The economic burden of systemic lupus erythematosus in United Arab Emirates

Abstract

Aims

Our study aims to provide an enhanced comprehension of systemic lupus erythematosus (SLE) burden in United Arab Emirates (UAE), over a five-year period from payer and societal perspective.

Materials and methods

A Markov model was established to simulate the economic consequences of SLE among UAE population. It included four health states: i) the three phenotypes of SLE, representing mild, moderate, and severe states, and ii) death. Clinical parameters were retrieved from previous literature and validated using the Delphi panel—the most common clinical practice within the Emirati healthcare system. We calculated the disease management, transient events, and indirect costs by macro costing. One-way sensitivity analysis was conducted.

Results

The estimated number of SLE patients in our study was 13,359. The number of SLE patients with mild, moderate, and severe phenotypes was 3,914, 8,109, and 1,336, respectively. Disease management costs, including treatment of each phenotype and disease follow-up, were AED 2 billion ($0.89 billion), whereas the costs of transient events (infections, flares, and consequences of SLE-related organ damage) were AED 1 billion ($0.44 billion). The productivity loss costs among adult-employed patients with SLE in the UAE were estimated at AED 7 billion ($3.1 billion). The total SLE cost over five years from payer and societal perspectives is estimated at AED 3 ($1.3 billion) and 10 billion ($4.4 billion), respectively. Additionally, the costs per patient per year from the payer and societal perspectives were AED 45,960 ($20,610) and AED 148,468 ($66,578), respectively.

Conclusion

Our findings demonstrate that the burden of SLE in the UAE is enormous, mainly because of the costly complications and productivity loss. More awareness should be created to limit the progression of SLE and reduce the occurrence of flares, necessitating further economic evaluations of novel treatments that could help reduce the economic consequences of SLE in the UAE.

Keywords:

• Emirates
• SLE
• economic burden
• costs
• consequences

JEL CLASSIFICATION CODES:

• C51
• C5
• C
• H51
• H5
• H

Introduction

Systemic lupus erythematosus (SLE) is a potentially severe, chronic, and multisystemic autoimmune disease associated with significant mortality and morbidity^1,2. SLE imposes a substantial burden on the healthcare system in terms of either disease diagnosis and treatment or the management of SLE-related organ damage².

Epidemiological data reflected the actual SLE burden in the United Arab Emirates (UAE). Al Dhanhani et al. (2017) demonstrated that the SLE crude incidence ratios in the UAE for 2009, 2010, 2011, and 2012 were 3.5, 1.1, 2.1, and 2.1, respectively, per 100,000 person-years³. Notably, the prevalence of SLE in the UAE is detectable⁴. Compared to similar Arab countries in the Gulf region, the prevalence of SLE in the UAE is estimated to be higher³. A recent comprehensive systematic analysis and modeling study showed that the UAE had the highest prevalence (166.92 per 100,000 persons), with an expected number of 16,505 patients⁴.

Despite recent improvements in SLE management, SLE patients incur a significant burden^5–7. For instance, patients confront multidimensional challenges starting from controlling the disease, dependency on glucocorticoids (GC), and management of adverse events (AEs) to prevent flares and improve treatment adherence^6,7. Furthermore, patients are at high risk of mortality and morbidity⁵.

Albrecht et al. and Lin et al. demonstrated the substantial economic burden after diagnosis of SLE^8,9. The claims data from a German statutory health insurance fund pointed out that the hospitalization rate rose from 13% in the year before disease diagnosis up to 40% during the first year post-diagnosis⁸. Further, the average number of drug prescriptions almost tripled from 3.4 in the year pre-diagnosis to 9.5 in the second year post-diagnosis⁸. Compared to a systematic review of 51 studies, the annual direct total costs per patient for moderate or severe SLE was $19,099–$82,391, while for the mild disease was $12,242–$29,233⁹.

