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2008 Acta Dermato-Venereologica. ISSN 0001-5555doi: 10.2340/00015555-0511

Acta Derm Venereol 88

CLINICAL REPORT

Acta Derm Venereol2008; 88: 495501

Many patients with moderate-to-severe plaque psoriasis

do not respond adequately to methotrexate monothera-

py. This pilot study, with a small patient population, was

performed to evaluate the effectiveness and safety of eta-

nercept and methotrexate combination in patients with

plaque psoriasis and inadequate response to methotrex-

ate. Outpatients with plaque psoriasis (Psoriasis Areaand Severity Index 8 and/or body surface area > 10%),

despite methotrexate treatment ( 3 months; 7.5 mg/

week) were randomized to either etanercept with metho-

trexate tapered and discontinued (n= 28) or etanercept

with continuous methotrexate (n = 31). Signicantly

more patients had a Physicians Global Assessment of

clear/almost clear in the combination group compa-

red with etanercept/methotrexate taper (66.7 vs. 37.0%,

respectively;p= 0.025). Adverse events were similar for

both groups, with no cases of tuberculosis, malignancies

or opportunistic infections reported. Addition of etaner-

cept to methotrexate achieved signicant improvement

in psoriasis after 24 weeks.Key words: etanercept; metho-

trexate; psoriasis.

(Accepted April 21, 2008.)

Acta Derm Venerel 2008; 88: 495501.

Claus Zachariae, Department f Dermatlgy, Cpenhagen

University Hspital, Gentfte, Niels Andersensvej 65, DK-

2900 Hellerup, Denmark. E-mail: [email protected]

Pra a rn, nammatry n drdr, t-mated t affect abut 2.5% f the glbal ppulatin and

apprximately 1.5% f peple in central Eurpe (1, 2).

Plaque psriasis is the mst cmmn frm, diagnsedin 80% f patients with psriasis (3). Abut a quarter fthse with psriasis have mderate-t-severe disease,

but psriasis f almst any severity has a prfundeffect n patients health-related quality f life (4, 5).This is cmmnly because f psychscial effects (e.g.ntmpatng d, and dft ntratng wtwr ag, famy and frnd r ndng a jb), rdft n prfrmng nrma day att (.g.using hands, walking, sleeping, standing r sitting fr

ng prd, r xa att) (4). T dntn fpsriasis severity includes the effect f the disease npatients quality f life, disease histry, signs and symp-tms. Fr example, the rule f tens fr current severepra dnd a at at 10% f bdy rfa ara(BSA) invlved, r a Psriasis Area and Severity Index

(PASI) scre f at least 10 r a Dermatlgy Life QualityIndex (DLQI) scre f at least 10 (6, 7).

Atg tpa tratmnt may f t ntrmild psriasis, mderate-t-severe psriasis ften requi-res the use f phttherapy, systemic drugs, r bth (1,8). Hwever, current systemic therapies fr mderate-t-severe psriasis are assciated with shrt- and lng-term txicity, and a cncmitant high level f patientdissatisfactin (8, 9). There is a need fr well-tleratedand mre effective therapies fr this patient grup.

Methtrexate is the mst cmmnly used systemictreatment fr mderate-t-severe plaque psriasis inEurpe (9, 10), and is effective in reducing disease seve-rity by at least 50% in the majrity f patients (11, 12).Hwever, methtrexate is assciated with ptentiallyserius txic effects, including haematlgical txicity,hepattxicity and lung disease, limiting the dse andduratin f treatment and requiring careful mnitringf hepatic, renal and haematlgical parameters (8).Methtrexate als lacks effectiveness in a substantial

prprtin f patients.Etanercept is a fully sluble, human tumur necrsis

fatr (TNF) rptr and rd t nammatryrespnse by inhibiting interactins between TNF andcell-surface receptrs (13, 14). Etanercept mntherapy

has been shwn t be effective in treating plaque ps-riasis in several randmized, duble-blind trials, andis als assciated with a gd safety and tlerabilitypr (1517). Rnt tra n patnt wt rma-tid arthritis wh had an inadequate respnse t meth-trexate mntherapy have shwn that the additin fetanercept prduces substantial clinical imprvementswithut an increase in adverse events (1820). Mre-ver, a study cnducted in a small number f patients(n = 6) with mderate-t-severe psriasis shwed thatetanercept can allw the tapering f methtrexate dse

