ClinicoEconomics and Outcomes Research Dovepress open access to scientific and medical research Open Access Full Text Article ORIGINAL RESEARCH Budget Impact Analysis Of Subcutaneous Belimumab In Patients With Systemic Lupus Erythematosus In Spain ClinicoEconomics and Outcomes Research downloaded from https://www.dovepress.com/ on 10-Mar-2022 This article was published in the following Dove Press journal: ClinicoEconomics and Outcomes Research Maria Cevey 1 Objective: To evaluate the budget impact and the direct costs of the introduction of Jaime Calvo-Alén 2 subcutaneous belimumab (SC) into the Spanish National Health Service (NHS) for patients Carlos Crespo 3 with systemic lupus erythematosus (SLE) in Spain. Angel Robles- Methods: This study was conducted from the Spanish NHS perspective with a time horizon For personal use only. of 3 years. The budget impact analysis compared the cost difference between two scenarios: Marhuenda 4 current market (standard therapy (ST) and intravenous belimumab (IV)) and other market in Lee Smolen 5 which patients switched from belimumab IV to belimumab SC until reaching 17% of the Josefina Cortés-Hernández 6 total market share. The eligible population was calculated to receive treatment with belimu- 1 Department of Market Access, mab, applying the EPISER (study of the prevalence of rheumatic diseases in adult population GlaxoSmithKline SA, Madrid, Spain; 2 Department of Rheumatology, University in Spain) prevalence (91 per 100,000 inhabitants), Autoimmune Systemic Diseases Study Hospital Araba, Vitoria, Spain; Group (GEAS) incidence (2 per 100,000 inhabitants), and the risk of annual mortality to the 3 Department of Genetics, Microbiology Spanish adult population. Patients with severe active lupus nephritis and with severe active and Statistics, Statistics Section, University of Barcelona, Barcelona, Spain; CNS lupus were excluded. Patients’ characteristics, flare rates and severity, and healthcare 4 Department of Internal Medicine, Hospital resource consumption were evaluated based on data from the literature and interviews with La Paz, Madrid, Spain; 5Modeling & an expert panel. A sensitivity analysis was performed. Analytics, Medical Decision Modeling Inc, Indianapolis, IN, USA; 6Department of Results: Currently, there is an estimated 34,697 adult patients with SLE in Spain and 3849 Internal Medicine, Vall d’Hebron Institut de patients who are eligible to be treated with belimumab. The introduction of belimumab SC Recerca (VHIR), Barcelona, Spain into the Spanish NHS could generate savings in direct healthcare costs of 6 million euros over the 3 years. Conclusion: The introduction of belimumab SC shows direct savings for the Spanish NHS. These savings could contribute to sustainability and decision-making. Keywords: belimumab, budget impact, Spanish National Health Service, NHS, Systemic Lupus Erythematosus Introduction Systemic lupus erythematosus (SLE) is a severe autoimmune disease which can affect multiple organs1 and which presents different clinical manifestations.2 It can affect any Correspondence: Josefina Cortés- organ or system, with joints, kidneys, and the skin the most commonly affected areas.3 Hernández Most patients have a relapsing and remitting clinical course in the form of flares or Department of Internal Medicine, Vall d’Hebron Institut de Recerca (VHIR), Vall exacerbations interspersed with periods of inactivity. These flares can lead mainly to d’Hebron University Hospital Research irreversible alterations of vital organs,1 which may affect the survival rate of patients Institute, Passeig Vall d’Hebron 119-129, Barcelona 08035, Spain with SLE.2 Likewise, SLE negatively impacts patient quality of life.4 Tel +34 934893000 The complexity of this disease and the time it takes before the appearance of Fax +34 934894438 Email fina.cortes@vhir.org severe symptoms make it difficult to make an early diagnosis in patients with SLE.5 submit your manuscript | www.dovepress.com ClinicoEconomics and Outcomes Research 2019:11 757–765 757 DovePress © 2019 Cevey et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. http://doi.org/10.2147/CEOR.S218464 php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Cevey et al Dovepress A study carried out in Germany showed that it is possible (€5968) was significantly higher than that of non-severe to reduce the time until the first rheumatology appointment patients (€3604) (p = 0.003).10 This cost may have been by making doctors and the health system aware of the higher if the social perspective had been taken into seriousness of this disease. This would result in better account in the study. A study showed that 36% of the management of the patient and disease activity, as well employed patients with SLE and 40% of those with rheu- as a reduction in the healthcare resources and benefit matoid arthritis had had at least one period of sick leave patients to continue to work.5 Early diagnosis, disease during the past 12 months.11 control, and adjustment of therapies according to the The budget impact has become a significant pharma- treat to target concept are important in avoiding severe coeconomic element in decision-making. It allows us to flares and irreversible organ damage and can maintain the estimate the financial viability of introducing new technol- patient in a state of remission or low disease activity.6 The ogies, providing very useful information for healthcare SLE clinical practice guidelines from the Ministry of decision-makers.12 The objective of this study was to