link.springer.com · Web viewA 12-week treatment model was developed based upon the dosages administered in the RCTs, as well as the manufacturer’s published guidelines for dosage,

Systematic Review of Cost-Effectiveness Analyses of Treatments for Psoriasis

Wei Zhang1,2, Nazrul Islam1,2, Canice Ma1, Aslam H. Anis1,2

1Centre for Health Evaluation and Outcome Sciences, St. Paul’s Hospital, 588-1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada

2School of Population and Public Health, University of British Columbia, 2206 East Mall

Vancouver, BC, V6T 1Z3, Canada

Corresponding Author

Aslam H. Anis PhD, FCAHS

Centre for Health Evaluation and Outcome Sciences

St. Paul’s Hospital

588-1081 Burrard Street, Vancouver, BC V6Z 1Y6

Tel: +1-604-806-8712

Fax: +1-604-806-8778

Email: [email protected]

APPENDIX-II

Table A-II: Summary of Economic Analyses

Author(s), Study year; Location; Cost year; Currency

Comparators Model design Perspectives Patient characteristics Time horizon

Sources of effectiveness evidence

Cost components considered

Cost-effectiveness measure and ratio Final conclusions

TOPICAL

Ashcroft et al., 2000; UK; 2000; £ [48]

Calcipotriol vs. dithranol Decision treeUK National Health Service

Mild-to-moderate psoriasis

Model 1: 12 weeksModel 2: up to 1 year

Degree of improvement in psoriasis via a 5-point patient-rated scale.

Drug costs

Cost difference between treatments/difference in successful days

Model 1: £577.70Model 2: £19.93

Short-contact dithranol as first line treatment may help contain costs and improve outcomes in terms of more durable remission following treatment.

Augustin et al., 2007; Germany; 2006*; € [49]

Fixed-dose calcipotriol/ betamethasone combination vs. a morning/eveningnon-fixed-dose calcipotriol/betamethasone combination

Markov modelGerman societal perspectives


48 weeks (model used 12 cycles consisting of 4 weeks)

DCDs: 1) state of marked improvement or clearance or 2) state of clearance of all lesions, collected from two previously published trials (no synthesis).

Medication unit costs; adverse events; UVB rescue therapy per session and visit

Cost difference between treatments/difference in DCDs

Marked improvement or clearance: Fixed combination: €3.47Non-fixed combination: €4.89

Clearance: Fixed combination: €21.38Non-fixed combination: €47.07

Non-fixed combination is dominated by fixed combination.

Fixed-dose calcipotriol/betamethasone combination is more cost-effective than a non-fixed-dose morning/evening combination.

Augustin et al., 2009; Germany; 2007*; € [50]

Treatments: A) Compound product containing calcipotriol/betamethasone, given once daily for 4 weeks, followed by daily calcipotriol for 4 more weeks; B) Tacalcitol, given once daily for 8 weeks; C) Separate administration in the morning/evening of calcipotriol and betamethasone, twice daily, for 8 weeks

Markov model Not mentioned


48 weeks (model used 12 cycles consisting of 4 weeks)

DCDs: 1) significant improvement in symptoms or 2) clearance, collected from previously published trials (no synthesis).

Drug costs; costs related to adverse effects; UVB phototherapy

Cost difference between treatments/difference in DCDs, compared to Treatment A

Marked improvement or clearance: Treatment A: €2.62Treatment B €4.18Treatment C: €3.38

Clearance: Treatment A: €16.14Treatment B €35.80Treatment C: €32.58

Treatment A is superior to Treatments B and C.

Fixed-dose calcipotriol/betamethasone combination is a more cost-effective treatment than a treatment with the single agents or tacalcitol monotherapy.

Bergstrom et al., 2003; USA; NR; USD [25]

Clobetasol foam to affected skin and scalp vs. clobetasol cream to the skin and clobetasol solution to the scalp

Trial-based Not mentioned

Moderate-to-severe psoriasis 2 weeks

1-point change in PASI score, estimated directly from the study participants.

Drug costs

Cost per 1-point change in PASI score

Foam users: $21.60Cream/solution users: $16.42

No significant difference in cost was appreciated between foam and cream/solution over the period after controlling for body surface area.






Bottomley et al., 2007; UK; 2006-2007; £ [51]

Multiple treatment sequence** Markov model

National Health Service in Scotland

Moderate-to-severe psoriasis 1 year

QALY, estimated from the review (without synthesis) of literature that derived EQ-5D utilities by PASI 75 response status.

Drug costs; GP consultation; specialist outpatient consultant consultation; specialist outpatient nurse consultation; nurse-led phototherapy course

Cost difference between treatments/QALY difference, compared to Treatment 1

Treatment 1 at maximal possible dose: £11,100 to £31,900

Treatment 1 dominated Treatments 2-5**.

With reduced costs and superior outcomes, the TCF ‘dominated’ the other treatments since the latter were associated with higher cost and lower utility or QALY gain.

Colombo et al., 2012; Italy; 2012; € [44]

Calcipotriol and betamethasone dipropionate gel vs. the ointment formulation

Markov model

Italian National Healthcare System as a third-party payer


1 year

PASI 75, collected from previously published trials (without synthesis).

Costs of medication; fees for specialist and GP visits

Mean annual cost per patient, assuming comparable efficacy

Gel: €406.63 Ointment: €499.90

The gel strategy appears to be favorable from the pharmacoeconomic point of view than the ointment formulation.

Devaux et al., 2012; France; 2010; € [66]

Vitamin D analogues plus topical steroids vs. vitamin D analogues alone

None Not mentioned Not mentioned 4 weeks

PASI 90 (treatment success) and PASI 75 (satisfactory response), estimated by meta-analysis.