The Combination of Etanercept and Methotrexate Increasesthe Effectiveness of Treatment in Active Psoriasis DespiteInadequate Effect of Methotrexate Therapy

Claus ZAchARiAe1

, Nils-Jrgen MRk2

, Tim ReuNAlA3

, HenrikloReNTZeN4

, Edvard FALK5

, Seija-Liisa kARvoNeN6

,Anders JoHANNESSoN7, Birgitta clARus8, Lne SKoV1, Gr MRk2, Sin WAlkeR9 and Susanne QVITZAU10

Departments of1Dermatology, Copenhagen University Hospital, Gentofte, Denmark, 2Rikshospitalet HF, Oslo, Norway, 3Tampere University Hospital,

Tampere, Finland, 4Frederiksberg, Denmark, 5Troms, Norway, 6Helsinki University Hospital, Finland, 7Vllingby, 8Farsta, Sweden, 9Wyeth Europa,

Maidenhead, UK, and10Wyeth Denmark, Copenhagen, Denmark

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496 C. Zachariae et al.

withut increasing liver txicity, infectins r myel-suppressin (21).

The bjective f this study was t evaluate the ef-fectiveness f cmbining etanercept with cntinuedmethtrexate treatment and f etanercept with meth-trexate taper in utpatients with active plaque ps-riasis (PASI > 8, BSA 10%), despite treatment withmethtrexate fr at least 3 mnths. The design f thestudy was chsen t be similar t rutine practice withsystemic therapies when treating psriasis patients. Thisis a 24-week, randmized, pen-label, parallel-grup,multicentre pilt study.

METHoDS

Study protocol

The study prtcl was apprved by lcal ethics cmmitteesand was cnducted in accrdance with the Declaratin f Hel-sinki and its amendments. Patients giving written infrmedcnsent were recruited frm tw centres in each f the fll-

wing cuntries: Denmark, Finland, Nrway and Sweden. Therandmizatin schedule was cmputer generated and perfrmedin randmly permuted blcks f fur, with ne randmizatinlist per centre. As this was an pen-label study, patients werent blinded t the treatment they were assigned.

Patients were invited t participate in this study if they were atleast 18 years f age and had active plaque psriasis invlvingat least 10% f their BSA and/r a minimum screening PASIscre f 8. In additin, patients had t have been treated withmethtrexate at a dse f at least 7.5 mg/week fr 3 mnthsbefre the study and had an inadequate respnse. The 3-mnthperid was chsen t btain a stable methtrexate dse, althughthe majrity f the patients had been n methtrexate treatmentfr many years. The minimum level f 7.5 mg methtrexate waschsen in rder nt t exclude the few patients wh had been

treated with higher dses f methtrexate, but where it had beennecessary t reduce dse due t gastrintestinal-symptms, livertxicity r ther side-effects such as tiredness.

Sexually active wmen f child-bearing age were required tuse a medically accepted frm f cntraceptin. Exclusin criteriaincluded: presence f predminantly guttate, erythrdermic rpustular psriasis; previus use f a TNF-inhibitr; skin cndi-tins ther than psriasis that culd interfere with effectivenessevaluatins f trial medicatins; use f systemic crticsterids,psralen plus ultravilet A radiatin, cyclsprine, acitretin,alefacept, efalizumab, tar cmpunds, vaccinatin with liveattenuated vaccine r the presence f active severe infectins inthe 4 weeks befre starting the trial; ultravilet light B (UVB),tpical grup III r IV sterids, tpical vitamin A r D r anthralinin the 2 weeks befre starting the trial; a histry f alchl r

drug abuse; lactatin; clinically relevant diseases.Randmzatn wa prfrmd at t ban t, and add-

tinal clinic visits were perfrmed at 2, 4, 8, 12, 18 and 24 weekst assess the effectiveness and safety f the trial medicatins.

