VALUE IN HEALTH REGIONAL ISSUES 5C (2014) 65–72

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Cost-Effectiveness of Biologic Agents in the Treatment of

Moderate-to-Severe Psoriasis: A Brazilian Public Health Service
Perspective
Bruno Salgado Riveros, MSc1, Patrícia Klarmann Ziegelmann, PhD2, Cassyano Januário Correr, PhD1,*
1
Pharmaceutical Sciences Department, Federal University of Parana, Curitiba, Brazil; 2Department of Statistics, Federal University of
Rio Grande do Sul, Porto Alegre, Brazil

AB STR A CT

Background: Psoriasis is a chronic disease that affects public health
and budget payers. In Brazil, biologic therapy for psoriasis is mostly
provided by means of lawsuit with no strategy for efficient allocation
of resources. Objective: This study aimed to identify which of the
available biologic alternatives for psoriasis is the most efficient from
the perspective of the Brazilian Public Health Service (SUS). Methods:
Direct costs and efficacy were expressed in Brazilian currency (real
[R$]; US $1 ¼ R$1.97) and Psoriasis Area Severity Index 75 (PASI75),
respectively. The Markov model process included 12 cycles of 3
months each, comprising 3 years of horizon. Adalimumab (80 mg at
week 0 followed by a maintenance dose of 40 mg at week 1 and then
every other week), etanercept (50 mg twice weekly for 12 weeks
followed by a maintenance dose of 25 mg weekly), infliximab (5 mg/
kg at weeks 0, 2, and 6 and then every 8 weeks), and ustekinumab
(45 mg at weeks 0 and 4 and then every 12 weeks) were assessed. One-
way and horizon sensitivity analyses were performed. Moreover,
probabilistic sensitivity analysis was applied to evaluate model
robustness. The final result was interpreted as the cost for each
patient who achieved and maintained PASI75 for at least 3 years.
Results: Adalimumab was the most cost-effective biologic therapy
(R$120,981.45/PASI75) for moderate-to-severe psoriasis, followed by
ustekinumab (R$126,336.67/PASI75), etanercept (R$225,074.71/PASI75),
and infliximab (R$377,656.28/PASI75). One-way sensitivity analysis
determined that the acquisition cost of biologics was the most
sensitive parameter of the model. Horizon analysis suggests that the
result was the same when the horizon was varied from 1 year to a
lifetime. Probabilistic sensitivity analysis showed that adalimumab
has 80% to 10% probability of being the most cost-effective biologic
considering a willingness-to-pay value ranging from R$50,000 to
R$500,000, whereas ustekinumab presented a probability of 20% to
90% for the same range. Conclusions: From the pharmacoeconomics
point of view, adalimumab 80 mg at week 0 followed by a main-
tenance dose of 40 mg at week 1 and then every other week should be
the first-line therapy for patients with plaque psoriasis concomitant
or not to psoriatic arthritis or nail psoriasis. This study does not have
the potential to evaluate the impact of incorporating a specific biologic
agent on the final budget. Its goal is to point out which of the
technologies is the most efficient, that is, the one that adds more
value to the financial resource invested.
Keywords: biological agents, cost effectiveness, drug therapy,
pharmacoeconomics, psoriasis.
Copyright & 2014, International Society for Pharmacoeconomics and
Outcomes Research (ISPOR). Published by Elsevier Inc.

than 10% of body surface area (BSA) affected by the disease, 2) a

Introduction
Psoriasis is a chronic autoimmune disease that affects mainly the
skin. Its prevalence around the world varies between 0.6% and 4.8%
[1]. There are different phenotypes for this disease, with plaque
psoriasis (or psoriasis vulgaris) being the most common and affecting
80% of all patients with such a clinical condition [2]. Concomitant
phenotypes are possible, such as psoriatic arthritis and plaque
psoriasis (40%), with or without nail psoriasis (35%–50%) [3]. Other
morphological combinations are less common, but possible as well.
Treatment is based on disease severity (mild, moderate, or
severe). There is no consensus in the way to classify it, but most
guidelines [4–13] suggest the “rule of 10” as an acceptable tool. The
aforementioned clinical approach considers patients with 1) more
score of 10 or more for the Dermatology Life Quality Index (DLQI), or
3) Psoriasis Area Severity Index (PASI) as patients with moderate-to-
severe psoriasis. Some authors consider those with a PASI value of
20 as suffering from a clinically severe condition [7]. In cases of mild
psoriasis, topic treatment is generally effective [14]. In cases of
moderate-to-severe psoriasis, systemic treatment is based on
phototherapy, methotrexate, acytretin, or cyclosporine. For patients
who do not respond to any of these therapeutic options or develop
adverse reactions, biologic agents are an option [15].
In the Brazilian Public Health System (SUS), the clinical
protocol for psoriasis does not indicate the best approach regard-
ing the use of biologics. One of the reasons for this might be that
there is a lack of economic evaluations that consider the SUS