Drug costs

Cost per treatment success

Vitamin D analogues + steroids:Calcipotriol + betamethasone: €111-123

Vitamin D analogues alone:Calcipotriol b.d.: €205-246Calcitriol b.d.: €128-153Tacalcitol: €135-162

The cost ⁄efficacy ratio was evaluated as 1.2–1.8 times higher for vitamin D analogues plus topical steroids than for vitamin D analogues alone.

Freeman et al., 2011; UK; 2008-09; £ [53]

Treatment pathways: 1) Two-compound formulation (TCF) followed by TCF; 2) Calcipotriol b.d. followed by TCF; 3) Combination [non-fixed-combination of calcipotriol (morning) and steroid (evening) or vice versa] followed by combination; 4) Tacalcitol followed by steroidReference pathway: Calcipotriol b.d. followed by steroid

Markov model Primary care perspective

Moderate-to-severe psoriasis 2 years

QALY; utility gained from PASI 75 response status from an earlier study.

Drug costs; GP consultation fees

Cost difference between treatments/QALY difference, compared to the reference pathway

No cost-effectiveness ratio was reported; however treatment pathways 1 and 2 dominated pathways 3 and 4 for primary care.

Relative to the reference treatment pathway, treatment pathways 1 and 2 are both cost-effective.

Harrington, 1995; UK; 1994 (NHS cost); £ [45]

Calcipotriol ointment twice daily for 8 weeks vs. dithranol once daily

Trial-based Not mentioned


8 weeks

Own outcome criteria from a scale of 1 to 4† as assessed by both the participants and the investigators of the study.

Drug costs

Cost per achieved outcome (based on own outcome criteria†)

Calcipotriol: 1) £163; 2) £187; 3) £152; 4) £175Dithranol: 1) £165; 2) £275; 3) £150; 4) £248

Calcipotriol should be used in any national treatment program for mild-to-moderate psoriasis over dithranol.






Marchetti et al., 1998; USA; 1997; USD [31]

Tazarotene 0.1%, tazarotene 0.05%, fluocinonide, and calcipotriene

Decision tree Third-party payer


1 year

DFD, the cost to achieve a day without psoriatic lesions, estimated by parameters from meta-analysis.

Costs for physician visits, drug acquisition, laboratory testing, and adverse events management

Cost per DFD, ranked from 1 to 4

Tazarotene 0.1%: $49.46Tazarotene 0.05%: $57.74Fluocinonide: $91.73Calcipotriene: $120.56

Tazarotene 0.1% was the most cost-effective option.

Oh et al., 1997; Canada; 1995; CAD [22]

Calcipotriene, betamethasone dipropionate, betamethasone valerate, fluocinonide

Decision treeGovernment payer perspective


1 year

QALY, estimated from the ‘utility’ for different health states, which was measured by interviewing 30 patients with psoriasis using standard gamble technique.

Costs of physician visits, laboratory tests, UVB therapy; the cost of PUVA therapy (including costs of psoralen tablets, physician fees, laboratory tests, and facilities fees to provide PUVA therapy; costs associated with failures and relapses (i.e., additional treatments, visits, and tests)

Cost difference between treatments/QALY difference, compared to calcipotriene

Betamethasone valerate: $414

Calcipotriene dominated fluocinonide and betamethasone dipropionate; however was dominated by betamethasone valerate.

Calcipotriene is cost-effective alternative to medium- to high-potency corticosteroids, both as second-line therapy to betamethasone valerate or when failure is with betamethasone valerate.

Papp et al., 2012; Belgium, Denmark, Finland, France, Germany, Norway, Portugal, Sweden, and Switzerland; NR; Respective local currency [64]

Bemethson ointment betnovate emulsion ⁄ solution, Diprolene cream, Celestan-V ointment, Clarelux foam, Ecural solution Elucon solution + bucky Elucon solution, Diprosalic lotion ⁄ Psodermil solution, Elocom solution, Dermovate sol ⁄ Dermoval sol, Daivonex solution, Dovobet-Daivobet lotion ⁄ Xamiol gel, Vehicle, No further treatment, Maintenance clobetasol propionate shampoo (CPS), Acute CPS

Decision tree Payer perspective


DFD, calculated from the study participants

Cost of physician visits and cost of interventions

Cost difference between treatments/difference in DFD, compared to the vehicle arm

No cost-effectiveness ratio reported; however CPS dominated the vehicle arm across all treatment types by country.

CPS is cost-effective in maintaining the success achieved.

Peeters et al., 2005; France, Germany, Spain and UK; 2004; € [65]

Calcipotriol/betamethasone (Daivobet), calcipotriol (Daivonex), and tacalcitol

Trial-basedFrench societal perspective

Mean PASI score ≈ 10; Mean age ≈ 51 years

8 weeks PASI 75, evaluated from the study.

Drug costs, hospital stays, days of hospital attendance, physician visits, lab tests, and costs of adverse events

Cost per PASI 75 responder

Daivobet: €241.22Tacalcitol: €476.70

Daivobet dominated tacalcitol.

Calcipotriol/betamethasone is more effective and less costly than tacalcitol.

