STUDY
`
`Recent Trends in Systemic Psoriasis Treatment Costs
`
`Vivianne Beyer, MD; Stephen E. Wolverton, MD
`
`Objectives: To analyze the current total cost of sys-
`temic therapy for psoriasis and to compare annual
`trends in the cost of both generic and brand-name
`therapies with trends in the Consumer Price Index–
`Urban since 2000.
`
`Design: A cost model was developed that includes costs
`for prescription drugs, office visits, and suggested labo-
`ratory tests and monitoring procedures. Annual trends
`in psoriasis drug costs from 2000 through 2008 were ana-
`lyzed by calculating the percentage change in the aver-
`age wholesale price from the previous year; these values
`were compared with changes in the yearly Consumer Price
`Index–Urban values.
`
`Setting: The United States.
`
`Main Outcome Measures: Total annual costs for sys-
`temic psoriasis therapies and trends in cost compared with
`
`the trends in Consumer Price Index–Urban values
`(equivalent to inflation).
`
`Results: Current total annual costs for systemic psoria-
`sis therapies ranged from $1197 (methotrexate) to $27 577
`(alefacept, two 12-week courses). Trends in the average
`wholesale price of brand-name psoriasis therapies from
`2000 through 2008 demonstrate an average increase of
`66% (range, −24% to ⫹316%); thus, costs of several brand-
`name psoriasis drugs greatly outpaced the rates of infla-
`tion for all items and all prescription drugs.
`
`Conclusions: Despite the higher monitoring costs as-
`sociated with traditional systemic therapies, annual costs
`of biologics exceed those of other available therapies. Cur-
`rent trends demonstrate that systemic psoriasis therapy
`costs are increasing at a much higher rate compared with
`general inflation.
`
`Arch Dermatol. 2010;146(1):46-54
`
`P SORIASIS IS A CHRONIC AUTOIM-
`
`mune disease that affects 1%
`to 3% of the general popula-
`tionandinvolvesanestimated
`4.5 million to 7.5 million
`Americans.1 The severity of psoriasis varies
`significantly,withdiseaserangingfromscat-
`tered papules to generalized scaly plaques.2
`The effect of the disease on the quality of life
`orphysicalandemotionalwell-beingofapa-
`tient differs for each patient and often relates
`to the extent and location of the lesions.2,3
`Therapeuticoptionsforpsoriasisarealsovar-
`ied: they consist of topical agents, photo-
`therapy,andsystemictherapies,suchasreti-
`noids, cyclosporine, methotrexate, and the
`5biologicagentsthatarecurrentlyapproved
`bytheFoodandDrugAdministration(FDA)
`for psoriasis and/or psoriatic arthritis. Pub-
`lished consensus guidelines recommend
`topical therapies for patients with mild, lo-
`calized disease that does not interfere with
`activities of daily living, whereas photo-
`therapy and systemic therapies are used for
`more extensive disease.4
`Up to one-third of Americans with pso-
`riasis have moderate to severe disease that
`cannot be controlled with topical treat-
`ments alone.5 Despite the increased effi-
`cacy of systemic therapies relative to topi-
`cal treatments in moderate to severe disease,
`
`these therapies appear to be underused.
`Studies6 have demonstrated that only 43%
`of patients with severe psoriasis are receiv-
`ing systemic therapy of any kind. Reluc-
`tance by physicians to prescribe systemic
`therapies or by patients to adhere to sys-
`temic treatment regimens may be owing to
`several factors, such as intolerance of treat-
`ment, adverse effects, patient affordability,
`and fear of potential adverse effects.7,8 The
`issue of affordability is especially relevant,
`with changing insurance plans, rising co-
`payments, and current trends in prescrip-
`tion drug prices increasing the cost bur-
`den of psoriasis. Newer, more expensive
`biologic therapies have increased the aware-
`ness of the cost of psoriasis therapy.9 De-
`spite their significant impact on disease con-
`trol and quality of life in patients with
`psoriasis, the high cost of biologic thera-
`pies relative to more traditional systemic
`therapies requires careful decision making
`when choosing among the therapeutic op-
`tions discussed in this article.
`Analysisoftreatmentcostisespeciallyim-
`portantwithregardtoachronicdiseasesuch
`as psoriasis, which often requires lifelong
`management. The heavy economic burden
`of psoriasis has been estimated to exceed $3
`billiontothehealthcareindustryannually.10
`Previous estimates of the direct cost of pso-
`
`Author Affiliations:
`Departments of Dermatology
`and Clinical Affairs
`(Dr Wolverton), Indiana
`University School of Medicine,
`Indianapolis (Dr Beyer).