Treatments

Patients were randmized t receive 24 weeks f treatment asfllws: (i) etanercept with methtrexate tapered and discn-tinued during the first 4 weeks f the trial r (ii) etanerceptcmbined with cntinued methtrexate treatment. Fr patientsin bth grups, etanercept was given subcutaneusly, 50 mgtwice weekly fr 12 weeks, and then 25 mg twice weekly frthe remaining 12 weeks f the study.

Outcome measures

The primary effectiveness variable was the prprtin f pa-tients wh were classified as clear (scre f zer) r almstclear (scre f ne) n the Physicians Glbal Assessment(PGA) scale at week 24. Secndary variables included the fl-lwing: PGA clear r almst clear at 12 weeks; PGA fhead, scalp and neck clear r almst clear at weeks 12 and24; time t PGA clear r almst clear; PASI imprvementat weeks 2, 4, 8, 12, 18 and 24; PASI 50, PASI 75 and PASI90 respnses (prprtin f patients with an imprvement fPASI f at least 50, 75 and 90% frm baseline, respectively)at weeks 12 and 24; patients glbal assessment f psriasis,itching, jint pain and tiredness (each criterin was assessedusing a scale frm 0 (gd, n itching, n pain, n tiredness,respectively), t 5 (severe, severe itching, severe pain and verytired, respectively) at weeks 12 and 24; and DLQI and EurQL5D (EQ-5D) scres at weeks 12 and 24. Safety was evaluatedby recrding adverse events, vital signs, physical examinatins,bld labratry tests and the prprtin f patients wh dis-cntinued due t adverse events.

Statistical analysis

The statistical analyses were perfrmed by PCG. SAS versin

8.02 ftwar wa d n a anay. Rt wr mmarzdby visit fr the full analysis set (FAS; i.e. randmized patientswh had taken at least ne dse f study medicatin and hada least ne pst-randmizatin bservatin). The primary ef-fectiveness variable was analysed using a tw-sided 95% cn-fidence interval (CI) fr the difference between treatments frthe prprtin f patients wh were "clear" r "almst clear"at week 24. A 2-test f difference between treatments wasperfrmed. Secndary utcme measures were analysed in thesame manner with the fllwing exceptins. Fr percentageimprvements in PASI scres, a tw-sided 95% CI fr the dif-ference between treatments was calculated at each respectivetime-pint. Differences between treatments were tested withANCoVA with baseline values as the cvariate. Time t PGAclear r almst clear used KaplanMeier estimates f timet clear r almst clear displayed in a graphical frmat anda crrespnding lg-rank test t lk fr any difference betweentreatments. Differences between treatments fr patients glbalassessment f psriasis were analysed with the extendedMantel-Haenszel mean scre statistic using mdified riditscre and adjusting fr value at baseline. DLQI and EQ-5Dscres were analysed by calculating a tw-sided 95% CI fr thedifference between treatments, with difference betweentreatments tested using ANCoVA with baseline value as thecvariate. Safety variables were analysed using descriptivestatistics, but n frmal statistical cmparisns were made.

A patient number f 60 fr this pilt study was estimated frpractical reasns rather than fr statistical cmparisn betweentreatment grups, as data cncerning the treatment f patientswith psriasis wh fail methtrexate therapy are sparse. Thus,this study was designed t gather infrmatin abut etanercept,with r withut cncurrent methtrexate, fr this difficult-t-treat grup f patients with plaque psriasis. Sixty patientsallws fr a precisin f 0.13 percentage pints fr the 95%CIs with respect t the primary effectiveness variable.

