Abstract
Objectives: To evaluate healthcare resource (HR) consumption associated with Systemic Lupus Erythematosus (SLE) management in adult patients with active autoantibody positive disease in the Russian Federation, Republic of Kazakhstan, and Ukraine.
Methods: The ESSENCE was a retrospective, observational study, and included data on patients’ clinical characteristics and SLE-related HR use (laboratory, biopsy, imaging tests, medications, visits to specialists, outpatient visits, hospitalizations) during 2010 from the 12 specialized rheumatologic centers.
Results: A total of 436 SLE patients were included in the analyses, with 232 patients being enrolled in Russia, 110 in Kazakhstan, and 94 in Ukraine. The mean age was 36–42 years and median SLE duration was 3–6.8 years across the countries. Extrapolation to total country population showed that, in 2010, visits to specialists (who assign treatment for organs involved/damaged by SLE) were the most frequently used HR (from 13,439 visits in Kazakhstan to 23,510 in Russia), followed by hospitalizations (from 2,950 in Kazakhstan to 6,267 in Russia) and outpatient visits (from 1,654 visits in Russia to 8,064 in Kazakhstan). Compared to chronic active patients (SLE persistent during last year), patients with relapsing-remitting SLE (at least one flare alternated by one remission per year) had a higher rate of visits to specialists (100% vs 60.8%, p < .001) and hospitalizations (98.9% vs 60.8%, p < .001). Compared to patients without flares, patients experiencing flares had a higher rate of unplanned visits to specialists (86.2% vs 6.3%, p < .001), were more often hospitalized (both ICU and non-ICU) (100.0% vs 50.0%, p < .001), and had a longer duration of ICU hospitalization (25.9 days vs 17.5 days, p < .001).
Conclusions: Specialist visits are the most frequently consumed SLE-related healthcare recourse in the Commonwealth of Independent States (CIS) countries. A relapsing-remitting SLE profile and the occurrence of flares significantly raise healthcare resource consumption.
Introduction
Systemic Lupus Erythematosus (SLE) is a multi-organ, autoimmune disease characterized by alternating periods of disease activity and remission. Numerous organs may be affected, leading to a wide combination of clinical manifestationsCitation1,Citation2.
SLE significantly impairs patients’ quality-of-life, proportionally to the symptoms and organs involvement, disease severity and activity, and flares. In the Tri-Nation Study carried out in Canada, the UK, and the US, overall resource utilization related to SLE did not vary significantly between the countries; however, within each resource category, differences were observed between countriesCitation3–5. SLE results in a great burden both for a patient and for societyCitation6. Long disease duration, high disease activity and damage, poor physical and mental health, and high education and employment levels due to SLE are associated with increased cost. Similarly, high disease activity and damage, poor physical health, certain disease manifestations, as well as poor family and social support, are associated with poor health-related quality-of-life outcomesCitation5–10.
The following categories contribute to the total direct medical cost for SLE management: laboratory, imaging tests, and biopsies (estimated at 7.7%, 2.0%, and 3.2% of the total cost, respectivelyCitation10); hospitalizations (accounted for 27.1% of total costCitation10); visits to specialists (may take ∼12.1%Citation10 and up to 27%Citation11 of total cost); and medications (which represent ∼25.7%Citation12,Citation13 and up to 53%Citation10 of the total cost). It has recently been highlighted that little research has been conducted that examines variations in healthcare resources utilization associated with disease activity, severity, disease manifestations, or with specific treatmentsCitation14.
Limited to no data on the healthcare resource utilization in the Russian Federation (Russia), Ukraine, and the Republic of Kazakhstan (Kazakhstan) have been published previously. In these, as well as other post-Soviet countries, there are no existing registries or databases of SLE patients. The healthcare system is multi-level: at the local level potential patients with SLE are identified and referred to specialized rheumatologic institutions for further diagnosis and treatment. Specialized medical care for SLE may be provided via both out-patient and in-patient routes. Although private centers may provide specialized medical care for SLE patients, it is predominantly paid for by the government, and the extent of medical care (including examinations and treatment) is regulated by the state healthcare authorities.
