Add-On Omalizumab in Persistent Difficult-To-Treat Asthma: a

1 Ospedale Orlandi, Bussolengo Verona, Italy
2 AdRes HE&OR, Torino, Italy
Dal Negro RW1, Pradelli L2, Micheletto C1, Tognella S1, Iannazzo S2
Add-On Omalizumab in Persistent Difficult-To-Treat Asthma: a
12-Month Study on Clinical, Economic Outcomes and Related
Cost/Utility
Objective
Methods (continued)
Omalizumab is an innovative treatment for difficult-to-treat
allergic asthma. Several studies on patients with moderate to
severe allergic asthma showed the clinical efficacy of
omalizumab in addition to the standard therapy (ICS + longacting beta-agonists – LABA)[1-8].
Results (continued)
Type of resource
Cost (€)
Source
Omalizumab 150 mg, 1 vial
315.12
13
Salmeterol 25mcg, 120 puffs
32.70
13
Formoterol 12mcg, 60 puffs
19.41
14
Fluticasone250 mcg, 120 puffs
53.07
13
Budesonide 400 mcg, 50 puffs
16.71
14
Montelukast 10 mg, 28 tablets
43.94
13
Prednisone 25 mg, 10 tablets
5.13
13
Betamethasone 4 mg, 3 vials
2.65
14
Theophylline 200 mg, 30 tablets
2.31
13
The administrative database of the Lung Department of the
Orlandi General Hospital - ULSS 22 of Veneto Region (NorthEastern Italy) holds the records corresponding to visits,
procedures, respiratory and biological test, hospitalizations
and treatments of all patients treated at the respiratory centre
from 1983. All subjects signed an informed consent form.
Theophylline 300 mg, 30 tablets
3.26
13
Salbutamol 100 mcg, 200 puffs
4.54
13
DB records were analyzed to select patients with severe and
resistant asthma and the sensitization to perennial antigens,
which started the treatment with omalizumab. Patients with at
least 12 months of clinical history preceding the beginning of
omalizumab were filtered.
Objective of this study is to assess real-world clinical and
economical outcomes associated to add-on omalizumab in
patients with persistent atopic asthma resistant to common
therapies treated with omalizumab for a circa-annual time
frame: the same parameters measured in the year preceding
omalizumab introduction were taken as reference values.
Drugs
Methods
23 patients (14 females and 9 males) were identified with a
mean of 10 months (range: 2-22) follow-up (omalizumab
observation period) from the treatment start T0.
Hospital
Ipratropium 20 mcg, 200 puffs
4.78
13
Tiotropium 18 mcg, 30 puffs
50.80
17
Amoxicillin + clavulanate 875+125 mg, 12
tablets
8.72
14
Moxifloxacin 400 mg, 5 tablets
22.81
13
Hospitalization for asthma exacerbation (DRG
96 and 97, weighted for their relative frequency
in Veneto according to 2005 discharge data)
1,759.20
10,15
Emergency unit accesses (brief observation)
200
10
Specialist visit
14.25
11
GP visit
12.32
12
T0
LO
Delta T0 – LO
TS
53.2
(8.9 - 85.0)
37.2
(11.7 - 59.3)
19.2
(-6.8 - 51.2)*
Utility
0.53
(0.18 – 1)
0.70
(0.46 – 0.98)
0.21
(- 0.07 – 0.55)*
Tab IV - St. George’s Respiratory Questionnaire and derived utility
TS: Total Score *p < 0.01 T0: enrollment, LO: last observation
The most evident modification in the consumption of health
care is the elimination for the observed period of
exacerbation-caused hospitalizations and emergency unit
accesses.
Monthly Costs (€)
Pre–
omalizumab
Post–
omalizumab
Difference
Drugs
90.97
(13.68 – 150.01)
585.93
(390.58 – 773.41)
494.96
(265.32 – 725.57)
Hospital
144.72
(0 – 317.37)
0
(0 – 0)
-144.72
(- 317.37 – 0)
Visits
5.80
(1.75 – 18.98)
0.79
(0 – 4.95)
-5.01
(- 18.98 – 2.56)
Total
241.49
(69.08 – 464.95)
586.71
(392.15 – 773.41)
345.22
(33.01 – 677.68)
Tab. V - Economic outcomes. Values are expressed as mean (95% CI).
However, the additional cost for omalizumab is only partially
offset by the reduction in other drugs and hospital costs,
leading to an increment of about 350 € per month in overall
costs (Tab.V).
Visits
Data retrieved included:
• Objective clinical parameters: FEV1, MMEF, reversibility of
airway obstruction, exacerbations, serum IgE levels.
• Subjective measures of asthma control: ACT symptom score,
St. George Respiratory Questionnaire (SGRQ), inactivity days
due to the illness.