ResulTs

Participant fow and baseline results

Fg. 1 w t w f patnt trg t tdy.Sixty patients were enrlled, f whm 59 were ran-


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497Effectiveness of etanercept and methotrexate in psoriasis

dmized t ne f tw treatments: etanercept withmethtrexate taper (n = 28) r etanercept cmbinedwith cntinued methtrexate treatment (n = 31), withne patient withdrawn due t a psitive tuberculsistest during screening. All 59 patients were included inthe safety analysis and effectiveness analysis (FAS). Allresults presented here are fr the FAS data-set.

Five patients (17.9%) withdrew frm the etanercept/methtrexate taper grup and 3 (9.7%) frm the cm-

binatin therapy grup during the curse f the trial.Fr the etanercept/methtrexate taper grup, 3 f these

withdrawals were because f serius adverse eventsand 2 were because f lack f effectiveness. Fr thecmbinatin therapy grup, ne patient each withdrew

because f lack f effectiveness, lack f cmpliance andthe decisin f the principal investigatr.

Baseline demgraphics and baseline effectivenessvariables are presented in Table I. The methtrexate dsereceived prir t initiatin f the study was similar in

bth the etanercept/methtrexate taper and cmbinatingrups (14.0 (range 7.525.0) and 13.4 (range 7.525.0)mg/w, rpty). T ny gnant dffrn

between treatment grups regarding baseline characte-ristics was that a larger prprtin f wmen were inthe etanercept/methtrexate taper grup cmpared withthe cmbinatin treatment grup (p = 0.046).

Effectiveness

Imprvements in psriasis symptms, as measured bythe primary and secndary effectiveness variables, were

bserved in bth treatment grups ver the curse f thestudy. The primary effectiveness variable (prprtin fpatients judged as clear r almst clear accrdingt the PGA at week 24) was superir fr etanerceptcmbined with cntinued methtrexate treatmentcmpared with etanercept/methtrexate taper (66.7vs. 37.0%, respectively;p = 0.025; adjusted fr gender

p = 0.027; Fig. 2). There were marked imprvements inPGA scres in the cmbinatin treatment grup, with86.6% f patients achieving scres f 02 at week 24cmpared with 74.0% fr the etanercept/methtrexatetaper grup.

Bth treatment grups demnstrated an imprve-

mnt n PAsi r frm ban. Rt wng tprprtin f patients with a PASI imprvement f at

Fig. 1. Patient owchart.

Table I. Characteristics at baseline of patients randomized to receive etanercept with methotrexate tapered over the rst 4 weeks oretanercept combined with continued methotrexate treatment

Characteristic or effectiveness measure

Treatment

Total

(n = 59)

Etanercept/methotrexate

taper (n = 28)

Etanercept with continued

methotrexate (n = 31)

Mean age, years 47.3 48.7 48.1

Mean body weight, kg 89.9 83.7 86.6

Mean body mass index, kg/m2 30.1 27.6 28.8

Mean body surface area involvement, % 24.9 26.2 25.6

Mean psoriasis duration, years 21.0 23.0 22.0Race, n (%) of patients

Caucasian

Asian/South American

27 (96.4)

1 (3.6)

30 (96.8)

1 (3.2)

57 (96.6)

2 (3.4)

Gender, n (%) of patients

Males

Femalesa17 (60.7)

11 (39.3)

26 (83.9)

5 (16.1)

43 (72.9)

16 (27.1)

PGA 2.9 3.2 3.0

PGA, assessment of head, scalp and neck 2.3 2.3 2.3

PASI 16.8 17.4 17.1

DLQI, total score 11.2 9.0 10.1

Methotrexate dose, mg/week 14.0 13.4 13.7

ap= 0.046 for percentage of females given etanercept/methotrexate taper vs. those given etanercept combined with continued methotrexate treatment.

