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Cost-Effectiveness Analysis of Tocilizumab in Comparison with
Infliximab in Iranian Rheumatoid Arthritis Patients with
Inadequate Response to tDMARDs: A Multistage Markov Model
Amir Hashemi-Meshkini, PharmD
1
, Shekoufeh Nikfar, PharmD, PhD
1
, Elizabeth Glaser, MS, MA
2
,
Ahmadreza Jamshidi, MD
3
, Seyed Alireza Hosseini, PharmD, PhD
1,4,
*
1
Department of Pharmacoeconomics and Pharmaceutical Management, School of Pharmacy, Tehran University of Medical Sciences,
Tehran, Iran;
2
The Institute for Global Health and Development, Heller School for Social Policy and Management, Brandeis University, Waltham, MA, USA;
3
Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran;
4
Clinical Trials Group, Food
and Drug Research Center, Iran Food and Drug Administration, Ministry of Health and Medical Education, Tehran, Iran
ABSTRACT
Objectives: To analyze the cost-effectiveness of two common treat-
ment strategies in Iran, comparing infliximab plus methotrexate with
tocilizumab plus methotrexate in patients with rheumatoid arthritis
with inadequate response to traditional disease-modifying anti-
rheumatic drugs. Methods: A multistage Markov decision model
was applied to assess the incremental cost-effectiveness ratio (ICER)
of a tocilizumab-containing regimen versus an infliximab-containing
regimen over a 5-year time period. In the case of no response, we
assumed that patients switched to the next treatment (adalimumab,
rituximab, or supportive care) in sequence for each strategy. We
considered major cost items, such as direct medical costs and direct
nonmedical costs, from a payer (patients and third-party payers)
perspective. A deterministic sensitivity analysis was conducted to
assess the robustness of the model results over the uncertainty of key
parameters. Results: In the base-case analysis, the ICER of the
tocilizumab-containing regimen was US $60,800 per quality-adjusted
life-year as compared to the infliximab-containing regimen. In
the sensitivity analysis, changes in the price of the drugs by
generic substitution, in utility scores, and in discount rate did not
change our overall conclusions. Among all inputs to the primary
study and the sensitivity analyses, however, the price of tocili-
zumab had the most impact on the ICER. Conclusions: Although
tocilizumab and methotrexate provide a larger gain in quality-
adjusted life-years, their current price is quite high as compared with
those of our other interventions. Therefore, a regimen containing
tocilizumab is not cost-effective as compared with an infliximab-
containing regimen for patients with rheumatoid arthritis in Iran.
Keywords: cost-effectiveness, infliximab, Iran, rheumatoid arthritis,
tocilizumab.
Copyright &2015, International Society for Pharmacoeconomics and
Outcomes Research (ISPOR). Published by Elsevier Inc.
Introduction
Rheumatoid arthritis (RA) is a chronic inflammatory disease
having a substantial impact on patients and society. It is
prevalent in between 0.24% and 0.33% of the population, with
the disease representing one of the top 50 causes of disability in
Iran and globally [1,2]. The distribution of RA varies by geo-
graphical region, with a higher prevalence found in northern
temperate regions than in tropical environments; similarly, there
is a higher prevalence in women than in men [3]. In younger
adults with RA, their initial disease symptoms may be well
managed and relatively stable. Disabling complications, how-
ever, accumulate over time, with patients typically depleting
traditional treatment options as they move toward their middle
years [4].
Given the chronic course of the disease and the associated
risk of mortality, it is not surprising that RA confers a consid-
erable economic burden on society. In 2009, the economic burden
of RA in the United Kingdom was estimated at more than £2.3
billion. Of these substantial costs, 78% were attributable to direct
medical care costs and the remainder to indirect costs such as
loss of productivity and impact on health-related quality of life
[5]. Direct medical costs alone have been estimated at approx-
imately €4100 per person per year, exclusive of productivity
losses or costs to the patient’s family [6]. Given the aging of
the population in many upper- and middle-income countries,
2212-1099$36.00 –see front matter Copyright &2015, International Society for Pharmacoeconomics and Outcomes Research (ISPOR).
