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Digestive and Liver Disease 39 (2007) 617–625

Alimentary Tract

Treatment cost of ulcerative colitisIs apheresis with Adacolumn® cost-effective?

J. Panes a, M. Guilera b, D. Ginard c, J. Hinojosa d, P. Gonzalez-Carro e,V. Gonzalez-Lara f, V. Varea g, E. Domenech h, X. Badia b,∗

a Gastroenterology Service, Hospital Clinic, Villarroel, 170, 08036 Barcelona, Spainb Health Outcomes Research Europe, a unit of IMS, Avda. Diagonal, 618, 1C-D, 08021 Barcelona, Spain

c Digestive System Service, Hospital Son Dureta, C/Andrea Doria, 55, 08014 Mallorca, Spaind Digestive Service Unit, Hospital Sagunto, Avda. Ramon y Cajal, s/n 46520 Valencia, Spain

e Digestive System Unit, Hospital La Mancha Centro, Avda. de la Constitucion, 3, 13600 Alcazar de San Juan, Ciudad Real, Spainf Digestive System Service, Hospital Gregorio Maranon, C/Dr. Esquerdo, 46, 28007 Madrid, Spain

g Gastroenterology Section, Hospital San Juan de Dios, Pg Sant Joan de Deu, 2, 08950 Esplugues de Llobregat, Barcelona, Spainh Digestive System Service, Hospital Germans Trias i Pujol, Ctra. Del Canyet, s/n 08916 Badalona, Barcelona, Spain

Received 7 July 2006; accepted 27 March 2007Available online 24 May 2007

bstract

Background. Scarce data are available in Europe on the cost of treatment for ulcerative colitis (UC).Aim. To assess the cost of illness of moderate-to-severe UC in two scenarios: traditional treatment versus alternative treatment incorporating

ranulocyte, monocyte adsorption – apheresis (GMA-Apheresis; Adacolumn®). To determine the relative cost-effectiveness of both optionsn steroid-dependent patients.

Methods. One-year cost-of-illness and cost-effectiveness analysis from the third-payer perspective using a decision tree model was carriedut. Probabilities of each event were derived from the literature and an expert panel. Direct medical costs were obtained from official sourcesD 2004). Effectiveness was measured by the proportion of patients achieving clinical remission.

Results. The average annual cost per patient treated with traditional treatment was estimated to be D 6740; with GMA-Apheresis, the costas estimated to be D 6959. In steroid-dependent patients, the average annual cost was D 6059 and D 11,436, respectively. The proportion ofatients achieving clinical remission with GMA-Apheresis was 22.5% higher. As second- and third-line therapy, a new course of corticosteroidsnd surgery was avoided in 18.5 and 4% of patients, respectively.

®

Conclusions. Incorporating GMA-Apheresis (Adacolumn ) in the therapeutic management of moderate-to-severe UC patients is cost-ffective and implies savings related to the reduction of adverse effects derived from corticosteroid use and to the decreased number of surgicalnterventions.

2007 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

ae

eywords: Apheresis; Costs; Ulcerative colitis

. Introduction

Granulocyte, monocyte adsorption – apheresis (GMA-pheresis; Adacolumn®) is an adsorptive type of apheresisevice that performs the adsorption of selective granulocyte

∗ Corresponding author. Tel.: +34 93 209 32 57; fax: +34 93 241 27 10.E-mail address: xbadia@es.imshealth.com (X. Badia).

iiiaei

590-8658/$30 © 2007 Editrice Gastroenterologica Italiana S.r.l. Published by Elseoi:10.1016/j.dld.2007.03.007

nd monocyte/macrophage from peripheral blood [1]. How-ver, its action is based not only on the removal of thosenflammatory cells but also on the regulation of the globalmmune response, which is mainly based on its capacity to

nduce a decline in the release of inflammatory cytokinesnd the down-modulation of adhesion molecules [2,3]. Sev-ral studies have confirmed the efficacy of its use, especiallyn corticosteroid-dependent patients [4–6].

vier Ltd. All rights reserved.