Sawyer et al., 2013; UK; 2011; £ [60]

Various combinations used in first, second, and third line therapy for the trunk/limbs or scalp: vitamin D o.d. (Vit D OD); vitamin D b.d. (Vit D BD); potent corticosteroid o.d. (PS OD); potent corticosteroid b.d. (PS BD); two-compound

Markov model UK National Health Service perspective

Patients with psoriasis of the trunk, limbs and scalp

1 year; extended to 3 and 10 years

QALY estimated from literature review which measured QALYs from EQ-5D by response for trunk/limb psoriasis and SF-6D by

Costs of topical agents, primary and secondary care visits and second-line therapies for treatment failures

Cost difference between treatments/QALY difference, compared with the next most expensive strategy

Trunk/limb: TCA – PS BD – Coal tar BD: £22,658TCF OD – PS BD – Coal tar BD:

Potent corticosteroids, used alone or in combination with vitamin D, are the most cost-effective treatment for patients with psoriasis of the trunk and limbs. Potent or very potent corticosteroids are the most cost-effective treatment for patients with scalp psoriasis.






formulation o.d. (TCF OD); two-compound application (TCA); very potent corticosteroid o.d. (VPS OD); very potent corticosteroid b.d. (VPS BD)

response for scalp psoriasis.

£179,439TCA – VitD BD – TCF OD vs. TCA – VitD BD – PS BD: £160,238TCF OD – VitD BD – PS BD vs. TCA VitD BD – PS BD: £173,028

Scalp:VPS OD – VPS BD – TCF OD: £19,706TCF OD – VitD BD – VPS OD vs. PS OD – VitD BD – VPS OD: £219,846

PHOTOTHERAPY

Aggarwal et al., 2013; India; NR; USD [69]

PUVA vs. PUVAsol Trial-basedPatient's and hospital's perspective


Percentage of improvement in PASI, directly estimated from the study as evaluated by the clinicians.

Costs of drugs, payment for phototherapy; consultation fee; transportation or travel cost; wages or salary lost; equipment cost; overhead costs; salaries of doctors and other staff

Cost per % of improvement in PASI

PUVA: $0.72PUVAsol: $0.37

Relative cost-efficiency ratio of PUVA to PUVAsol is 1.95:1.

PUVAsol had a clinical efficacy comparable with PUVA and favourable cost-effectiveness ratio.

Koek et al., 2010; Netherlands; 2003; € [58]

Home vs. outpatient UVB phototherapy Trial-based Societal

perspectiveMild-to-severe psoriasis

17.6 weeks (mean duration at the end of phototherapy); 68.4 weeks (mean duration one year after the end of phototherapy

QALY, calculated by interviewing the study participants using EQ-5D or SF-6D quality of life questionnaire.

Outpatient phototherapy; consultation with dermatologist, and GP; medication travelling costs; parking costs for visits to hospital; parking costs for visits to GP; absence from paid work; reduced productivity while at paid work; absence from unpaid work; side effects (that did not vary across groups)

Cost difference between treatments/QALY difference

Phototherapy for 17.6 weeks: €9276 (EQ-5D); €7908 (SF-6D)

Phototherapy for 68.4 weeks: €4646 (EQ-5D); €7802 (SF-6D)

Phototherapy for 17.6 weeks was dominated by the other treatment strategy.

Home UVB phototherapy is not more expensive than phototherapy in an outpatient setting and proved to be cost effective.

Snellman et al., 1998; Spain (Finnish Patients); 1988-90; FIM [63]

Time; before and after heliotherapy Trial-based Not

mentionedModerate-to-severe psoriasis

1 year before and after a 4-week treatment

Difference in mean Psoriasis Severity Index (PSI) ‡ as estimated from the study participants.

Ward treatment, phototherapy in outpatient clinics, lab X-ray, physician consultations, medication at home, trips for treatments, self-arranged sun-bathing holidays, productivity loss due to absenteeism and unpaid help

No cost-effectiveness ratio was reported; however the mean annual costs were 7335 FIM and 5700 FIM before and after heliotherapy respectively.

The cost of heliotherapy exceeded manifold the mean monthly cost of conventional psoriasis therapy. There was no overall savings using heliotherapy in moderate to moderately severe psoriasis; it saved costs only in severe psoriasis that required expensive medication.

SYSTEMICSTRADITIONAL SYSTEMICS

Ellis et al., Methotrexate-based vs. Markov model Payers’ Moderate-to- 10 years Years clear of Acquisition of medications, Cost difference between Overall costs associated with the






2002; USA; 1999; USD [27]

cyclosporine-methotrexate rotation treatment strategies perspective severe psoriasis

psoriasis, modelled by parameters from literature review.

laboratory and physician fees, and costs of treating side effects

treatments/difference in number of years clear of psoriasis

Cyclosporine: $2700-$4100 (range was reported due to variation in being 1-20x as effective as methotrexate)

cyclosporine rotational strategy were higher than the costs associated with the methotrexate strategy; however the rotational strategy could provide 2 additional clear years.

Hakkaart-van Roijen et al., 2001; Canada, Spain, Turkey, UK; 1997; USD [68]

Tapered vs. abrupt discontinuation of oral cyclosporine

Trial-based Societal perspective

Patients from Canada, Spain, Turkey, and the UK with chronic plaque psoriasis inadequately controlled with topical treatment

1 year

Number of systemic therapy-free days calculated directly from the study.

Costs of medication; visits to the dermatologist; laboratory tests; costs of lost production due to illness and/or its treatment costs; adverse events (did not vary across groups)

Cost difference between treatments/difference in systemic therapy-free days

Tapered treatment dominated abrupt discontinuation of cyclosporine in 3 out of the 4 patient groups (excluding Canada, which had a ICER of +1.4).

Tapering cyclosporine was more cost effective than abruptly stopping cyclosporine.

BIOLOGICS

Ahn et al., 2013; USA; 2010; USD [23]

Various doses of adalimumab, alefacept, etanercept, infliximab, and ustekinumab

A 12-week treatment model, and annual biologic treatment models based on another study

Third-party payer

Moderate-to-severe psoriasis

12 weeks; modeled for annual cost-effectiveness analysis as well

PASI 75 and DLQI MID, synthesized from systematic review taking the weighted average.