Published by Elsevier Inc.
http://dx.doi.org/10.1016/j.vhri.2015.10.003
Conflict of interest: The authors have indicated that they have no conflicts of interest with regard to the content of this article.
E-mail: ahosseini110@yahoo.com
*Address correspondence to: Seyed Alireza Hosseini, Number 30, Iran FDA building, Fakhr-e-Razi Avenue, Enghelab Street, Tehran, Iran.
Postal code: 1314715311.
VALUE IN HEALTH REGIONAL ISSUES 9C (2016) 42–48
including Iran, the costs attributable to RA and its associated
conditions are expected to increase in the next decade [7,8].
Disease-modifying antirheumatic drugs (DMARDs), which
change the course of the underlying illness, are the treatment
of choice for RA [9]. Traditional DMARDs (tDMARDs) such as
methotrexate, hydroxychloroquine, and sulfasalazine can be
quite effective. But up to 25% of the patients who begin tDMARDs
will eventually require a change in treatment [10]. Over the past
decade, new classes of biopharmaceutical drugs have been
developed for the treatment of adults with moderate-to-severe
RA after an inadequate response to tDMARDs [11–13]. Immuno-
therapy with biological DMARDs (bDMARDs) may be of initial
benefit, but an emerging body of research suggests that therapy
with methotrexate, a tDMARD, in combination with a bDMARD,
such as etanercept, adalimumab, infliximab, rituximab, or tocili-
zumab, is more effective than monotherapy [14].
Among these new biopharmaceutical treatments for RA,
tocilizumab is the newest drug available, albeit at a very low
volume, on the pharmaceutical market in Iran. Although these
medications can greatly improve the quality of life for those
living with RA, the high retail price makes them unaffordable for
those without coverage by third-party payers, such as private
insurers or government payers. It is necessary to develop clinical
guidelines for appropriate and efficient use of bDMARDs to
prioritize treatment strategies for this disease.
In Iran, we could find only one previous economic evaluation
on biological treatments for refractory RA. In that study, ritux-
imab was not found to be a cost-effective strategy as compared
with tDMARDs [15].
In this study, which is part of a health technology assessment
project, we analyzed the cost-effectiveness of two common
treatment strategies in Iran, comparing infliximab plus metho-
trexate to tocilizumab plus methotrexate in patients with RA
with inadequate response to tDMARDs.
Methods
Because there were no extant clinical studies but only scant
observational studies to derive effectiveness and costs of
bDMARDs for RA in Iran, we adapted secondary data sources
from the literature to inform our model for cost-effectiveness.
We applied a multistage Markov model because it encom-
passes the chronic and relapsing nature of RA, the frequent
transition of patients between health states over time, and the
need to switch to other strategies with waning response to
treatment [16–18]. The model was run in Microsoft Excel, version
2010 (Microsoft Inc, Redmond, WA).
Constructed Sample, Base-Case Analysis
We simulated a hypothetical cohort of patients with RA with
active disease and inadequate response to or failure in their past
therapy with tDMARDs. The constructed sample consisted of
1000 patients, 18 years or older, with a mean age of 52 years.
Women comprised 70% of the cohort, representing the greater
prevalence of women in the Iranian population with RA [2].We
compared two common treatment sequences for RA in Iran,
initiating either with tocilizumab plus methotrexate or with
infliximab plus methotrexate, as shown in Fig. 1. We also
determined a care regimen in each arm for those patients with
RA who did not respond to DMARDs. Because there were no
published therapeutic guidelines in Iran for this group, we
interviewed a national expert on RA (Ahmadreza Jamshidi, head
of Iran rheumatology research center, personal communication,
2014) to determine the common clinical practice in Iran for
patients not responsive to previous treatment.
Model Structure and Assumptions
Fig. 2 illustrates the structure of the multistage Markov model.