The clinical course of SLE is characterized by periods of remission interspersed by SLE flares, indicating an increase in disease activity¹⁰. As in previous research, the mean annual number of flares (any severity) during the 1-year post-diagnosis period is 3.5 per patient, with 95.1% of patients reporting at least one flare post-diagnosis¹¹. Notably, flares are associated with increased SLE¹². Furthermore, the more severe the SLE flares, the higher the annual SLE medical expenditure¹². For instance, annual expenditures among US patients with moderate and severe flares were 1.6 and 4.3 folds higher, respectively, than those among patients with no flares¹². Therefore, the mean annual direct medical costs for patients with SLE without flares were $6,607, and those for SLE patients with mild, moderate, and severe flares were $7,079, $10,471, and $25,118, respectively¹².

The severity of SLE is an important parameter to be considered in cost-of-illness (COI) study. Patients with SLE and high disease activity status have a higher risk of developing accrual organ damage, flares, and additional exposure to GC to control the disease¹³. For instance, the annual cost was $52,951 for severe SLE patients in the US from 2012 to 2015, contrary to a mean annual cost of $21,052 and $28,936, respectively, for mild and moderate SLE patients¹⁴.

Owing to the episodic nature of the disease, patients develop SLE-related comorbidities¹⁵. In the UAE, 62.5% of SLE patients develop hematological manifestations³, whereas 51% develop renal involvement¹⁶. Compared to the overall SLE population, patients with SLE-related comorbidities in the US have higher annualized direct medical costs, ranging between $38,986 and $74,433, depending on the affected organ¹².

Over three years (2016–2018), Grabich et al. assessed the real-world data of SLE respondents in comparison to non-SLE respondents in the US¹⁷. In the SLE cohort, the frequencies of emergency room (ER), outpatient, and inpatient visits were higher¹⁷. Therefore, total annual healthcare expenses were approximately two-fold higher in the SLE cohort (US$17,270 for SLE vs US$8,350 for non-SLE)¹⁷. Additionally, there was greater deterioration in the quality of life (QoL) of patients with SLE, such as limitations in physical activity, depression, and poor mental health¹⁷. The pooled data from 2016 to 2018 indicated that the mean number of missed work days due to illness/injury for SLE and non-SLE patients was 9 and 5 days, respectively¹⁷.

Regarding the substantial impact of SLE on the healthcare system, existing studies that evaluated the economic burden of SLE in the UAE were limited. In this context, our COI study aimed to provide an enhanced understanding of the considerable burden of SLE in the UAE, considering direct and indirect costs over a period of five years among patients with SLE.

Methodology

Our COI model was used to reflect the economic burden and cost of SLE after diagnosis in the UAE. We used a Markov model, an analytical framework that is frequently used in decision analysis, and use disease states to represent all possible consequences of certain medications. These are mutually exclusive and exhaustive and so each individual represented in the model can be in one and only one of these disease states at any given time. On SLE diagnosis, patients were classified as mild, moderate, or severe, considering physician interpretation and the severity of clinical manifestations according to the British Isles Lupus Assessment Group (BILAG)¹⁸. Our COI study established a state-transition model to estimate SLE costs based on disease progression. The model structure was built on the most standardized local clinical practice in the UAE and validated by the local Delphi panel. Our COI study calculated the disease cost over a five-year time horizon.

The SLE monetary effect was quantified using the most commonly used method in COI, a prevalence-based approach. The prevalence of SLE in the UAE population (166.9/100,000) was extracted from a recently published comprehensive systematic analysis and modeling study that aimed to quantify the epidemiology (incidence/prevalence) of SLE at global, regional, and country-specific levels⁴. The target population in our model was the adult population in the UAE aged ≥ 15 years and diagnosed with SLE.