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2.3. Cost-effectiveness analysis

18 J. Panes et al. / Digestive an

Scarce data on costs of illness in moderate-to-severe activelcerative colitis (UC) patients are available in Spain and,o our knowledge, no cost-effectiveness studies comparingherapeutic alternatives for UC treatment have been per-ormed. The first aim of this study was to assess the costf illness for UC patients showing moderate-to-severe activeisease through a probabilistic decision tree by modelling twolternative therapeutic strategies, a traditional treatment andn alternative treatment incorporating GMA-Apheresis interoid-dependent patients. A secondary aim was to performcost-effectiveness analysis (CEA) comparing both thera-

eutic strategies in the subset of steroid-dependent patients.ecent studies have confirmed the positive effect of this pro-edure in this subpopulation [7,8].

Estimation of probabilities used in the model come primar-ly from uncontrolled studies and may overestimate efficacyutcomes. However, these estimates were weighted by aanel of Spanish gastroenterologists experienced in the usef apheresis therapy [9].

. Methods

.1. Design

A 1-year cost-of-illness analysis was carried out using aecision tree model from a prevalence approach [10]. Theecision tree includes the health status probabilities alonghe therapeutic management of the disease and the costf direct medical health resources applied in each status.ost estimations are made for an average patient with aoderate-to-severe UC flare-up throughout the treatment of

cute disease and maintenance over 12 months of follow-p.

Treatment patterns were applied according to broadly

ccepted international recommendations and current practicen Spain [11]. The probabilities of occurrence of the events

odelled in the decision tree were derived from the litera-ure, when available, and an expert consensus panel of seven

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Fig. 1. Cost-of-illness algorithm for traditional therapy or optical treatme

Disease 39 (2007) 617–625

astroenterologists validated its applicability to the Span-sh current practice [9]. This study was conducted from ahird-payer perspective, and only direct costs were included12,13].

.2. Cost-of-illness model

The patient enters the model with moderate-to-severective UC, and the cost of illness under two different thera-eutic scenarios is compared:

A). Traditional treatment: Consists of prednisone (0.75 mg/kg/day per 10 days) in the acute phase and is fol-lowed by a tapering dose regimen over 2–3 months.After this acute treatment, the standard regimen incor-porates 5-aminosalicylates as maintenance therapy inthose patients achieving remission, or immunosuppres-sors (azathioprine (AZA), cyclosporine) and surgery innon-responders, as required in current practice. All ofthese drugs were defined as main drugs. Other concomi-tant medication costs, including calcium, vitamin D andheparin, were negligible. Following the standard prac-tice, all patients developing corticosteroid-dependence(defined as patients presenting a new flare-up within 6months [14]) will receive AZA therapy (Fig. 1a, branchA).

B). Alternative treatment: It replicates the previous sce-nario, but GMA-Apheresis (1 apheresis/week per 5weeks) is incorporated as an alternative to AZA in 40%of patients developing corticosteroid-dependence. Thismarket penetration rate was set up according to theexpert panel (Fig. 1a, branch B).

In the CEA we focused only on the subset of steroid-ependent patients, and the cost and effectiveness of the tworeviously reported therapeutic scenarios were compared:

nt including Adacolumn® in moderate-to-severe flare-up of UC.

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A). Traditional treatment: All patients received AZA(Fig. 1a, branch A).

B). Alternative treatment: GMA-Apheresis is incorporatedas additional therapy (Fig. 1a, branch B).

The effectiveness of first-line therapy was defined as theroportion of patients achieving clinical remission withouteceiving a second course of corticosteroid therapy or surgeryithin the 1-year follow-up. Clinical remission was defined

s the absence of clinical symptoms and normal biomarkersf disease activity (C-reactive protein and erythrocyte sed-mentation rate). Effectiveness in second-line therapy wasefined as patients achieving clinical remission after receiv-ng a new course of corticosteroids and AZA but avoidingurgery. Effectiveness in third line was achieved by surgery,ith or without complications. The outputs of the model are

xpressed in terms of incremental cost-effectiveness ratioICER) between both therapeutic strategies, which repre-ent the additional cost that needs to be expended in ordero achieve an additional unit of effectiveness. In other words,t expresses the cost per moderate-to-severe active UC patientchieving clinical remission after incorporation of GMA-pheresis in the treatment.