In this model, five states are defined according to the American
College of Rheumatology (ACR) outcome criteria for RA [19].
The ACR outcome criteria assess the count and percent change
in the tenderness of the affected joints as well as changes in
physical disability, pain, and disease activity by 20%, 50%, or
70% [20]. Three of the five states use the ACR criteria, with two
additional states for no response/withdrawal and all-cause
death. The length of each cycle was 6 months over a 5-year
time horizon. The 6-month cycle intervals follow the treatment
and assessment cycles in clinical trials of DMARDs for RA. The
5-year time horizon as opposed to lifetime is consistent with
the recommendation of Gabriel et al. [21] in the OMERACT 6
Economics Working Group report and also with studies by
Coyle et al. [22],Kobeltetal.[23], Welsing et al. [24], and Wong
et al. [25].
In both arms, the patients who experience treatment failure
for either regimen in the first cycle or the following cycle are
assumed to switch to the next available regimen. Accordingly,
“no response/withdrawal”was defined as a temporary state and
treatment would be switched for this group of patients. In the
event that a patient fails to respond to all the treatments during
the sequence, the person would be placed on supportive care
(tDMARDs plus other supportive care).
Model Assumptions
In this study, we used the following assumptions:
1. Transitions: In clinical trials, the transition probabilities
between ACR states were not reported; therefore, for simplic-
ity’s sake, we assume that there are no transitions between
ACR states for patients who respond to treatment. For
instance, patients in the ACR 50 state never go to the ACR
20 state or the ACR 70 state in the next cycle.
Fig. 1 –Schematic presentation of treatment sequences in the
model. IR, inadequate response; DMARDs, disease-modifying
antirheumatic drugs; tDMARDs, traditional DMARDs.
VALUE IN HEALTH REGIONAL ISSUES 9C (2016) 42–48 43
2. Supportive care: Patients on supportive care no longer expe-
rienced improvement by ACR outcome criteria. Therefore,
patients on supportive care either have no response/no
change or die.
3. Patients have only one opportunity to partake of a regimen.
4. Fixed utility score: The patients who respond to treatment
might not experience a change in utility score over time (ACR
20/50/70); similarly, the utility scores of patients who are
receiving supportive care (without any ACR response) do not
change with time.
Efficacy, Transition Probabilities, and Mortality
The clinical literature was used to extract the transition proba-
bilities between differing states. Because there were no published
trials that explicitly compared the effectiveness of tocilizumab
plus methotrexate with that of infliximab plus methotrexate, we
used the results of a published systematic review and network
meta-analysis using Bayesian indirect comparison of the efficacy
of biological treatments for RA [26].
In this meta-analysis, the efficacy of biological treatments was
assessed as first-line therapy in patients with inadequate
response to tDMARDs. From the meta-analysis, we derived fixed
effect estimations on the proportion of patients with response to
tocilizumab plus methotrexate as compared with those with
response to infliximab plus methotrexate using ACR 20/50/70
criteria.
To extract efficacy data on treatment with adalimumab, we
used the work of Van der Bijl et al. [27] in which the efficacy of
adalimumab was evaluated in patients with previous failure to
infliximab. In lieu of any published data on patient response to
rituximab after nonresponse to tocilizumab, the result of the
aforementioned meta-analysis was used after a 15% reduction in
ACR response of rituximab, as adjustment (assumption number 5).
We used data from Cohen et al. [28] to derive the ACR
response of rituximab in the second treatment sequence, after
failure to infliximab and adalimumab. The nonoverlapped
response rate was calculated for ACR 20, ACR 50, and ACR 70
criteria [29], respectively. The long-term studies were used to
extract the no response/withdrawal probabilities for each treat-
ment after the first cycle [30–33].