Our model simulated four health states: i) three phenotypes of SLE, including mild, moderate, and severe SLE, and ii) death. Throughout the disease course, patients with SLE can experience transient events such as infections, flares, and complications due to SLE-related organ damage. Owing to the lack of local data, the percentages of SLE patients with mild, moderate, and severe phenotypes after diagnosis were extracted from a population-based analysis that aimed to evaluate the real-world data of SLE patients (N = 20,181 patients) using Taiwan’s National Health Insurance Research Database between 1 January 2014 and 31 December 2019²¹. The percentage of each phenotype was validated using a local Delphi panel. This Delphi panel composed of eight experts; four reputable rheumatologists affiliated to Mediclinic Airport, Al Kuwait Hospital, Tawam Hospital, Dubai Hospital, three payers affiliated to Dubai Health Authority and SEHA, Emirates and one health economist. We collected insights from experts through three rounds virtual meetings by using the quasi-Delphi panel approach. The experts’ insights included the current local clinical practice and treatment patterns within the Emirati healthcare settings. Owing to the natural course of the disease, patients may transit and enter a health state of a more severe disease (i.e. from mild to moderate/severe phenotypes or from moderate to severe phenotypes). The transition to a more severe phenotype was obtained from a study that assessed 462 SLE patients for a median of 36 months to outline the transition in disease severity²². Figure 1 shows the structure of the model used in the COI study.

Figure 1. The model structure for SLE patients. Abbreviations. SLE, Systemic lupus erythematosus

This manuscript was written according to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement²³. The parameters were extracted from the literature review of all clinical trials and validated by a local Delphi panel. The Delphi panel consensus included commonly used treatment strategies for SLE patients within the Emirati healthcare system.

The transition to a more severe phenotype was assumed to occur during a four-week cycle. The probability to go from mild to moderate in 36 months is 29.1% while it is 20.7% to directly go from mild to severe based on Nikolopulos et al.²². We transferred this probability to 4 weeks transition probability by using this equation: tp1 = 1-(1-tpT)^(1/t) where tp1 is 4 weeks transition probability and tpT is overall probability over time t and then extrapolate it to 5 years. A half-cycle correction was applied to adjust the cost distribution through a model according to the International Society for Health Economics and Outcomes Research (ISPOR) modeling good research report²⁴.

The cost parameters included in our model were as follows: disease management costs (i.e. treatment strategies used for mild, moderate, and severe phenotypes, along with disease follow-up); transient event costs (i.e. management of infections, flares, and SLE-related organ damage); indirect costs (productivity loss costs among living and dead adults who employed Emirati SLE patients). Our study simulates the perspectives of the payers and society. Both the payer and societal perspectives simulated the costs of disease management and transient events, while the societal perspective included productivity costs as well. Costs were discounted at a rate of 3% in the base case (mean value) as recommended by other economic evaluations conducted in the UAE²⁵.

Clinical inputs

The model input parameters are shown in Table 1. The adult population aged ≥ 15 years (8,003,042) in the UAE was extracted from recently published population data by the World Bank in 2022 (population aged 15–64 and 65 years and above)^19,20. According to a recently published comprehensive systematic analysis and modeling study, the prevalence of SLE in the Emirati population is 166.92 per 100,000 persons⁴. Therefore, the target population for the COI model included 13,359 patients. According to a local Delphi panel, the average adult weight in the UAE was 76 kg.

Table 1. The input parameters of the model.