.4. Clinical input parameters

Several health statuses are common for both therapeutictrategies. The probability of a patient having a remissionfter a course of corticosteroids in the acute phase was esti-ated using the Truelove and Witts study [15]. In this study,

linical remission was observed in 44.2% of patients withoderate-to-severe UC after 6 weeks of initiating treatmentith corticosteroids. Patients who failed to respond to cor-

icosteroids after 6 weeks were defined as corticosteroidefractory (55.8%) (Fig. 1a).

.4.1. Clinical inputs after acute corticosteroidreatment

Patients showing remission following treatment with cor-icosteroids were given maintenance therapy with 5-ASA.n accordance with the results found by Faubion et al., 1ear after a systemic course of corticosteroids is admin-stered, it is estimated that 49% of patients would remainn remission with 5-ASA maintenance therapy, 22% wouldave another flare-up within 6 months (this group has beenefined as steroid-dependent) and the remaining 29% wouldave another flare-up after 6 months [14]. According to thexperts’ opinion, most patients in the latter group will beiven a second course of steroids (82.5%), and those withhe most serious conditions may require surgery (17.5%).Fig. 1a)

.4.2. Clinical inputs in steroid-dependent patientsAccording to the literature, clinical remission with AZA

s achieved in 60–70% of patients after the 1-year treatmenteriod; 35% of these patients will have another flare-up within

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Disease 39 (2007) 617–625 619

his time period [16,17]. In order to calculate the remissionate with AZA for 1 year, the following formula was drawnp:

P(remission maintained with AZA for 1 year)

= P(remission with AZA) × 1

−P(new attack within 1 year)

Using this formula, there is a probability of8.5% of maintaining remission with AZA for 1 yearP = 0.6 × (1 − 0.35) = 0.385).

The remission rate achieved with GMA-Apheresis wasbtained by calculating the weighted average responsebserved in uncontrolled studies in patients with UC and wasstimated at 61% (CI 95%; 45–77.2%) [18–22].

As second-line therapy, a new course of corticosteroidslus AZA (82.5%) or surgery (17.5%) was contemplatedor patients who had not achieved clinical remission dur-ng first-line therapy or relapsed during follow-up. Amongatients requiring surgery, the proportion of patients withr without complications was stated at 15 versus 85%,espectively, which was the same in both therapeutic optionsFig. 1b).

.4.3. Clinical inputs in corticosteroid-refractoryatients

According to the panel of experts, 95% of patients withteroid refractory UC would undergo treatment with intra-enous cyclosporine, whilst surgery may be indicated for theemaining 5% (Fig. 1a). The probability of remission follow-ng treatment with cyclosporine was obtained from the studyy Cohen et al. [23]. According to the expert panel consen-us, it was accepted that following the acute treatment withyclosporine, 30% of the patients would receive monother-py with AZA [24,25] and 70% would receive combinedherapy with oral cyclosporine plus AZA. The probabilitiesf remission during each therapy were presumed to be simi-ar; that is, 38.5% of patients who received monotherapy orombined therapy would maintain remission for the rest ofhe year (Fig. 1a).

.5. Data source for resource use and costs

In Tables 1 and 2, mean unit costs for the pharmaco-ogical treatment (aminosalycilates, corticosteroids, AZA,yclosporine; Adacolumn®) and medical resources (adversevents, medical visits, laboratory, radiology, endoscopy, inpa-ient service, hospitalisation, surgery) are shown.