Conflict of interest: The authors have indicated that they have no conflicts of interest with regard to the content of this article.
* Address correspondence to: Cassyano Januário Correr, nº 632, Pref. Lothario Meissner Avenue, Curitiba 81540050, Brazil.
E-mail: cassyano.correr@gmail.com
2212-1099$36.00 – see front matter Copyright & 2014, International Society for Pharmacoeconomics and Outcomes Research (ISPOR).
Published by Elsevier Inc.
http://dx.doi.org/10.1016/j.vhri.2014.09.002
66 VALUE IN HEALTH REGIONAL ISSUES 5C (2014) 65–72
perspective [7]. Moreover, biologics for the treatment of psoriasis
remain unavailable in the SUS [16], making lawsuit the only way
for patients to access such expensive treatment.
Therefore, we aimed to identify the most cost-effective bio-
logic agent for moderate-to-severe psoriasis according to the
perspective of the SUS.
Methods
This is a cost-effectiveness analysis in which costs were
expressed in real (R$, Brazilian currency) and efficacy in PASI75
response (PASI75). The exchange rate between real and US dollar
was US$ 1 ¼ R$1.97 at the time of the study. This outcome
corresponds to an improvement of 75% to 100% in the basal PASI
score. Because the chosen outcome corresponds to efficacy and
not effectiveness, it is important to highlight that data extracted
from clinical trials were obtained in a controlled environment
and not in a real-world scenario.
The result was interpreted as the amount of money spent for
a patient who achieve and maintain PASI75 for at least 3 years.
The adopted perspective is that of the SUS. A Markov model
process with 12 cycles of 3 months each was built to assess the
scenario of patients with moderate-to-severe psoriasis, eligible
for treatment based on biologics, following Brazilian Consensus
of Psoriasis [6].
This pharmacoeconomic study is part of a broader project that
involved systematic reviews of clinical efficacy and safety [17]
and patient-related outcomes. Moreover, a mixed treatment
comparison for these three outcomes and a benefit-risk multi-
criteria decision analysis were carried out. These studies are
under review in scientific journals.
Population
Patients with moderate-to-severe psoriasis treated within the
SUS who had an indication to start a biologic agent were our
targeted population. Efficacy data of each biologic agent were
obtained from the literature [18–22]. Thus, our results are appli-
cable to patients with characteristics described in Table 1, which
corresponds to the weighted average of the population evaluated
in each clinical trial.
Technologies Assessed
The evaluated biologic agents were the ones approved by the
National Health Surveillance Agency (ANVISA) for marketing up
to the end of 2012, and selected dosages were the ones indicated
by Brazilian Consensus of Psoriasis [6]. Thus, adalimumab (80 mg
at week 0 followed by a maintenance dose of 40 mg at week 1 and
then every other week), etanercept (50 mg twice weekly for 12
weeks followed by a maintenance dose of 25 mg weekly),
Table 1 – Characteristics of the population with
psoriasis from which data about efficacy were
extracted.
Characteristic Mean ⫾ SD
Age (y) 44.8 ⫾ 1.31
Men (%) 67.8 ⫾ 2.14
Patients with PsA (%) 29.7 ⫾ 3.54
Disease duration (y) 19.5 ⫾ 1.18
PASI score 19.6 ⫾ 1.9
DLQI score 11.7 ⫾ 0.66
DLQI, Dermatology Life Quality Index; PASI, Psoriasis Area Severity
Index; PsA, psoriatic arthritis.
infliximab (5 mg/kg at weeks 0, 2, and 6 and then every 8 weeks),
and ustekinumab (45 mg at weeks 0 and 4 and then every 12
weeks) were assessed.
Markov Model
The proposed model, which consisted of four health states, was
based on Woolacott et al. [23]: (Fig. 1):
 PASI75—patients who achieved an improvement of 75% to
100% in their basal PASI score.
 PASI50-75—patients who achieved an improvement of 50% to
75% in their basal PASI score.
 Failure—patients who did not achieve an improvement of 50%
to 75% in their basal PASI score nor achieved better scores,
patients who achieved an improvement of 50% to 75% in their
basal PASI score but after 12 weeks did not improve their
response to PASI75, or patients who developed an adverse
event preventing the maintenance of biologic therapy.
 Death—includes all death cases regardless of cause.
Each Markov cycle corresponds to 12 weeks, and the study
time horizon was 3 years. Discounting of 5% [24] was applied
following Brazilian statements. The outcome was assessed con-
sidering the number of patients with PASI75 health state at the
end of the model.
The first 12 weeks of treatment is not shown in the model. It
was, however, represented in cycle 0, and costs were expressed
as initial costs. Thus, _stage¼0 corresponds to a period between 12
and 24 weeks after treatment initiation.
Because all models are a simplified way to understand a
complex situation, all of them have assumptions [25]. The
present model assumes the following:
1. After therapeutic failure with any biologic agent, patient did
not use any other biologic.
2. Temporary interruptions of biologics were not considered in
this model.
3. Patients who achieved PASI75 interrupted biologic therapy
only if they
a. got a clinical response worse than 50% of improvement or
b. developed adverse reaction or any adverse event that
increased the risks over the benefits.
4. Patients with an improvement of 50% to 75% in their basal
PASI score for more than 12 weeks had their biologics
interrupted.
5. Only the clinical efficacy of biologics was taken into account,
regardless of association with topic or systemic drugs or
phototherapy treatment.
Probabilities
Data of PASI75 were extracted from the literature to serve as
foundations for transition probabilities (Table 2). The selected
randomized controlled trials (RCTs) were the ones that 1)
assessed the same dose regimen as us, 2) showed low risk of
bias by means of Cochrane Collaboration’s tool, 3) presented
long-term results (at least 1 year of follow-up), and 4) had a
number of participants weighing more than 500 lb. Probabilities
related to the short-term treatment were retrieved from an
network meta-analysis involving the four biologics assessed [18].
From the second year of treatment, efficacy data were
extrapolated from the last known result. This assumption was
based on literature findings [19,20,22].
Death probability was extracted from the Life Table pub-
lished by the Brazilian Institute of Geography and Statistics
(IBGE) [26].
 VALUE IN HEALTH REGIONAL ISSUES 5C (2014) 65–72 67