The ESSENCE study was designed to describe SLE characteristics, health services utilization, and procedures contributing to the total disease resource consumption for adult SLE patients with active, autoantibody positive disease in selected cities from Russia, Ukraine, and Kazakhstan. Rheumatologic clinical centers were selected to collect the data. The clinical characteristics of these patientsCitation15 and the prevalence and incidence of SLECitation16 in the study cities have been described previously. In this paper, estimates on healthcare resource consumption associated with SLE will be presented. Direct medical cost for SLE-related healthcare resource consumption will be the subject of a future publication.
Methods
Study design
Data from the ESSENCE study (EPI116387) were used to estimate healthcare resource consumption. ESSENCE was a retrospective, multinational, multi-center, epidemiological study carried out across three countries (Russia, Kazakhstan and Ukraine) in 12 rheumatologic centers. Six centers in Russia (Moscow, St-Petersburg, Voronezh, Yekaterinburg, Kursk, and Yaroslavl), three centers (Kyiv, Donetsk, Vinnitsa) in Ukraine, and three centers (Almaty, Semey, Shymkent) in Kazakhstan participated.
Data capture
Investigators in the selected countries captured data from patient medical records using a standardized case report form, including patients’ demographic and clinical characteristics, SLE severity and activity profile, SLE flares, laboratory and imaging tests, SLE treatment, and healthcare resource utilization in the year 2010.
The data were captured at rheumatologic centers that provide primary care for patients with lupus. The study population predominantly consisted of city population; however, rural patients were also included in this study, except for Kiev, Ukraine, because in Ukraine rural patients usually receive care in regional hospitals.
Trained medical staff identified all patients ≥18 years old with an established SLE diagnosis according to the American College of Rheumatology (ACR) criteria (presence of four or more criteria) or clinical judgment before December 31, 2010 according to medical records. Patients were required to have evidence of autoantibody-positive disease and to have made at least one clinic visit in 2010. Autoantibody-positive disease was defined as antinuclear antibody (ANA) and/or antibodies to double-strained DNA (anti-dsDNA)-positive test at or prior to the last clinic visit in 2010. Patients with miscoded diagnoses and drug-induced lupus as well as patients diagnosed with SLE after 2010 or deceased before 2010 were excluded.
The patient’s medical (ambulatory) card was the main source of the data; it contained the information received from the patient’s outpatient visits, as well as hospital discharge cards for the entire period of follow-up. According to routine practice of the study centers, medical documents were filled manually by the treating physician (rheumatologist), who tracks any changes in a patient’s condition (in Ukraine and Kazakhstan), or (in Russia) medical documents were stored in the electronic database. Medical documents received from other medical institutions (e.g. discharge epicrisis) were taken into account during data collection.
In all study countries, the Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for Systemic Lupus Erythematosus (SLICC/ACR Damage Index) are not used routinely; therefore, their score were reproduced on the basis of entries in patients’ medical records.
As described previouslyCitation15, a relapsing-remitting profile was defined if episodes of activity alternated with periods of precise remission; not less than one remission and one flare during the last year (before the time of assessment). Chronic active profile was defined if the disease was persistent in a varying degree and did not attenuate during at least the last year (before the time of assessment). SLE profile was captured at the last patient visit to the site in 2010.
For each patient, the occurrence of lupus flares during 2010 was captured from the medical records; for the purposes of the study, a flare was identified and categorized as mild/moderate or severe, based on treatment changes (i.e. increasing dose of corticosteroids and/or initiating a new SLE treatment) and/or hospitalization based partially on a modified SELENA-SLEDAI Flare Index (SFI):
Mild/Moderate flare:
Increase in prednisone (or equivalent corticosteroid dose), but under 30 mg/day.
Added NSAID or hydroxychloroquine for SLE activity.
Severe flare:
Increase in prednisone (or equivalent corticosteroid dose) to at least 30mg/day.
New cyclophosphamide, azathioprine, methotrexate, or mycophenylate for SLE activity.
New biological drugs for SLE activity.
Hospitalization for SLE activity.
Healthcare resource evaluation
Use of healthcare resources related to SLE (outpatient visits and hospitalizations, visits to specialists (who assign treatment for organs involved/damaged by SLE), laboratory tests, biopsy, and imaging tests) were collected at each site. All healthcare resources used were collected from the medical records for each patient.