Data on medication, blood tests, other diagnostic proce-ures and mean hospital length of stay for patients with UCere gathered from a questionnaire filled out by the expert

anel. The inputs detailed for each health status included theosing regimen of each treatment, the number of patients whonderwent each procedure, the number of medical visits andhe average hospital stay. The incidence of adverse effects of

620 J. Panes et al. / Digestive and Liver Disease 39 (2007) 617–625

Table 1Unit costs for main medication and adverse events

Medication Mean dose Mean duration Cost × course

PrednisoneAcute course 0.75 mg/kg/day 11.5 days D 48.5Tapering 2.3 months D 169.8

5-ASA 2–2.5 g/day 8 months D 991.3

Azathioprine 2–2.5 mg/kg/day 9 months D 181.3

Cyclosporine IV 4 mg/kg/day 7 days D 60.6

Cyclosporine oral 8 mg/kg/day 4.5 months D 1519.8

Adacolumn® One infusion/session 5 weeks D 6500.0

SurgeryColectomy D 2168.7Colectomy + proctectomy D 3000.0

Adverse events Patient (%) DRG Unit cost × DRG Mean cost × patient

Corticosteroid acute courseMild neuropsychiatry reaction 25 432 D 1585.6 D 396.4Severe neuropsychiatry reaction 2 426 D 3184.0 D 47.7Infectious reaction 12.7 416 D 5352.8 D 679.8

Corticosteroid chronic courseOsteopenia 30 244 D 1299.8 D 389.9Osteoporosis 10 244 D 2599.5 D 259.9

AzathioprineAllergic reaction 2 447 D 1300.9 D 26.0Pancreatitis 3.3 204 D 2347.0 D 77.5Severe myelotoxicity 2 414 D 2338.9 D 46.8

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he main drugs used in the study (corticosteroids [26–29] andZA [16]) was derived from the literature and validated by

he expert panel.Cost per patient was calculated by combining three com-

onents: the resource consumed and the unit costs of eachesource along with the clinical input probabilities in each

atD

able 2nit costs applied according to the proportion of patients using the resource and th

Unit cost per item(D 2004)

Percentag

eneral practitioner 14.9 45astroenterologist 64.9 100ther specialists 47.8 21lood test 9.3 100lood cyclosporine levels 31.1 100lain abdominal X-ray 17.2 55bdominal ultrasonography 56.4 55arium enema 72.7 28mall bowel follow-through 35.1 7.5bdominal scintigraphy 1440.7 10olonoscopy plus colonic biopsy 192.6 100one densitometry 108.8 80ospitalisation (cost per day) 273.4 20a Average proportion of patients using the resource in all different treatment p

zathioprine, cyclosporine, GCAP).b Mean number of resources used in different treatment phases.

D 1389.7 D 4.2

ealth status. Costs per patient from each disease status wereombined to obtain the total mean cost.

The data on unit costs were taken from official databasesvailable in Spain: the Catalogue of Pharmaceutical Special-ies (for drugs) and SOIKOS (for health resources) [30,31].iagnosis-related groups (DRG) were used as a cost mea-

e number of items applied

e of patientsa Number of resourcesb Mean cost perpatient (D 2004)

2.25 15.12.60 168.91.25 12.55.3 58.84.5 139.82.5 23.61 311 20.41 2.61 144.11 192.61 878 437.4

hases (acute and chronic course of corticosteroids, 5 ASA maintenance,

J. Panes et al. / Digestive and Liver

Table 3Cost-of-illness model

Traditional % GCAP %

Average costs (D )Main drugs D 1205.00 18 D 1454.00 21Concomitant medication D 32.00 0.1 D 32.00 0.1Visits and diagnostic procedures D 1316.89 20 D 1033.59 15Hospitalisations (+surgery) D 2131.11 32 D 2397.41 34Adverse events D 2055.00 30 D 2042.00 29

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ncremental cost D +219

nnual medical costs of moderate-to-severe UC patients.

urement unit for adverse effects. All data on costs refer touros in 2004.

As the model had been conducted for a period of time noonger than 1 year, it was not necessary to discount costs orenefits [12,13].

.6. Sensitivity analysis

Univariate sensitivity analyses were conducted in bothodels to cope with uncertainty in the cost estimates and

o assess the robustness of the model. The most relevantariables in each individual analysis were the cost of dailyreatment with AZA and the cost of the adverse effectsaused by AZA during the maintenance phase. Plausiblealue ranges based on expert opinion were used.