Drug costs; physician visits; lab tests; intravenous infusion procedures

Cost difference between treatments/difference in PASI 75 or DLQI MID (if applicable), compared to placebo

Partial results (annual treatment paradigms): - Infliximab (3 mg/kg IV): $9,407 (DLQI MID); $23,275 (PASI 75)- Etanercept (25 mg SQ o.w.): $17,341 (DLQI MID); $66,027 (PASI 75)

Infliximab (3 mg/kg IV) was the most cost-effective biologic agent with respect to both the cost per patient achieving PASI 75 and the cost per patient achieving a DLQI MID.

Anis et al., 2011; USA; 2007; USD [24]

Adalimumab, etanercept (25 mg biw), high-dose etanercept (50 mg now for 12 weeks, then 25 mg biw) infliximab, alefacept, efalizumab

Markov model based on York model

Not mentioned

Patients who failed conventional therapies

Not clear; annualized results reported

QALY, calculated from previous RCTs by analyzing the relationship between health utility measure EQ-5D and PASI response.

Drug and related costs; hospitalization costs; productivity cost; justified for not using the cost of adverse events

Cost difference between treatments/QALY difference, compared to the next least costly treatment under threshold ($50,000 per QALY)

Treatment sequence: 1) Adalimumab vs. etanercept: $544; 2) Etanercept is least costly; 3) High-dose etanercept is least costly; 4) Infliximab vs. efalizumab: $39,763; 5) Efalizumab is least costly; 6) Alefacept is least costly

The optimal sequence in prescribing biologics is adalimumab, etanercept, infliximab, efalizumab, and alefacept.

Blasco et al., 2009; Spain; 2008; € [41]

Various dose regimens for adalimumab, infliximab, etanercept, efalizumab

Decision tree Spanish National Health System payer


10-24 weeks PASI 75, estimated by meta-analysis.

Drug cost only Cost difference between treatments/difference in PASI 75, compared to placebo

The most efficient biologic agent in terms of the cost/efficacy ratio was adalimumab.






perspective

Partial results: - Adalimumab (80 mg + 40 mg/2 weeks for 16 weeks): €8013- Etanercept (2 x 25 mg/week for 12 weeks): €9370- Infliximab (50 mg/kg for 10 weeks): €10,523

de Portu et al., 2010; Italy; 2008; € [46]

After 24 weeks: infliximab (5 mg/kg), etanercept (25 or 50 mg biw, 50 mg weekly, step down), adalimumab (40 eow)After 48-50 weeks: infliximab (5 mg/kg), etanercept (50 mg biw, step down), adalimumab (40 mg eow)

None

Italian health-care system (third party payer)


24 weeks, and 48-50 weeks (based on randomized controlled trials)

PASI 75 and DLQI MID, estimated from previously published studies.

Direct medical costs with specific reference to the cost of therapy

Cost difference between treatments/difference in PASI 75, compared to infliximab

Partial results:- Adalimumab: €16,069.94 (after 24 weeks); €22,506.62 (after 48-50 weeks)- Etanercept step down: €2,839.82 (after 24 weeks); €2,839.82 (after 48-50 weeks)- Etanercept (50 mg biw) is dominant over infliximab for both time horizons.

Despite infliximab being dominated by etanercept, the authors conclude it is the most cost-effective in the therapy of psoriasis.

Ferrandiz et al., 2012; Spain; 2010; € [52]

Adalimumab, etanercept, infliximab and ustekinumab Decision tree

Spanish National Health System payer perspective


PASI 75, estimated from systematic review, and meta-analysis (where more than 1 studies were available).

Only drug cost

Cost difference between treatments/difference in PASI 75, compared to placebo

Partial results:- Adalimumab: €8013- Etanercept (2 x 25 mg/week): €9110- Ustekinumab (45 mg at week 0 and 4): €9627

Adalimumab was the most cost-efficient.

Greiner & Braathen, 2009; Switzerland; 2006; CHF [54]

Infliximab, etanercept, adalimumab, efalizumab, alefacept

Decision treeSwiss healthcare system


PASI 50, PASI 75, and PASI 90, gathered from previously published RCTs.

Drug acquisition costs (i.e. medication, administration, and monitoring) and costs incurred by adverse events


Infliximab: CHF 29,826Etanercept: CHF 35,399Adalimumab: CHF 29,254Efalizumab: CHF 32,771Alefacept: CHF 48,762

Infliximab and adalimumab generated the lowest ICERs at 36 weeks.

Igarashi et al., 2013; Japan; NR; USD [71]

Adalimumab, infliximab, ustekinumab

York model Japanese National Health Insurance (NHI)


2 years PASI 75, estimated by meta-analysis.

Drug costs Cost per PASI 75 responder

Adalimumab: $40,464 (year 1); $38,965 (year 2)Infliximab: $46,820 (year 1); $39,268 (year 2)Ustekinumab: $35,978 (year 1);

Ustekinumab was more cost-efficient than adalimumab or infliximab.






$31,157 (year 2)

Liu et al., 2012; USA; 2011; USD [29]

Adalimumab 40 mg eow, etanercept 50 mg biw, ustekinumab 45 mg, ustekinumab 90 mg, infliximab 5 mg/kg

None Not mentioned


PASI 75 (responder) and PASI 90 (remitter), estimated by meta-analysis.

Drug acquisition and administration costs

Cost per responder or remitter

Partial results (PASI 75):- Adalimumab: $9,756- Infliximab: $12,828- Ustekinumab (45 mg): $13,821- Etanercept: $21,770- Ustekinumab (90 mg): $25,327

3-month cost per responder was lowest for adalimumab.

