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29PHARMACEUTICS
PHARMACOECONOMIC ANALYSIS OF ACID SUPPRESSIVE THERAPY OF VARIOUS FORMS OF GASTROESOPHAGEAL REFLUX DISEASE (GERD)
Osedlo V.
Senior Lecturer, Department of Military Pharmacy, Ukrainian Military Medical Academy, Kyiv
Abstract
The system of drug supply of servicemen should take into account the pharmacoeconomic parameters of modern medications with the predominant use of domestic drugs. Making a list of drugs to treat gastroesophageal reflux disease which are optimal from the pharmacoeconomic point of view will improve the effectiveness and quality of treatment and avoid unreasonable budget costs. When using esomeprazole in patients with erosive gastroesophageal reflux disease, a higher cost effectiveness and a higher level of cost utility are achieved along with a more rapid reduction in clinical and instrumental manifestations of the disease compared to omeprazole. When treating nonerosive gastroesophageal reflux disease at standard doses of omeprazole and esomeprazole, the use of omeprazole is reasonable from the pharmacoeconomic point of view.
Keywords: pharmacoeconomic analysis, gastroesophageal reflux disease, esomeprazole, omeprazole.
The urgency of the problem. The creation of the modern system of drug supply of servicemen (DSoS) should be based on the results of pharmacoeconomic research. The theoretical foundation of such research is pharmacoeconomics which evaluates the results and cost of treatment in order to make a decision on their further practical use [1]. When conducting pharmacoeconomic research, 5 types of pharmacoeconomic analysis are used: cost-of illness — COI, cost-minimisation analysis — CMA, cost-effectiveness analysis — CEA, cost-benefit analysis — CBA, cost-utility analysis — CUA. The cost-utility analysis compares the ratio between the costs and improvement in patient's health for different treatments taking into account the patient's quality of life (QOL) indicators [4].
Proton pump inhibitors (PPIs) are recognized as the most effective medicines for the treatment of patients with gastroesophageal reflux disease (GERD) [5, 6]. By blocking the final phase of hydrogen proton secretion, PPIs are the most effective acid-inhibiting agents. Their effectiveness has been proven in controlled multicenter studies [10], and the molecular mechanism of action causes a low frequency of side effects. However, different classes of PPIs differ in their pharmacokinetics, pharmacodynamic properties and clinical effect which depends on their chemical structure and metabolic rate. The molecules of esomeprazole and rabeprazole have benefits in this respect [12].
Esomeprazole is one of the most effective and safe PPIs in the treatment of GERD. The effectiveness of the original esomeprazole and its benefits in the treatment of GERD have been proven in randomized clinical trials and meta-analyses [7-9, 11]. The practice of DSoS provides for the primary use of domestic medicines. Therefore, the marketing analysis of the pharmaceutical market of PPIs for the treatment of GERD in servicemen and the conduct of the pharmacoeconomic analysis of the monotherapy with domestic esomepra-zole and omeprazole are relevant.
The study objective was to conduct a marketing and pharmacoeconomic analysis of the PPIs market and to assess the effectiveness of esomeprazole and
omeprazole in patients with erosive and nonerosive GERD.
Material and study methods. To achieve this objective, the following study methods were used: systemreview, bibliographic, mathematical and statistical, marketing analysis and pharmacoeconomic methods.
At the first stage, a marketing analysis of the pharmaceutical market of omeprazole and esomeprazole in Ukraine was conducted with an analysis of the average cost of a standard package, tablet/capsule and DDD of 36 drugs presented (20 names of omeprazole and 16 names of esomeprazole). The study materials were the data of the analytical system "Pharm Explorer of Proxima Research Ukraine" for 2019-2020 [3]. The priority was to a domestic manufacturer with its constant presence on the market and uninterrupted supply of drugs, which is an important component when supplying servicemen.
At the second stage, the results of DSoS with various forms of GERD with traditional and isomeric forms of domestic PPIs were analyzed. To conduct a pharmacoeconomic effectiveness analysis of mono-therapy with esomeprazole and omeprazole in patients with GERD, the indicators of cost-of illness, cost-effectiveness analysis and cost-utility analysis in patients with erosive and nonerosive GERD were compared:
Group I, 40 patients with erosive GERD of Grade A according to the Los Angeles Classification, of which: Group I-A (20 patients) received esomepra-zole at a dose of 40 mg/day for 4-8 weeks; Group I-B (20 patients) received omeprazole at a dose of 40 mg/day for 4-8 weeks.