. Results

.1. Effects on resources

.1.1. Cost of illnessTable 3 shows the average medical costs for each treatment

ption. The average annual cost per patient with a moderate-o-severe flare of UC following traditional treatment wasstimated at D 6740. The average annual cost per patient with

C incorporating GMA-Apheresis was estimated at D 6959.he percentage of patients incorporating GMA-Apheresis

n the cost-of-illness model was 3.8%, and the differentialost between the scenarios was D 219. Medical costs due to

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Year 1

Azathioprin

emission maintained with first-line treatmenta 385emission in second line with combined therapyb 507emission achieved by surgery without complicationsc 92emission achieved by surgery with complicationsc 16

reated patients 1000a Clinical remission achieved after first-line therapy without receiving a new coub Clinical remission achieved after second-line therapy with a new course of cortc Clinical remission achieved with surgery.

Disease 39 (2007) 617–625 621

ospitalisation (including surgery) represented the highestroportion of the total costs (32 vs. 34%, respectively), fol-owed by costs due to adverse events (30 vs. 29%), costs of

ain drugs (18 vs. 21%) and costs due to visits and diagnosticrocedures (20 vs. 15%), respectively (Table 3).

.2. Clinical efficacy outcomes

Table 4 shows the effectiveness in steroid-dependentatients. Assuming a hypothetical cohort of 1000 patientsreated with the traditional treatment compared to GMA-pheresis, remission would be achieved in 385 cases

ompared to 610, which is a 22.5% higher proportionn patients treated with GMA-Apheresis. A total of 507atients would go into remission after second-line therapyn the traditional AZA plus corticosteroid combined therapyption compared to 322 on the option incorporating GMA-pheresis; thereby treatment with corticosteroids is avoided

n 18.5% of the patients in the GMA-Apheresis group. Fur-hermore, the number of surgical interventions would be 108ompared to 68, respectively, which means that 4% of surgi-al interventions would be avoided in the group treated withMA-Apheresis (Table 4).

.2.1. Cost-effectiveness analysisTable 5 shows the estimates from the CEA. The aver-

ge annual cost per steroid-dependent patient achievinglinical remission on traditional treatment was estimatedt D 6059. The average annual cost per patient with UCncorporating GMA-Apheresis was estimated at D 11,436.

total of 38.5% of patients achieved clinical remissionith the traditional treatment, compared to 61% of patientsith GMA-Apheresis which leads to D 15,738 and D 18,748er remission, respectively. Therefore, incorporating GMA-pheresis in the treatment of steroid-dependent patients

esulted in D 23,898 per patient achieving clinical remis-ion, without receiving an extra course of corticosteroids orurgery.

Costs due to adverse events accounted for the highest pro-

ortion of costs in the group of patients following traditionalherapy with AZA (47 vs. 21%), whilst the proportion ofhe costs attributed to main drugs was the highest in patientsreated with GMA-Apheresis (4 vs. 57%), respectively. Hos-

% Difference

e treatment GCAP treatment

610 +22.5322 −18.5

58 −4.010

1000

rse of corticosteroids or surgery.icosteroids and azathioprine.

622 J. Panes et al. / Digestive and Liver

Table 5Cost-effectiveness model

AZA % GCAP %

Average costs (D )Main drugs D 254.00 4 D 6572.00 57Concomitant medication D 25.00 0.1 D 27.00 0.1Visits and diagnostic procedures D 1000.10 17 D 888.20 8Hospitalisations (+surgery) D 1909.90 32 D 1533.80 13Adverse events D 2870.00 47 D 2415.00 21

Total cost D 6059 D 11436

Incremental cost D +5377Effectivenessa 38.5% 61%Incremental effectiveness 22.5%Cost per remission D 15738b D 18748c

ICER D 23898d

Annual medical costs of corticosteroid-dependent moderate-to-severe UCper patient. ICER, incremental cost-effectiveness ratio.

a Clinical remission achieved under first-line treatment without receivinga new course of corticosteroids or surgery.

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italisation (including surgery) accounted for 32 versus 13%f costs, and costs due to medical visits and diagnostic pro-edures were 17 versus 8%, respectively (Table 5).

.3. Result of the sensitivity analysis

When the costs of AZA (D 0.67, range 0.59–0.75) andZA-related adverse events (D 128, range 93–210) were

ncreased or lowered accordingly, the cost of traditionalherapy and the alternative therapy after introducing GMA-pheresis did not show much variation in the global costs.he differential cost remained constant throughout the rangef values analysed for each variable.