Martin et al., 2011; USA; NR; USD [32]

Ustekinumab and etanercept Trial-based Not mentioned


PASI 75, estimated directly from the study participants.

Drug costs


Ustekinumab: $17,842Etanercept: $20,077

The cost per responder was lower for ustekinumab than for etanercept.

Menter & Baker, 2005; USA; 2003; USD [21]

1) Alefacept 15 mg IM weekly for two 12-week courses; 2) Efalizumab 1 mg/kg SC weekly; 3) Etanercept 50 mg SC twice weekly for 12 weeks followed by a maintenance dose of 50 mg weekly

Decision analytic model without clear description

Managed care perspective

Moderate-to-severe psoriasis 18 months

PASI 75, gathered from previously published trials.

Drug costs, IM/SC injection fees, office visit fees, costs for laboratory monitoring; costs incurred due to adverse events


Alefacept: $66,668.75Efalizumab: $75,828.48Etanercept: $61,041.13

Cost-efficacy of alefacept, efalizumab and etanercept was comparable.

Nelson et al., 2006; USA; 2004; USD [33]

Alefacept, efalizumab, etanercept, infliximab, and adalimumab

None Not mentioned

Severe psoriasis 12 weeks

PASI 75 and mean DLQI improvement, gathered from previously published trials. Weighted average was used for PASI 75 in cases of multiple studies.

Drug cost; costs of the physician visits; required laboratory testing, and infusions

Cost per PASI 75 or DLQI MID responder

Partial results:- Adalimumab (40 mg SC eow): $8,466 (PASI 75); N/A (DLQI MID)- Infliximab (3 mg/kg IV): $9,768 (PASI 75); $5,019 (DLQI MID)- Etanercept (25 mg SC biw): $13,827 (PASI 75); $3,289 (DLQI MID)

Adalimumab and infliximab appear to be the most cost-effective biologic agents.

Nelson et al., 2008; USA; 2006; USD [34]

Adalimumab, alefacept, efalizumab, etanercept, infliximab

A 12-week treatment paradigm was developed on the basis of dosage, administration, and laboratory monitoring utilized in the RCTs, the manufacturer’s published guidelines, and clinical practice

Third-party payer

Mean age range: 43-47 years; predominantly male; mean baseline PASI Score: 14.2-23.4

12 weeks

PASI 75 and DLQI MID, gathered from systematic review, and meta-analysis, as applicable.

Costs of drug, lab, physician, and infusion; justification given for not using long-term adverse effects

Cost difference between treatments/difference in PASI 75 or DLQI MID (if applicable), compared to placebo

Partial results: - Etanercept (25 mg o.w.): $2,250 (DLQI MID); $19,111 (PASI 75)- Infliximab (3 mg/kg IV): $3,508 (DLQI MID); $8,797 (PASI 75)- Adalimumab (40 mg SQ eow): $3,511 (DLQI MID); $11,657 (PASI 75)

Etanercept at a dose of 25 mg administered subcutaneously once weekly was the most cost-effective agent in cost per patient achieving DLQI MID; infliximab IV at a dose of 3 mg/kg was the most cost-effective agent in terms of cost per patient achieving PASI 75 improvement.

Pan et al., 2011; Canada;

Ustekinumab vs. etanercept Markov model Ontario Ministry of


12 weeks (extended to

QALY, calculated by transforming

Drug cost; monitoring cost; outpatient visits

Cost difference between Ustekinumab dominated etanercept






NR; CAD [35] Health 10 years)

DLQI into EQ-5D utilities using a linear regression in earlier trials.

treatments/QALY difference

Incremental cost is $2718 less for ustekinumab with a 0.0046 incremental increase in mean annual QALY.

because of lower costs and higher utility values.

Poulin et al., 2009; Canada; 2009; CAD [37]

Adalimumab, ustekinumab, infliximab, etanercept, efalizumab, alefacept

None Not mentioned


PASI 75, retrieved from product monograph from selected pharmaceutical agencies.

Drug costs


Adalimumab: $8330Alefacept: $71,371

Adalimumab is the most cost-effective.

Schmitt-Rau et al., 2010; Germany; 2009; € [61]

Adalimumab, etanercept, infliximab, and ustekinumab

A cost-effectiveness model based on authors’ literature search

German third-party payer’s perspective

Moderate-to-severe psoriasis 12 weeks PASI 75, estimated

by meta-analysis.

Drug costs; cost of physician visits; laboratory and monitoring costs, and costs of chest X-rays


Partial results: - Adalimumab: €11,286.51- Etanercept (25 mg biw): €16,895.57 - Infliximab (3 mg/kg): €10,568.19- Ustekinumab (90 mg): €12,089.28

Infliximab at a dose of 3 mg/kg was the most cost-effective agent; however, marked overlap of cost-effectiveness ratios was observed in sensitivity analysis.

Villacorta et al., 2013; USA; 2011; USD [40]

Ustekinumab vs. etanercept Markov model US societal perspective


12 weeks (extended to 3 years)

QALY, estimated from a previous study that measured utility using ‘time trade-off procedure’ by level of PASI response; as a sensitivity analysis, from a previous study that mapped DLQI to EQ-5D utilities.

Direct cost; physician visit; costs for receiving subcutaneous injections at the physician’s office; traveling, waiting, and actually receiving treatment at the physician’s office

Cost difference between treatments/difference in QALY

Ustekinumab (90 mg) vs. etanercept (50 mg): $384,401

Ustekinumab (45 mg) dominated etanercept (50 mg)

Ustekinumab 45 mg is the most cost-effective compared to etanercept 50 mg therapy.