Health, Social Services and Equality,1 the Spanish estimate the budget impact of incorporating belimumab Society of Rheumatology (SER),7 and the Spanish SC within the Spanish National Health Service (NHS) as Society of Internal Medicine (SEMI)8 agree that the an adjuvant treatment for SLE in adult patients with posi- main objective of the drug therapy for patients with SLE tive autoantibodies and high disease activity in Spain. is to avoid flares of disease in order to prevent irreversible Patients with severe active lupus nephritis or severe active organ damage. Central Nervous System (CNS) lupus were excluded. The Systemic LUpus Erythematosus Cost of Care In Europe Study (LUCIE) on the burden of SLE illness Materials And Methods carried out in 5 European countries, including Spain, con- A budget impact model was developed from the perspec- cluded that inadequate management of SLE activity pro- tive of the Spanish NHS. Direct health costs: pharmacolo- duces an increase in severe flares; this entails an increase gical treatments, administration, and management of flares in the associated costs, mainly in hospital admissions.9 In were evaluated. The costs were estimated for a time hor- the retrospective study reviewing medical records across 5 izon of 3 years (2018 to 2020) without applying a discount hospitals in Spain, the healthcare resources associated with rate, as indicated in the international guidelines.11 Indirect the managing and treating SLE and its flares, and the costs were not included. associated direct cost, were studied from a Spanish NHS The model was completed with data from published litera- perspective. We included adult patients with SLE (ACR ture, official publications, market research data, and through a criteria) with positive autoantibodies, receiving medical questionnaire conducted with a panel of experts comprising treatment and with active disease. The patients were clas- specialists in Rheumatology and Internal Medicine, which sified into severe and not severe. Severe patients were addressed those assumptions where data were not available. defined as having at least one major domain involved at In addition, the panel of experts also validated the data used. inclusion (renal, neurological, cardiovascular, or respira- This study was funded by GlaxoSmithKline and the panel of tory) and requiring prednisone equivalent dosages >7.5 experts were not blinded about the study. mg/day and/or immunosuppressants. Patients’ disease The budget impact model compared the cost difference activity and severity were assessed at baseline. In this in each year in two scenarios: a current market scenario: study, only direct costs were included: laboratory and standard therapy and belimumab IV without belimumab diagnostic tests, drug therapies, specialist visits, and hos- SC; and a new market scenario: in which the patients pital admissions. Despite treatment, management of dis- switched from belimumab IV to belimumab SC until ease activity was inadequate in the majority of patients, reaching approximately 17% of the market share. The with 90.7% presenting at least one flare during a two-year assumption of the proportion of patients in both scenarios follow-up period. The major component of the healthcare according to their distribution in the different drug thera- cost related to hospital admissions, which constituted pies over the 3-year horizon was made taking into account 44.8% of the total cost. It was found that the average the company’s internal data, market research, and assess- annual direct cost associated with the management of ment by the expert panel. The following distribution of SLE was €4833 per patient. The cost associated with the patients was assumed as a percentage in the different treatment and management of patients with severe disease scenarios: submit your manuscript | www.dovepress.com ClinicoEconomics and Outcomes Research 2019:11 758 DovePress Powered by TCPDF (www.tcpdf.org) Dovepress Cevey et al ● Current scenario: belimumab IV + standard therapy The pharmacoeconomic model assumed that in the first (22.8% in year 1, 23.7% in year 2, 23.2% in year 3) year the prevalence includes the mortality and the new and standard therapy (77.2% in year 1, 76.3% in the cases of the first 6 months. For this reason, the incidence year 2, 76.8% in year 3). of the first year would be half that of subsequent years. ● New scenario: belimumab SC + standard therapy (7.5% in year 1, 14.5% in year 2, 16.8% in year 3); Treatments And Costs belimumab IV + standard therapy (15.3% in year 1, Annual treatment costs of different pharmacological treat- 9.2% in year 2, 6.4% in year 3) and standard therapy ments were calculated using the ex-factory price.25 (77.2% in year 1, 76.3% in year 2, 76.8% in year 3). According to Summary Product of Characteristics, the recommended dose of belimumab IV is 10 mg/kg on days 0, 14, and 28, and then at 4-week intervals.26 Therefore, in the first year, the patient receives 15 administrations and from Population Eligible For Treatment With the second year receives 13 administrations. As Benlysta IV Belimumab depends on weight, the average weight (69 kg) of the Study The estimated eligible population to receive belimumab of Belimumab Subcutaneous in Subjects with SLE trial treatment was calculated from the general population of [BLISS-SC] was used as a reference for calculating annual adults in Spain (≥18 years), according to data from the treatment cost.27 National Institute of Statistics.13 Epidemiological data on According to Summary