DLQI: Dermatology Life Quality Index; PASI: Psoriasis Area and Severity Index; PGA: Physicians Global Assessment of psoriasis.


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least 50, 75 and 90% frm baseline are shwn in Fig.2. Achievement f PASI 75 ver time is shwn in Fig.3. Rt fr PAsi 75 at bt 12 w and 24 wwr gnanty bttr fr mbnatn tratmnt tanetanercept/methtrexate taper even when adjusted fr

gndr dffrn. Rt fr man prntag mpr-vements in PASI scres frm baseline shw that by 18w f tratmnt, mbnatn trapy wa gn-cantly superir t etanercept/methtrexate taper (79.9vs. 62.8, respectively; p = 0.023; adjusted fr gender

p = 0.019), an effect that was maintained until the endf the study (76.4 vs. 51.3%, respectively; p = 0.019;adjusted fr genderp = 0.021).

Patients glbal assessment f psriasis shwed sig-nant mprmnt at w 12 (p = 0.011) and week24 (p = 0.012) fr etanercept cmbined with cntinuedmethtrexate treatment vs. etanercept/methtrexatetaper. PGA f head, scalp and neck clear r almstar aftr 12 w wa a gnanty bttr frcmbinatin than etanercept/methtrexate taper treat-ments (93.1 vs. 65.4%, respectively;p = 0.010; adjustedfr genderp = 0.023), but by week 24 this differencewa n ngr gnant (86.7 . 66.7%, rpty;

p = 0.072, adjusted fr gender,p = 0.155).DLQI scres indicated an imprvement in quality

f life ver the study perid fr bth grups. At week24, there were greater reductins in DLQI frm base-line fr patients in the cmbinatin treatment grupthan thse in the etanercept/methtrexate taper grup(imprvements f 74 and 48%, respectively;p = 0.076;adjusted fr genderp = 0.12). Likewise, EQ-5D screswere imprved in bth grups at 24 weeks althughthe difference between the treatment grups did nt

ra gnan (p = 0.217). The actual increases inEQ-5D scres f 0.19 and 0.12 fr the cmbinatin andetanercept/methtrexate taper grups, respectively, arecnsidered a clinically meaningful change in quality flife (utility), where a minimally imprtant differenceis 0.07 (22).

Safety and tolerability

There was very little difference between treatmentgrups fr the number f patients experiencing adverseevents r the ttal number f adverse events reprted

(Table II). A ttal f 101 adverse events were reprted:51 in the etanercept/methtrexate taper grup and 50in the cmbinatin treatment grup. The mst cmmnrgan system class affected by adverse events wasinfectins, where 7 (25.0%) and 12 (38.7%) adverseevents were reprted fr the etanercept/methtrexatetaper and cmbinatin grups, respectively. This wasfllwed by general disrders and administratin sitecnditins with 8 (28.6%) and 5 (16.1%), respecti-vely, and skin and subcutaneus tissue disrders with7 (25.0%) and 5 (16.1%) events, respectively. A ttalf 7 adverse events were cnsidered serius, 5 eventsreprted in 4 patients in the etanercept/methtrexate

taper grup and 2 events reprted in ne patient in thecmbinatin grup, all f which were cnsidered t berelated t the study medicatin. Three f these seriusadverse events were infectins (2 in the etanercept/methtrexate taper grup and ne in the cmbinatingrp). Ptar pra, art nfny and atrabratn a rrd n t tanrpt/mttrxattaper grup and vmiting ccurred in the cmbinatingrup. Three patients discntinued due t adverseevents in the etanercept/methtrexate taper grup, butnne in the cmbinatin treatment grup. N cases f

Fig. 2. The proportion of patients (A) classied as clear or almost clear

on the Physicians Global Assessment (PGA) of psoriasis scale and (B) with

an improvement of Psoriasis Area and Severity Index (PASI) of at least 50%,

75% and 90% from baseline, respectively, at weeks 12 and 24 (data for all

non-missing observations are shown).