Based on the census data for the year 2016 obtained from official web sources (gks.ru; stat.gov.kz; ukrstat.org), the number of adult patients with lupus was estimated for each country, using the SLE prevalence estimated previouslyCitation16: 9.0 per 100,000 in Russia, 20.6 per 100,000 in Kazakhstan, and 14.9 per 100,000 in Ukraine. To estimate the annual healthcare resource consumption for the national population, the number of SLE patients in each country was multiplied by the mean number and frequency (%) of a resource usage.
Statistical analysis
Statistical analysis was performed using IBM SPSS Statistics Version 18.0. All variables were analyzed independently at the country level in a descriptive way: the data obtained from the study sites were pooled for the country-specific analysis. Healthcare resources were combined into categories consisting of one or several units (e.g. tests or procedures). For each category the percentage of patients with at least one unit performed in 2010 was calculated, as well as the mean number of the units per year. The analysis of the healthcare resources by SLE profile or flare occurrence was performed in patients with valid data (data available in medical records). For sub-group comparison, t-test was used for quantitative variables and Fisher’s exact test was used for categorial variables; the differences were considered statistically significant when p < .05.
Results
A total of 436 consecutive eligible patients (232 in Russia, 110 in Kazakhstan, and 94 in Ukraine) were included in the analysis.
Clinical characteristics
reports patient demographic and clinical characteristics as per the last visit in 2010. Patients’ mean age was 36.1 in Russia, 36.9 in Kazakhstan, and 41.7 years in Ukraine. The SLE patient populations were largely female across all countries; 92.7% of patients were Asians in Kazakhstan, while in other countries Caucasians predominated. The median SLE duration (from the date of diagnosis to 2010) ranged from 3.0–6.8 years.
Table 1. Demographic and clinical SLE patients’ characteristics at the last visit in 2010.
Healthcare resource utilization
reports the number of medical resources used by the patients in each country.
Table 2. Healthcare resource utilization in 2010.
Laboratory and imaging tests
Over the study period, all patients had at least one laboratory test. The most frequently performed parameters were anti-dsDNA (double-stranded DNA antibodies) and ANA (antinuclear antibodies) in the immunology test; C-reactive protein, serum SGOT (serum glutamate-oxalacetic-transaminase), SGPT (serum glutamate-pyruvate-transaminase), serum creatinine, blood urea nitrogen, and total bilirubin (in the biochemistry test).
The number of patients with blood tests performed (immunology, blood chemistry, hematology with full blood count) was >80% in all three countries. The number of patients with urine analysis performed was ∼70% (urine protein measurement), and creatinine in urine was evaluated in 34.0–63.8% of patients.
Approximately 80–100% of patients underwent various imaging tests. Among them, ultrasound (61.6–88.2%), X-ray (46.1–58.2%) and other methods (44.7–66.4%) were used more frequently. Magnetic resonance and computer tomography were used rarely. The latter was used in Russia only.
The number of patients with kidney biopsy performed in 2010 was 9.5% in Russia and 3.2% in Ukraine; there were no patients with such procedure in Kazakhstan.
SLE-related hospitalizations and outpatient visits
During 2010, the rate of hospitalizations in units other than intensive care (non-ICU [Intensive Care Unit]) was 71.1% in Russia; 96.4% in Kazakhstan, and 85.1% in Ukraine. Mean duration of non-ICU hospitalizations was 17.0, 16.0, and 16.5 days, correspondingly; the maximum duration was 135 days in Russia, 81 days in Kazakhstan, and 79 days in Ukraine. The rate of outpatient visits was 21.6% in Russia, 76.4% in Kazakhstan, and 36.2% in Ukraine. Only three patients in Russia (1.3%) and two in Kazakhstan (1.8%) were hospitalized in ICU, and 4.6%, 5.5%, and 0% patients, correspondingly, had emergency calls due to SLE in 2010. These values are under-estimated, because ICU hospitalizations/emergency calls are often performed locally, outside the study sites, and their results are not included in the medical documentation at the study sites.
Visits to specialists
At least one planned visit to a rheumatologist was made by 56.5% patients in Russia, 59.1% patients in Kazakhstan, and 37.2% patients in Ukraine. At least one unscheduled visit to a rheumatologist due to flare was made by 39.2%, 75.5%, and 74.5% of patients, respectively.