Product of Characteristics, the the prevalence of SLE from the EPISER epidemiological recommended dose of belimumab SC is 200 mg once a study (91 per 100,000 inhabitants) were applied,14 of which week, administered subcutaneously and the dosage is not 88% of the cases are diagnosed.15 Based on the study by based on weight.28 We estimate 52 administrations per year. Somers et al16 and the Spanish study by Rúa-Figueroa et al17 The standard therapy, according to the Clinical Practice 32% of the SLE population was excluded due to suffering Guidelines from the Ministry of Health, Social Services and from severe active lupus nephritis or severe active Central Equality1 and the distribution allocated by the panel of Nervous System (CNS) lupus, as set out in Summary Product experts, encompassed 83% corticosteroids, 83% anti-malar- of Characteristics.18 Likewise, only 59% of the population ials, 52% non-biological immunosuppressants (non-biolo- had positive autoantibody tests (99% based on ANA) and gical immunosuppressants: methotrexate, intravenous active disease.19 Finally, we identified the subgroup of cyclophosphamide, leflunomide, azathioprine, cyclospor- patients with high disease activity despite standard therapy ine, and mycophenolate), 20% NSAIDs, 13% other biologic (35%)9 and who are on pharmacological treatment (90%).14 immunosuppressants used off-label such as rituximab, 2% In order to estimate the direct cost offsets related to intravenous immunoglobulins, and 0.07% plasmapheresis. belimumab SC, a pharmacoeconomic study was conducted. Drug cost price was based on ex-factory price.25 Taking into This model was developed in Excel 2010 and complies with account, the weight of SLE patients (69 kg)26 and the body the International Society for Pharmacoeconomics and surface area (1.8 m2),29 in necessary cases, and the rate of Outcomes Research (ISPOR)12 best practice guidelines. plasma exchange,30–32 the average annual treatment cost In the model, the annual incidence of SLE (2 per 100,000 calculated of standard therapy was €1034.71. Doses of population-year) from the GEAS group20 and the adjusted different pharmacological treatments were validated by Spanish mortality21 for patients with SLE were taken into the expert panel. In the case of standard therapy adminis- account. In order to estimate the mortality, the SLE specific tered with belimumab SC and IV, the average annual treat- mortality risk from Bultink22 for patients under 40 years (RR: ment cost calculated of standard therapy was €438.42, 4.87) and from the Bernatsky study23 for the other patients because it did not include other biologic treatments. (between 40 and 59 years RR: 3.5 and for 60 years or more RR: 1.5) was applied to the all-cause mortality risk in Spain. Estimated Cost Of Administration The age distribution of the Spanish Rheumatology Society The cost of administration of intravenous treatments was SLE Registry (RELESSER-T) study was used.24 The risk of calculated using administration hospital fees (€260.67).32–40 annual mortality of patients with SLE for Spain is 0.129% for The average cost calculated for standard therapy patients <40 years, 0.635% for patients of 40–59 years, and administration was €205.62 per patient. However, the 5.484% for patients of ≥60 years. average cost of standard therapy administration when it submit your manuscript | www.dovepress.com ClinicoEconomics and Outcomes Research 2019:11 759 DovePress Powered by TCPDF (www.tcpdf.org) Cevey et al Dovepress was administered together with belimumab SC and IV was percentage of patients with positive autoantibodies and €103.96 per patient, because it did not include other bio- active disease, the percentage of patients without severe logic treatments. active lupus nephritis or severe active CNS lupus, the percentage of patients treated, weight, the percentage of patients diagnosed, the percentage of patients according to Estimated Costs Of Managing Severe And age, and relative risk of mortality. These assumptions were Non-Severe Flares validated and agreed with the panel of experts. The number of flares per treatment was estimated based on changes in the SELENA-SLEDAI score, changes in the Results signs or symptoms of disease activity, changes in predni- It is currently estimated that there are 34,697 adult patients sone dose, use of new drugs due to disease activity, and with SLE, 88% (30,533) of whom have been diagnosed. A changes in the physician’s global assessment (PGA). Non- total of 20,610 of these are patients without severe active severe flares were defined as flares triggered by an lupus nephritis or severe active CNS lupus, decreasing to increase of ≥3 in the SELENA-SLEDAI score. Serious around 3849 patients with positive autoantibodies and high flares were defined as flares triggered by an increase of disease activity on pharmacological treatment (Table 1). >12 in SELENA-SLEDAI score or a flare requiring hos- The 3-year projection for this subgroup of patients with pital admission. Considering that the efficacy of belimu- SLE with positive autoantibodies and high disease activity mab SC and IV is equivalent,41 the same number of severe is 3891 patients in the first year, 3943 in the second year, and non-severe flares was used for both formulations of and 3995 in the third year, assuming an average annual belimumab. Adding belimumab to standard therapy incidence of 85 patients and an annual mortality of 33 showed an average of 2.15 non-severe flares per year, patients. while standard therapy alone showed an annual average