For the probability of transition to death in each cycle, we
used RA-adjusted [34] age-dependent mortality data of Iranian
population extracted from the World Health Organization life
table in the model. We assumed that there was no relationship
between mortality probability and the states of disease (ACR
criteria) (assumption number 6). We used the Grade system as a
framework for quality assessment of the evidence [35]. The
transition probabilities used in this study are presented in
Table 1. We used the following formula to transform the rate to
a probability (when necessary) and to calculate the transition
probability for a different time interval [36,37]:
p¼1ert
r¼1
t1n 1p
where pis probability, ris rate, and tis time.
We double-checked the face validity of the model (the struc-
ture and assumptions) and the input data and probabilities lists
with expert clinicians at the Rheumatology Research Center of
Iran (Imam Khomeini Hospital) [38].
Cost
In this study, a payer perspective (patients and third-party
payers) was taken for cost analysis. The major cost items in
terms of direct medical costs and direct nonmedical costs were
considered in the analysis. Because the cost of health services in
Iran is different in public and private sectors, all cost values
were obtained from the real price list of the public sector
(minimum prices) in 2014; therefore, no inflation adjustment
Fig. 2 –Simple model structure representing the pattern of transitions between different states of disease after treatment.
ACR, American College of Rheumatology.
VALUE IN HEALTH REGIONAL ISSUES 9C (2016) 42–4844
was needed. The market exchange rate used was 26,000 Iran rial
(IRR) to 1 US dollar (USD), as declared by the Iran Central Bank.
The cost items in our model were broken down into five
categories:
1. Fixed cost items, that is, those items repeating in all cycles
regardless of the disease state, for example, cost of medicine,
infusion cost, and transportation cost;
2. State-dependent cost items, for example, rehabilitation cost
for patients receiving supportive care or the number of
physician visits per cycle. According to common clinical
practice in Iran (A. Jamshidi, personal communication,
2014), 4, 3, 2, and 1.5 visits per cycle were assigned to no
response, ACR 20, ACR 50, and ACR 70 states, respectively.
Patients on supportive care were assumed to have four visits
per cycle;
3. Treatment-dependent cost items such as hoteling cost and
hospitalization cost were assigned only to patients receiving
treatment that might typically require a short hospitalization
for infusion;
4. One time per patient cost items, for example, the cost of total
auxiliary devices;
5. One time per each treatment cost items; for example, labo-
ratory tests were assumed to be prescribed before starting a
new treatment.
To streamline the model, we did not include the half-cycle
adjustment in each year of the model (assumption number 7).
Cost of Medicine
Treatment sequence 1
In this treatment strategy, we assumed that the patient would
receive six infusions of tocilizumab 400 mg per cycle, and also
two vials of rituximab equivalent to a standard 1000 mg infusion
in the cost calculation of each cycle for patients with no response
switching to rituximab.
Treatment sequence 2
In the analysis, we used the recommended prescribing practice in
Iran for infliximab, consisting of infliximab 300 mg (3 100-mg
vials of infliximab) given every 2 months. Because patients may
require additional doses of the drug during treatment initializa-
tion, we assumed that the patient may receive four infusions of
300 mg infliximab in the first 6-month cycle. For patients with no
response to infliximab, two infusions of adalimumab 40 mg per
month (12 per cycle) were considered in the analysis. The
cost calculation of rituximab, for nonresponders to adalimumab,
did not differ between treatment sequence 1 and treatment
sequence 2.
We used the retail price of both the original brand name drug
and the lowest priced generic, if available in the market, to set
our drug costs. Table 2 represents the different cost items in
detail. In this study, we used a 5-year Markov model with a 3%
discount rate for time preferences of costs in the cost analysis.
Utilities
We assumed that utility is transferable between populations
(assumption number 8), in particular, because we lacked any
published studies on health-related quality of life with RA in Iran,
utility measures in Iran, and mapping studies between ACR
response and EuroQol five-dimensional questionnaire (EQ-5D),
the most popular instrument for measuring utility in health.
Therefore, we used an international mapping study to determine
the utility score of each of the ACR criteria (ACR 20/50/70) [39].