`Dr Beyer is currently a
`transitional year intern at St
`Vincent Hospital in
`Indianapolis. She will begin her
`dermatology residency at the
`Medical University of South
`Carolina, Charleston, in 2010.
`
`(REPRINTED) ARCH DERMATOL/ VOL 146 (NO. 1), JAN 2010
`46
`
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`Page 00001
`
`

`

`riasis, including drugs and hospitalizations, have demon-
`strated total costs of $649.6 million for 1.4 million patients
`with psoriasis in 1997.11 However, recent approval of costly
`biologic therapies and changing health care costs call for up-
`dated cost analyses. In addition, awareness of current trends
`in prescription drug costs, which demonstrate that increas-
`ing prescription drug costs have outpaced Consumer Price
`Index–Urban (CPI-U) rates, which are generally considered
`synonymouswiththerateofinflation,12isalsoessentialwhen
`makingtherapeuticdecisions.Wehypothesizedthatthiscur-
`rent trend also applies to the cost of prescription medica-
`tions for the treatment of psoriasis. This study compares the
`current cost of treatment among different systemic psoria-
`sis therapies and compares recent trends in psoriasis drug
`costs to trends in general CPI-U rates and all prescription
`drugcosts.Findingsfromthisstudywillhelpphysiciansand
`employers understand the current costs and trends associ-
`ated with psoriasis treatment.
`
`METHODS
`
`A cost model based on continuous, year-long treatment was de-
`veloped for each therapy, which includes costs of medications,
`office visits, laboratory tests, and monitoring procedures. The cost
`model was based on clinical experience and published and manu-
`facturer’s guidelines.13-15 Specifically, costs for alefacept (Ame-
`vive; Biogen Idec, Cambridge, Massachusetts) were based on two
`12-week treatment courses per year or one 16-week treatment
`course.16 Despite its withdrawal from the US market in 2009, we
`included data with regard to efalizumab for the sake of compari-
`son with other available therapies in the analyzed period. Costs
`for UV-B and psoralen–UV-A (PUVA) therapy were based on a
`total of 42 treatments per year, with 12 weeks of thrice-weekly
`induction treatments and maintenance therapy of 2 treatments
`per month for 9 months per year. Costs for the first year of treat-
`ment with adalimumab include a 80-mg loading dose at week 1,
`followed by 40 mg at week 2, followed by 40 mg every other week.
`Estimates of cost for the first year of treatment for etanercept in-
`clude a loading dose of 50 mg subcutaneously twice weekly for
`12 weeks followed by 50 mg subcutaneously weekly. Costs for
`the first year of infliximab therapy include a dose of 5 mg/kg at
`weeks 0, 2, and 6 and then every 8 weeks. Because of the vari-
`ability in guidelines for laboratory monitoring during treatment
`with biologic therapies, the cost model includes only those moni-
`toring tests recommended by the FDA.
`Costs for each therapy were assessed from the perspective of
`the third-party payer by use of the average wholesale price (AWP)
`of each drug.17 When calculating medication costs, we assumed
`a patient weight of 80 kg and, in the case of the biologics efali-
`zumab and infliximab, assumed that vials of medication were fully
`used during treatment. Costs for infliximab were based on a 3-hour
`infusion time. Monitoring costs for methotrexate include a liver
`biopsy (Current Procedural Terminology [CPT]18 code 47000) to
`factor in the highest potential cost for this drug therapy (even
`though the liver biopsy would be performed less than yearly).
`Costs of outpatient office visits, laboratory testing, infusions,
`and other suggested laboratory and related monitoring proce-
`dures were determined by means of the 2008 Medicare National
`Median Physician Reimbursement schedule and Clinical Labo-
`ratory Fee schedule (Table 1 and Table 2).19 Under the as-
`sumption that most patients with psoriasis are established pa-
`tients, the costs of office visits were calculated in the same manner
`as level 3 return visits. We used CPT codes to search for costs of
`laboratory tests and procedures.20 All costs were calculated in US
`dollars. Additional direct costs, such as hospitalizations or costs
`
`Table 1. Laboratory and Procedure Costs in US Dollars
`
`Item/CPT Codea
`Level 3 established patient/99213
`Eye examination/92012
`Fundus photographs/92250
`Liver biopsy/47000
`Intravenous infusion up to 1 hour/90765
`Intravenous infusion, per additional hour/90766
`UV-B therapy/96910
`PUVA therapy/96912
`Chest x-ray examination/71020
`PPD/86580
`Absolute CD4/CD8 cell count/86360
`CBC with differential/85025
`Triglycerides/84478
`Cholesterol/82465
`Lipid panelb/80061
`Creatinine/82565
`Urea nitrogen/84520
`Uric acid/84550
`Magnesium/83735
`Potassium/84132
`BMP/80048
`CMP/80053
`SGOT/84450
`SGPT/84460
`Hepatic function panel/80 076
`
`Medicare
`Reimbursement, US $
`65.33
`76.56
`75.73
`297.93
`80.72
`25.80
`64.08
`81.97
`36.20
`9.15
`88.71
`14.68
`10.86
`8.22
`18.72
`9.67
`7.45
`8.53
`12.65
`8.67
`15.98
`19.96
`9.76
`10.00
`15.43
`
`Abbreviations: BMP, basic metabolic panel; CBC, complete blood cell
`count; CMP, comprehensive metabolic panel; CPT, Current Procedural
`Terminology ; PPD, purified protein derivative (tuberculin);
`PUVA, psoralen–UV-A; SGOT, serum glutamic oxaloacetic transaminase;
`SGPT, serum glutamic pyruvic transaminase.