. Discussion

The average annual cost per patient with moderate-to-evere active UC per year in Spain following traditionalreatment with corticosteroids is D 6740, and the costf an alternative treatment, including GMA-ApheresisAdacolumn®), in steroid-dependent patients is D 6959.herefore, the study shows that including GMA-Apheresis

n the therapeutic management of UC would entail a costncrease per patient of only D 219 compared to the traditionalreatment. This increase in the overall cost of the disease isxplained by the dilution of the incremental cost by incorpo-ating GMA-Apheresis in a small subset of patients – thoseho, by relapsing within 6 months of the previous diseaseare-up, are defined as steroid-dependent.

To our knowledge, no previous studies comparing costsetween alternative therapies in UC have been published.onetheless, several cost-of-illness analyses have been done

n Europe and in the U.S. [32–35]. Despite disparities in

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Disease 39 (2007) 617–625

lobal cost estimates, surgery and in-patient costs accountor the largest part of UC medical costs in those studies: 56%n the U.S, 58% in Sweden and 49% in the U.K. [33,34,35]. Inur model, those items have accounted for 32–34%, respec-ively, of the global expenditure. However, it is importanto point out that, compared to other studies, our model hasncluded the costs derived from adverse events due to medi-ation, which accounts for approximately 30% of the overallC expenditures in both arms. This may explain why, on aver-

ge, our cost estimates were higher. Moreover, our algorithmodels an average patient with moderate-to-severe active UC

nd projects his hypothetical course along 12 months; there-ore, it is difficult to make comparisons with the cost estimatesrom studies including overall disease stages from diagnosishrough lifetime treatment, cure or remission. Additionally,ther differences, such as the study time period, the method-logical approach or health systems divergences prevent toake comparisons [33,34,35].Our estimates are close to those found in a single study

f cost of illness in IBD, which reports data on UC patientsathered in Spain [36]. A Delphi questionnaire methodologyas employed to assess the global costs for UC and Crohn’sisease in 2004 [36]. Although individual costs for UC areot available, on average, D 7382 per IBD patient-year waseported. Again, hospitalisation and surgery accounted forhe largest part of the direct costs (76.8%) [36].

In the second step, using the same methodology, a CEAn steroid-dependent patients showing a new flare-up within

months was developed. Treatment with AZA or GMA-pheresis was compared. The decision algorithm for the

nnual cost of patients treated with AZA was estimated at6059, and for patients treated with GMA-Apheresis, it wasstimated at D 11,436. According to the results published inhe literature in this subset of patients, treatment with GMA-pheresis is one and a half times more effective than withZA; thus, a cost of D 15,738 and D 18,748 per remission withZA and GMA-Apheresis was calculated, respectively, and a

ost of D 23,898 per patient per year achieving clinical remis-ion, without the patient receiving an additional course oforticosteroids or surgery, was found. Despite the incrementalffect of GMA-Apheresis costs among the therapeutic items,t has to be noted that an important reduction in the use of med-cal services, hospitalisations, surgery and adverse event costsssociated with steroids and AZA will be obtained by intro-ucing GMA-Apheresis. These results are in accordance withrevious studies [37]. One study assessing outpatient careeported that the use of corticosteroids and the managementf osteoporosis had an impact on annual costs in Germany37]. Moreover, by reducing hospitalisations and surgery, aotential reduction in indirect and intangible costs should beredicted. If the number of medical visits, adverse events andospitalisations decline, patient productivity would increase,

nd a parallel improvement in quality of life would take place,s has been reported in studies where evaluation of quality ofife has been performed using validated tests [32,33,35,38].hese additional expenditures not contemplated in the cur-

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ent study would clearly offset the incremental cost of UCreatment incorporating Adacolumn®.