Accordingly, the utility scores were 0.68, 0.80, 0.84, and 0.53 for
ACR 20, ACR 50, ACR 70, and no response states, respectively. We
also used a 3% discount rate in our base-case analysis for time
preference during the years of the model, similar to the discount
rate for costs.
Cost-Effectiveness Ratio
The incremental cost-effectiveness ratio (ICER) was calculated by
obtaining the difference in total cost between the two treatment
sequences, divided by the difference in their total effectiveness
(as measured in quality-adjusted life-years [QALYs]). As per the
World Health Organization’s cost-effectiveness guidelines, the
ICERs are compared to between one and three times the gross
domestic product per capita of Iran (130,300,000–390,900,000 IRR
or US $5,110–US $15,346) [40]. If the tocilizumab-containing
regimen was cost-effective, then it would cost less than US
Table 1 –Transitional probabilities for each
treatment.
Parameter
(mortality)
Quantity
(age-dependent)
Reference
(WHO Iran
life table)
ACR 20
Tocilizumab 0.207 [16]
Infliximab 0.257 [16]
Rituximab (first
sequence)
0.217 [16]
Rituximab (second
sequence)
0.24 [18]
Adalimumab 0.18 [17]
ACR 50
Tocilizumab 0.161 [16]
Infliximab 0.177 [16]
Rituximab (first
sequence)
0.201 [16]
Rituximab (second
sequence)
0.15 [18]
Adalimumab 0.15 [17]
ACR 70
Tocilizumab 0.282 [16]
Infliximab 0.148 [16]
Rituximab (first
sequence)
0.09 [16]
Rituximab (second
sequence)
0.12 [18]
Adalimumab 0.13 [17]
Withdrawal/no response (first cycle)
Tocilizumab 0.35 [16]
Infliximab 0.418 [16]
Rituximab (first
sequence)
0.492 [16]
Rituximab (second
sequence)
0.49 [18]
Adalimumab 0.54 [17]
Withdrawal/no response (following cycle)
Tocilizumab 0.02 [20]
Infliximab 0.15 [21]
Rituximab (first
sequence)
0.05 [22]
Rituximab (second
sequence)
0.02 [22]
Adalimumab 0.06 [23]
ACR 20/50/70, American College of Rheumatology criteria; WHO,
World Health Organization.
VALUE IN HEALTH REGIONAL ISSUES 9C (2016) 42–48 45
$14,250 per QALY gained; if it was highly cost-effective, it would
cost less than US $4,750 per QALY gained; and if it was not cost-
effective, then it would cost more than US $14,250 per QALY
gained as compared to the infliximab-containing regimen.
Sensitivity Analysis
We conducted a one-way deterministic sensitivity analysis (DSA) to
assess the robustness of the model results around key parameters.
In the first step, a DSA was conducted around the changes in
discount rate, utility scores, and drug costs by generic substitution
(if available in the market). For this purpose, the price of generic
equivalents, ⫾10% of utility scores, and two scenarios for discount
rate (no discount for QALY and 5% for both QALY and cost) were
used. In the next step, a DSA was conducted around the uncertainty
of medicine prices using ⫾10% of the price of each medicine in a
Tornado sensitivity analysis (SensIt Tornado-Spider Trial version
add-in for Microsoft Excel 2011). We focused more on the costs in
our sensitivity analysis because it comprised the largest category of
costs by percent within each sequence in the base-case analysis.
Results
Base-Case Analysis
The results for our hypothetical cohort of 1000 patients in the
base-case 5-year Markov model indicated that the total cost of a
tocilizumab-containing regimen was US $6,759,656 more than
that of an infliximab-containing regimen. The tocilizumab-
containing regimen resulted in 111 more QALYs gained as
compared with the infliximab-containing regimen.
In other words, the estimated ICER in this study is US $60,800
per QALY gained for the tocilizumab-containing regimen as
compared with the infliximab-containing regimen. This result
far exceeds our minimum cost-effectiveness threshold of US
$15,346, and therefore the tocilizumab-containing regimen could
not be considered a cost-effective strategy in Iran.