`aFrom the American Medical Association Web site (laboratory values for
`the midpoint of 2007).18
`bLipid panel includes high-density lipoprotein cholesterol, total serum
`cholesterol, total lipoprotein cholesterol, triglycerides, and low-density
`lipoprotein cholesterol calculation.
`
`associated with medication adverse effects, and indirect costs, such
`as time away from work, were not included in this analysis.
`Annual trends in psoriasis drug costs from 2000 until 2008
`were analyzed by calculating the percentage change in AWP from
`the previous year. In addition, total percentage change from 2000
`to 2008 was calculated by means of the following formula: 100
`(AWP [2000] − AWP [2008])/AWP (2000). Changes in CPI-U
`rates for all items and for prescription drugs were determined by
`the use of CPI values for all urban consumers (US city average)
`because these values are generally considered equivalent to the
`rate of inflation.21 Therefore, any discussion of trends in infla-
`tion rates in this study is solely based on CPI-U values.
`
`RESULTS
`
`Our analyses were developed to answer 2 questions. First,
`what is the current, direct cost of systemic therapy for
`psoriasis? Second, what is the trend in these costs rela-
`tive to general inflation?
`
`COST OF PSORIASIS TREATMENT
`
`To assess costs for psoriasis therapy, we used a cost model
`to compare the direct annual costs of phototherapy,
`systemic agents, and biologics (Tables 1 and 2). Results
`of our cost analysis are summarized in Table 3. The
`
`(REPRINTED) ARCH DERMATOL/ VOL 146 (NO. 1), JAN 2010
`47
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`

`Table 2. Annual Monitoring Guidelines for All Drugs Discussed
`
`Therapy
`UV-B phototherapy
`
`None
`
`Laboratory Testing and Specialty Examinations
`
`PUVA
`Acitretin
`
`Methotrexate
`
`Cyclosporine
`
`Adalimumab
`Alefacept
`
`Efalizumaba
`Etanercept
`Infliximab
`
`Twice-yearly eye examinations, yearly fundus photographs
`Measurement of triglycerides, cholesterol, SGOT (AST), SGPT (ALT), and
`CBC monthly for 3 mo, then once every 3 mo
`Measurement of CBC, SGOT, and SGPT initially every 2 wk for 2 mo,
`eventually every 2 mo, 1 liver biopsy
`Measurement of CMP (initiation of therapy), BUN, creatinine,
`triglycerides, cholesterol, SGOT, SGPT, uric acid, potassium, and
`magnesium initially every 2 wk for 1-2 mo, then every other month
`Yearly PPD test
`CD4/CD8 cell counts weekly during treatment (24 CD4/CD8 cell counts
`for 2 courses of 12 wk, 16 counts for 16-wk course)
`Initially monthly CBCs for 3 mo, then every 3 mo (6 total CBCs)
`Yearly PPD skin test
`Yearly PPD skin test
`
`Frequency of Office Visits, Return Level 3
`Monthly during induction phase (3 mo),
`then every 3 mo during maintenance
`Same as UV-B
`Monthly initially (3 mo), then every 3 mo for
`6 visits annually
`Monthly initially (3 mo), then every 3 mo for
`6 visits annually
`Every 2 wk for 1-2 mo, then every 2 mo for
`7 visits annually
`
`4 Visits yearly
`24 Visits for 2 courses of 12 wk, 16 visits
`for 16-wk course
`4 Visits yearly
`4 Visits yearly
`4 Visits yearly
`
`Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; CBC, complete blood cell count; CMP, comprehensive
`metabolic panel; PPD, purified protein derivative (tuberculin); PUVA, psoralen–UV-A; SGOT, serum glutamic oxaloacetic transaminase; SGPT, serum glutamic
`pyruvic transaminase.