The profile of other specialists’ consultations varied between countries. The most frequent profiles were therapist, nephrologist, dermatologist (Kazakhstan), neurologist (Ukraine), and cardiologist (all countries). Surgeons, psychiatrists, and pulmonologists were visited by less than 15% of the patients across all countries. The frequency of visits to specialists may be associated with the presence of specific organ/system disorder (that was established by the investigator based on medical records and his/her clinical judgment and was classified as active involvement or non-reversible damageCitation15). The following data were found in this study:
The proportions of patients visiting a nephrologist (frequencies of planned/unplanned visits) were 3%/2% (Russia), 17%/22% (Kazakhstan), 2%/3% (Ukraine). The proportion of patients with kidney disorders (including nephritis) was 45% in Russia, 74% in Kazakhstan, and 31% in Ukraine.
The proportions of patients visiting a therapist (frequencies of planned/unplanned visits) were 4%/3% (Russia), 40%/42% (Kazakhstan), and 1%/1% (Ukraine). The proportion of patients with general disorders (e.g. pyrexia, weight loss, lymphadenopathy/splenomegaly, fatigue/malaise/lethargy, anorexia/nausea/vomiting) was 41%, 79%, and 66%, respectively. At the same, patients with other disorders could also visit a therapist.
The proportions of patients visiting a dermatologist (frequencies of planned/unplanned visits) were 5%/3% (Russia), 23/26% (Kazakhstan), and 4%/20%, respectively. The proportion of patients with skin/mucocutaneous disorders was 50%, 84%, and 70%, respectively.
The proportions of patients visiting a cardiologist (frequencies of planned/unplanned visits) were 21%/10% (Russia), 16%/21% (Kazakhstan), and 2%/25% (Ukraine). The proportion of patients with cardiac and/or respiratory disorders was 43%, 64%, and 70%, respectively.
The proportions of patients visiting a neurologist (frequencies of planned/unplanned visits) were 9%/4% (Russia), 11%/15% (Kazakhstan), 4%/29% (Ukraine). The proportion of patients with nervous system disorders was 23%, 20%, and 40%, respectively.
Extrapolation of SLE associated healthcare resource consumption to total country adult population
Based on the SLE prevalence estimated previouslyCitation16, an attempt was made to extrapolate the healthcare resource consumption to the total country population. The potential number (per year and per patient/year) of hospitalizations, outpatient visits, and visits to specialists due to SLE in each country is presented in . We can assume that nearly 8,000 SLE patients in Russia, 3,000 in Kazakhstan, and 5,000 in Ukraine are hospitalized due to SLE per year; a similar number require specialist consultations, and ∼2,000 patients in each country make outpatient visits to clinics.
Table 3. Extrapolation of SLE associated healthcare resource use to the country adult population in 2010.
Healthcare resource utilization by SLE profile
Healthcare resource utilization in 2010 was analyzed by SLE profile in Russia and Kazakhstan only, as in Ukraine there was a small number in the sub-group with chronic active SLE. As reported in , protein in urine analysis, outpatient visits, and visits to specialists were performed in patients with a relapsing-remitting SLE profile more frequently. Patients with relapsing-remitting SLE also had a longer duration of non-ICU hospitalization in Russia (22.7 vs 13.5 days, p = 0.001) and in Kazakhstan (18.9 vs 15.4 days, p = 0.006) compared to those with chronic active disease.
Table 4. Healthcare resource utilization in 2010, by SLE profile (proportion of patients with at least one unit performed; Russia and Kazakhstan only).
As for the number of healthcare resource units in 2010, in Russia there was a higher mean number of visits to specialists (3.5 vs 2.2 in relapsing-remitting vs chronic active patients, correspondingly), including both planned (2.2 vs 1.4) and unplanned visits (1.3 vs 0.8). In Kazakhstan, similarly the patients with a relapsing-remitting SLE profile had a higher mean number of visits to specialists (10.0) compared to those with chronic active SLE (5.3), both for the planned (4.0 vs 2.6) and unplanned visits (5.3 vs 2.1, respectively), as well as the number of outpatient visits (5.0 for relapsing-remitting vs 3.8 for chronic active profile).
Healthcare resource utilisation by SLE flares occurrence
Data on SLE flares in 2010 were available in 173 patients in Russia (64 without flares, 109 with flares, and for 59 data were unknown), 107 patients in Kazakhstan (two without flares, 105 with flares, and for three data were unknown), and in 94 patients in Ukraine (22 without flares and 72 with flares). Due to the small number of patients without flares in Kazakhstan, the comparison of healthcare resource units was made for Russia and Ukraine.