Woolacott et al., 2006; UK; 2004-05; £ [67]

Etanercept, efalizumab, and supportive care York model UK NHS Moderate-to-

severe psoriasis 10 years

QALY, based on changes in utility (by EQ-5D) mapped by considering changes in DLQI for all levels of PASI response and different baseline DLQI.

Cost of drugs and of their administration and monitoring, and the cost of outpatient visits and of inpatient stays; justification given for not using cost of adverse events

Cost difference between treatments/QALY difference, compared to supportive care

Etanercept (25 mg intermittent): £35,000 Etanercept (25 mg continuous): £45,000Etanercept (50 mg intermittent): £65,000Efalizumab: £45,000

Both etanercept and efalizumab could be cost-effective depending on patient characteristics and the threshold the NHS is willing to pay per QALY (e.g. £60,000 per QALY gained).

MIXED






Chen et al., 1998; USA; NR; USD [26]

Methotrexate vs. Goeckerman therapy Decision tree US societal

perspective


52 weeks

Clearing rates, gathered from literature review; utility assessed by willingness-to-pay or visual analog scale by interviewing patients with psoriasis, faculty and residents.

Costs for supplies, laboratory tests, and medications; physician fees and hospital fees

Cost difference between treatments/difference in utility (grouped by patients, dermatologists, or society) with a threshold of $35,000

Partial results (severe psoriasis):- Patients: $27,872- Dermatologists: $33,192- Society: $27,752

Mixed findings: in severe psoriasis, only methotrexate demonstrates a net benefit. Both therapies were cost-effective compared with no therapy. Liquid methotrexate should be chosen over the tablet form since it was cheaper and had the same outcome. Goeckerman was cost-effective against liquid methotrexate in severe, but not in mild or moderate psoriasis.

Colombo et al., 2009; Italy; 2008; € [43]

Etanercept vs. non-systemic therapy


Italian National Health Service’s perspective


QALY, taken from an earlier study that used time trade-off method.

Hospitalization; day-hospital admissions; specialist medical examinations; laboratory tests and instrumental investigations; costs of phototherapy or drug therapies


Etanercept (PASI ≥10): €33,216 Etanercept (PASI ≥20): €25,486

Intermittent etanercept is a cost-effective therapeutic option compared with non-systemic therapy.

de Argila et al., 2007; Spain; 2002/2004; € [42]

Methotrexate vs. PUVA Decision tree

Societal (direct + indirect costs) and Public Health Service of Extremadura (direct costs only)


PASI 50, retrieved from previously published literature.

Drug costs; physician visits; costs of PUVA sessions; follow-up tests; treatment to adverse reactions; costs of transport and lost working time

Cost difference between treatments/difference in PASI 50

Methotrexate: €1,519.06PUVA: €1,085.18PUVA vs. methotrexate: €150.65

PUVA more cost-effective than with methotrexate; however, indirect costs (borne by patients in the Spanish Health System) are higher for PUVA therapy, a fact that raises an issue of equity.

Feldman et al., 2003; USA; 2002; USD [28]

Methotrexate, UVB, PUVA, acitretin, cyclosporine, etanercept, infliximab, alefacept

Cost model using direct cost from third-party payer perspective, and indirect costs from patients' perspective

Third-party payer


PASI 75, gathered from previously published studies.

Drug costs; costs of office visits during treatment; lab works


UVB: $5,100Methotrexate: $5,400PUVA: $5,700Cyclosporine: $14,200Acitretin: $17,300Infliximab: $22,500Etanercept: $35,900Alefacept: $40,600

UVB appears to be the best first line agent for control of psoriasis. Methotrexate, PUVA, alefacept, etanercept, and infliximab are appropriate second line agents, which is dependent on patient input and physician judgment.

Hankin et al., 2005; USA; 2004; USD [20]

Biologics vs. oral systemic medications vs. phototherapy None

US managed health care systems


PASI 1 (PASI 50 and PASI 75 were estimated by multiplying the costs for PASI 1 by 50 and 75 respectively).

Costs for medication or phototherapy; treatment administration; monitoring for potential treatment-related adverse events, and treatment of adverse events

Cost per % improvement in PASI

Partial results (PASI 75):- Methotrexate (7.5 mg): $2,290- PUVA: $3,111- Broadband UVB + acitretin (25 mg): $4,149

Oral systemic medications, UV therapy, and UV therapy combined with acitretin appear to be the most cost-effective therapies.

Hankin et al., Biologics vs. oral systemic None US managed Moderate-to- 1 year PASI 1 (PASI 75 Drug wholesale acquisition Cost per % improvement in PASI Methotrexate was the most cost-effective.






2010; USA; 2008; USD [19]

medications vs. phototherapy health care systems severe psoriasis

was estimated by multiplying the costs for PASI 1 by 75).

cost; administration of IV infusion or phototherapy; alefacept IM injection and infliximab IV infusion (where applicable)

Partial results (PASI 75):- Methotrexate (7.5 mg/week): $2,611- Cyclosporine (3 mg/kg/d): $6,029- PUVA: $7,013

Hartman et al., 2002; Netherlands; 1998; € [55]

Psoriasis care instruction programme with short contact dithranol, UVB phototherapy, and inpatient dithranol treatment

Trial-based Societal perspective


PASI 90, and the number of clearance-days, estimated directly from the study.

Drug costs; hospital stay; use of the UVB unit including time of nurse; use of the day-care unit including time of nurse; dermatologist fee; nurse fee; outpatients visits dermatologist fee; GP fee; outpatients visits other specialists fee; absence from paid work; travelling costs

Cost difference between treatments/difference in PASI 90 or number of clearance days, compared to short contact dithranol

Inpatient dithranol: €6065/0.28UVB: comparable effectiveness; thus when based on cost only, short contact treatment was more expensive.