of 2.5 non-severe flares. Likewise, adding belimumab to Direct Costs standard therapy showed an annual average of 0.54 severe The annual cost of treatment with belimumab SC was flares compared to 1.01 with standard therapy alone.42 €11,902.80 per patient. The annual cost of treatment with To calculate the cost of management severe flares, the belimumab IV was €12,448.28 per patient on ongoing average cost of hospital admission for connective tissue phase (13 administrations per year) and €14,363.40 per disorder with complications was assumed at €4840.29/ patient on loading phase (15 administrations per year). event.43 This cost was based on DRG (Diagnosis Related Likewise, the annual cost of administration calculated Groups) 240: Connective tissue disorders with complica- for treatment with belimumab IV was €3388.72 per patient tions that group patients according to admission for a on ongoing phase and €3910.07 per patient on loading connective tissue disease such as SLE, rheumatoid arthri- phase. tis, amyloidosis, juvenile rheumatoid arthritis, etc. To cal- Table 2 shows the annual costs per patient associated culate the cost of management non-severe flares was with flares according to severity and the direct savings assumed: a visit to the specialist (€92.54), a laboratory associated with flares treated with belimumab. Treatment test (€68.32)43–49,50 and that 10% of the patients required with belimumab shows an annual reduction in the cost of hospital admission, applied to the average cost of DRG non-severe and severe flares per patient versus standard 241: Connective tissue disorders without complications therapy of €2444.48. (€386.26/event).42 This means the cost of treating a non- severe flare was €547.12. Budget Impact Analysis The total budget impact of introducing belimumab SC Sensitivity Analysis treatment in the Spanish NHS for adult patients with Taking into account that economic models have a certain SLE with positive autoantibodies and high disease activity level of uncertainty associated with the assumptions made, despite standard treatment was calculated as the cost dif- in this budget impact analysis a sensitivity analysis was ference between the current scenario and the new scenario. carried out using a tornado diagram to assess the robust- Direct health costs were considered in order to calculate ness of the results. The various assumptions were the total budget impact: pharmacological treatments, adminis- percentage of patients with high disease activity, the tration, and management of flares. The introduction of submit your manuscript | www.dovepress.com ClinicoEconomics and Outcomes Research 2019:11 760 DovePress Powered by TCPDF (www.tcpdf.org) Dovepress Cevey et al Table 1 Estimated Adult Population With SLE With High Disease Activity And Positive Autoantibodies In Spain N References Spanish adult population 38,128,226 National Institute of Statistics (INE) 201713 Population with SLE 34,697 EPISER14 and systemic auto-immune disease (GEAS) group Diagnosed with SLE 30,533 Expert panel15 SLE population without severe active lupus nephritis or severe active 20,610 Adapted from: Somers EC et al 200916 and Rúa-Figueroa I CNS lupus et al 201417 SLE population with positive autoantibodies and disease activity 12,220 Lupus Monitor19 SLE population with high disease activity 4277 Adapted from Cervera et al 201310 On pharmacological treatment 3849 Expert panel15 Table 2 Annual Costs Per Patient Associated With Flares According To Severity Treatment Cost Of Non-Severe Flares Cost Of Severe Flares Belimumab SC + Standard Therapy €1172.41 €2640.22 Belimumab IV + Standard Therapy €1172.41 €2640.22 Standard Therapy €1367.81 €4889.30 Reduction in annual costs €195.40 €2249.08 Total reduction in annual costs €2,444.48 belimumab SC into the Spanish NHS could generate sav- facilities mainly in day hospitals, to the benefit of patients and ings in direct healthcare costs of €6,038,803 over the 3 healthcare professionals. In addition, subcutaneous adminis- years. The results are shown in Figure 1. tration is a less invasive treatment than intravenous adminis- Pharmacological budget impact was calculated, con- tration and has a reduced administration time of only a few sidering only pharmacological costs. The introduction of minutes. It can be a self-administered treatment. belimumab SC within the Spanish NHS could generate Taking into account that belimumab SC is administered as savings of €863,193.20 over the 3 years. The results of a weekly fixed-dose regimen of 200 mg regardless of patient pharmacological budget impact are shown in Table 3. This weight, there will therefore be a predictable budget impact. saving comes from the lower annual treatment cost of The introduction of belimumab SC into the Spanish belimumab SC compared to belimumab IV on loading or NHS could, in its first 3 years of commercialization, gen- ongoing phase. erate a saving of approximately 800 thousand euros in pharmacological costs, and a total saving of direct health Sensitivity Analysis costs of 6 million euros. The sensitivity analysis confirmed the estimated savings to SLE is a chronic, serious condition that affects patients of the Spanish NHS, due to the introduction of belimumab working age. Given that the disease occurs in women with an SC to the pharmacological treatments available for treating average age of 38 years,51 there are also significant indirect adult patients with SLE. This cost saving ranges between 3 costs associated with SLE. A real clinical practice study con- and 