`aThis drug was withdrawn from the US market in April 2009. However, since this study is an analysis of psoriasis drug costs from 2000 to 2008, data with
`regard to efalizumab were included for the sake of comparison to other therapies.
`
`Table 3. Comparison of Annual Costs for Psoriasis Phototherapy and Systemic Therapy
`
`Therapy
`UV-B phototherapy, induction
`UV-B phototherapy, maintenance
`PUVA phototherapy (with methoxsalen
`[Oxsoralen-Ultra])
`PUVA phototherapy, maintenance
`Acitretin
`
`Methotrexateb
`
`Cyclosporinec (Neoral)
`
`Adalimumab
`Year 1d
`Year 2
`
`Alefacept
`
`Efalizumabe
`Etanercept
`Year 1f
`Year 2
`Infliximab
`Year 1g
`
`Year 2
`
`Dose and Frequency
`Twice weekly for 3 mo
`Twice monthly
`30 mg twice weekly for 3 mo
`
`Twice monthly
`
`25 mg/d
`50 mg/d
`
`7.5 mg/wk
`15 mg/wk
`
`300 mg/d
`400 mg/d
`
`Includes 80-mg loading dose
`40 mg subcutaneously every other
`week
`
`Two 12-wk courses, 15 mg
`intramuscularly per week
`One 16-wk course
`1 mg/kg subcutaneously weekly
`
`Includes loading dose
`50 mg subcutaneously weekly
`
`5 mg/kg intravenously, 400 mg
`maximum daily
`5 mg/kg intravenously, 400 mg
`maximum daily
`
`Medication
`Cost (AWP),a $
`
`1843
`
`1382
`
`8450
`16 900
`
`197
`393
`
`6690
`8921
`
`23 267
`21 605
`
`23 880
`
`15 920
`24 090
`
`26 591
`21 605
`
`22 308
`
`19 520
`
`Phototherapy
`Cost, $
`1538
`1153
`1967
`
`1475
`
`Monitoring
`Cost, $
`
`229
`
`229
`
`321
`321
`
`608
`608
`
`621
`621
`
`10
`10
`
`2129
`
`1419
`88
`
`10
`10
`
`1070
`
`936
`
`Office Visit
`Cost, $
`196
`261
`196
`
`Total Annual
`Cost, $
`1734
`1414
`4235
`
`261
`
`392
`392
`
`392
`392
`
`457
`457
`
`261
`261
`
`1568
`
`1045
`261
`
`261
`261
`
`261
`
`261
`
`3347
`
`9163
`17 613
`
`1197
`1393
`
`7768
`9999
`
`23 538
`21 876
`
`27 577
`
`18 384
`24 439
`
`26 862
`21 876
`
`23 639
`
`20 717
`
`Abbreviations: AWP, average wholesale price; PUVA, psoralen–UV-A.
`aAll costs based on brand-name AWP for 2008; costs in US dollars.
`bMonitoring cost includes 1 liver biopsy.
`cComprehensive metabolic panel performed on initiation of therapy.
`dAdalimumab year 1: regimen of 80 mg at week 1, 40 mg at week 2, 0 mg at week 3, then 40 mg every other week.
`eThis drug was withdrawn from the US market in April 2009. However, since this study is an analysis of psoriasis drug costs from 2000 to 2008, data with
`regard to efalizumab were included for the sake of comparison to other therapies.
`fEtanercept year 1: loading dose of 50 mg subcutaneously twice weekly for 12 weeks, followed by 50 mg weekly.
`gInfliximab year 1: loading dose of 5 mg/kg at weeks 0, 2, and 6 and then every 8 weeks (year 1: 8 total infusions, year 2: 7 infusions). Monitoring costs include
`1 purified protein derivative (tuberculin) and infusion costs ($132.32 for 3 hours). The 400-mg dose is based on a patient weight of 80 kg.