(A) Eligible patients:	Base case	Low value	High value	References
Number of target population ≥ 15 years	8,003,042	6402434	9603650	^1920
Prevalence of SLE in UAE (%)	0.17%	0.0013	0.0020	^4
Mild SLE (%)	29.3%	0.23	0.35	^21
Moderate SLE (%)	60.7%	0.49	0.73
Severe SLE (%)	10.0%	0.08	0.12
(B) Baseline patient characteristics:
Weight (Kg)	76	61	91	Delphi panel
Hematologic manifestations (%)	50%	0.4	0.6	^27
Joint manifestations (%)	86%	0.7	1.0	^16
Skin manifestations (%)	73%	0.6	0.9
Neuropsychiatric manifestations (%)	16%	0.1	0.2
Cardiovascular manifestations (%)	18%	0.1	0.2	^31
Peripheral vascular manifestation (%)	11%	0.1	0.1	^30
Pulmonary manifestations (%)	13%	0.1	0.2	^29
Renal manifestations (%)	41%	0.3	0.5	^28
Renal patients progressed into ESRD (5 years) (%)	14%	0.1	0.2	^32
ESRD managed by renal transplantation (%)	25%	0.2	0.3	Assumption
ESRD managed by dialysis (%)	75%	0.6	0.9
(C) Clinical parameters: (1) Transition to severe state:
Mild to moderate SLE (%) on 3 years	29.10%	0.23	0.35	^22
Mild to severe SLE (%) on 3 years	20.70%	0.17	0.25
Moderate to severe SLE (%) on 3 years	29.40%	0.24	0.35
(2) OS
OS: exponential λ	−0.0036407	−0.0029	−0.0044	^26
(3) Risk of flares
SLE patients experience flares annually (%)	95%	0.8	1	^11
Mean annual mild flare rate per patient	1.1	0.9	1.3
Mean annual moderate flare rate per patient	2.2	1.8	2.6
Mean annual severe flare rate per patient	0.2	0.2	0.2
(4) Risk of infection
Risk of serious infection	14.5%	0.12	0.17	^33
(D) Discount rate:
Discount rate	3%	0.024	0.036	^25
(E) Indirect cost parameters:
Labor force among population ≥ 15 years (%)	74%	0.6	0.9	^34
Work productivity impairment among mild-SLE (%)	15%	0.1	0.2	^35
Work productivity impairment among moderate-SLE (%)	38%	0.3	0.5
Work productivity impairment among severe-SLE (%)	50%	0.4	0.6
Mean monthly sick days per patient	2.3	1.8	2.8	^36
Emirati GDP per capita (AED)	197,426	157941	236911	^37

Abbreviations. SLE, Systemic lupus erythematosus; ESRD, End stage renal disease; OS, Overall survival; GDP, Gross domestic product; AED, Emirati Dirham; UAE, United Arab of Emirates.

In our Markov model, the main cause of mortality is disease specific based on our Delphi panel. The estimation of transition probabilities from a live health state (different SLE phenotypes/states) to death (absorbing health state) was captured from a retrospective study that assessed 72 SLE patients from January 2013 to December 2020 (15 had hematological malignancies, while 57 did not) in the Chinese population²⁶. To simulate lifetime patient-level data based on parametric models, the overall survival (OS) Kaplan-Meier’s (KM) curves of 57 SLE patients without hematological malignancies were extrapolated²⁶. An exponential parametric function provided a plausible fit for the OS curves.

According to a literature review and the Delphi panel, most patients with SLE in the UAE develop hematologic manifestations (anemia), joint manifestations (arthritis), lupus nephritis (LN), cardiovascular (CV) manifestations, pulmonary complications, and peripheral vascular (Raynaud’s phenomenon) and cutaneous manifestations. The percentage of SLE-patients with hematological manifestations (mainly anemia, 50%) was extracted from a review of anemia in patients with SLE²⁷. By utilizing data of 110 Arab SLE-patients captured from a study that evaluated a cohort of 151 SLE-patients in Dubai Hospital between January 2002 and January 2007, the percentages of SLE patients with skin manifestations and arthritis were 72.6% and 86.2%, respectively, whereas those of neuropsychiatric manifestations were 15.6%¹⁶. A study evaluating 91 SLE patients in Tawam Hospital (a tertiary care teaching hospital in the UAE) showed that LN accounted for 41% among SLE patients in the UAE²⁸. The proportion of SLE patients who experienced lung involvement (13.3%) was extracted from a study that compared 15 SLE patients without LN (93.3% of the cohort were from the UAE) and 10 LN patients (100% of the cohort were from the UAE)²⁹. Regarding Raynaud’s phenomenon, a study that evaluated 28 SLE patients (Arabs and Asians) in the UAE pointed out that the prevalence of Raynaud’s phenomenon among SLE patients was 10.5%³⁰. The percentage of SLE with CV complications (18.0%) was retrieved from a study that aimed to assess the occurrence/prevalence of CV complications among SLE patients (n = 189 patients) in Saudi Arabia³¹. The proportion of LN patients with disease progressing to end stage renal disease (ESRD) within five years (average of 16% and 11%) was retrieved from a systematic review and Bayesian meta-analysis that included 187 studies (18,309 patients) to estimate the risk of ESRD³². We assumed that 75% of ESRD were managed by hemodialysis, while the remaining were managed by renal transplantation.