Fig. 3. Improvements in Psoriasis Area and Severity Index (PASI) scores of at

least 75% from baseline at all time-points assessed (data for all non-missing

observations are shown) *p < 0.05 for the difference between study groups

(with and without adjustment for gender).


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malignancies, opportunistic infections or tuberculosiswere observed.

DISCUSSION

This study reports on the effectiveness of the additionof etanercept to methotrexate treatment in patients withactive plaque psoriasis despite methotrexate therapy.Treatment benefit with etanercept plus methotrexatewas demonstrated across a wide range of measures andno concerns were raised relating to the tolerability of

combination therapy.Improvements in psoriasis symptoms from baselinewere observed in both treatment arms, with the com-

bination group demonstrating statistically superiorresults compared with etanercept/methotrexate taperin PGA clear or almost clear, mean percentageimprovement in PASI score from baseline and PASI75 scores. This pilot study was conducted in a small

patient population which may have contributed to thefailure to reach a statistically significant difference inPASI 50 and PASI 90 results despite the combinationgroup demonstrating higher numerical rates of impro-vement compared with etanercept/methotrexate taper

at all time-points from 4 weeks.Quality of life also improved for both groups, with

greater improvement observed in the combinationtreatment arm compared with etanercept/methotrexatetaper. However, the difference between treatments didnot achieve statistical significance. Quality of life mea-surements are generally considered more variable thanclinical endpoints, which could explain the failure toreach a statistically significant difference.

The effectiveness findings are important because thepatient population studied is notoriously difficult to

treat. Patients in this study have suffered from psoriasissymptoms for an average of 22 years in total and PASIscores upon entry into this study were well above theminimum entry criteria (average 17.1; range 842).Therefore these patients represent a group with severe

psoriasis symptoms, who have responded inadequatelyto methotrexate treatment. Patients were receiving anaverage methotrexate dose of 13.7 mg per week. Ina large number of patients the initial methotrexatedose had been reduced due to intolerance for differentreasons, such as gastrointestinal complaints, tiredness

and liver toxicity. The patient population in this studyrepresent the daily situation for the clinicians in der-matological departments, where a large number of the

psoriasis patients with prolonged disease symptoms aretreated with methotrexate and other systemic therapies.It is therefore important to consider new therapeuticoptions in patients with severe disease despite metho-trexate treatment.

Data on PASI scores prior to methotrexate therapycould not be obtained for patients in this study. It iscommon for psoriasis studies to have a washout periodof systemic therapy prior to baseline, which enables atrue PASI response to the study treatment to be recor-

ded. However, this was not possible with this particularstudy design. Taking this into consideration, a truePASI response to etanercept and methotrexate combi-nation in treatment-nave patients would be expected to

be higher than the PASI 75 of 70% at week 24 reportedfor this study. However, the effectiveness results forPGA and PASI were very favourable for patients in theetanercept and methotrexate combination group, sug-gesting an additive effect for these two agents.

The additive effect observed in the present trialbetween etanercept and methotrexate is not surprising,

Table II. Summary of adverse events

Etanercept/methotrexate taper (n =28) Etanercept with continued methotrexate (n =31)

Number (%) of patients

Any adverse event 21 (75.0) 19 (61.3)

Any serious adverse events 4 (14.3) 1 (3.2)

Infection, hospitalized

Pustular psoriasis in handsa

Pneumonia

Heart insufficiency/atrial fibrillation

Vomited (blood in vomit)/respiratory infection

1 (3.6)

1 (3.6)

1 (3.6)

1 (3.6)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (3.2)

Discontinuation of study treatment due to adverse event 3 (13.0) 0 (0.0)

Number (%) of events

Total adverse events 51 50

Related to study medication 28 26

Most common adverse event by organ system class

Infections

General disorders and administration site conditions

Skin and subcutaneous tissue disorders

7 (25.0)

8 (28.6)

7 (25.0)

12 (38.7)

5 (16.1)

5 (16.1)

Total serious adverse events 5 2

Related to study medication 5 2

aThis was not a transformation of disease.


