2009 Convegno Malattie Rare Salvarani [22 01]

LA TERAPIA DELLAMALATTIA DI BEHÇET CON FARMACI BIOTECNOLOGICIFARMACI BIOTECNOLOGICI

C. Salvarani and N. PipitoneC. Salvarani and N. Pipitone

Unità Operativa di Reumatologia Unità Operativa di Reumatologia

Ospedale di Reggio Emilia Ospedale di Reggio Emilia

La Terapia della Malattia di Behçet

�� EULAR recommendations for the management of BDEULAR recommendations for the management of BD�� AntiAnti--TNF therapy in the management of BD: review TNF therapy in the management of BD: review

and basis for recommendationsand basis for recommendations�� Infliximab for the treatment of NeuroInfliximab for the treatment of Neuro--BehçetBehçet�� Infliximab in the treatment of BuddInfliximab in the treatment of Budd--Chiari syndrom e Chiari syndrome

in patients with BDin patients with BD�� InterferonInterferon--alpha2a in the treatment of BD uveitisalpha2a in the treatment of BD uveitis

EULAR Recommendations for EULAR Recommendations for the management of Behçet’s diseasethe management of Behçet’s disease

Ann Rheum Dis, 2008; 67:1656Ann Rheum Dis, 2008; 67:1656--16621662

Management of Behçet’s disease: a systematic literature Management of Behçet’s disease: a systematic literature review for the EULAR evidence based Recomreview for the EULAR evidence based Recom--review for the EULAR evidence based Recomreview for the EULAR evidence based Recom--

mendations for the management of Behçet’s diseasemendations for the management of Behçet’s diseaseAnn Rheum Dis published online 17 Apr 2008Ann Rheum Dis published online 17 Apr 2008

G Hatemi, D Bang, B Bodaghi, AM Chamberlain, A Gul, MH Houman, I G Hatemi, D Bang, B Bodaghi, AM Chamberlain, A Gul, MH Houman, I Kötter, I Olivieri, C Salvarani, PP Sfikakis, A Silman, A Siva, Kötter, I Olivieri, C Salvarani, PP Sfikakis, A Silman, A Siva,

MR Stanford, N Stübiger, S Yurdakul, H YaziciMR Stanford, N Stübiger, S Yurdakul, H Yazici

EULAR RECOMMENDATIONS FOR THEMANAGEMENT OF BEHÇET’S DISEASE

�� Objectives:Objectives: to develop EULAR recommendations for the to develop EULAR recommendations for the management of Behçet’s Disease (BD), in an evidence and management of Behçet’s Disease (BD), in an evidence and expert opinion based approach expert opinion based approach

�� Methods:Methods:-- the multidisciplinary expert committee consisted of 9 the multidisciplinary expert committee consisted of 9 -- the multidisciplinary expert committee consisted of 9 the multidisciplinary expert committee consisted of 9 rheumatologists, 3 ophthalmologists, 1 internist, 1 rheumatologists, 3 ophthalmologists, 1 internist, 1 dermatologist and 1 neurologist, representing 6 European dermatologist and 1 neurologist, representing 6 European countries, Tunisia and Korea countries, Tunisia and Korea

-- Systematic literature search was performed using MedLine Systematic literature search was performed using MedLine and Cochrane library through December 2006 and Cochrane library through December 2006

-- Strength of each recommendation was determined Strength of each recommendation was determined according to the level of evidence and the experts opinions according to the level of evidence and the experts opinions


1. 1. Any patient with BD and inflammatory eye disease Any patient with BD and inflammatory eye disease affecting the posterior segmentaffecting the posterior segmentshould be on a should be on a treatment regime, which includes azathioprine and treatment regime, which includes azathioprine and systemic corticosteroids systemic corticosteroids