The number of clearance days was comparable across the treatment types; therefore no ICERs were calculated.

UVB was most cost-effective.

Heinen-Kammerer et al., 2007; Germany; NR; € [56]

Etanercept vs. non-systemic therapy


Perspectives of health insurance


QALY, calculated with the aid of EQ-5D, was used in the model with parameters obtained from pooled estimates of relevant RCTs.

Drug costs; physician's fee; costs of side effects


PASI and DLQI > 10: €45,491PASI and DLQI < 15: €32,058PASI and DLQI > 20: €18,154

Etanercept is a cost-effective measure within the German healthcare system.

Knight et al., 2012; Sweden; 2008; Swedish kronor/€ [57]

Non-systemic therapy, etanercept 50 mg once weekly, intermittent, and adalimumab 40 mg every other week

Markov modelSwedish societal perspective


QALY, calculated from EQ-5D by mapping with DLQI with the following formula: 0.956-0.0248*DLQI. The DLQI score was retrieved from Wyeth submission to NICE.

Drug cost; resource cost (administration as an outpatient visit); cost per initial treatment; cost per re-treatment following interruption; hospitalisation cost; cost of absenteeism, and cost of unemployment, due to psoriasis

Cost difference between treatments/QALY difference, compared to non-systemic therapy

Etanercept: 93,629 kr (€9,925)Adalimumab: 434,782 kr (€46,087)Adalimumab vs. etanercept: 1,559,939 kr (€165,354)

Once-weekly etanercept 50 mg, used intermittently, is a cost-effective treatment compared with adalimumab and non-systemic standard of care.

Lloyd et al., 2009; UK; 2006; £ [59]

Etanercept 50 mg biw, etanercept 25 mg biw, and no systemic therapy


UK National Health Service


12 weeks (extended to 10 years)

QALY, estimated from EQ-5D by mapping with DLQI (synthesized from three RCTs) by means of regression equation.

Drug costs; costs of initial outpatient and follow-up outpatient visits; costs of adverse events, and inpatient days

Cost difference between treatments/QALY difference, compared to no systemic therapy

Etanercept (50 mg): £6217Etanercept (25 mg): £4297Etanercept (50 mg vs. 25 mg): £11,710

Etanercept 50 mg biw is cost effective in the UK.

Marchetti et al., 2005; USA;

Calcipotriene + corticosteroid (betamethasone), ICI

Decision tree Payer’s perspective

Mild-to-moderate

1 year TFD and RD, obtained from

Drug costs; costs of office visits during treatment and

Cost per TFD or RD Addition of the 308-nm excimer laser to the rotational mix of treatments is expected






2003; USD [30]

(triamcinolone acetonide), excimer laser, UVB, PUVA (UVA + methoxsalen capsules), anthralin + corticosteroid (clobetasol), tazarotene + corticosteroid (clobetasol)

psoriasis previously published studies.

during remission; costs of management of adverse events

First line therapy + excimer laser: $41.61 (TFD); $10.73 (RD)First line therapy + ICI: $35.53 (TFD); $9.65 (RD)Stand-alone excimer laser: $9.36 (TFD); $10.56 (RD)Stand-alone ICI: $3.75 (TFD), $5.16 (RD)

to add incremental clinical benefit for patients without incremental cost for payers.

Pearce et al., 2006; USA; 2003; USD [36]

Acitretin, alefacept, cyclosporine, efalizumab, etanercept, infliximab, methotrexate, NB-UVB, and PUVA

A 12-week treatment model was developed based upon the dosages administered in the RCTs, as well as the manufacturer’s published guidelines for dosage, administration, duration, and recommended laboratory monitoring determined from the package inserts.

Not mentioned


PASI 75, estimated as weighted average from the systematic review.

Physician office visits; nursing visits; and laboratory costs

Cost difference between treatments/difference in PASI 75, compared to the next most efficacious therapy (i.e. methotrexate)

Cyclosporine: $156PUVA: $1457

Methotrexate dominated all other treatments.

Methotrexate appears to be the most cost-effective agent.

Shani et al., 1999; Israel; NR; USD [70]

Dead Sea climatotherapy, topical, phototherapy, and systemic treatments

None Not mentioned

Severe psoriasis 4-24 weeks

Combined score from (1) percentage of patients cleared, (2) length of treatment, (3) mean remission, and (4) annual cost, obtained from previously published studies.

Direct (round-trip flight, round-trip transfer to the hotel, hotel accommodation, medical treatment, and solarium fee), and indirect costs (loss of productivity during the 4-week treatment plus 2-day flights, and treatment of possible side-effects, and the remission time)

Assigned a score based on clearance, treatment length, remission time, and treatment cost.

Partial results:- Climatotherapy: 9- Methotrexate: 24- UVB (with or without dithranol): 25

Climatotherapy leads as the most cost-effective.

Sizto et al., 2009; UK; 2005/2006; £ [62]

Methotrexate, cyclosporine, supportive care, etanercept 25 mg intermittently, etanercept 50 mg intermittently, efalizumab, adalimumab, etanercept, infliximab


UK National Health Service perspective


Not clear; annualized estimates presented

QALY, calculated by analyzing EQ-5D data by level of PASI response from previously published trials.

Drug and associated monitoring and administration costs; cost of hospitalizations; cost of productivity considered in sensitivity analysis; justified for not using cost of adverse effect

Cost difference between treatments/QALY difference, compared to supportive care

Partial results:- Adalimumab: £30,538- Etanercept: £37,284- Efalizumab: £39,948

Methotrexate and cyclosporine were dominated by supportive care.

Methotrexate and cyclosporine are cost effective but require monitoring for toxicities. Of the biologics, adalimumab was the most cost effective.