7 million euros for the total budget impact (Figure 2). ducted in Spain evaluated variables of healthcare resource consumption and absence from work, after 6 months of treat- Discussion ment with IV belimumab in patients with SLE. The patients The introduction of belimumab SC shows relevant savings for treated with belimumab IV presented a reduction in the use of the Spanish NHS in the 3-year period studied. The results of healthcare resources directly related to the management of the this study show that direct healthcare costs were lower in disease, such as the use of corticosteroids, as well as a sub- patients treated with belimumab SC compared to those treated stantial reduction in the days of absence from work.52 with belimumab IV. This new subcutaneous formulation will Additionally, the subcutaneous formulation will offer greater not only reduce the direct costs derived from its administration comfort and ease of administration, reducing absence from and acquisition but it will also be able to free-up healthcare work as the drug may be administered outside the hospital and submit your manuscript | www.dovepress.com ClinicoEconomics and Outcomes Research 2019:11 761 DovePress Powered by TCPDF (www.tcpdf.org) Cevey et al Dovepress 48.00 € Millions 40.30 € 39.15 € 41.27 € 39.02 € 41.57 € 38.93 € 40.00 € 32.00 € 24.00 € 16.00 € 8.00 € - € -1.15 € -2.25 € -2.64 € -8.00 € Year 1 Year 2 Year 3 Scenario without belimumab SC Scenario with belimumab SC Net Impact Figure 1 Total budget impact of the introduction of belimumab SC in the Spanish NHS. even offers an option for patients in whom it is difficult to SLE from the Ministry of Health, Social Services and access veins for injection. Equality1 clinical practice guide of the Study Group of It should also be noted that this disease has associated Autoimmune Diseases (GEAS) of the Spanish Society of direct costs derived from clinical management, highlight- Internal Medicine (SEMI)19 and the Consensus of the ing the recurrent hospital admissions of patients mainly Spanish Society of Rheumatology (SER) on the use of due to flares and associated organ damage. The LUCIE biological therapies in SLE.6 study showed that the major component of the health cost To carry out this study and develop the budget impact corresponded to hospital admissions.9 Patients treated with model, the same efficacy has been set out for both formula- belimumab in addition to standard therapy showed a tions. In a network meta-analysis with the objective of estab- reduced average number of flares per year compared to lishing the comparability of both formulations of belimumab patients treated with standard therapy alone.42 IV and SC in patients with SLE, it was demonstrated that in The use of belimumab is recommended in different patients with high disease activity, the efficacy of the SC national clinical guidelines: clinical practice guide on formulation was comparable to that of the IV formulation.53 Table 3 Pharmacological Budget Impact Of The Introduction Of Belimumab SC Year 1 Year 2 Year 3 Total number of patients eligible for belimumab 3891 3943 3995 Total patients on belimumab treatment 889 (22.8%) 934 (23.7%) 927 (23.2%) Scenario without belimumab SC Belimumab IV + ST €11,002,596.27 €11,568,022.00 €11,481,887.90 Standard Therapy €1,693,285.12 €1,716,054.31 €1,738,631.99 Total €12,695,881.38 €13,284,076.31 €13,220,519.90 Scenario with belimumab SC Belimumab SC + ST €3,452,758.06 €6,763,692.63 €7,932,655.42 Belimumab IV + ST €7,385,521.46 €4,482,603.39 €3,172,082.01 Standard Therapy €1,693,285.12 €1,716,054.31 €1,738,631.99 Total €12,531,564.63 €12,962,350.33 €12,843,369.43 Net Impact - €164,316.75 - €321,725.98 - €377,150.47 Abbreviation: ST, standard therapy. submit your manuscript | www.dovepress.com ClinicoEconomics and Outcomes Research 2019:11 762 DovePress Powered by TCPDF (www.tcpdf.org) Dovepress Cevey et al High disease activity [25%;40%] Positive autoantibodies and high disease activity… Without lupus nephritis and severe active CNS [60%;75%] Eligible to be treated [80%;100%] Weight [65 kg;72 kg] Diagnosed [85%;90%] Age <40 [40%;60%] Age 40-59 [30%;47%] Relative Risk of Mortality. Age 40-59 [2;5] Relative Risk of Mortality. Age <40 [1.93;12.3] 3.00 € 4.00 € 5.00 € 6.00 € 7.00 € Millions COST-SAVING Figure 2 Tornado diagram: univariate sensitivity analysis. This means that both formulations have the same costs in the study55 and, therefore, our results could be affected by the terms of disease management, but with different administra- new estimate. In addition, it would be advisable to have long- tion and pharmacological direct costs. term epidemiological studies in the future that allow the rele- Belimumab has been shown to have a positive effect vance of SLE to be demonstrated with real data, both at a on the quality of life of patients, both in the physical clinical and economic level, thus better contextualising the component and in the vitality domain of the SF-36 and consequences of the disease. in the fatigue score (FACIT-Fatigue).54 These clinically significant improvements are consistent with the reduction Conclusions of disease activity. Therefore, the use of belimumab in This study provides pharmacoeconomic information that patients with positive autoantibodies and high disease can aid in decision-making related to the prescription of activity despite standard therapy may offer benefits both treatments for patients with SLE. The introduction of economically and clinically. belimumab SC demonstrates direct savings for the