2. If the patient has 2. If the patient has severe eye diseasesevere eye diseasedefined as >2 lines defined as >2 lines of drop in visual acuity on a 10/10 scale and/or retinal of drop in visual acuity on a 10/10 scale and/or retinal disease (retinal vasculitis or macular involvement) it is disease (retinal vasculitis or macular involvement) it is recommended that either recommended that either cyclosporine A or infliximabcyclosporine A or infliximabbe used be used in combination in combination with azathioprine and with azathioprine and corticosteroids; corticosteroids; alternatively interferonalternatively interferon--alphaalpha with or with or without corticosteroids could be usedwithout corticosteroids could be used


3. 3. There is no firm evidence to guide in the managing There is no firm evidence to guide in the managing major vessel disease in BD.major vessel disease in BD.For the management of For the management of acute acute deep vein thrombosisdeep vein thrombosisimmunosuppressive agents immunosuppressive agents like corticosteroids, azathioprine, cyclophosphamide or like corticosteroids, azathioprine, cyclophosphamide or cyclosporine are recommended. For the management of cyclosporine are recommended. For the management of both pulmonary and peripheral arterial aneurysms, both pulmonary and peripheral arterial aneurysms, cyclophosphamide and corticosteroids are cyclophosphamide and corticosteroids are both pulmonary and peripheral arterial aneurysms, both pulmonary and peripheral arterial aneurysms, cyclophosphamide and corticosteroids are cyclophosphamide and corticosteroids are recommendedrecommended

4. There are 4. There are no controlled data on, or evidence of benefit no controlled data on, or evidence of benefit from uncontrolled experiencefrom uncontrolled experiencewith: with: anticoagulants, anticoagulants, antianti--platelet or fibrinolytic agentsplatelet or fibrinolytic agents in the management of in the management of deep vein thrombosis or for the use of deep vein thrombosis or for the use of anticoagulationanticoagulationfor the arterial lesions for the arterial lesions


5. There is no evidence based treatmentthat can be recommended for the management of gastrointestinal involvement of BD.Agents such as sulfasalazine, corticosteroids, azathioprine, TNF sulfasalazine, corticosteroids, azathioprine, TNF antagonists or thalidomide should be tried first before surgery, except in emergencies

6. In most patients with BD, arthritis can be managed with colchicine


7. There are no controlled datato guide the management of CNS involvement in BD. For parenchymal involvementagents to be tried may include corticosteroids, interferon-alpha, azathioprine, cyclophosphamide, methotrexate and azathioprine, cyclophosphamide, methotrexate and TNF antagonists. For dural sinus thrombosiscorticosteroids are recommended

8. Cyclosporine should not be usedin BD patients with CNS involvementunless necessary for intraocular inflammation


9. The decision to treat skin and mucosa involvementwill depend on the perceived severity by the physician and the patient. Mucocutaneous involvement should be treated according to the dominant or co-dominant lesions present

• Topical measures (i.e. local steroids) should be the first line of treatment for isolated oral and genital ulcers

• Acne-like lesionsare usually of cosmetic concern only. Thus, topical measures as used in acne vulgaris are sufficient


Colchicine should be preferred when the dominant lesion is genital ulcer or erythema nodosum

Leg ulcersin BD might have different causes. Leg ulcersin BD might have different causes. Treatment should be planned accordingly

Azathioprine, interferon-alpha and TNF antagonistsmay be considered in resistant cases

AntiAnti--TNF therapy in the management of BD TNF therapy in the management of BD ––review and basis for recommendationsreview and basis for recommendations

Rheumatology, 2007Rheumatology, 2007

PP Sfikakis, N Markomichelakis, E Alpsoy, S PP Sfikakis, N Markomichelakis, E Alpsoy, S PP Sfikakis, N Markomichelakis, E Alpsoy, S PP Sfikakis, N Markomichelakis, E Alpsoy, S AssaadAssaad--Khalil, B Bodaghi, A Gul, S Ohno, Khalil, B Bodaghi, A Gul, S Ohno,