Group II, 40 patients with nonerosive GERD, of which: Group II-A (20 patients) received esomeprazole at a dose of 40 mg/day for 4 weeks; Group II-B (20 patients) received omeprazole at a dose of 20 mg/day for 4 weeks. In the absence of the effectiveness at a therapeutic dose of omeprazole for 4 weeks, the dose was increased to 40 mg/day.
The integral indicator of the treatment efficacy, which takes into account the dynamics of clinical manifestations and QOL, was calculated using the formula of A. P. Gradov, V. B. Grinevich, 2000 [2] (1):
E = clinical efficacy (points) • 0.7 + AQOL • 0.3, (1) where: AQOL is an increase in the quality of life of the examined during the course of treatment, in points.
Clinical efficacy was calculated using the formula
(2):
Clinical efficacy = Ki Xei + K2-Xe2, (2) where: Xei is an efficacy parameter (from 1 to 7 points) which is inversely proportional to the term of regression of heartburn;
Xe2 is an efficacy parameter (from 1 to 7 points) which is directly proportional to the rate of epitheliali-zation of erosions (in the erosive form) and to the rate of elimination of mucosal hyperemia of the distal esophagus (in the nonerosive form);
Ki and K2 are the corresponding coefficients of significance (Ki = 0.4, K2 = 0.6).
The cost of an extra cost-utility unit (CU) per patient was calculated using the formula (3):
ACU = CUi-CU2/n, (3)
where: n is the number of patients. The primary efficacy criterion for the treatment of erosive GERD was the rate of epithelialization of erosions in the distal esophagus, for nonerosive GERD — the rate of elimination of gastric mucosal hyperemia.
At the time of the study, the cost of drugs in the pharmacy chain was: esomeprazole (40 mg No. 14) — UAH 110, omeprazole (20 mg No. 30) — UAH 42. The cost of endoscopic examination was UAH 350. The cost of consultation with a gastroenterologist was UAH 250. The drug doses for the treatment of patients were selected according to the Unified and Local Clinical Protocol for the Diagnosis and Treatment of GERD. The cost of a one-month course of drug treatment for patients with various forms of GERD who received esomeprazole was UAH 220. The cost of such a course for patients with erosive GERD who received
Cost of illness of DSoS in
When supplying servicemen with omeprazole, the extra cost of a cost-utility unit per patient was UAH 25.5/point compared to esomeprazole, and the cost-utility for a course of treatment with esomeprazole was 1.4 times higher than for treatment with omeprazole (Table 3).
Thus, the supply of servicemen with esomeprazole for the treatment of erosive GERD is cost effective
omeprazole was UAH 84, for patients with nonerosive GERD — UAH 42.
Study results and their discussion. When conducting a marketing analysis followed by a cost-minimization analysis, the average cost of a standard package, tablet/capsule and DDD of the presented medicines was taken into account. It has been found that esomeprazole, under the trade name Esonexa, Farmak (Ukraine, Kyiv), 40 mg tablets, No. 14, is cost effective for the DSoS with the average cost of a package, a tablet and DDD during the study period of UAH 113.41, UAH 8.10 and UAH 6.08, respectively. This is 3.8 times lower than the cost of the brand name drug Nexium, AstraZeneca (Great Britain), 40 mg tablets, No. 14, with the average cost of a package, a tablet and DDD of UAH 428.72, UAH 30.62 and UAH 22.97, respectively. When analyzing the omepra-zole market, it has been found that Omeprazole, Farmak (Ukraine, Kyiv), 20 mg capsules, No. 30, is cost effective for the DSoS with an average cost of a package during the study period of UAH 43.17, a tablet and DDD — UAH 1.44. This is 1.9 times lower than the cost of Omez, Dr. Reddy's Laboratories Ltd (India), 20 mg capsules, No. 30, with an average cost of a package of UAH 83.79, a tablet and DDD — UAH 2.79. It should be noted that there is no branded omeprazole on the Ukrainian pharmaceutical market.
When analyzing the cost of various antisecretory treatments, it was stated that the cost of treatment in Group I-A was 2.6 times higher than in Group I-B due to the higher cost of esomeprazole in comparison with omeprazole. But ultimately the cost-of illness turned out to be lower for the esomeprazole group (Table 1).
When analyzing the cost-effectiveness and cost-utility of DSoS with esomeprazole and omeprazole, a higher (1.5 times) cost-effectiveness indicator was found in the group of patients with erosive GERD who received esomeprazole (Table 2).