`
`(REPRINTED) ARCH DERMATOL/ VOL 146 (NO. 1), JAN 2010
`48
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`

`Table 4. Psoriasis Systemic Therapy AWP Trends (Price per Dose)
`
`AWP, $a
`
`2000
`6.16
`
`2001
`6.16 (0)
`
`2002
`6.77 (9.9)
`
`2003
`6.77 (0)
`
`2004
`7.79 (15.1)
`
`2005
`12.97 (66.5)
`
`2006
`22.17 (70.9)
`
`2007
`22.17 (0)
`
`Percentage
`Changeb/
`CPI-U
`Percentage
`Change (Years
`Analyzed)c
`2008
`25.61 (15.5) 315.7/25.8 (9)
`
`8.99
`
`11.71 (30.3)
`
`12.29 (5.0)
`
`13.55 (10.3)
`
`14.91 (10)
`
`17.70 (18.7)
`
`18.72 (5.8)
`
`21.84 (16.7)
`
`23.15 (6.0)
`
`157.5/25.8 (9)
`
`1.66
`
`1.66 (0)
`
`1.26 (−24)
`
`1.26 (0)
`
`1.26 (0)
`
`1.26 (0)
`
`1.26 (0)
`
`1.26 (0)
`
`1.26 (0)
`
`−24.1/25.8 (9)
`
`4.47
`
`4.47 (0)
`
`4.14 (−7.4)
`
`4.39 (6.0)
`
`4.36 (−0.7)
`
`4.36 (0)
`
`4.46 (2.3)
`
`4.56 (2.2)
`
`4.80 (5.3)
`
`7.0/25.8 (9)
`
`6.11
`
`6.11 (0)
`
`6.11 (0)
`
`6.11 (0)
`
`6.11 (0)
`
`6.11 (0)
`
`6.11 (0)
`
`6.11 (0)
`
`6.11 (0)
`
`0/25.8 (9)
`
`−4.0/23.8 (8)
`
`Generic Name
`(Trade Name),
`Dose
`Methoxsalen
`(Oxsoralen-
`Ultra), 10 mg
`Acitretin
`(Soriatane),
`25 mg
`Methotrexate
`(Trexall),d
`2.5 mg
`Methotrexate
`(generic),d,e
`2.5 mg
`Cyclosporine
`(Neoral),d
`100 mg
`Cyclosporine
`(Gengraf ),d
`100 mg
`Adalimumab
`(Humira),
`40 mg
`Alefacept
`(Amevive),
`15 mg
`Efalizumab
`(Raptiva),f
`125 mg
`Etanercept
`(ENBREL),
`25 mg
`Infliximab
`(Remicade),
`100 mg
`
`5.50
`
`5.50 (0)
`
`5.50 (0)
`
`5.50 (0)
`
`5.50 (0)
`
`5.28 (−4)
`
`5.28 (0)
`
`5.28 (0)
`
`653.30
`
`577.11 (−11.7) 690.15 (19.6) 719.86 (4.3)
`
`755.14 (4.9)
`
`830.96 (10)
`
`27.2/18.7 (6)
`
`995.00
`
`995.00 (0)
`
`995.00 (0)
`
`995.00 (0)
`
`995.00 (0)
`
`995.00 (0)
`
`0/18.7 (6)
`
`343.00
`
`360.15 (5.0)
`
`404.63 (12.4) 432.95 (7.0)
`
`463.26 (7.0)
`
`35.1/15.0 (5)
`
`141.49 148.43 (4.9)
`
`155.70 (4.9)
`
`163.33 (4.9)
`
`164.47 (0.7)
`
`172.54 (4.9)
`
`179.96 (4.3)
`
`188.78 (4.9)
`
`207.74 (10)
`
`46.8./25.8 (9)
`
`611.33 665.65 (8.9)
`
`691.61 (3.9)
`
`691.61 (0)
`
`691.61 (0)
`
`691.61 (0)
`
`662.68 (−4.2) 670.96 (1.2)
`
`697.13 (3.9)
`
`14.0/25.8 (9)
`
`Abbreviations: AWP, average wholesale price; CPI-U, Consumer Price Index–Urban.
`aNumbers in parentheses indicate percentage change in AWP of medication from previous year.
`bPercentage change calculated from first year of availability until 2008 (for most drugs, calculated change is from 2000 to 2008).
`cYears analyzed includes number of total years the medication has been approved by the Food and Drug Administration since 2000, with the corresponding CPI
`increase (all items) during that period.
`dPrices for methotrexate and cyclosporine based on oral therapy.
`eGeneric cost of methotrexate calculated as average of Trexall and Rheumatrex.
`fThis drug was withdrawn from the US market in April 2009. However, since this study is an analysis of psoriasis drug costs from 2000 to 2008, data with
`regard to efalizumab were included for the sake of comparison to other therapies.
`
`annual costs ranged from $1197 for methotrexate, 7.5
`mg weekly, to $27 577 for two 12-week courses of ale-
`facept. Phototherapy costs ranged from $3083 per year
`for UV-B therapy to $7288 for PUVA annually (includ-
`ing induction and maintenance costs). Costs for acitre-
`tin, 25 mg daily ($9163), were comparable to those for
`cyclosporine, 400 mg daily ($9999); however, some pa-
`tients require 50 mg/d of acitretin, which translates to
`an annual cost of $17 613.