Fig. 1 – Markov model for patients with moderate-to-severe psoriasis treated with biologics. PASI, Psoriasis Area
Severity Index.

Considering the absence of data for patients treated with
infliximab after 1 year, a linear regression based on available data
was developed and the linear equation was predicted considering
unknown responses. External validation and graphs are available
in full detail in Appendix 1 in Supplemental Materials found at
http://dx.doi.org/10.1016/j.vhri.2014.09.002.
First, extracted data (epidemiological values) had to be cali-
brated, and then inserted in the model. The calibration method
aimed to predict transition probabilities among health states to
respect both epidemiological evidence and natural history of the
disease. Probabilities applied to the model and other details are
available in Appendix 2 in Supplemental Materials found at
http://dx.doi.org/10.1016/j.vhri.2014.09.002.
According to the International Society of Pharmacoeconomics
and Outcomes Research, external validation is essential to
establishing the credibility of any model [27]. Thus, we validated
it considering the epidemiologic data regarding PASI75 response
(Table 2) and the reproducibility of these results by the model. In
other words, we sought to identify whether the model was
capable of retrieving the same PASI75 response as shown in the
RCT [19–22].
Costs
Direct costs were assessed from the perspective of the SUS,
including costs for biologics, conventional therapy, drug admin-
istration, laboratory and imaging tests, hospitalization, consulta-
tions, and adverse event management. First, the main costs were
identified, then measured, and finally valued. Costs varied
according to the technology involved, cycle, and health state. In

Table 2 – PASI75 efficacy data extracted from the literature.