Staidle et al., Acitretin, alefacept, A cost-efficacy Third-party Moderate-to- 1 year PASI 75 and DLQI Costs of medication; office Cost difference between Phototherapies and methotrexate are the






2011; USA; 2010; USD [38]

adalimumab, cyclosporine (5 mg/kg/day), etanercept infliximab, PUVA, methotrexate, NB-UVB, home NB-UVB, ustekinumab

model considering US health-system-based annual costs, clinical and quality-of-life improvements

payers severe psoriasisMID, gathered from previously published sources.

visits; laboratory tests and monitoring procedures

treatments/difference PASI 75 or DLQI MID, compared to placebo

Partial results: - NB-UVB: $3,032 (DLQI MID)- Alefacept: $59,564 (DLQI MID)- Methotrexate: $657-$1,094 (PASI 75)- Alefacept: $124,800 (PASI 75)

most cost-effective options.

Stern, 1988; USA; NR; USD [39]

Topical tar vs. UVB None Not mentioned Not mentioned Not

mentioned

Cost to clearing (no PASI or DLQI). Source of ‘clearing’ data was not clear.

Direct cost; transportation, parking, days of work lost, leisure days lost

Cost to clearing

Inpatient therapy with tar: $6,300 (low); $10,500 (medium); $14,700 (high)Day care with tar: $1,680 (low); $3,360 (medium); $5,040 (high)Outpatient UVB with emollients: $480 (low); $840 (medium); $1,200 (high)

Tar is NOT a cost-effective option compared to UVB.

Vano-Galvan et al., 2012; Spain; NR; € [47]

Home phototherapy vs. biologics (etanercept, adalimumab, infliximab)

Decision tree Payer's perspective

Moderate-to-severe psoriasis; n=12

16 weeksPASI 75, measured directly from the study participants.

Drug cost; consultation fees; screening tests; costs of phototherapy (costs of unit, delivery and collection of the unit, consultations, tests) as applicable

Cost difference between treatments/difference in PASI 75

Phototherapy vs. biologics: €37,668

Home-based phototherapy with narrow-band UVB radiation was cost-effective compared with biologic drugs.

* Cost year was not explicitly stated in the original article, thus what was reported in this review was an estimate based on the context of the article.

** (1) TCF (two compound formulation), first-choice, once daily for 4 weeks; followed by TCF, second-choice, once daily for 4 weeks; (2) calcipotriol, first choice, once daily for 4 weeks; followed by potent steroid betamethasone dipropionate (BDP), second-choice, daily for 4 weeks; (3) calcipotriol, first-choice, twice daily for 4 weeks; followed by potent steroid (BDP), second-choice, daily for 4 weeks; (4) Potent steroid (BDP), first-choice, daily for 4 weeks; followed by calcipotriol, second-choice, once daily for 4 weeks; (5) Concurrent calcipotriol, first-choice, once daily (morning) and potent steroid (BDP) once daily (evening) for 4 weeks; followed by the same regimen, second-choice, for a further 4 weeks

† (1) Satisfactory response: overall clinical response of "cleared" or "marked improvement" by both the investigator and the patient, and the cosmetic acceptability of treatment rated as "excellent" or "good" by the patient; (2) Very satisfactory response: criteria for a "satisfactory response" with addition that no lesional or perilesional irritation was experienced by the patient; (3) Satisfied patient: "satisfactory response" with exception that only the patient's overall clinical response was evaluated; (4) Very satisfied patient: "satisfied patient" but who also experienced no lesional or perilesional irritation whilst using treatment.

‡ Degree of psoriasis was estimated separately for head (h), body (b), upper limb (u) and lower limb (l) for scaling (S), thickness (T) and area (A) of skin involvement. Scaling and thickness were scored from 0 to 3 (0: no signs, 1: slight involvement, 2: moderate involvement, 3: severe involvement)

and skin involvement area was scored as percentage of the body area in question. The Psoriasis Severity Index (PSI) was calculated as: 0.1∗{[ 0.1 Ah ( Sh+T h ) ]+[0.35 Ab ( Sb+Tb ) ]+0.2 Au ( Su+T u ) ]+[0.35 A l ( S l+T l )]}.The constants in the brackets represent the share of head, body,

upper limbs and lower limbs in the total body area; the PSI can range from 0 to 60.DCDs= disease-controlled days; DFD= disease-free days; TFD= treatment-free day; RD = remission day; NR= not reported; USD= United States dollar; CAD= Canadian dollar; £= British pound sterling; €= Euro; FIM= Finnish markka; CHF= Swiss franc; NHS= National Health Service; NICE= National Institute for Health and Care Excellence, formerly known, and originally established, as National Institute for Clinical Excellence; RCT= randomized controlled trial; QALY= quality-adjusted life years; PASI= Psoriasis Area Severity Index; HRQOL= health-related quality of life; DLQI= Dermatology Life Quality Index; MID= minimally important difference; EQ-5D= European Quality of Life-5 Dimensions (also abbreviated as EuroQol-5D); SF-36= 36-Item Short Form Health Survey; SF-6D: Short Form- 6 Dimensions; UVB= ultraviolet-B; NB-UBV= narrow-band UVB; PUVA= psoralen + ultraviolet A (UVA) phototherapy; PUVAsol= psoralen + natural sunlight; ICI= intralesional corticosteroid injections; o.d. = once daily; b.d.= twice daily; eow= every other week; o.w. = once weekly; biw= twice weekly; IM= intramuscular; SC= subcutaneous; IV= intravenous; GP = general practitioner.

Documents

link.springer.com · Web viewA 12-week treatment model was developed based upon the dosages administered in the RCTs, as well as the manufacturer’s published guidelines for dosage,