As reported in , patients with SLE flares compared to those without flares had significantly higher healthcare resource consumption (frequency and mean number of units during 2010). In both countries the mean number of visits to specialists was higher in patients with flares than in patients without flares; that is in line with clinical practice: the main reason for visiting specialists is a specific pathology, when a treating physician has to organize the consultation of the appropriate specialist.
Table 5. Healthcare resource utilisation in 2010, by SLE flares (proportion of patients with at least one unit performed).
In Ukraine, a higher healthcare resource consumption in patients with flares was found for immunological analysis, blood chemistry, urine protein, urine creatinine, ultrasound, X-ray, hospitalization (and duration of hospitalization), and unplanned visits to specialists. In Russia, usage of kidney biopsy and duration of hospitalization were significantly higher in patients with flares than in patients without flares in 2010.
Discussion
The ESSENCE study provides data on healthcare resource utilization for SLE management for the first time in post-Soviet countries, such as Russia, Kazakhstan, and Ukraine. Patient clinical characteristics were described previouslyCitation15. The demographic characteristics of patients were similar to those reported by other international studiesCitation4,Citation7,Citation8,Citation11–13. Patients in the ESSENCE study were 10–15 years younger than those from a recent European retrospective study, The LUpus erythematosus Cost of Illness in Europe study (LUCIE)Citation10; a potential reason may be that the patients in post-Soviet countries do not receive adequate medical care at the local level and are directed to rheumatologic institutions (the study centers) quite early. However, the proportion of median age to patients’ life expectancy at birth (taken from World Health Organization (WHO) data) was similar: 0.504 for the ESSENCE study (weighted proportion), and 0.543 for the LUCIE study. Between the study countries, both median age and the proportion of median age to life expectancy at birth were slightly different (median age was 33 years and the proportion of median age to life expectancy was 0.468 for Russia, 36.5 years and 0.520 for Kazakhstan, and 41 years and 0.575 for Ukraine).
The analysis of healthcare resource utilization revealed some peculiarities in the study countries, as contrasted to European countries. Thus, in the large epidemiological study conducted in five European countries (France, Germany, Italy, Spain, and the UK) biopsies were conducted in 18.3% of patients, more frequently in severe than in non-severe patients (27.8% vs 8.8%)Citation10, whereas in the study countries in ESSENCE kidney biopsy was rare (14.3% in severe patients vs 1.9% in non-severe patients in Russia and much less in Kazakhstan and Ukraine). At the same time, the frequency of imaging tests was 79.8–99.1%, which was higher than in Europe (65.8%)Citation10; however, the main contributors were ultrasound and X-ray, whereas the magnetic resonance (1.8–5.2%) and computer tomography (0–8.2%) were used more rarely that could be related to the high cost of these tests. The distribution of visits to specialists is similar to the data obtained in European studiesCitation8,Citation10,Citation11.
Similarities across the countries include diagnostic tests for lupus (e.g. standard tests include hematology, biochemistry, immunology), widespread of USI and X-ray, and rare usage of more expensive tests (CT, MRI). Utilization of expensive treatment (immunology), only in Russia there were some. In all countries SLE activity measurements using international standard scales (SELENA-SLEDAI, SLICC-ACR) is uncommon. A typical profile of a patient who is monitored at the study sites is a patient with a reliable diagnosis of SLE (ACR of at least four criteria), monitoring at least twice a year, with indications of hospitalization.
It is also notable that the rate of kidney biopsy was low across all study countries; this phenomenon may be caused by the lack of imaging tests (e.g. magnetic resonance) control (that is needed for safety biopsy performance) and the lack of qualified morphologists. In Ukraine, additionally, healthcare financing might play a role, as such tests are paid for mainly out-of-pocket by the patient themselves.
Based on statistic data at the study centers, the overall picture of HCRU in the study countries (including low availability of CT, MRI, biopsy) has not been significantly changed since 2010.