Cycle

0 1 2 3 4 5 6 7

Months 0–3 3–6 6–9 9–12 12–15 15–18 18–21 21–24

_stage 0 1 2 3 4 5 6

Drug
Adalimumab 0.58* 0.67† 0.64† 0.6† 0.59† 0.59† 0.57† 0.54†
Etanercept 0.52* 0.60‡ 0.60‡ 0.63‡ 0.6‡ 0.55‡ 0.55‡ 0.52‡
Infliximab 0.8* 0.82§ 0.74§ 0.61§ 0.51ǁ 0.40ǁ 0.30ǁ 0.20ǁ
Ustekinumab 0.69* 0.76¶ 0.72¶ 0.64¶ 0.61¶ 0.61¶ 0.61¶ 0.61¶
Note. Italic values correspond to data obtained through linear regression.
PASI, Psoriasis Area Severity Index.
* Reich et al. [18].
†
Gordon et al. [20].
‡
Tyring et al. [22].
§
Reich et al. [21].
ǁ
Calculated by the author.
¶
Kimball et al. [19].
68 VALUE IN HEALTH REGIONAL ISSUES 5C (2014) 65–72
Appendix 3 in Supplemental Materials found at http://dx.doi.org/
10.1016/j.vhri.2014.09.002, all these data were thoroughly
described. The sources used for valuing each cost component
were the SIGTAP [28] (a database of procedures performed by the
SUS) and the CMED [29] (the Regulation Chamber Drug Market in
Brazil). For biologic agents, the costs were retrieved from Sistema
Brasileiro de Informação sobre Medicamentos (Brazilian System
of Informations about Medications), a database for drugs
obtained through lawsuit. Adalimumab 40-mg vial costs R$
1,792.56, whereas etanercept 25 and 50 mg, infliximab 100 mg,
and ustekinumab 45 mg cost R$1093.22 and R$571.22, R$1896.32,
and R$7527.15, respectively. In addition, for adverse events
management and hospitalizations, we extrapolated and adjusted
findings from cost-of-illness studies [30–32]. First, we identified
how much a given health problem costs yearly. Then, we updated
this value to the present days by means of Índice Nacional de
Preços ao Consumidor Amplo (National Consumer Price Index
Board) and we adjusted its annual cost for each Markov cycle.
Efficacy
The outcome considered is PASI75. It is interpreted as an
improvement of 75% to 100% in the basal score measured by
the PASI questionnaire, which assesses the area, erythema,
induration, and desquamation of psoriasis injuries around the
body [33]. The model was built to use the percentage of patients
at PASI75 health state at the end of 3 years as the measure of
efficacy.
Sensitivity Analysis
Following the statements provided by Brazilian Guideline for
Economic Evaluations [24], one-way sensitivity analysis and
probabilistic sensitivity analysis were performed. Moreover, the
impact of time horizon was assessed in the final result.
All the parameters of the model were submitted to one-way
sensitivity analysis. The range used for each parameter corre-
sponds to the 95% confidence intervals. Time-horizon analysis
considered scenarios ranging from 1 year up to the lifetime
period; thus, probabilities from 2 years were extrapolated to the
lifetime period. In addition, probabilistic sensitivity analysis was
performed considering all variables of the model. Costs were
distributed using gamma distributions in which hyperparameters
for biologic agents were calibrated so that lowest and highest
prices registered in Sistema Brasileiro de Informação sobre
Medicamentos corresponded to 0.95 probability interval. Proba-
bility parameters were distributed using beta (nodes with two
branches) or Dirichlet (nodes with more than two branches)
distributions. The hyperparameters for these distributions were
calibrated considering the number of participants in each study
by which PASI responses were extracted. A total of 10,000
iterations were applied. Hyperparameters of each distribution
as well as the ranges used for one-way analysis are available in
Appendix 4 in Supplemental Materials found at http://dx.doi.org/
10.1016/j.vhri.2014.09.002.
Table 3 – Results from 3 y of treatment with biologics.
Biologic agent Cost (R$) Effectiveness (PASI75)
Adalimumab 64,422.62 0.5325
Infliximab 74,813.71 0.1981