`Annual costs of the biologics used for psoriasis therapy
`ranged from $18 384 to $27 577. The therapies that re-
`quire loading doses (adalimumab, etanercept, and in-
`fliximab) were more costly during the first year of treat-
`ment compared with subsequent years ($23 538 vs
`$21 876 for adalimumab, $26 862 vs $21 876 for etaner-
`cept, and $23 639 vs $20 717 for infliximab). Overall,
`prices for the recommended dosing of the biologics were
`comparable. However, estimates of total costs of bio-
`logic regimens that have been studied in clinical trials22
`but are not the current recommended regimen were found
`
`to vary considerably from our cost calculations. For ex-
`ample, patients treated with efalizumab, 2 mg/kg subcu-
`taneously weekly, accumulate an annual cost $48 530,
`whereas treatment with etanercept, 50 mg, sustained at
`this dose twice weekly incurs an annual cost of $43 732.
`
`RECENT TRENDS IN TREATMENT COST
`
`We analyzed trends in AWP for the various brand-name
`and generic systemic psoriasis treatments from 2000
`through 2008 (Table 4). The percentage changes in drug
`prices between 2000 and 2008 ranged from −24.1% for
`methotrexate to ⫹316% for the brand-name version of
`methoxsalen (Oxsoralen-Ultra; Valeant Pharmaceuti-
`cals International, Aliso Viejo, California). Acitretin (So-
`riatane; Stiefel Laboratories Inc, Coral Gables, Florida)
`had the second largest increase (157.5%) during this pe-
`riod. Conversely, 1 brand-name version of cyclosporine
`(Neoral; Novartis Pharmaceuticals Corporation, Basel,
`Switzerland) did not increase in price during this 8-year
`
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`all prescription drugs during the same period. There was
`an increase of 25.8% for all items and a 30.1% increase
`in prescription drug costs (Table 5). The increase in
`CPI-U values, which is considered equivalent to general
`inflation, was greatest between 2007 and 2008 (4.2%),
`whereas prescription drug prices increased by a signifi-
`cant 6.0% between 2000 and 2001. Costs for all psoria-
`sis medications except methotrexate, cyclosporine, ale-
`facept, and infliximab have increased at a substantially
`greater rate than the CPI-U rate for all items and pre-
`scription drugs (Tables 4 and 5, and Figure 2A and B).
`
`COMMENT
`
`DIRECT COST OF PSORIASIS TREATMENT
`
`The results of our cost analysis, summarized in Table 3,
`revealed that the most costly of the currently recom-
`mended treatment regimens is alefacept (two 12-week
`treatments) at $27 577 per year, whereas the least costly
`treatment is methotrexate ($1197-$1393 annually, de-
`pending on the dose). Published cost-effectiveness analy-
`ses have demonstrated annual costs for psoriasis medi-
`cation of up to $37 000; however, these analyses included
`costs for treatment regimens that are often prescribed but
`not currently published as recommended regimens, such
`as adalimumab, 40 mg weekly, or efalizumab, 2 mg/kg
`subcutaneously weekly.9,16 Indeed, using our cost model,
`we calculated an annual cost of $48 530 for efalizumab,
`2 mg/kg subcutaneously weekly.
`Our analysis demonstrated a greater annual cost for
`PUVA therapy ($7288) relative to UV-B therapy ($3083);
`this is in part owing to the increasing cost of methox-
`salen therapy, as well as additional costs associated with
`required monitoring during PUVA therapy. Thus, our cost
`estimates for PUVA therapy are substantially greater than
`those previously published.23 The results of our cost analy-
`sis are similar to previously published cost analyses; dis-
`crepancies may be accounted for by the use of different
`monitoring guidelines and increasing costs of medica-
`tions, procedures, or clinical laboratory fees. Although
`various studies24,25 have recommended laboratory screen-
`ing and monitoring tests for patients treated with bio-
`logic therapies, our cost model included only those guide-
`lines recommended by the FDA. Including additional
`screening tests would have caused a nominal increase in
`the annual cost of biologic therapies. Our analysis did
`not include indirect costs, such as time away from work,
`direct costs such as hospitalizations, or costs related to
`adverse effects. In addition, costs were calculated by means
`of the 2008 Medicare National Median Physician Reim-
`bursement schedule and Clinical Laboratory Fee sched-
`ule; retail costs for patients who do not qualify for Medi-
`care may be higher. However, because our cost model
`analyzes annual costs for therapies, many of which are
`not given for a full year, the model may overestimate costs
`of certain drug regimens.
