (60% compared to 30% in base case).

Results

Patients on secukinumab

Combining all three indications (psoriasis, PsA, and AS), the total patient population in Italy treated with secukinumab over the 3-year timeframe was projected to be 6,648 in the first year, 10,042 in the second year, and 12,001 in the third year. Results are shown in detail in Figure 2.

Figure 2 Total patients treated with secukinumab over the 3-year timeframe in Italy. Abbreviations: AS, ankylosing spondylitis; PsA, psoriatic arthritis; PsO, psoriaris.

Budget impact analysis

Overall population

The introduction of secukinumab in Italy in psoriasis, PsA, and AS indications (all three combined) resulted in cumulative savings of 5% over the 3-year period, compared to the scenario without secukinumab in market (Table 4). This corresponds to per patient savings of about €1,855 and overall population savings of €66.1 million over the 3 years. The major proportion of cost savings was contributed by the adoption of secukinumab in AS (58%), followed by PsA (29%) and psoriasis (13%).

Table 4 Budget impact results in the overall population (psoriasis, PsA, AS) Abbreviations: AS, ankylosing spondylitis; PsA, psoriatic arthritis.

Psoriasis

The introduction of secukinumab for moderate-severe plaque psoriasis treatment resulted in savings of 1% in the first year and 2% for the second and third year, compared to the scenario without secukinumab in market (Table 5). These correspond to savings of €1.9 million in the first year and savings increase in the following years, with €2.9 million and €3.5 million in the second and third years, respectively. The cumulative budget impact of introducing secukinumab is estimated to yield savings of €8.3 million over the 3-year period (Table 5). The cost savings per patient was €132 in the first year, €238 in the third year, and the cumulative result per patient was €568 over 3 years.

Table 5 Budget impact results in psoriasis, PsA and AS populations Abbreviations: AS, ankylosing spondylitis; PsA, psoriatic arthritis.

Psoriatic arthritis

The introduction of secukinumab for the treatment of PsA reveals savings of 2% in the first year, 4% in the second year, and 5% in the third year, compared to the scenario without secukinumab in market. These correspond to savings of €4.1 million in the first year and savings increase in the following years, with €7 million and €8.2 million in the second and third years, respectively. The cumulative budget impact of introducing secukinumab is estimated to yield savings of €19.3 million over the 3-year period (Table 5). Cost savings per patient were €329 in the first year, increasing to €645 in the third year with the cumulative per patient savings of €1,527 over 3 years.

Ankylosing spondylitis

The introduction of secukinumab for treatment of AS reveals savings of 8% in the first year, 13% in the second year, and 16% in the third year, compared to the scenario without secukinumab in market. These correspond to savings of €8.4 million in the first year and savings increase in the following years, with €13.4 million and €16.7 million in the second and third years, respectively. The cumulative budget impact of introducing secukinumab is estimated to yield savings of €38.5 million over the 3-year period (Table 5). Per patient cost results showed savings of €1,010 in the first year, which increased to €1,968 in the third year with the cumulative per patient savings of €4,568 over 3 years.

Sensitivity and scenario analyses

In Figure 3, a tornado diagram shows one-way sensitivity analysis results for the overall population scenario (combining patients with all three indications). This analysis demonstrated that budget impact results were most sensitive to change in secukinumab cost and the cost of secukinumab was the main cost driver in the analysis.

Figure 3 Tornado diagram for the sensitivity analysis results: ±10% variation of parameters in the overall per member BI scenario. Notes: BI per member cumulative result in the overall population (combining three indications): €1,855. Tornado diagram is useful to compare the relative importance of variables considered in sensitivity analysis. For each variable, we estimated the effect of a ±10% change from BI baseline. Abbreviations: AE, adverse event; BI: budget impact; IV, intravenous.

To assess the impact of a potential growth of biologic-naïve patients, twice the number of secukinumab AS and PsA biologic-naïve patients was assumed compared to that in base case scenario (in base case, 30% of PsA and AS eligible patients were biologic-naïve). With regard to combined PsA and AS population, the increase in biologic-naïve patients resulted in incremental cumulative savings of about €27.7 million over 3 years against base case scenario (€93.8 vs €66.1 million), as shown in Table 6.

Table 6 BIA results: base case vs twice PsA and AS biologic-naïve patients starting with secukinumab (150 mg secukinumab uptake) Abbreviations: AS, ankylosing spondylitis; PsA, psoriatic arthritis.

The increase of PsA biologic-naïve population led to incremental cumulative savings of €16.2 million over the 3 years against base case scenario (€35.5 vs €19.3 million). Therefore, the market share assumed for secukinumab changed from 14.4%, 24.7%, and 30.9% in base case to 18.7%, 32.1%, and 40.2% in the first, second, and third year, respectively. With regard to AS population, the increase in biologic-naïve patients resulted in incremental cumulative savings of €11.5 million over the 3 years against base case scenario (€50 vs €38.5 million). In this case, market share for secukinumab 150 mg changed from 15.9%, 25.2%, and 31.1% in base case to 20.6%, 32.8%, and 40.5% in the first, second, and third year, respectively.