Different types of flares in patients with SLE were simulated using the COI model. A retrospective cohort study that assessed 2,227 SLE-patients in the US between January 2005 and December 2014 pointed out that the annual percentage of SLE patients experiencing flares was 95.1%, with mean mild, moderate, and severe flares per patient of 1.1, 2.2, and 0.2, respectively¹¹. The risk of serious infection (14.5%) among SLE patients was retrieved from a time-to-event analysis that followed up 346 SLE-patients for a mean period of 6.6 years³³.

Costs

Our model simulates the following costs: disease management, transient events, and indirect costs. Disease management costs included all treatment regimen costs for different SLE phenotypes and disease follow-up, whereas transient event costs represented the costs of SLE-related organ damage, infections, and flares. Furthermore, transient event costs were measured according to the average resources used and the length of hospital stay, if needed, to treat a single event.

Total healthcare costs were calculated by multiplying the resource use by the unit costs of each component. All of the healthcare resources utilization (HCRU) was informed by Delphi panel according to the most standardized local clinical practice within the Emirati healthcare system. All unit costs were obtained from the Dubai Health Authority lists, measured in Emirati Dirham (AED) based on the financial year 2023. Local currency conversions to international dollar were performed using the purchasing power parity rate, sourced from World Bank. Table 2 lists all the unit costs used in our model.

Table 2. The model unit costs.

Cost parameters
(1) Disease management	Base case	Low value	High value	References
Hydroxychloroquine 200mg	AED 2	1	2	Dubai Health Authority
Methotrexate 10mg	AED 5	4	6
Folic acid 1mg	AED 0.2	0.1	0.2
Cyclosporine 100mg	AED 13	10	16
Azathioprine 50mg	AED 1	0	1
MMF 500mg	AED 16	13	19
Cyclophosphamide 500mg	AED 10	8	12
Belimumab 200mg/mL (SC)	AED 1,228	982	1473
Belimumab 120 mg/Vial (IV)	AED 510	408	612
Belimumab 400 mg/Vial (IV)	AED 1649.5	1320	1979
HIV test	AED 529	423	635
HBS blood Tests	AED 125	100	150
HCV blood Tests	AED 202	162	242
TB Infection test	AED 380	304	456
Vaccination against influenza	AED 81	65	97
Vaccination against pneumococcus	AED 536	429	643
(2) Disease follow-up
KFT cost	AED 951.59	761	1142
LFT cost	AED 1,012.60	810	1215
CBC cost	AED 100.00	80	120
C3/C4 cost	AED 92.50	74	111
Anti-dsDNA antibodies cost	AED 112.50	90	135
ESR cost	AED 64.62	52	78
CRP cost	AED 170.88	137	205
Physician visit	AED 575.00	460	690
(3) Flares management
Prednisone 5mg	AED 0.44	0	1
Prednisone 10mg t	AED 2.67	2	3
Prednisone 20mg	AED 1.45	1	2
Methylprednisolone 500mg	AED 61.00	49	73
Ward day cost	AED 493.00	394	592
Calcium/vitamin D supplements	AED 1.38	1	2
(4) Infection management
Ciprofloxacin 250mg	AED 3	2	4
(5) Organ complications	Base case	Low value	High value
Ferrous sulphate 200mg	AED 0.38	0	0
Triamcinolone 40mg	AED 11.00	9	13
Ramipril 2.5mg	AED 1.40	1	2
Atorvastatin 20mg	AED 3.47	3	4
Isosorbide mononitrate 20mg	AED 1.00	1	1
Nintedanib 150mg	AED 260.33	208	312
Nifedipine 30mg	AED 0.78	1	1
Aspirin 81mg	AED 0.60	0	1
Sildenafil 50mg	AED 9.63	8	12
Sildenafil 100mg	AED 15.50	12	19
Capillaroscopy	AED 160.53	128	193
Topical steroids	AED 18.00	14	22
Renal biopsy cost	AED 8,040.98	6433	9649
Hemodialysis session cost	AED 2,605.50	2084	3127
Renal transplantation cost	AED 59,926.50	47941	71912
ECG cost	AED 980.09	784	1176
ECHO cost	AED 784.38	628	941
Lipid profile	AED 120.00	96	144