Ustekinumab 75,663.03 0.5989
Etanercept 116,678.73 0.5184
PASI, Psoriasis Area Severity Index.
Results
Table 3 presents base-case results of a cost-effectiveness model
with a 3-year time horizon using direct costs in the SUS perspec-
tive. Adalimumab is the most cost-effective technology because
each patient who achieves and maintains PASI75 for at least 3
years cost R$120,981.45. It is followed by ustekinumab (R
$126,336.67/PASI75), etanercept (R$225,074.71/PASI75), and inflix-
imab (R$377,656.28/PASI75). Our findings suggest that adalimumab
is dominant over etanercept and infliximab and show an incre-
mental cost-effectiveness ratio (ICER) of R$169,283.28/incremental
PASI75 between adalimumab and ustekinumab. Considering the
threshold for each incremental PASI75 response, the lowest paid
value for each response (R$120,981.45/PASI75), the ICER between
ustekinumab and adalimumab suggests adalimumab (80 mg at
week 0 followed by a maintenance dose of 40 mg at week 1 and
then every other week) as the most cost-effective technology.
Sensitivity Analysis Findings
Figure 2 shows a Tornado diagram expressed in ICER considering
adalimumab as the common comparator. Dotted lines corre-
spond to the ICER value in the base-case scenario. One-way
sensitivity analysis pointed out the acquisition cost of biologics
(c_ADA, c_ETA, c_INF, C_UST) as the most sensitive parameter
of the model. None of the other variables was able to alter the
final interpretation of base-case results.
Important information regarding one-way sensitivity analysis
is the identification of threshold values. Decreasing the acquis-
ition cost of ustekinumab by 16.7% makes this technology
dominant over all other drugs, whereas a reduction of 5.3%
matches efficiency (cost-effectiveness ratio) with adalimumab.
The acquisition cost for etanercept should decrease 50% to have
the same efficiency as well. There were no scenarios in which
infliximab was as efficient as adalimumab.
The impact of the time horizon on the cost-effectiveness ratio
was assessed varying the number of cycles of the model.
Scenarios from 1 year up to the lifetime period were simulated.
Figure 3 shows the final result up to 5 years. It is seen that cost-
effectiveness ratios for adalimumab and ustekinumab are very
similar through the years, whereas etanercept and infliximab
increase their ratio compared with other biologics. Analysis with
a longer time horizon maintained that tendency. In the first
6 months of treatment, infliximab is the most effective treat-
ment, with 82% of PASI75 response [21] (see Table 2). In this time
horizon, adalimumab is the most cost-effective treatment
(R$27,847.92/PASI75) followed by ustekinumab (R$30,559.99/
PASI75), infliximab (R$41,648.74/PASI75), and etanercept
(R$63,572.69/PASI75). A reduction in the acquisition cost of
ustekinumab, infliximab, and etanercept by 11%, 36%, and 67%,
respectively, would change their cost-effectiveness ratio to that
shown by adalimumab.
Probabilistic sensitivity analysis was undertaken as recom-
mended by the Brazilian Guideline for Economic Evaluations [24].
Cost-effectiveness Incremental cost-effectiveness ratio
(R$/PASI75)
120,981.45 –
377,656.28 Dominated
126,336.67 169,283.28
225,074.71 Dominated
 VALUE IN HEALTH REGIONAL ISSUES 5C (2014) 65–72
Fig. 2 – Tornado diagram expressed in terms of ICER impact.
(A) Etanercept (ETA) vs. adalimumab (ADA). (B) Infliximab
(INF) vs. adalimumab. (C) Ustekinumab (UST) vs.
adalimumab. ICER, incremental cost-effectiveness ratio.
A cost-effectiveness acceptability curve was obtained from the
simulation whereby distributions were applied for all parameters
in the model (Fig. 4). This graph shows the probability of a given
69