`Of note, annual costs were assessed by means of the
`AWP for each therapy, which may not accurately reflect
`market prices for medications. The AWP is a reference
`price reported in publications such as the Red Book17 and
`
`2000 AWP
`2002 AWP
`2004 AWP
`2006 AWP
`2008 AWP
`
`Methoxsalen,
`10 mg
`
`Acitretin,
`25 mg
`
`Methotrexate,
`2.5 mg
`
`Cyclosporine,
`100 mg
`
`Item
`
`∗ ∗
`
`∗ ∗
`
`∗ ∗
`
`Adalimumab,
`40 mg
`
`Alefacept,
`15 mg
`
`Efalizumab,†
`125 mg
`Item
`
`Etanercept,
`25 mg
`
`Infliximab,
`100 mg
`
`30.00
`
`25.00
`
`20.00
`
`15.00
`
`10.00
`
`5.00
`
`0
`
`1200.00
`
`1000.00
`
`800.00
`
`600.00
`
`400.00
`
`200.00
`
`0
`
`A
`
`Cost, US $
`
`B
`
`Cost, US $
`
`Figure 1. Trends in cost of traditional and biologic psoriasis therapies from
`2000 to 2008. A, Traditional therapies. Methoxsalen had the largest
`percentage increase in drug cost (315.7%), whereas acitretin increased in
`price by 157.5%. Costs for methotrexate and cyclosporine did not increase.
`B, Biologic therapies. Efalizumab increased in cost by 35.1% during a 4-year
`interval, whereas the average wholesale price (AWP) of adalimumab
`increased by 27.2% from 2003 until 2008. Etanercept increased steadily in
`cost by 46.8% from 2000 to 2008. *Years when corresponding medications
`were not yet available. †This drug was withdrawn from the US market in
`April 2009. However, since this study is an analysis of psoriasis drug costs
`from 2000 to 2008, data with regard to efalizumab were included for the sake
`of comparison to other therapies.
`
`interval, whereas another (Gengraf; Abbott Laborato-
`ries, Abbott Park, Illinois) decreased in price by 4.0%.
`When analyzing trends in drug costs for the biologics,
`the interval must be considered because a few of these
`therapies have only been available since 2003 or 2004.
`For example, efalizumab (Raptiva; Genentech Inc, South
`San Francisco, California) increased in cost by 35.1% dur-
`ing a 4-year interval. Similarly, the AWP of adalimumab
`(Humira; Abbott Laboratories) increased by 27.2% dur-
`ing a 5-year interval (from 2003 to 2008). Etanercept (EN-
`BREL; Immunex Corporation, Thousand Oaks, Califor-
`nia) increased in cost by 46.8% from 2000 to 2008,
`whereas infliximab increased by only 14.0%, and the cost
`of alefacept has not changed during the same interval.
`Annual percentage change in drug prices fluctuate widely
`(Table 4, Figure 1, and Figure 2); for example, a sig-
`nificant increase in the cost of the brand-name version
`of methoxsalen (Oxsoralen-Ultra) was observed be-
`tween 2004 and 2006 (184.6%). Therapies such as ac-
`itretin, adalimumab, efalizumab, and etanercept have in-
`creased in cost steadily every year, whereas methotrexate,
`cyclosporine, and alefacept have seen minor, if any, in-
`creases in price since 2000.
`To test our hypothesis that psoriasis treatment costs
`have been increasing at a rate greater than the CPI-U,
`trends in psoriasis treatment costs from 2000 through
`2008 were compared with the CPI-U21 for all items and
`
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`2000-2002
`2002-2004
`2004-2006
`2006-2008
`
`∗ ∗ ∗
`
`∗ ∗ ∗ ∗
`
`All Items
`(CPI-U)
`
`Prescription
`Drugs
`(CPI-U)
`
`Methoxsalen,
`10 mg
`
`Acitretin,
`25 mg
`
`Methotrexate,
`2.5 mg
`
`Cyclosporine,
`100 mg
`
`Item
`
`∗ ∗
`
`∗ ∗ ∗ ∗
`
`∗ ∗
`
`∗
`
`Adalimumab
`
`Alefacept
`
`Efalizumab†
`
`Etanercept
`
`Infliximab
`
`All Items
`(CPI-U)
`
`Prescription
`Drugs
`(CPI-U)
`
`Item
`
`200
`
`150
`
`100
`
`50
`
`0
`
`–50
`
`30
`
`25
`
`20
`
`15
`
`10
`
`5 0
`
`Percent Change
`
`Percent Change
`
`A
`
`B
`
`Figure 2. Biannual percentage changes in average wholesale price for systemic psoriasis therapies compared with Consumer Price Index–Urban (CPI-U) values.
`A, Methoxsalen increased in price by 184.6% during a 2-year interval. *Intervals when the cost did not change (percentage change equals zero). B, Increasing CPI
`values are often outpaced by increasing costs of adalimumab, efalizumab, etanercept, and infliximab. Asterisks correspond to intervals when the medication was
`not yet available (2000-2004 for adalimumab, efalizumab, and alefacept) or when the cost did not change (2004-2008 for alefacept). †This drug was withdrawn
`from the US market in April 2009. However, since this study is an analysis of psoriasis drug costs from 2000 to 2008, data with regard to efalizumab were
`included for the sake of comparison to other therapies.