Table 1
various forms of GERD
from the pharmacoeconomic point of view despite the higher cost compared to omeprazole. It may have an economic effect in the treatment of large populations along with higher clinical efficacy and increased QOL.
The cost analysis of different antisecretory treatments of nonerosive GERD at standard drug doses indicates that the cost of treatment in Group II-A is 5.2 times higher than in Group II-B due to the higher
Parameter Erosive GERD Nonerosive GERD
Esomeprazole 40 mg/day Omeprazole 40 mg/day Esomeprazole 40 mg/day Omeprazole 20 mg/day
Cost of 4-week treatment (per patient), UAH • Number of patients 220-20 = 4,400 84-20 = 1,680 220-20 = 4,400 42-20 = 840
Extra cost of 4-week treatment • Number of patients 220-4 = 880 84-9 = 756 220-2 = 440 42-6 = 252
Additionally (EGDS), UAH • Number of patients 350-4 = 1,400 350-9 = 3,150 350-2 = 700 350-6 = 2,100
Additionally, consultation with a gastroenterologist, UAH • Number of patients 250-4 = 1,000 250-9 = 2,250 250-2 = 500 250-6 = 1,500
Total, UAH 7,680 7,836 6,040 4,692
cost of esomeprazole in comparison with omeprazole (Table 1). When analyzing the cost-utility of DSoS with esomeprazole and omeprazole, a comparable cost effectiveness indicator was found in the group of patients with nonerosive GERD who received esomeprazole, which was 1.0 (Table 2). The extra cost of a cost-utility unit when using esomeprazole was UAH 1.8/point per patient compared to omeprazole, and the cost-utility did not exceed 1 (Table 3).
Thus, the drug supply of servicemen to treat nonerosive GERD with the inclusion of esomeprazole at a standard dose has no pharmacoeconomic benefits compared to omeprazole, despite the higher rates of clinical efficacy and QOL of patients when using esomeprazole due to the significant difference in the cost of treatment course.
Table 2
Cost-effectiveness analysis of DSoS in various forms of GERD
Parameter Erosive GERD Nonerosive GERD
Esomeprazole 40 mg/day Omepra- zole 40 mg/day Esomeprazole 40 mg/day Omeprazole 20 mg/day
Total costs, UAH 7,680 7,836 6,040 4,692
Clinical efficacy index, points 5 3.3 5.4 4.2
Cost-of illness, UAH/point 1,536.0 2,374.5 1,118.5 1,117.1
Cost-effectiveness ratio of DSoS between omeprazole and esomeprazole 1.5 1.0
Therefore, for the treatment of large groups of patients with the nonerosive GERD at standard doses of esomeprazole/omeprazole, omeprazole can be recommended for procurement, the cost of which is significantly lower than the cost of esomeprazole.
Table 3
Cost-utility analysis of DSoS in various forms of GERD_
Parameter Erosive GERD Nonerosive GERD
Esomeprazole 40 mg/day Omeprazole 40 mg/day Esomeprazole 40 mg/day Omeprazole 20 mg/day
Total costs, UAH 7,680 7,836 6,040 4,692
Clinical efficacy index, points 5 3.3 5.4 4.2
Increase in the quality of life (points) 6.1 5.6 5.9 5.3
Integral indicator of treatment efficacy 5.3 4.0 5.6 4.5
Cost-utility analysis (UAH/point) 1,449.1 1,959 1,078.6 1,042.7
Cost of an extra cost-utility unit of DSoS (UAH/point) per patient 25.5 1.8
Cost-utility ratio of DSoS between esomeprazole and omeprazole 1.4 1.0
Conclusions
1. The pharmacoeconomic analysis of DSoS with acid suppressive medicines for the treatment of various forms of GERD indicates the need for a differentiated approach to the choice of traditional and iso-meric forms of PPIs.
2. The conducted marketing analysis of the Ukrainian pharmaceutical market of omeprazole and esomeprazole is evidence of the economic feasibility of esomeprazole (Esonexa) and omeprazole (Omepra-zole), Farmak (Ukraine, Kyiv), for DSoS with various forms of GERD.
3. When supplying servicemen with the erosive GERD with esomeprazole, the quality of life increases significantly and higher cost-effectiveness (by 1.5 times) and cost-utility (by 1.4 times) are achieved along with a rapid reduction in clinical manifestations and epithelialization of erosions compared to omepra-zole.
4. When supplying servicemen with the nonerosive GERD, omeprazole is a cost effective PPI, the use of which provides a significant cost reduction with no pharmacoeconomic benefits of esomeprazole in this case.
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