Hospitalizations are important contributors to the total cost of SLE management. A large proportion of patients in our study were hospitalized during 2010, primarily in non-ICU units (71–96% patients), which is higher than in European studies—43% of patients were admitted to hospital at least once on an inpatient basisCitation8,Citation10, up to 69% of patients with flaresCitation11. A fairly low number of patients were admitted to the ICU across the three countries (1.3% in Russia. 1.8% in Ukraine, 0.0% in Kazakhstan) compared to European data of ∼22%Citation11. This could be related to possible differences in the healthcare systems or to the study design; for example, a patient might have attended the nearest hospital rather than the specialized center in the case of emergency, and this hospitalization might not have been reported to the specialized SLE center. Therefore, the currently presented SLE associated burden (including hospitalizations) can be considered as a conservative estimate, as the true SLE burden in the participating countries might be higher than observed in this study.
Differences between countries were observed in terms of distribution of various categories of resources. Kazakhstan, where the highest SLE activity was seenCitation15, was characterized by the highest proportion of patients hospitalized due to SLE, frequency of imaging tests, and outpatients visits. Compared to other countries, there was a large proportion of patients with expensive tests in Russia, such as kidney biopsy, magnetic resonance imaging, and computer tomography. The highest proportion of patients visiting specialists was observed in Ukraine.
Differences between countries could be explained by the different set-up of healthcare systems, financing structures, and patient management. The frequency of complex procedures (e.g. biopsy) almost directly depends on the budgeting. The organization of the healthcare system predisposes that the cost of biopsy and other medical care is covered by obligatory medical insurance, but it can be “out-of-pocket” (especially, in Ukraine). In Kazakhstan, a higher level of hospitalization and outpatient visits may be caused due to the fact that patients are not identified/diagnosed in the early stages of their disease by a qualified rheumatologist, or do not have adequate medical care because of the lack of specialized specialists, or due to budget constraints. Such organizational and financial problems are common for many countries of Central Asia (e.g. Kazakhstan, Kyrgyzstan, Tajikistan, Uzbekistan). The higher SLE activity in Kazakhstan, compared to Russia and Ukraine, could also be associated with racial factors (93% of patients self-reported their race as “Asians”, whereas in Russia and Ukraine almost 100% of patients were Caucasian). We earlier reported about higher SLE activity (higher mean SELENA-SLEDAI score) and higher organ damage at the time of diagnosis in Kazakhstan, compared to Russia and UkraineCitation15. Similarly, Golder et al.Citation17, in a single-center study conducted in Australia, found that Asian patients had a disease significantly more severe with higher time-adjusted mean SLEDAI score, higher maximum SLEDAI score, and more frequently persistent disease activity compared with non-Asians (most of them whites). Separate studies of the Kazakh population have not been conducted; however, globally it is known that Asian patients with lupus may experience a more severe disease than whitesCitation18. Both the genetic component and socio-economic status contribute to the variability of lupus expression and outcomes across different races/ethnicities, but in our study the difference in socio-economic status across countries is quite minimal. Thus, the influence of racial factor on the extent of healthcare resource use in Kazakhstan can not be excluded.
This study also demonstrated that a relapsing-remitting SLE profile and occurrence of flares (the most predictable proxy of SLE resource use) tend to have significant effects on healthcare resource consumption. Both these factors may be associated with a more extensive usage of outpatient visits, specialists’ consultations, laboratory and instrumental tests, and longer SLE-related hospitalization. This finding suggests that prevention or effective treatment of flares could significantly decrease the clinical burden of SLE.
This study has several strengths and limitations which require further clarification. As databases or registries of SLE patients are absent in CIS (Commonwealth of Independent States) countries, this study provides the first real-life picture concerning healthcare resources consumed associated with SLE in three post-Soviet countries. This study was conducted across several large specialized SLE clinics in each country and, therefore, provides the best possible information concerning SLE management in a routine practice. The data were captured at specialized centers that provide primary care for patients with lupus. The study population predominantly consisted of city populations; however, rural patients were also included in this study, except for Kiev, Ukraine, because in Ukraine rural patients usually receive care in regional hospitals. It is known that in all studied countries the patients from rural areas do not receive adequate medical care locally (only minimal laboratory tests are provided and often there is a lack of rheumatologists at the local level), therefore they have to visit specialized centers (such as study centers) due to their disease activity, on average twice per year, in order to perform laboratory and instrumental tests and receive treatment to achieve remission.