treatment being the most cost-effective (or efficient) alternative
for a range of willingness-to-pay (WTP) values. On varying the
WTP value from R$50,000 to R$500,000, the probability of adali-
mumab being the most cost-effective treatment varies from 80%
to 10%, respectively. For the same WTP range, the probability of
ustekinumab being the most cost-effective treatment varies from
20% to 90%, respectively. When the WTP is R$240,000, both
biologics have 50% probability of being the most cost-effective
treatment. For the assessed WTP range, etanercept and inflix-
imab have probabilities close to 0%. The ICER between adalimu-
mab and ustekinumab showed a mean of R$197,000/incremental
PASI75, and the most likely values are between R$100,000 and R
$200,000/incremental PASI75. Nevertheless, the aforementioned
ICER shows a probability of 62% to be above the considered WTP.
Discussion
This is the first pharmacoeconomic analysis that assessed bio-
logics in the treatment of moderate-to-severe psoriasis in the
Brazilian Public Health Service (SUS). In this context, the follow-
ing five issues deserve special attention, and, thus, discussion
was carried out by considering the following.
Why Not Cost-Utility Analysis?
Until the present date, pharmacoeconomic studies assessing
biologic agents in the long-term treatment of moderate-to-
severe psoriasis have not considered PASI75 response as an
outcome. This is the first study that considered PASI75 response
as an outcome. Previous studies used cost-utility analysis [34–41]
or cost-effectiveness for assessing short-term treatment [42,43].
Studies that have used Markov models were based on the one
proposed by Woolacott et al. [23], which consists of health states
defined by PASI response, in which a value of the DLQI is
attributed to each health state and then changed by the EuroQol
five-dimensional questionnaire (EQ-5D) utility through a linear
equation. It is already known that psoriasis has a high-level
impact on quality of life [44]. Thus, cost-utility analyses compar-
ing biologic agents are of great relevance to analyze psoriasis
treatment in a broader way. Norlin et al. [45], however, demon-
strated that PASI response and the EQ-5D instrument have low
correlation (r ¼ 0.25; P o 0.001), and, thus, suggest that defining
utility values by means of PASI response seems to have a high
level of bias. Moreover, the Markov model proposed by Woolacott
et al. may not be feasible for cost-utility analysis assessed by the
EQ-5D. Considering this new evidence, we chose to develop a
cost-effectiveness analysis considering PASI75 as a clinical out-
come because it is the tool used most often to assess psoriasis.
Patients Benefited from This Study
People with moderate-to-severe psoriasis treating their disease in
the SUS were the target population for our study. Because efficacy
data were extrapolated by clinical trials up to now, their charac-
teristics remained unknown. These results should ideally be
applied to patients with clinical particularities given in Table 1.
Thus, children with psoriasis are not covered by our results. Our
team developed a psoriasis cost-of-illness model and determined
the characteristics of patients with moderate-to-severe psoriasis
using biologics [32]. The profile of these patients is different from
that of patients included in RCTs, especially regarding age and
time of disease. We understand, however, that these patients are
representative of the real ones benefited when the SUS start
dispensing such biologic drugs. For the moment, patients with
psoriasis get access to these drugs by the SUS; they will start the
treatment earlier, and so their profile will tend to be similar to
that of patients included in RCTs.
70 VALUE IN HEALTH REGIONAL ISSUES 5C (2014) 65–72