Sensitivity Analysis
The results of a one-way DSA showed that our base-case results
did not change because of variations of 10% in utility score or
because of changes in the discount rate. With generic price
substitution for rituximab and methotrexate, the only available
generics in Iran, the ICER decreased by 20% (126,464,000 IRR or US
$48,640). It did not, however, drop sufficiently to recommend it as
a cost-effective strategy.
The result of the Tornado sensitivity analysis on the drug
price illustrated that overall cost-effectiveness is highly depend-
ent on the prices of bDMARDS in the regimen. As is shown in
Fig. 3, the ICER of this analysis is most dependent on the price of
tocilizumab, with a 10% price reduction yielding a 55% drop in
ICER, from US $60,800 to US $27,181, per QALY gained.
Discussion and Conclusions
According to the results of this study, the tocilizumab treatment
sequence could not be considered a cost-effective regimen for RA
as compared with an infliximab-containing regimen. The sensi-
tivity analysis also supported the robustness of estimated results,
reinforcing that the drug price was the most important parameter
Table 2 –Treatment-related cost used in the model.
Cost item Price per item (IR Rial) item (IR Rial) Description
Physician visit Public: 140,000 The number of visits per cycle was considered as
being associated with ACR criteria
Tocilizumab Lowest priced generic: not available
Original brand: 33,000,000
Infliximab Lowest priced generic: not available
Original brand: 12,700,000\
Rituximab Lowest priced generic: 21,500,000
Original brand: 55,420,000
Adalimumab Lowest priced generic: not available
Original brand: 16,000,000
Methotrexate Lowest priced generic: 29,500
Original brand: 48,000
Infusion 100,000 For all medicines
Hospitalization 520,000 The administration of infliximab and rituximab
needs a 1-d hospitalization of patients
Transportation 150,000 The average two-way transportation cost for visiting
physician and injecting medicine
Hoteling for patient or family 1,500,000 This item was used only for the patients who
needed to be hospitalized for infusion of their
medicines. It was ignored for the regular visit of
physician separately
Auxiliary devices 2,000,000 For all patients in one of the treatment strategies,
one set of these auxiliary devices was considered
in 5-y costs
Laboratory and diagnostic
tests
600,000 For each treatment start or switching, the cost of
one set of these tests including CBC, PTT,
hepatitis, HIV, and chest x-ray was estimated
Rehabilitation 200,000 Only for the patients who were in supportive care
group
ACR, American College of Rheumatology; CBC, complete blood cell count; IRR, Iran rial; PTT, partial thromboplastin time.
VALUE IN HEALTH REGIONAL ISSUES 9C (2016) 42–4846
when determining the comparative cost-effectiveness between
tocilizumab- and infliximab-containing regimens.
In our search for published cost-effectiveness analyses on
tocilizumab, our results were not congruent with those from the
extant literature. According to a cost-utility analysis by Diaman-
topoulos et al. [41], tocilizumab treatment was considered cost-
effective, compared with other biologics, from a payer perspec-
tive in Italy. Similarly, adding tocilizumab to the standard of care
for patients with RA with inadequate response to tDMARDs was a
cost-effective strategy in Switzerland [42]. Finally, tocilizumab
treatment was a cost-effective strategy when compared with
infliximab, etanercept, and adalimumab treatments in Mexico
[43]. Although it might not be a significant factor, the pharma-
ceutical manufacturer financially supported all the three studies
that suggested the superiority of tocilizumab over other treat-
ment regimens. In contrast, an independent study from Serbia
suggested that the tocilizumab and methotrexate combination
was not cost-effective [44]. The difference between our results
and those of the other studies may be due to the higher overall
costs for bDMARDs in Iran as compared with that in other
countries or lower direct medical costs for care in Iran. In the
studies from Switzerland and Italy, the yearly costs of medicine
were reported as US $28,913 and US $15,507, respectively, as
compared to a cost of US $14,160 in Iran, but it is not clear
whether the services were comparable to overall medical services
offered for similar patients in Iran. In two other studies, the
annual cost of medicines or their average sale prices are not
reported.