Discussion

This analysis demonstrated considerable cost savings for INHS with the introduction of secukinumab in the market for the treatment of moderate-to-severe plaque psoriasis, PsA, and AS. Considering total direct medical costs from the INHS perspective, cumulative savings resulted to about €66.1 million after 3 years of secukinumab introduction. The highest savings were observed in AS patients (€38.5 million), followed by PsA (€19.3 million) and psoriasis (€8.3 million) patients. Within a fixed health care budget, such savings with the introduction of secukinumab could allow treatment of more patients with psoriasis, PsA, and AS in Italy. Potentially with these aforementioned savings, approximately an additional 5,925 patients (230 for psoriasis, 392 for PsA, and 5,302 for AS) could be treated. Sensitivity analyses confirmed the base case findings in most cases, and secukinumab cost was found to be the main cost driver in the analysis. As revealed in alternative scenario analysis, the savings could potentially increase if secukinumab would be used more in biologic-naïve AS and PsA patients, thus providing a better cost-saving treatment. In view of the strong clinical and comparative evidence provided by several randomized controlled trials supporting the efficacy and safety of secukinumab for psoriasis, PsA, and AS treatment,^{46,48–54,66–69} this analysis showed the budget impact of the introduction of secukinumab from the INHS perspective.

The budget impact model results presented in this analysis were consistent with other recent studies available in literature from different countries. Duteil et al⁷⁰ assessed the budget impact of the introduction of secukinumab for patients with moderate-to-severe psoriasis, AS, and PsA in France. This analysis demonstrated that secukinumab utilization led to savings of €83.6 million over a 6-year time period. Halliday et al⁷¹ estimated the budget impact of introduction of secukinumab in the UK in patients with AS. The cumulative budget savings over a 5-year period were estimated to be €49.2 million.

There are few limitations of this analysis. Outcomes of the analysis are based on population and market share projections. Some input data were not available to Italian context, and when not available, data from other countries or assumptions were entered into the model. Furthermore, there could be a limit in the identification of the target population, as the model has considered separately the psoriasis, PsA, and AS populations, and there is lack of studies able to provide information regarding patients on treatment with simultaneous presence of these diseases.

The BIA, according to the INHS perspective, included only direct costs. In view of the huge impact on work productivity of these diseases, potential savings could be higher if we had included indirect costs as well. Therefore, it would be interesting to plan further analyses taking into account total costs to define the composition of direct and indirect costs and the real burden on patients and the Italian society. Although the robustness of results was confirmed by sensitivity analysis, real-world evidence could further confirm our assumptions and results in future.

In conclusion, this analysis demonstrated that secukinumab is a cost-saving option for INHS when introduced for psoriasis, PsA, and AS treatment, particularly cost-savings was the highest in AS and PsA patients.

Acknowledgments

The authors would like to thank Alessandro Roccia from Novartis Pharma Italy, Martina Oselin and M Chiara Valentino from S.A.V.E. Research Center, and Niraj Modi from Novartis Healthcare Private Limited, Hyderabad for editorial writing support. This analysis was funded by Novartis Pharma S.p.A., Origgio, Italy.

Authors contributions

SMJ and PG designed the original model framework. SDM adapted the model to the Italian perspective. GLC reviewed and validated the model adaptation and wrote the manuscript. CM supported the model adaptation and in writing the manuscript. MN interpreted the data and decided on manuscript content and structure. GMB supervised the project and helped in writing the manuscript. All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work.

Disclosure

GLC, GMB, CM, and SDM are employees of S.A.V.E. S.r.l and consultants for Novartis. SMJ is an employee and shareholder of Novartis Pharma AG, Basel, Switzerland. PG is an employee of Novartis Product Life Cycle Services-NBS, Novartis Healthcare Private Limited, Hyderabad, India. MN is an employee of Novartis Pharma, Origgio, Italy. The authors report no other conflicts of interest in this work.

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Supplementary materials

References

Table S1 PsO population without and with secukinumab over a 3-year horizon and respective change in market share for treatments Note: Changing % market share of treatments over a 3-year horizon are shown in brackets. Abbreviation: PsO, psoriasis.

Table S2 PsA population without and with secukinumab over a 3-year horizon and respective change in market share for treatments Note: Changing % market share of treatments over a 3-year horizon are shown in brackets. Abbreviation: PsA, psoriatic arthritis.

Table S3 AS population without and with secukinumab over a 3-year horizon and respective change in market share for treatments Note: Changing % market share of treatments over a 3-year horizon are shown in brackets. Abbreviation: AS, ankylosing spondylitis.

Table S4 Resource use and costs associated with PsO, PsA, and AS treatment Notes: Cost data obtained from Italian national formulary;1 phototherapy-related data from De Compadri and Koleva;2 frequency data for PsO from NICE clinical guidance3 and for PsA and AS from Greenberg et al.4 aFor NSAIDs and DMARDs, cost has been estimated as weighted cost as the global model. Abbreviations: AS, ankylosing spondylitis; DMARD, disease-modifying antirheumatic drugl NSAID, nonsteroidal anti-inflammatory drug; PsA, psoriatic arthritis; PsO, psoriasis.

Table S5 Annual rates of adverse events associated with PsO, PsA, and AS treatment Notes: Only serious adverse events due to malignancies and severe infections requiring hospitalization were included in the analysis. Severe infections included sepsis, tuberculosis, skin and soft tissue infections, bone and joint infections, pneumonia, and urinary tract infections. aData obtained from product label. bAssumed same as corresponding branded drug. “-” Indicates a treatment (at a given dose strength) is not considered for the indication mentioned. Abbreviations: AS, ankylosing spondylitis; NMSC, non-melanoma skin cancer; PsA, psoriatic arthritis; PsO, psoriasis.

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