Spanish NHS. This decrease in direct costs will allow a Study Limitations better management of Spanish NHS resources, contribut- Our study is not free from the limitations inherent to esti- ing to its sustainability. This is a study based on estimates mating the budget impact made using models. However, the and assumptions about future impact. Further develop- information with the most available evidence has been used. ments could be possible to demonstrate the real impact Also, the data have been validated by a panel of clinical in a retrospective study. experts with real experience in the management and treat- ment of patients with SLE in Spain. Acknowledgment It should be noted that the estimated number of patients The original model was developed by Timothy M. Klein, being treated who will eventually receive SC belimumab is Senior Research Analyst, Modelling & Computer Science, obviously speculative, and may depend on various aspects, Medical Decision Modelling Inc. including the low prevalence of the disease, the detection of positive autoantibodies, as well as the clinical criteria and the Disclosure difficulty in accessing all patients who received treatment. This study was funded by GlaxoSmithKline (Study code: HO- However, the estimated number of patients receiving treatment 17-18309). M Cevey is an employee of GlaxoSmithKline. comes from the EPISER study,13 which was conducted more Jaime Calvo, Carlos Crespo, Angel Robles, Lee Smolen than a decade ago, and the results may be outdated. For this and Josefina Cortés received consulting fees from reason, the Spanish Society of Rheumatology has re-launched GlaxoSmithKline during their participation in the study. Dr. submit your manuscript | www.dovepress.com ClinicoEconomics and Outcomes Research 2019:11 763 DovePress Powered by TCPDF (www.tcpdf.org) Cevey et al Dovepress Crespo Palomo reports personal fees from GlaxoSmithKline, 12. Sullivan SD, Mauskopf JA, Augustovski F, et al. Budget impact analysis-principles of good practice: report of the ISPOR 2012 during the conduct of the study; grants and personal fees from Budget Impact Analysis Good Practice II Task Force. Value Health. advising outside the submitted work; and he received grants or 2014;17(1):5–14. doi:10.1016/j.jval.2013.08.2291 personal fees from Novartis, Pfizer, Abbvie, Gebro, Takeda, 13. INE. Resident population by date, sex and age. National results. Inst Nac Statistics. 2017 Shire, Mundipharma, Almirall, Boston Scientific, Dexcom, 14. Spanish Society of Rheumatology. Episer studio. Available from: Hospital Clinic of Barcelona, Ferrer, Daichi, Boehringer, http://www.ser.es/episer/. Accessed October 25, 2019. 15. Cevey M, Calvo-Alén J, Crespo C, Robles-Marhuenda A, Cortés J. Gilead, IESE, Sanofi, Roche, Roche diagnostic, Vifor, Systemic lupus erythematosus in Spain in patients with high activity of EuroQoL, Angellini and Medtronic. Lee J Smolen over the the disease in the next 5 years. Reumatol Clin. 2018;14(Spec Cong):28–286. course of the past 36 months Medical Decision Modeling has 16. Somers EC, Marder W, Lewis EE, et al. Michigan Lupus Epidemiology & Surveillance Program (MILES): increased propor- received financial remuneration from GlaxoSmithKline plc tion of target-organ threatening involvement among male versus (GSK) for consultant services related to pharmacoeconomic female SLE patients. In: American College of Rheumatology ACR- investigations regarding the use of belimumab in the treatment ARP Annual Meeting. Philadelphia (PA); 2009:235 [Abstract # 302]. 17. Rúa-Figueroa Í, Richi P, López-Longo FJ, et al. Comprehensive description of system lupus erythematosus (SLE). The authors report no of clinical characteristics of a large systemic lupus erythematosus cohort other conflicts of interest in this work. from the spanish rheumatology society lupus registry (RELESSER) with emphasis on complete versus incomplete lupus differences. Med (United States). 2015;94(1):e267. doi:10.1097/MD.0000000000000267 18. Summary Product of Characteristics of Benlysta (belimumab) subcuta- References neous. GlaxoSmithKline. 2018. Available from: https://cima.aemps.es/ 1. Working group of the Clinical Practice Guideline on Systemic Lupus cima/pdfs/en/ft/111700004/FT_111700004.pdf. Accessed October 25, Erythematosus. Clinical practice guideline on systemic lupus erythe- 2019. matosus. Clinical Practice Guidelines in the Spanish NHS. Ministry 19. Ipsos Healthcare. Lupus Monitor market research 2016. Madrid 2017 of Health, Social Services and Equality Evaluation Service of the 20. Study Group of Systemic Autoimmune Diseases (GEAS). Spanish Canary Islands Health Service; 2015 Society of Internal Medicine (SEMI). Clinical Guidelines of 2. Pons-Estel GJ, Ugarte-Gil MF, Alarcón GS. Epidemiology of sys- Systemic Autoimmune Diseases. Disseminated Lupus temic lupus erythematosus. Expert Rev Clin Immunol. 2017;13 Erythematosus. 2011. Available from: https://www.fesemi.org/sites/ (8):799–814. doi:10.1080/1744666X2017.1327352 default/files/documentos/publicaciones/guia_les_2011.pdf. Accessed 3. Trujillo-Martín MM, Rúa-figueroa Fernández de Larrinoa I, Ruíz- November 08, 2019. Irastorza G, et al. Clinical practice guidelines for systemic lupus erythe- 21. National Statistics Institute. Mortality tables by year, sex, age and func- matosus: recommendations for general clinical management. Med Clin tions. Results by Autonomous Communities and Provinces. Inst Nac (Barc). 2016;146(9):413.e1–413.e14. doi:10.1016/j.medcli.2016.01.013 Statistics. 