500000

Cost Effectiveness ratio (R$/PASI75)

450000
400000
350000
300000 Adalimumab
250000 Etanercept
200000
Infliximab
150000
100000 Ustekinumab
50000
0
0.5 0.75 1 1.25 1.5 1.75 2 3 4 5
Fig. 3 – Time-horizon analysis from 1 to 5 years and its impact on the cost-effectiveness ratio. The horizontal line represents
the time horizon expressed in years.

Study Horizon critical parameter. The uncertainty around it can be known and
measured because a decision maker knows exactly how much will
Because psoriasis is a chronic disease, its treatment lasts for lifetime.
each vial of a biologic agent cost. Other parameters such as
So, the ideal scenario to evaluate it would be a model capable of
discounting, hospitalization, and adverse event costs and short-
predicting changes and interruptions during the treatment, as well as
and long-term probabilities were not able to change the final result.
its effectiveness for many years. The main limitation to such a model
Important data provided by this analysis were the required costs for
is the lack of data to support long-term transition probabilities.
each biologic agent vial to change the found results (described in
The horizon defined in different studies varies. Knight et al. [37],
the Results section). These data can be useful for stakeholders
Marcellusi et al. [38], and Lloyd et al. [41] defined 10 years, extrapolat-
when defining a specific price for a determined market.
ing the last known data through the next cycles up to the end of the
Regarding probabilistic sensitivity analysis, 10,000 iterations were
study. Verma and Dharmarajan [46] defined 5 years, Villacorta et al.
performed and the interpretation was based on the cost-effectiveness
[40] 3 years, Ahn et al. [47] 1 year, and Ferrándiz et al. [42] 6 months.
acceptability curve. Because the perspective’s WTP is unknown, the
Our choice of 3 years was sustained by the available evidence
cost-effectiveness acceptability curve provides a range of values,
[19,20,22] and its feasibility with the real world. In other words, it is
defined by us from R$50,000 to R$ 500,000. In scenarios with limited
frequently seen that patients treat psoriasis with biologic agents up to
financial resources—WTP values up to R$240,000—adalimumab had
3 years, but not 10 years, for instance. It is important to highlight that
the highest probability to be the most efficient. By considering greater
a 3-year time horizon is unable to capture costs, benefits, and adverse
values, ustekinumab is the best option. Considering the least cost-
events that occurred after these 3 years of treatment.
effectiveness ratio (R$120,981.45/PASI75) as the WTP for each incre-
Our horizon analysis shows the same tendency for a very
mental patient who achieves and maintains PASI75 for at least 3
broad horizon range. This evidence provides more reliability for
years, adalimumab (80 mg at week 0 followed by a maintenance dose
our results, though there are some biases around the results from
of 40 mg at week 1 and then every other week) is the most likely
3 years to lifetime because probabilities were extrapolated to
biologic agent to be cost-effective. Moreover, probabilistic sensitivity
make this analysis possible.
analysis showed that the ICER between adalimumab and ustekinu-
mab is more likely to be above the proposed WTP value.

Sensitivity Analysis
Although one-way sensitivity analysis pointed out the acquisition First-Line Therapy Definition
cost of biologics as a sensitive parameter for the model, we consider Choosing a biologic agent to be used as first-line therapy for
the final results robust. It can be explained by the nature of this psoriasis is not easy. After all, many variables such as