Taking into account previous results on SLE prevalence, this study provided an opportunity to estimate the SLE burden at the national level. The study design allowed for the conduct of a sub-group analysis to identify potential factors associated with higher resource consumption. Data were captured by the investigators from patient medical records of those patients who visited the 12 specialized rheumatologic centers during the study period (2010). Patients who did not visit the specialized centers were left out of this analysis; however, SLE is not diagnosed or followed up outside of specialized centers and, thus, with this study an attempt has been made to capture resource utilization of all diagnosed patients in the target study cities. Additionally, differences in the level of healthcare resources consumed between countries could reflect differences in the SLE management or might be related to differences in healthcare systems.
An interesting research topic would be to explore how the prevalence of SLE in a specific country may affect HCRU; this needs more in-depth analysis. In general, prevalence estimates can be served as input for health policy-makers to provide an overview of the disease burden in a country, rank a wide range of diseases per their burden in the country for prioritization purposes, instruct and implement disease management policies to reduce/eliminate the burden, and finally to inform healthcare budget allocation decision-making. Previously, in the epidemiological part of the ESSENCE study, SLE prevalence was estimated as 9.0 per 100,000 in Russia, 20.6 per 100,000 in Kazakhstan, and 14.9 per 100,000 in Ukraine. We did observe a higher level of disease activity and hospitalization rate in Kazakhstan compared to other participating countries, however, more in-depth analysis is warranted to explore this effect, which serves as a topic for future research. Furthermore, future research could be focused on conducting a prospective study with population-based screening to capture undiagnosed SLE as well as SLE diagnosed in specialized centers, resource utilization across all healthcare settings, plus capture of patient-reported outcomes such as impact on productivity. Also, exploring the distance lived from the specialized center, patient income level, and other factors associated with HCRU would be an interesting topic for future research.
In conclusion, the ESSENCE study revealed that a visit to specialists (due to concomitant pathology) is the most frequently SLE-related healthcare resource consumed in the CIS countries. It showed that a relapsing-remitting SLE profile and occurrence of flares significantly raises healthcare resource consumption. The information collected on healthcare resource consumption will be helpful for health policy-makers in CIS countries to optimize the management of SLE in the CIS countries.
Transparency
Declaration of funding
The funding for the study was provided by GlaxoSmithKline, Brentford, Middlesex, UK.
Declaration of financial/other relationships
AG reports having received personal fees from GlaxoSmithKline, during the conduct of the study; personal fees from GlaxoSmithKline and Novartis Pharma, outside the submitted work. OI reports having received personal fees from GlaxoSmithKline, during the conduct of the study; personal fees from GlaxoSmithKline, MSD, Abbott, Servier, and Roche, outside the submitted work. S. Shevchuk reports having received personal fees from GlaxoSmithKline, during the conduct of the study; personal fees from AstraZeneca and Boehringer Ingelheim, outside the submitted work. EN, S. Soloviev, AL, RI, GT, CB, and ZhO reported receiving Investigators grant fee from GlaxoSmithKline. AV and JM are employed by GlaxoSmithKline. JD and LT are employed by and own stock in GlaxoSmithKline. Peer reviewers on this manuscript have received an honorarium from JME for their review work, but have no other relevant financial relationships to disclose.
Data availability statement
Information related to the study is available at: http://www.gsk-clinicalstudyregister.com/. GlaxoSmithKline eTrack study identifier: EPI116387. GlaxoSmithKline study acronym: ESSENCE.
Ethics approval
The study was reviewed and approved by Independent Ethic Committees in each country according to the local requirements (Russia: The Independent Interdisciplinary Ethics Committee of Ethical Review for Clinical Trials; Ukraine: Central Commission on Ethics of the Ministry of Health of Ukraine; Kazakhstan: Central Ethics Committee of the Ministry of Health of Kazakhstan). The study followed local data protection laws; patient and data confidentiality were respected.
Acknowledgments
We thank all investigators for their contribution to the study, allowing the first clinical epidemiology research in SLE to happen in Russia and CIS countries with a high level of integrity and the contract research organization, Synergy Research Group, which was funded by GlaxoSmithKline, performing the study organization and conduct. All authors acknowledge editorial support in the form of production of draft outline, editorial suggestions to draft versions of this paper, collating author comments, assembling tables and figures, referencing, and copyediting by Caroline Wirtzbiki at GlaxoSmithKline and Julia She at Synergy Research Group. Patient consent was obtained.
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