2016. Available from: https://www.ine.es/. Accessed 4. Chaigne B, Chizzolini C, Perneger T, et al. Impact of disease activity on November 27, 2019. health-related quality of life in systemic lupus erythematosus – a cross- 22. Bultink I, de Vries F, van Vollenhoven R, Lalmohamed A. A population- sectional analysis of the Swiss Systemic Lupus Erythematosus Cohort Study based study on mortality and the influence of medication use in 4356 (SSCS). BMC Immunol. 2017;18:17. doi:10.1186/s12865-017-0200-5 patients with systemic lupus erythematosus and 21845 matched controls 5. Albrecht K, Huscher D, Richter J, et al. Changes in referral, treatment from the United Kingdom. Lupus Sci Med. 2018;5(Suppl 1):S6A: 4. and outcomes in patients with systemic lupus erythematosus in 23. Bernatsky S, Boivin JF, Joseph L, et al. Mortality in systemic lupus erythe- Germany in the 1990s and the 2000s. Lupus Sci Med. 2014;1(1): matosus. Arthritis Rheum. 2006;54(8):2550–2557. doi:10.1002/art.21955 e000059. doi:10.1136/lupus-2014-000059 24. Rúa-Figueroa I, López-Longo FJ, Calvo-Alén J, et al. National reg- 6. Rodríguez Almaraz ME, Cámara Fernández I, Pablos Álvarez JL. istry of patients with systemic lupus erythematosus of the Spanish Disseminated Lupus Erythematosus evaluation of the disease. Treatment Society of Rheumatology: objectives and methodology. Clinical management of complications. Med - Continued Accredited Medical Reumatol. 2014;10(1):17–24. doi:10.1016/j.reuma.2013.04.013 Form Program. 2017;12(25):1440–1447. doi:10.1016/j.med.2017.01.002 25. Consejo General de Colegios Oficiales. Database of Medicine. Bot 7. Calvo-Alén J, Silva-Fernández L, Úcar-angle E, et al. Consensus of the Plus. 2017 Spanish Society of Rheumatology on the use of biological therapies in 26. Summary Product of Characteristics of Benlysta (belimumab) for solution systemic lupus erythematosus. Reumatol Clin. 2013;9(5):281–296. for infusion. GlaxoSmithKline. 2018. Available from: https://cima.aemps. 8. Ramos-Casals M, Ruiz-Irastorza G, Jimenez-Alonso J, Khamashta es/cima/dochtml/ft/11700001/FT_11700001.html. Accessed October 25, MA. Recommendations on the use of belimumab in systemic lupus 2019. erythematosus. Clinical Practice Guide GEAS-SEMI. Rev Clin Esp. 27. Stohl W, Schwarting A, Okada M, et al. Efficacy and safety of subcuta- 2013;213(1):42–58. doi:10.1016/j.rce.2012.10.004 neous belimumab in systemic Lupus Erythematosus: a fifty-two-week 9. Doria A, Amoura Z, Cervera R, et al. Annual direct medical cost of active randomized, double-blind, placebo-controlled study. Arthritis Rheum systemic lupus erythematosus in five European countries. Ann Rheum Dis. (Hoboken, NJ). 2017;69(5):1016–1027. doi:10.1002/art.40049 2014;73(1):154–160. doi:10.1136/annrheumdis-2012-202443 28. AEMPS. Technical Sheet Subcutaneous Benlysta. Madrid; 2018. 10. Cervera R, Rúa-Figueroa I, Gil-Aguado A, et al. Direct cost of Available from: https://cima.aemps.es/cima/pdfs/en/ft/111700004/ management and treatment of active systemic lupus erythematosus FT_111700004.pdf. Accessed October 25, 2019. and its outbreaks in Spain: the LUCIE Study. Rev Clin Esp. 2013;213 29. National Institute of Statistics European Survey of Health in Spain (3):127–137. doi:10.1016/j.rce.2012.11.018 National results. Madrid 2017 11. Zink A, Fischer-Betz R, Thiele K, et al. Health care and burden of 30. Official Gazette of Aragon ORDER of September 17, 2015, of the disease in systemic lupus erythematosus compared to rheumatoid Directors of the Treasury and Public Administration and of Health, by arthritis: results from the National Database of the German which the Public Prices for the Provision of Services or Realization of Collaborative Arthritis Centers. Lupus. 2004;13(7):529–536. Own Activities of the Aragonese Public Bank Entity are Created. doi:10.1191/0961203304lu1054oa Saragossa; 2015 submit your manuscript | www.dovepress.com ClinicoEconomics and Outcomes Research 2019:11 764 DovePress Powered by TCPDF (www.tcpdf.org) Dovepress Cevey et al 31. Official Gazette of Cantabria Approval of the Price Tariff of the Products 45. Boletín oficial de Aragón. Resolución de 30 de Julio de 2012, de La and Services Provided by the Blood and Tissue Bank of Cantabria for Dirección Gerencia Del Servicio Aragonés de Salud, Sobre Revisión the Year 2017 in the Autonomous Region of Cantabria. Santander; 2017 de Las Tarifas a Aplicar Por La Prestación de Servicios Sanitarios a 32. Banc de sang i teixits de Catalunya. Llista de Preus. Barcelona; 2018 Terceros Obligados Al Pago o a Usuarios Sin Derecho a Asistencia 33. Official Bulletin of the Canary Islands. Resolution of March 29, 2017, Sanitaria En L. Zaragoza; 2012. of the Director, by which the Amount of the Public Prices of Sanitary 46. Osakidetza. Tarifas Para Facturación de Servicios Sanitarios y Services Provided is Modified in Decree 81/2009, of June 16, Whereby Docentes de Osakidetza Para El Año 2018. Vitoria; 2018. the Public Prices of Health Services are Established P. 2017 47. Boletín oficial de La Rioja. Resolución Número 169, de 26 de Enero 34. Official Gazette of Aragon RESOLUTION of July 30, 2012, of the de 2012, Del Consejero de Salud y Servicios Sociales Por La Que Se Management of the Aragonese Health Service, on Revision of the Dispone La Publicación de Las Tarifas Por Servicios Sanitarios Fees to be Applied for the Provision of Sanitary Services to Third Prestados a Particulares En Los Centros Del Servicio Riojano de Parties Obligatory to the Payment or to Users Without Right to Salud. Logroño; 2012. Sanitary Assistance in L. Zaragoza; 2012. 