• Health care resource consumption: number and duration of
hospitalizations for respiratory causes, drug use (inhaled and
systemic corticosteroids, bronchodilators, antileukotrienes,
xantines, antibiotics, and omalizumab), medical examinations
by specialists and GPs.
Tab. I - Unit costs used for the analysis
Results
Data relating to clinical events and resource consumption
during the observation period was normalized to one year, in
order to permit a homogeneous comparison with data
collected in the year preceding omalizumab initiation.
Costs were evaluated adopting the perspective of the
Regional Health System. Hospitalizations were costed
according to the DRG tariffs of the Veneto Region [10], and
specialist visits valued on the base of the regional rate manual
[11]. GP visits were valued as opportunity cost according to
the findings of the DYSCO study [12] .
The calculation of the utility was based on SGRQ Total
Scores, according to Stahl et al [16].
Incremental cost/effectiveness and cost/utility ratios were
constructed as the ratio of the differential costs over
differential effectiveness/utility and presented as mean and
95% CI. Considered effectiveness/utility increments are
relative to the difference between baseline values (T0) and
the last available measurement (LO – last observation). In
other words, for the computation of cost/QALY, it has been
assumed that the utility measured at T0 was representative of
the mean utility during the “pre” year, and that the last
available value represented mean utility in the “post” period.
Mean (95%CI)
Cost/FEV
21.9 ( dominant – 104.0) €/%FEV1
Cost/ACT
57.3 (0.96 – 154.9) €/ ACT point
Cost/QALY
25,983.33 (dominant – 94.010) €/QALY
Tab. VI – Incremental cost/effectiveness results
Cost/FEV: cost per month with one FEV1 predicted percentage point gained;
cost/ACT: cost per month with one ACT point gained
Spirometric values (FEV1 and MMEF), IgE concentrations,
and the ACT score were recorded monthly, the SGRQ was
administered every six months, while the recording of drug
consumption was performed every four months.
Descriptive statistics (mean and 95% CI – or minimummaximum range) of data collected in the two periods were
calculated and tested for statistically significant differences
according to Student’s T test for paired data.
Indicator
Characteristic
Value
Gender
9 m, 14 f
Age (mean, min - max)
46.5 (27 - 70)
BMI (mean, min - max)
25.75 (19.8 - 37.5)
Smoking habit
16 never 5 ex 2 current
IgE (mean, CI 95%)
240 (34 - 622) UI/mL
Follow-up (mean, CI 95%)
10 (2 – 22) months
Conclusions
The introduction of omalizumab into the therapeutic regimen
of patients with perennial atopic asthma poorly controlled has
induced a dramatic reduction in respiratory symptoms,
functional impairment and drug consumption.
Tab. II - Sample characteristics at T0
Clinical effectiveness data (Tab. III) indicate a general
improvement in asthma control during omalizumab therapy:
FEV1 increased in 21 of 23 patients and ACT scores improved
in all patients. Exacerbations were observed in 35% of
patients (9/23), without any hospitalization, while in the
preceding year all patients experienced exacerbations, for a
total of 21 admissions. No adverse event was recorded during
the observation.
Parameter
Preomalizumab
Postomalizumab
Pre-post
difference
P value
FEV1
(% predicted)
57.61
(33.55 – 89.7)
75.46
(45.1 – 104.3)
17.85
(-2.30 – 43.63)
< 0.01
ACT (score)
11.87
(7.55 – 17)
19.40
(13.2 – 23.6)
7.53
(2.89 – 15.22)
< 0.01
Exacerbations
(n/year)
2
(1 – 4)
0.52
(0 – 3)
-1.48
(-4.00 – 1.45)
< 0.01
Inactivity
(days/year)
17.61
(0.55 – 58.15)
0
-17.61
(-58.15 – 0.55)
< 0.01
Tab. III - Clinical outcomes expressed as mean (95%CI)
Frequency and severity of exacerbations and the consequent
recourse to hospitals diminished. Patients’ quality of life
substantially improved.
These clinical outcomes translated into a reduction of health
care resource consumption. Consistent with the findings of
other authors [2], the present study shows no hospitalization
during the up to 22 month omalizumab treatment period for
any of the subjects.
From a strict financial point of view, the therapeutic regimen
encompassing omalizumab is significantly more expensive
(about €350 a month), despite the systematically observed
reduction of all other sanitary costs.
The estimated 26,000 €/QALY relative to one year of
omalizumab treatment can be considered very cost/effective
according to the World Health Organization (cost per life year
gained lower than per capita GDP) [17]. One QALY
corresponds to a life year in the best imaginable health state;
in 2007, Italy’s per capita GDP was of 25,968 € [18].
Acknowledgements
This study was partially funded by a research grant from
Novartis Farma, Origgio (VA), Italy
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