Abbreviations. MMF, Mycophenolate mofetil; HCV, Hepatitis C; HBS, Hepatitis B; HIV, Human immunodeficiency virus; ECG, Electrocardiogram; ECHO, Echocardiogram; ACE, Angiotensin-converting enzyme; CRP, C-reactive protein; ESR, Erythrocyte sedimentation rate; UTI, Urinary tract infection; C4, Complement component 4; C3, Complement component 3; anti-dsDNA, Anti-double stranded DNA, LFT, Liver function test, KFT, Kidney function test; CBC, Complete blood count, TB, Tuberculosis; SC, subcutaneous; IV, Intravenous.

The indirect costs in our model simulated productivity losses among living and dead adult patients with Emirati SLE-patients. The mean labor force within the Emirati population aged ≥ 15 years (73.75%) was captured from the World Bank in 2022³⁴. The proportion of patients with mild, moderate, and severe SLE-patients with work impairment was retrieved from a study that evaluated a large cohort (689 SLE patients) to determine the SLE burden on work productivity and employment in the US³⁵. An evaluation of the work disability and productivity loss within 344 SLE patients and 322 matched controls showed that the mean monthly sick days per patient were 2.3 days³⁶. The Emirati patients’ average wage/hour was estimated using the most recently published gross domestic product (GDP) published by the World Bank in 2022³⁷.

Treatment regimens and follow up

Among patients in the UAE, hydroxychloroquine is the foundation for managing SLE, regardless of disease activity. For SLE patients with moderate and severe phenotypes, immunosuppressants and biological treatment (belimumab) were added to stop organ damage and ensure better outcomes. According to the Delphi panel, Emirati SLE-patient received only one type of immunosuppressant. As immunosuppressants were selected based on disease manifestations, we applied the average cost of the most commonly used immunosuppressants (azathioprine, mycophenolate mofetil, MMF, methotrexate, cyclophosphamide, and cyclosporine) in our model. Before immunosuppressant initiation, patients were required to be vaccinated mainly against seasonal influenza (annually) and pneumococcal infections (once every five years). Notably, SLE-patients allocated to biologics were screened before treatment initiation for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and tuberculosis (TB). Table 3 lists the treatment doses used in the model.

Table 3. The treatments doses and regimens.