N Pipitone, M Schirmer, M Stanford, B Wechsler, C N Pipitone, M Schirmer, M Stanford, B Wechsler, C Zouboulis, P Kaklamanis, H YaziciZouboulis, P Kaklamanis, H Yazici

Posterior segment intraocular inflammation

�� In unilateral involvementIn unilateral involvement with visual acuity < 0.2 with visual acuity < 0.2 IFX can be considered; IFX can be considered; in bilateral involvementin bilateral involvement IFX IFX can be used as first line treatmentcan be used as first line treatment

�� In patients with 2 or more relapses/yearIn patients with 2 or more relapses/yeardespite, or despite, or intolerant to, adequate doses of AZA and/or Cs, or intolerant to, adequate doses of AZA and/or Cs, or interferon interferon αα--2a, combined with prednisolone (<7.5 2a, combined with prednisolone (<7.5 mg/day), IFX can be usedmg/day), IFX can be used

Parenchymal CNS involvement

�� In patients refractory to treatment In patients refractory to treatment with pulse with pulse cyclophosphamide and prednisolone cyclophosphamide and prednisolone (1 mg/Kg/day), or in those who relapse while (1 mg/Kg/day), or in those who relapse while (1 mg/Kg/day), or in those who relapse while (1 mg/Kg/day), or in those who relapse while on maintenance with AZA and prednisolone on maintenance with AZA and prednisolone (< 7.5 mg/day) IFX may be tried(< 7.5 mg/day) IFX may be tried

Intestinal inflammation

�� In patients who have failed In patients who have failed two two immunosuppressive agents (AZA, Cs, immunosuppressive agents (AZA, Cs, MTX, thalidomide, interferon MTX, thalidomide, interferon αα--2a)2a) and and MTX, thalidomide, interferon MTX, thalidomide, interferon αα--2a)2a) and and require prednisolone at a dosage > 7.5 require prednisolone at a dosage > 7.5 mg/day, IFX may be usedmg/day, IFX may be used

Mucocutaneous manifestations

�� In patients with poor quality of life In patients with poor quality of life despite, or intolerant to, adequate doses despite, or intolerant to, adequate doses of AZA, colchicine or thalidomide and of AZA, colchicine or thalidomide and of AZA, colchicine or thalidomide and of AZA, colchicine or thalidomide and require prednisolone at a dosage > 7.5 require prednisolone at a dosage > 7.5 mg/day, etanercept or IFX may be usedmg/day, etanercept or IFX may be used

Arthritis

�� In patients who have failed In patients who have failed two two immunosuppressive agents including immunosuppressive agents including MTX and require prednisolone at a MTX and require prednisolone at a MTX and require prednisolone at a MTX and require prednisolone at a dosage > 7.5 mg/day, etanercept or IFX dosage > 7.5 mg/day, etanercept or IFX may be usedmay be used

Infliximab for the Treatment of NeuroInfliximab for the Treatment of Neuro--Behçet’s Behçet’s disease: a case series and review of the literaturedisease: a case series and review of the literature

Arthritis Rheum, 2008Arthritis Rheum, 2008

N Pipitone, I Olivieri, A Padula, S D’Angelo, N Pipitone, I Olivieri, A Padula, S D’Angelo, A Nigro, G Zuccoli, L Boiardi, C SalvaraniA Nigro, G Zuccoli, L Boiardi, C Salvarani

Neuro-Behçet syndromeAkmar-Demir et al, Neuroradiology 2003

The reported frequency ranges from 2.2% to 49%The reported frequency ranges from 2.2% to 49%with 2 major types:with 2 major types:

�� 1) Parenchymal involvement (meningo1) Parenchymal involvement (meningo--encephlitis): encephlitis): �� 1) Parenchymal involvement (meningo1) Parenchymal involvement (meningo--encephlitis): encephlitis): -- the lesions are usually in the brainthe lesions are usually in the brain--stem, basal stem, basal

ganglia or deep hemisphere white matterganglia or deep hemisphere white matter-- tendency to resolve over timetendency to resolve over time