In this study, we used a systematic approach in identifying
evidence-based strategies for RA [45]. The results of a published
network meta-analysis were also applied for pooling the reported
efficacy in different randomized clinical trials (RCTs) and dealing
with the lack of head-to-head studies [46]. Indirect comparison of
efficacy is a controversial technique because of the potential for
methodological flaws [47], but in the case of comparison between
drugs in RCTs it has been shown that the results of such
estimations are more reliable [48]. In the case of RCTs of
bDMARDS to treat patients with inadequate response to
tDMARDs, bDMARDS are compared with tDMARDs so that the
results of indirect comparison (network meta-analysis) could be
reliable. To achieve more reliable results, we also included
time dependency in our model. For this purpose, we used the
probability of response from reported trials that had evaluated
drug efficacy in nonresponsive patients. Then, the transition
probabilities in each cycle were set related to the varying
probabilities of death in each cycle and were linked to the mean
age of the population. The mortality rate, however, was the only
time-varying parameter in the model, and the other factors
including previous cycle behaviors were not included here.
There were also some limitations in our study. The first was
that the treatment options before entering supportive care were
different between the two sequences. In the first sequence, there
was no adalimumab therapy between tocilizumab and rituximab
for nonresponsive patients. The lack of balance between regimens
could affect both efficacy and cost results in the model. Our model,
however, reflects the routine and common treatment of RA in Iran.
The second limitation was that we estimated utility scores from
the literature and, therefore, might be in error. Although the use of
secondary sources is acceptable according to the pharmacoeco-
nomic literature, there are many controversies on the general-
izability of utility and QALY interpretation among different
nations and countries [49]. The third limitation was that by
excluding indirect costs, we lost the value of a broader social
perspective to our analysis. Indirect cost items include income loss
due to work absenteeism and permanent or long-time disability.
Additional indirect costs including income losses to family care-
givers are substantial, and therefore exclusion of such data could
adversely affect our results. This study is part of a greater program
(a health technology assessment project by request of Iran
National Institute of Health Research) focused on health insur-
ance, and therefore a payer perspective was taken. A more
comprehensive approach, however, would include indirect costs.
The fourth limitation was that we did not include the costs of joint
replacement as a treatment option in drug nonresponders. Joint
replacement, though a high-cost intervention, can have a signifi-
cant impact on overall quality of life. But because this is not a
common option in Iran at this time, we excluded surgery from our
scenario. The fifth limitation was that we opted to use a one-way
DSA rather than the more typical probabilistic sensitivity analysis.
We decided to focus our sensitivity analysis primarily around drug
costs because these comprised the largest percentage of costs,
overall, and the factor that was most likely to change over time.
This study is the first full economic evaluation with modeling
in Iran on the impact of biological DMARDs for patients with RA.
The results of this study could be used in policy decision making
by national drug regulatory agencies, ministries of health, and
health insurance organizations in Iran and particularly those of
in an upper middle-income country. Our use of secondary
sources allows a bridge for countries to implement clinical
practice guidelines in rheumatology while establishing the
means to derive primary data within country. More economic
studies are needed, however, to evaluate the effectiveness and
cost of medicines for RA in Iran, and similar middle-income
countries, to obtain more precise and reliable evidence.
Fig. 3 –Tornado diagram of sensitivity analysis. The effect of the price of tocilizumab on the ICER was more than that of
other medicines in both treatment sequences. DMARDs, disease-modifying antirheumatic drugs; ICER, incremental cost-
effectiveness ratio.
VALUE IN HEALTH REGIONAL ISSUES 9C (2016) 42–48 47
We conclude that in Iran, tocilizumab-containing regimens for
RA are not a cost-effective treatment strategy at current price as
compared with infliximab-containing regimens.
Source of financial support: This study was financially sup-
ported by Iran National Institute of Health Research.
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