`
`used by Medicaid programs and most third-party payers
`when deciding reimbursement formulas.26 The AWP is
`derived from manufacturer and supplier data; the final
`price negotiated by intermediaries and obtained by hos-
`pitals, pharmacies, insurance companies, and physi-
`cians is often significantly lower than the AWP.27 A re-
`port28 by the Office of the Inspector General of the
`Department of Health and Human Services stated that
`the average sales price of more than 2000 medications,
`based on actual sales transactions, is lower than the AWP
`by a median percentage of 49%. Although the AWP may
`therefore overestimate the true cost of therapy to the pa-
`tient, it is an important drug-pricing benchmark and helps
`monitor trends in drug costs.
`The importance of calculating all disease-related costs
`in a pharmacoeconomic analysis must be emphasized be-
`cause limiting an analysis to a comparison of drug ac-
`quisition costs would significantly underestimate the total
`cost of psoriasis therapy.29 Additional costs include those
`of laboratory monitoring, office visits, procedures such
`as a liver biopsy, and costs related to complications of
`emergency department visits and hospitalizations.11,30 For
`example, despite the low cost of methotrexate relative
`to other psoriasis therapies, frequent office visits and labo-
`ratory tests, as well as recommended periodic liver bi-
`opsies, increase the annual cost somewhat.31 A cost-
`minimization analysis that compared methotrexate and
`cyclosporine showed that although the direct costs of cy-
`closporine were higher, largely because of higher drug
`acquisition prices, higher indirect and follow-up costs were
`observed in the methotrexate group.31
`
`Table 5. Consumer Price Index: US City Average
`for All Urban Consumers20
`
`Cost (Percentage Increase), $a
`
`Year
`2000
`2001
`2002
`2003
`2004
`2005
`2006
`2007
`2008
`Total change, %
`
`All Items
`174.0 (3.4)
`176.7 (1.6)
`180.9 (2.4)
`184.3 (1.9)
`190.3 (3.3)
`196.8 (3.4)
`201.8 (2.5)
`210.0 (4.1)
`218.8 (4.2)
`25.80
`
`Prescription Drugs
`290.0 (3.6)
`307.3 (6.0)
`321.2 (4.5)
`329.1 (2.5)
`340.7 (3.5)
`355.7 (4.4)
`362.3 (1.9)
`374.4 (3.3)
`377.4 (0.8)
`30.10
`
`aNumbers in parentheses are percentage increases in Consumer Price
`Index from December of previous year. The 2008 Consumer Price Index
`value is for June.
`
`INDIRECT COSTS ASSOCIATED
`WITH PSORIASIS TREATMENT
`
`Although not included in this analysis, indirect costs
`should also be considered when making therapeutic de-
`cisions. Also referred to as “forgotten costs” or “lost op-
`portunity costs,” indirect costs include time away from
`work, transportation costs, and time spent in personal
`care.29 The decreasing use of phototherapy, despite its
`low direct cost and favorable safety profile, has been par-
`tially attributed to the lost work productivity and incon-
`
`(REPRINTED) ARCH DERMATOL/ VOL 146 (NO. 1), JAN 2010
`51
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`venience associated with treatment.5 Simpson and col-
`leagues5 propose that decreasing physician reimbursement
`rates and high out-of-pocket expenses for patients, ow-
`ing to copayments with every treatment, place disincen-
`tives on phototherapy use. Given the inconvenience and
`costs associated with office-based phototherapy, home
`UV phototherapy (not included in this cost analysis) has
`become a more attractive option in certain settings be-
`cause it helps defray indirect and direct costs. Alterna-
`tively, patients who are discouraged with the logistics and
`frequent copayments associated with office-based pho-
`totherapy may be encouraged to use more expensive bio-
`logics, the cost of which is generally mostly covered by
`insurance companies.
`
`INSURANCE CONTRIBUTIONS
`
`The contribution of insurance companies to prescrip-
`tion drug cost, however, does not necessarily translate
`to lower cost for the patient. A report by the Kaiser Fam-
`ily Foundation32 showed that, among the 75% of work-
`ers covered by a 3-tier or 4-tier cost-sharing plan for pre-
`scription drugs, average copayments in 2007 ranged from
`$11 per generic drug to $71 for fourth-tier prescription
`drugs. Several insurance plans have recently added a
`fourth tier for expensive lifestyle drugs and biologics, and
`plans such as B