�� 2) Dural sinus occlusion 2) Dural sinus occlusion


�� Objective:Objective: To evaluate the efficacy of infliximab in a To evaluate the efficacy of infliximab in a series of patients with NBseries of patients with NB

�� Methods:Methods:�� Methods:Methods:-- We reviewed all patients with a diagnosis of BD followed We reviewed all patients with a diagnosis of BD followed

at two Italian rheumatological centers at two Italian rheumatological centers

-- We report 8 cases of NB treated with TNFWe report 8 cases of NB treated with TNF--α blockers α blockers

-- Furthermore, the published papers on the use of antiFurthermore, the published papers on the use of anti--

TNFTNF--α therapy for NB were reviewedα therapy for NB were reviewed

Results:Results:�� Including the 4 published cases, IFX was prescribed Including the 4 published cases, IFX was prescribed

for newfor new--onset NB in 8 patients and for relapsing NB onset NB in 8 patients and for relapsing NB in 4 others in 4 others

�� Adjunct therapy given together with IFX included Adjunct therapy given together with IFX included �� Adjunct therapy given together with IFX included Adjunct therapy given together with IFX included glucocorticoids, methotrexate, cyclophosphamide, glucocorticoids, methotrexate, cyclophosphamide, ciclosporin, and colchicineciclosporin, and colchicine

�� In all cases, IFX was used at a dose of 5 mg/kg In all cases, IFX was used at a dose of 5 mg/kg except for two cases in which the dose was 3 mg/kg except for two cases in which the dose was 3 mg/kg

Results:Results:�� All patients had a satisfactory clinical response, All patients had a satisfactory clinical response,

while brain MRI showed partial regression of while brain MRI showed partial regression of parenchymal lesions in all 10 patients in whom it parenchymal lesions in all 10 patients in whom it was performed before and after IFX therapy was performed before and after IFX therapy

�� At followAt follow--up, virtually all patients were in clini cal up, virtually all patients were in clinical remission remission

�� No sideNo side--effects were noted effects were noted


��Conclusion: Conclusion: Taken together, these data suggest that Taken together, these data suggest that Taken together, these data suggest that Taken together, these data suggest that infliximab may be effective and safe to treat infliximab may be effective and safe to treat NeuroNeuro--Behçet’s diseaseBehçet’s disease

Sindrome di Budd-Chiari nella Malattia di Behçet Bayraktar et al, Am J Gastroenterol 1997

�� 14/493 (2,8%) pazienti avevano trombosi delle vene 14/493 (2,8%) pazienti avevano trombosi delle vene sovraepatichesovraepatiche

�� 10/14 pazienti associavano trombosi totale della vena 10/14 pazienti associavano trombosi totale della vena cava inferiore e rappresentava il subset a prognosi cava inferiore e rappresentava il subset a prognosi peggiore (sopravvivenza media: 10,3 mesi)peggiore (sopravvivenza media: 10,3 mesi)

�� il 26% dei casi di sindrome di Buddil 26% dei casi di sindrome di Budd--Chiari Chiari associavano malattia di Behçetassociavano malattia di Behçet

Infliximab in the treatment of hepatic vein thrombosis (Budd-Chiari syndrome) in 3 patients with BD

Seyahi E et al, Rheumatology 2007

�� Two patients died, but they had almost endTwo patients died, but they had almost end--stage stage liver failure when IFX was givenliver failure when IFX was given

�� In the third patients, although there was a regression In the third patients, although there was a regression �� In the third patients, although there was a regression In the third patients, although there was a regression in the size of the thrombus in the inferior vena cava, in the size of the thrombus in the inferior vena cava, IFX was stopped for the simultaneous development IFX was stopped for the simultaneous development of cranial sinus thrombosis of cranial sinus thrombosis

�� The experience of 3 patients with BD and BuddThe experience of 3 patients with BD and Budd--Chiari syndrome was not promisingChiari syndrome was not promising