GMA-Apheresis is an emergent procedure which may rep-esent an option for delaying or even avoiding surgery in someC patients [22]. In the current study we estimated the costsf Adacolum treatment by assuming every patient wouldeceive five apheresis sessions. This was based on the onlyulticentre randomised trial comparing 5 versus 10 aphere-

is sessions and showing similar efficacy [39]. Further studiesre being performed not only to assess its implication as anlternative for acute flare-up treatment but also to evaluatets role in maintaining disease in remission [1,2]. Proce-ures decreasing hospitalisation and surgery could lowerotal medical costs substantially. In order to illustrate thisoint, a budget impact analysis was performed taking intoccount current Spanish epidemiologic data on prevalence,ncidence and mortality due to UC [40–42]. Assuming thatMA-Apheresis would be administered to 15% of steroid-ependent patients in 2005 and a projected 70% of patientsn 2010, the additional cost of UC treatment incurred byhe Spanish Health System by introducing GMA-Apheresisould only increase 3.4% in 2010.This study has a number of limitations. First of all, the

evelopment of our decision tree algorithm was based ononditional probabilities of reaching a health status or a treat-ent regimen according to existing published evidence, when

vailable. The expert panel validated those data, and whenata could not be found in the literature, estimates werehosen based on the panel consensus. Rough data, such ashe effectiveness of GMA-Apheresis reported in observa-ional non-controlled studies, have been applied. Althoughhe probabilities introduced in the model could over- or under-stimate real estimates for UC management in Spain, thexpert panel confirmed the applicability of these data to thepanish daily practice environment. Moreover, by modellingn average patient through a decision algorithm based oniterature review and a validation panel, the selection bias,hich would tend to include too mild or too severe patients

rom insurance claims data or convenience samples charteviews, are avoided. However, overestimation of efficacyy using uncontrolled studies or of relapse rate by usinghe Truelove data cannot be ruled out. Secondly, it wasssumed in the model that GMA-Apheresis would be appliedo 40% of steroid-dependent patients. Setting up this assumedroportion at a lower or a higher level would modify ourodel estimates. However, the model for budgetary impact

onfirms the slight increase of the cost after adding GMA-pheresis from market penetrations of 15–70%. Thirdly,ther costs, such as those of intensive care unit admissions orarenteral nutrition use, were not considered, and this wouldave introduced an underestimation for hospitalisation coststimates in both therapeutic options. Finally, the cost of

nfliximab, which has recently shown efficacy for the treat-

ent of UC, was not incorporated in the model, as it has notet been incorporated in the current practice of UC treatment43,44].

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Disease 39 (2007) 617–625 623

In summary, we can conclude that adding GMA-ApheresisAdacolumn®) to the overall management of patients withoderate-to-severe flare-ups of UC entails a reasonable addi-

ional cost that could be afforded by the Spanish Healthystem [45].

Practice points

• The average annual cost per moderate-to-severe patient treated with traditionaltreatment in Spain is D 6740 and with GMA-Apheresis is D 6959.

• In steroid-dependent patients the averageannual cost per remision was D 15,738 andD 18,748 for patients treated with AZA andGMA-Apheresis, respectively.

• The proportion of patients achieving clinicalremission with GMA-Apheresis was 22.5%higher than with traditional treatment.

• A new course of corticosteroids and surgerywas avoided in 18.5 and 4% of patientstreated with GMA-Apheresis, respectively.

• The overall management of patients withmoderate-to-severe flare-ups of UC entailsa reasonable additional cost that could beafforded by the Spanish Health System.

Research agenda

• Sham-controlled studies have yet to estab-lish the efficacy of apheresis in UC.

• Characterisation of the efficacy of apheresisin difficult-to-treat patients such as those withsteroid-refractory or steroid-dependent dis-ease is needed.

• The optimal treatment regimen in terms ofnumber and frequency of apheresis remainsto be established.

• Treatment of specific population subgroupssuch as children or pregnant women maybenefit from safe treatments and need to beevaluated.

• Reassessment of costs of medical treatmentafter approval of infliximab for the treatmentof ulcerative colitis should be considered.

onflict of interest statementhis study was financially supported by Otsuka Pharmaceu-

ical S.A. Spain.

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cknowledgements

Special thanks to Raul Lafuente, MD, for his scientificupport. This study was financially supported by Otsukaharmaceutical S.A. Spain.

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