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given that it is established practice t use ratinal cm-binatins f treatments with different mdes f actint treat psriasis (1, 23).Thus, althugh the mechanismf actin f methtrexate is nt fully understd, it isthught t act as an immunsuppressant and targetsympd fntn, wra tanrpt paytargets TNF (1, 8, 24).

The effectiveness f etanercept alne fr mderate-t-severe psriasis is well dcumented, bth ver 1224weeks (1517), and ver much lnger perids f up t 3years (25, 26). Such studies reveal high respnse rates:PASI 75 was achieved in 5459% f patients at week24 in three previus trials (1517). The lwer PASI 75respnse bserved here in the etanercept/methtrexatetaper grup (37% f patients achieved PASI 75 at week24) is a cnsequence f multiple factrs. First, as explai-ned fr the cmbinatin grup, the true PASI respn-ses that culd be achieved with etanercept alne in treat-ment-nave r washed-ut patients wuld be higherthan thse btained in this study with etanercept after

withdrawal f methtrexate. Secndly, a reduced rate fimprvement fllwing the withdrawal f methtrexatein these patients with severe disease and an inadequaterespnse t prir methtrexate mntherapy. A similarsituatin was bserved when ne agent was withdrawnfrm cmbined methtrexate and cyclsprine therapyadministered t patients with severe psriasis (27).

Etanercept was well tlerated in bth treatmentgrups, with n new safety signals. Mrever, therewere n cases f malignancies, pprtunistic infectinsr tuberculsis in the study reprted here. Hwever,malignancies due t treatment wuld nt be expected

t appear in the time curse f this study. These eventshave been bserved with methtrexate, and, rarely, withetanercept mntherapy (8, 13). The results f this studyare cnsistent with safety data frm larger, lng-termstudies f cmbinatin therapy with etanercept and meth-trexate. In a 3-year study f patients with rheumatidarthritis treated with the cmbinatin f etanercept andmethtrexate, clinical imprvements were sustainedthrugh 3 years with n latent tlerability issues (28).

In cnclusin, this study shwed that patients withactive plaque psriasis despite methtrexate treatmentbntd gnanty frm t addtn f tanrptt their methtrexate treatment regimen with n adverse

effect n safety. This study warrants repetitin in alarger patient chrt and ver a lnger study perid tnrm t nta bratn. Nnt, tresults are prmising as they prvide clinicians with afrtr ptn t addr t dft-t-trat patnt

ppulatin. Patients with psriasis are a hetergeneusgrup and respnd differently t the available therapies.Thus, the treatment regimen needs t be adapted t suitthe individuals needs taking int accunt disease seve-rity, impact n quality f life, practicality f treatmentand treatment histry.

Given the results presented here, clinicians shuldcnsider the additin f etanercept fr patients respn-ding inadequately t methtrexate.

Conflicts of interest: Dr C. Zachariae has served as a speakerand cnsultant fr Wyeth. Drs N.-J. Mrk, A. Jhannessnand S.-L. Karvnen have served as speakers fr Wyeth. Dr H.Lrentzen has served as a speaker and cnsultant fr Wyeth, andhas received funding fr his research wrk. Dr S. Walker is an

emplyee f Wyeth Eurpa and Dr S. Qvitzau is an emplyee fWyt Dnmar. Dr T. Rnaa, e. Fa, B. car, l. sand G. Mrk have n cnflicts f interest.

This study was spnsred by Wyeth Eurpa, Maidenhead,Berkshire, UK.

Editrial supprt was prvided by Fishawack Cmmunica-tins Ltd, UK.

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