INTERFERON INTERFERON αα--2a2aINTERFERON INTERFERON αα--2a2a

Rationale for using IFN alfa in BD

�� The mechanism of action remains to be The mechanism of action remains to be elucidatedelucidated

�� Viral and bacterial infections, mainly Viral and bacterial infections, mainly herpes simplex and certain strains of herpes simplex and certain strains of streptococci, have been proposed as streptococci, have been proposed as etiologic agentsetiologic agents

Lehner et al, 1995 Lehner et al, 1995

Rationale for using IFN alfa in BD

�� It improves the elimination of foreign antigens: It improves the elimination of foreign antigens: -- enhancement of HLA class I antigen expression onenhancement of HLA class I antigen expression on

lymphoid cells lymphoid cells

-- enhancement of T and NK cell cytoxicityenhancement of T and NK cell cytoxicity

-- it diverts the T cell response in the direction of Th1it diverts the T cell response in the direction of Th1-- it diverts the T cell response in the direction of Th1it diverts the T cell response in the direction of Th1

�� It inhibits the proliferation of It inhibits the proliferation of γδγδ T cellsT cells

�� It inhibits the adhesion of T cells to endothelial It inhibits the adhesion of T cells to endothelial cellscells

Belardelli et al, Immunol Today 1996; Hasan et al, Lancet 1996Belardelli et al, Immunol Today 1996; Hasan et al, Lancet 1996

Interferon alfa for the uveitis of BDAuthorsAuthors IFN IFN

typetype

CombinedCombined

therapytherapy

DesignDesign Patient Patient

numbernumberHamurydan et al,Hamurydan et al,IMAJ 2002IMAJ 2002

αα 2b2b AzaAza openopen 1010

Alpsoy et al,Alpsoy et al,Arch Dermatol 2002Arch Dermatol 2002

αα 2a2a -- Randomized, Randomized, placeboplacebo--controlled, controlled,

4444Arch Dermatol 2002Arch Dermatol 2002 double blinddouble blind

ÇÇalgalgüüneri et al,neri et al,Ann Rheum Dis 2003Ann Rheum Dis 2003

αα -- Retrospective,Retrospective,OpenOpen

2929

KKötter et al,ötter et al,Br J Ophthalmol 2003Br J Ophthalmol 2003

αα 2a2a -- Prospective,Prospective,OpenOpen

5050

TugalTugal--Ttkun et alTtkun et al,,Graefe’s Arch Clin Graefe’s Arch Clin Exp Ophthalmol 2006Exp Ophthalmol 2006

αα 2a2a -- Retrospective,Retrospective,OpenOpen

4444

Interferon alfa for the uveitis of BDAuthorsAuthors CriteriaCriteria

for BDfor BD

Therapy Therapy durationduration

Ocular Ocular diseasedisease

Hamurydan et al,Hamurydan et al,IMAJ 2002IMAJ 2002

ISGISG 24 weeks24 weeks 10 (100%)10 (100%)

Alpsoy et al,Alpsoy et al,Arch Dermatol 2002Arch Dermatol 2002

ISGISG 3 months3 months 9/44 (20%)9/44 (20%)Arch Dermatol 2002Arch Dermatol 2002

ÇÇalgalgüüneri et al,neri et al,Ann Rheum Dis 2003Ann Rheum Dis 2003

ISGISG Mean: Mean: 22 months22 months

17/29 (59%)17/29 (59%)

KKötter et al,ötter et al,Br J Ophthalmol 2003Br J Ophthalmol 2003

ISGISG 24, 52 weeks24, 52 weeks 50 (100%)50 (100%)

TugalTugal--Ttkun et alTtkun et al,,Graefe’s Arch Clin Exp Graefe’s Arch Clin Exp Ophthalmol 2006Ophthalmol 2006

ISGISG Mean:Mean:12 months12 months

44 (100%)44 (100%)