Fig. 4 – Cost-effectiveness acceptability curve. Willingness to pay for each incremental case of PASI75 varies between R$50,000
and R$500,000.
 VALUE IN HEALTH REGIONAL ISSUES 5C (2014) 65–72
comorbidities and severity affect this decision [48,49]. The most
sensible analysis is dividing the population with psoriasis requir-
ing biologics into subgroups. Although this study was based on
patients with moderate to severe psoriasis, the population profile
included in clinical trials [18–22] allowed us to infer about some
subgroups.
Patients with severe psoriasis, defined by some authors as
those with a PASI value of more than 20, benefit from treatment
based on infliximab (5 mg/kg at weeks 0, 2, and 6 and then every 8
weeks) because of its quick response [50]. Findings from this
study show that its cost-effectiveness ratio is close to that of the
best option, adalimumab (80 mg at week 0 followed by a
maintenance dose of 40 mg at week 1 and then every other
week) for more than 6 months of treatment. In this subgroup, we
recommend starting infliximab 5 mg/kg and switching to adali-
mumab (80 mg at week 0 followed by a maintenance dose of 40
mg at week 1 and then every other week) as soon as PASI75 is
achieved. Besides the pharmacoeconomic aspect, we believe in
this modification therapy because secondary failure (failure after
therapeutic response) with infliximab has the potential to impair
the efficacy of other anti–TNF-α agents [48], such as adalimumab
and etanercept.
Psoriatic arthritis is presented in 6% to 10% of the patients with
psoriasis and in 40% in those who have severe disease [3]. For
patients who have plaque psoriasis concomitant to joint involve-
ment, we suggest adalimumab (80 mg at week 0 followed by a
maintenance dose of 40 mg at week 1 and then every other week)
as first-line therapy because it is the most efficient treatment
among anti–TNF-α agents when the outcome is PASI score. Atteno
et al. [51] assessed the efficacy of anti–TNF-α agents for psoriatic
arthritis by means of the American College of Rheumatology 20
outcome. It was found that 72% of the patients treated with
etanercept (50 mg twice weekly for 12 weeks followed by a
maintenance dose of 25 mg weekly) achieved an improvement
of 20%, measured by the American College of Rheumatology 20
outcome, compared with 70% of the patients treated with adali-
mumab (80 mg at week 0 followed by a maintenance dose of 40 mg
at week 1 and then every other week) and 75% of the patients
treated with infliximab (5 mg/kg at weeks 0, 2, and 6 and then
every 8 weeks) [51]. Considering these slight differences among the
results, we believe that adalimumab (80 mg at week 0 followed by
a maintenance dose of 40 mg at week 1 and then every other
week) has the best cost-effectiveness ratio when plaque psoriasis
is associated with psoriatic arthritis. Ustekinumab is contraindi-
cated for these patients because this biologic (anti–IL-12/23) does
not have satisfactory efficacy in psoriatic arthritis [52,53].
Nail psoriasis is rarely presented alone but in combination
with some other phenotypes (50% of the cases) [5]. In cases in
which plaque psoriasis is diagnosed with or without nail psor-
iasis, and there is indication to start using a biologic agent, we
suggest adalimumab (80 mg at week 0 followed by a maintenance
dose of 40 mg at week 1 and then every other week) as first-line
therapy.
Patients with hepatitis B or C are discouraged to use anti–TNF-
α agents because of the risk of the disease being reactivated [54].
Thus, from the clinical and pharmacoeconomic points of view,
ustekinumab (45 mg at weeks 0 and 4 and then every 12 weeks)
should be the first-line therapy. German [4] and British [8] guide-
lines suggest that etanercept may not be involved in hepatitis C
reactivation. We recommend, however, this biologic as second-
line therapy because of our pharmacoeconomic findings.
When antinuclear factor or antibodies are positive, it is not
recommended to start treatment based on anti–TNF-α agents
because there is evidence of the use of such biologic agents
leading to drug-induced lupus erythematosus [55]. So, the bio-
logic chosen in these patients is ustekinumab (45 mg at weeks 0
and 4 and then every 12 weeks).
71
Psoriasis can assume many phenotypes, such as plaque (or
vulgar), nail, erythrodermic, guttate, inverse, and pustular psor-
iasis. For most of the patients, more than one phenotype can
occur concomitantly, including joint involvement called psoriatic
arthritis [2]. PASI75 response is the main outcome for psoriasis
because it is the criterion standard used to evaluate plaque
psoriasis, which is the most common phenotype affecting 80%
[2] of the patients. This outcome, however, cannot properly
evaluate all the phenotypes. Although in clinical trials there were
individuals with other phenotypes, we recommend these results
for those with plaque psoriasis, with or without concomitant
psoriatic arthritis and nail psoriasis, in which the main objective
of the treatment is to control the disease in the skin. It is
important to highlight that for some cases, such as pustular
psoriasis, anti–TNF-α agents are contraindicated [8].
Conclusions
From the pharmacoeconomic point of view, in Brazilian SUS,
adalimumab (80 mg at week 0 followed by a maintenance dose of
40 mg at week 1 and then every other week) should be the first-
line therapy among the biologics used for the treatment of
patients with moderate to severe psoriasis. We recommend
adalimumab (80 mg at week 0 followed by a maintenance dose
of 40 mg at week 1 and then every other week) for patients with
plaque psoriasis with or without concomitant psoriatic arthritis,
or nail psoriasis, whereas those with contraindication to anti–
TNF-α agents should be treated with ustekinumab (45 mg at
weeks 0 and 4 and then every 12 weeks).
This study does not have the potential to evaluate the impact
of incorporating a specific biologic agent on the budget. Its goal
was to point out which of the assessed technologies is the most
efficient, that is, the one that adds more value to the financial
resources invested.
Supplementary Materials
Supplemental material accompanying this article can be found in
the online version as a hyperlink at http://dx.doi.org/10.1016/j.
vhri.2014.09.002 or, if a hard copy of article, at www.valuein
healthjournal.com/issues (select volume, issue, and article).
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