48. Diari Oicial de la Generalitat de Catalunya. SLT/30/2013, de 20 de 35. Official Gazette of the Region of Murcia Ministry of Finance and Febrero, Por La Que Se Aprueban Los Precios Públicos Del Servicio Public Administration. Order of February 16, 2017 Number 48. Catalán de La Salud. Barcelona; 2013. Murcia; 2017 49. Boletín oficial de Madrid. Orden 727/2017, de 7 de Agosto, Del 36. OSAKIDETZA (Basque Health Service) Rates for Invoicing of Consejero de Sanidad, Por La Que Se Fijan Los Precios Públicos Sanitary Services and Teachers of Osakidetza for the Year 2018. Por La Prestación de Los Servicios y Actividades de Naturaleza Vitoria; 2018 Sanitaria de La Red de Centros de La Comunidad de Madrid. 37. Official Gazette of La Rioja Resolution Number 169, of January 26, Madrid; 2017. 2012, of the Minister of Health and Social Services for which the 50. Boletín Oficial de la Junta de Andalucía. Orden de 14 de Octubre de Publication of the Rates for Health Services Provided to Individuals is 2005, Por La Que Se Fijan Los Precios P–blicos de Los Servicios Provided in the Centers of the Riojan Health Service. Logroño; 2012. Sanitarios Prestados Por Centros Dependientes Del Sistema Sanitario 38. Official Diari of the Generalitat de Catalunya. SLT/30/2013, of Público de Andalucía. Sevilla; 2005. February 20, Whereby the Public Prices of the Catalan Health 51. Stohl W, Schwarting A, Okada M, et al. Efficacy and safety of Service are Approved. Barcelona 2013. subcutaneous Benlysta in systemic lupus erythematosus: a rando- 39. Official Bulletin of Madrid. ORDER 727/2017, of August 7, of the mized, double-blind, placebo-controlled, 52-week study. Arthritis Minister of Health, by which the Public Prices for the Provision of Rheum. 2017. doi:10.1002/art.40049 the Services and Activities of Sanitary Nature of the Network of 52. Cortés J, Andreu JL, Calvo J, et al. Evaluation of use of benlysta in Centers of the Community of Madrid are Fixed. Madrid 2017 clinical practice settings (Observe Study) in Spain: health resource 40. Official Gazette of the Council of Andalusia ORDER of October 14, 2005, utilization and labor absenteeism. Value Health. 2014;17(7):A534. Whereby the Public Prices of Health Services Provided by Dependent doi:10.1016/j.jval.2014.08.1703 Centers of the Public Health System of Andalusia. Sevilla, 2005. 53. Parks D, Ramachandran S, Kurtinecz M, Asukai Y, Alfonso- 41. Parks D, Ramachandran S, Kurtinecz M, Asukai Y, Alfonso-Cristancho Cristancho R. SAT0223 indirect comparative clinical effectiveness R. Indirect comparative clinical effectiveness of intravenous and sub- of intravenous and subcutaneous formulations of belimumab for the cutaneous formulations of Benlysta for the treatment of adult patients treatment of adult patients with active, autoantibody-positive sys- with active, autoantibody-positive systemic lupus erythematosus with temic lupus erythematosus with high disease activity. In: EULAR high disease activity. Ann Rheum Dis. 2017;76(Suppl 2). Congress. Poster Presentations. BMJ Publishing Group Ltd and 42. Cevey M, Calvo-Alén J, Crespo C, Robles-Marhuenda A, Cortés J European League Against Rheumatism; 2017:857.3–858. Direct cost offsets related to belimumab subcutaneous administration doi:10.1136/annrheumdis-2017-eular.4701 in patients with systemic lupus erythematosus in Spain. Available 54. Strand V, Levy RA, Cervera R, et al. Improvements in health-related from: https://tools.ispor.org/ScientificPresentationsDatabase/ quality of life with belimumab, a B-lymphocyte stimulator-specific Presentation/85326?pdfid=56520. Accessed October 25, 2019. inhibitor, in patients with autoantibody-positive systemic lupus erythe- 43. Ministry of Health, Social Services and Equality Institute of Health matosus from the randomized controlled BLISS trials. Ann Rheum Dis. Information. Registration of registrations – CMBD 2015. MSSSI 2017. Available from: https://www.msssi.gob.es/estadEstudios/estadisticas/ 2014;73(5):838–844. doi:10.1136/annrheumdis-2012-202865 55. Seoane-Mato D, Sánchez-Piedra C, Silva-Fernández L, et al. sisInfSanSNS/aplicacionesConsulta/home.htm. Accessed November 2017 44. Boletín Oficial de Canarias. Resolución de 29 de Marzo de 2017, Del Prevalence of rheumatic diseases in the adult population in Spain Director, Por La Que Se Modifica La Cuantía de Los Precios (EPISER 2016 study). III. Objectives and methodology. Clinical Públicos de Servicios Sanitarios Previstos En El Decreto 81/2009, Reumatol. 2017. doi:10.1016/j.reuma.2017.06.009 de 16 de Junio, Por El Que Se Establecen Los Precios Públicos de Los Servicios Sanitarios P.; 2017. ClinicoEconomics and Outcomes Research Dovepress Publish your work in this journal ClinicoEconomics and Outcomes Research is an international, peer- organization also constitute important areas of coverage. The manu- reviewed open-access journal focusing on Health Technology script management system is completely online and includes a very Assessment, Pharmacoeconomics and Outcomes Research in the areas quick and fair peer-review system, which is all easy to use. Visit of diagnosis, medical devices, and clinical, surgical and pharmacological http://www.dovepress.com/testimonials.php to read real quotes from intervention. The economic impact of health policy and health systems published authors. Submit your manuscript here: https://www.dovepress.com/clinicoeconomics-and-outcomes-research-journal submit your manuscript | www.dovepress.com ClinicoEconomics and Outcomes Research 2019:11 765 DovePress Powered by TCPDF (www.tcpdf.org)