Kötter et al, The use of interferon alfa in BD: review of the literatureSemin Arthritis Rheum 2004

�� 32 reports and 4 abstracts were included in the 32 reports and 4 abstracts were included in the analysis (reports published until July 2002)analysis (reports published until July 2002)

�� IFNIFNαα was administered to 338 pts: was administered to 338 pts: IFNIFNαα--2a: 264 pts, 2a: 264 pts, �� IFNIFNαα was administered to 338 pts: was administered to 338 pts: IFNIFNαα--2a: 264 pts, 2a: 264 pts, IFNIFNαα--2b: 74 pts2b: 74 pts

�� Higher Higher IFNIFNαα doses were more effective than low doses doses were more effective than low doses and led to up to 56% longand led to up to 56% long--term remissions after term remissions after IFNIFNααdiscontinuation: discontinuation:

-- median dosage in studies with relapses: 3.000.000 iU per week median dosage in studies with relapses: 3.000.000 iU per week -- median dosage in studies with long term remission: 24.000.000 median dosage in studies with long term remission: 24.000.000

iU per weekiU per week

Comparison of IFNα-2a and IFNα-2bKötter et al, The use of interferon alfa in BD:

review of the literature, Semin Arthritis Rheum 2004

�� Complete remissions were more common with Complete remissions were more common with IFNIFNαα--2a than with 2a than with IFNIFNαα--2b:2b:-- 91% vs 6% for ocular manifestations91% vs 6% for ocular manifestations-- 91% vs 6% for ocular manifestations91% vs 6% for ocular manifestations

-- 53% vs 6% for mucocutaneous 53% vs 6% for mucocutaneous manifestationsmanifestations

-- 74% vs 32% for articular symptoms74% vs 32% for articular symptoms

Comparison of IFNα-2a and IFNα-2bKötter et al, The use of interferon alfa in BD:


�� However complete + partial remissions were However complete + partial remissions were similarsimilar::-- 94% vs 100% for ocular manifestations94% vs 100% for ocular manifestations-- 94% vs 100% for ocular manifestations94% vs 100% for ocular manifestations

-- 93% vs 61% for mucocutaneous 93% vs 61% for mucocutaneous manifestationsmanifestations

-- 95% vs 100% for articular symptoms95% vs 100% for articular symptoms

Adverse effectsThe use of interferon alfa in BD:


�� FluFlu--like syndrome: 88%like syndrome: 88%

�� Mild leukopenia: 30%Mild leukopenia: 30%�� Mild leukopenia: 30%Mild leukopenia: 30%

�� Alopecia: 10%Alopecia: 10%

�� IFNIFNαα discontinuation: 2 pts for alopecia, 2 pts for discontinuation: 2 pts for alopecia, 2 pts for diarrhea, 2 pts for leukopenia diarrhea, 2 pts for leukopenia

�� to start with a higher dosage: 6 or even to start with a higher dosage: 6 or even 9,000,000 iU per day 9,000,000 iU per day

�� reduce it to 4,500,000 iU per day after 4 weeks, reduce it to 4,500,000 iU per day after 4 weeks, and to 3,000,000 iU per day after another 4 and to 3,000,000 iU per day after another 4

Recommended INF-α regimenThe use of interferon alfa in BD:


and to 3,000,000 iU per day after another 4 and to 3,000,000 iU per day after another 4 weeksweeks

�� then reduce to the maintenance dosage of then reduce to the maintenance dosage of 3,000,000 iU 3 per week after remission is 3,000,000 iU 3 per week after remission is achievedachieved

�� continue it for at least 8 weeks after remissioncontinue it for at least 8 weeks after remission

Long-term efficacy and safety of low-dose interferon alpha2a in severe uveitis associated with BD

Gueudry et al, Am J Ophthalmol 2008

�� A retrospective study showing control of inflammation in A retrospective study showing control of inflammation in 88% of 32 BD patients with uveitis relapsing despite 88% of 32 BD patients with uveitis relapsing despite corticosteroids and immunosuppressive agents treated with corticosteroids and immunosuppressive agents treated with IFNIFN--alpha2a 3alpha2a 3 million U thrice a weekmillion U thrice a week

-- mean observation period: 70.6 months (30mean observation period: 70.6 months (30--129 months)129 months)-- mean observation period: 70.6 months (30mean observation period: 70.6 months (30--129 months)129 months)

-- median visual acuity improved from 0.52 to 0.33 (p = 0.005) median visual acuity improved from 0.52 to 0.33 (p = 0.005) 2 years after initiation of therapy2 years after initiation of therapy

-- the relapse rate decresed significantly during treatment (from the relapse rate decresed significantly during treatment (from 1.681.68++1.22 relapses/patient/year to 0.111.22 relapses/patient/year to 0.11++0.20, p < 0.0001)0.20, p < 0.0001)

-- IFNIFN--alpha2a was discontinued in 68% of patients after 32 months of alpha2a was discontinued in 68% of patients after 32 months of treatment (16treatment (16--50 months)50 months)

-- after discontinuation (mean followafter discontinuation (mean follow--up: 43 months) the relapse rate up: 43 months) the relapse rate increased from 0.08increased from 0.08++0.21 relapses/person/year to 0.740.21 relapses/person/year to 0.74++1.40 (p=0.04) 1.40 (p=0.04)

Long-term efficacy and safety of low-dose interferon alpha2a in severe uveitis associated with BD

Gueudry et al, Am J Ophthalmol 2008

�� Conclusions: Conclusions: IFNIFN--alpha2a is efficient and safe alpha2a is efficient and safe for the longfor the long--term management of severe term management of severe uveitis associated with BD. It has a potent uveitis associated with BD. It has a potent corticosteroidcorticosteroid--sparing effect. Meanwhile it sparing effect. Meanwhile it seems to be a suspensive therapeutic seems to be a suspensive therapeutic strategy, even though longstrategy, even though long--term remission is term remission is possible in some patientspossible in some patients

�� In this era of evidencedIn this era of evidenced--based medicine, based medicine, there is an urgent need for controlled, there is an urgent need for controlled, randomized studies with randomized studies with TNFα and TNFα and IFNIFNαα--2a using standardized outcome 2a using standardized outcome

Future perspectives

IFNIFNαα--2a using standardized outcome 2a using standardized outcome measuresmeasures

�� Its efficacy and costIts efficacy and cost--effectiveness should effectiveness should be compared with standard immunosupbe compared with standard immunosup--pressants to determine its hierarchy in the pressants to determine its hierarchy in the treatment of BDtreatment of BD

Cost long-term maintenance therapy with infliximab and IFN-alpha2a

Cost for both drugs in the first year for Cost for both drugs in the first year for

a patient of 75 Kg of body weighta patient of 75 Kg of body weight

InfliximabInfliximab375 mg per infusion, 5 mg/Kg of 375 mg per infusion, 5 mg/Kg of

IFNIFN--alpha2aalpha2a3MU, 3 times a week 3MU, 3 times a week 375 mg per infusion, 5 mg/Kg of 375 mg per infusion, 5 mg/Kg of

body weight every 6 weeksbody weight every 6 weeks3MU, 3 times a week 3MU, 3 times a week

for one yearfor one year

Real cost for Real cost for the hospitalthe hospital 1923.26 X 8.5 = 16,347.71 1923.26 X 8.5 = 16,347.71 €€ 10.27 X 156 = 1602.12 10.27 X 156 = 1602.12 €€

AIFA costAIFA cost 3186.6 X 8.5 = 27,086.1 3186.6 X 8.5 = 27,086.1 €€ 25.21 X 156 = 3923.76 25.21 X 156 = 3923.76 €€

Health & Medicine

2009 Convegno Malattie Rare Salvarani [22 01]