Medication	Doses
Hydroxychloroquine	400mg daily dose
Methotrexate	A single dose not to exceed 20 mg/week orally
Folic acid	1 mg oral everyday with methotrexate with methotrexate to decrease the risk for side effects
Cyclosporine	2.5mg/kg/day (190mg daily)
Azathioprine	2 mg/kg/day (152mg daily)
MMF	2gm daily
Cyclophosphamide	500 mg IV every 2 weeks for 6 doses (3mos)
Belimumab	200 mg SC weekly
Ciprofloxacin	250mg q12hr for 14 days
Prednisolone	0.2–0.4 mg/kg (Mild flares) 0.5 mg/kg (Moderate flares) 0.8mg/kg (Severe flares)
Methylprednisolone	500mg daily
Calcium/vitamin D	1 tablet twice daily
Ferrous sulphate	200mg once daily
Triamcinolone	40mg injected in the affected joint
Ramipril	2.5 mg orally once daily
Isosorbide mononitrate	20 mg orally twice daily
Atorvastatin	20 mg orally daily
Nintedanib	150 mg orally twice daily
Nifedipine	30mg (extended release) orally once daily
Aspirin	Low-dose aspirin: 81mg daily
Sildenafil	80mg once to twice daily

Abbreviations. MMF, Mycophenolate mofetil; SC; Subcutaneous; IV, Intravenous.

*All doses of medications used in common clinical practice in Emirates and validated by Delphi panel.

Patients receiving hydroxychloroquine should visit an ophthalmologist once in the first five years and then annually. Disease follow-up was based on SLE phenotypes in accordance with the Delphi panel. Follow-up (complete blood count [CBC], kidney function test [KFT], liver function test [LFT]) for patients with mild and moderate-to-severe SLE was performed every three months and one month, respectively. Immunological assessments using anti-double-stranded DNA (anti-dsDNA), complement component 3 (C3), and complement component 4 (C4) were performed once every three months.

According to our Delphi panel, the most common type of infection among Emirati SLE-patients was urinary tract infection (UTI), which required management with an oral antibiotic (ciprofloxacin) without hospitalization.

When flares occurred, patients were managed according to flare severity using prednisone and tapered to the least allowed daily dose to avoid GC-related AEs^38,39. The initial dose of prednisone lasted for two weeks and was tapered once every two weeks (5 mg decrease)⁴⁰. Regardless of the type of flare, patients were evaluated for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and physician visits. Contrary to patients with mild and moderate flares, patients with SLE and severe flares required hospitalization for five days (ward days). Owing to GC administration, patients require concomitant treatment (calcium/vitamin D supplements) to protect against prednisone-related AEs.

Owing to nonspecific disease symptoms and complexity, the interval between the onset of symptoms and the time to accurate diagnosis is considerably long (mean, 47 months)⁴¹. Consequently, most SLE patients develop signs of accrual organ damage at the time of diagnosis. Therefore, we used SLE-related organ damage from the first cycle. Anemia was managed by administering ferrous sulfate tablets for six months. Patients with SLE-related non-erosive arthritis were managed with physiotherapy (15 sessions) with injected GC (triamcinolone, up to three times annually). In the case of LN, patients were initially assessed by renal biopsy and followed up by a nephrologist (three times annually). An angiotensin-converting enzyme (ACE) inhibitor (ramipril) was administered to patients with LN without ESRD. Atherosclerosis is the most common CV complication in Emirati patients with SLE. Therefore, patients required annual assessment by echocardiography (echo, once annually), electrocardiography (ECG, once annually), lipid profile (once annually), and cardiologist follow-up. Furthermore, vasodilators (isosorbide mononitrate) and statins (atorvastatin) were administered. The management of pulmonary complications (interstitial lung disease) requires nintedanib and pulmonologist follow-up. In cases of peripheral vascular disease (Raynaud’s disease), patients were followed up by capillaroscopy, with the administration of a calcium channel blocker (nifedipine), aspirin, and sildenafil. For cutaneous manifestations, patients were managed with topical steroids and followed up by a dermatologist (three times annually).

Sensitivity analysis

One-way sensitivity analysis was performed to ensure the robustness of the results. Various parameters were varied by a plausible range, 10–20% above or below their base case values as performed in many health economic studies. The parameters tested were epidemiological data, clinical parameters, and unit cost data for all treatments.

Results

The estimated number of target patients with SLE in the UAE for our COI study was 13,359. At diagnosis, the numbers of SLE patients with mild, moderate, and severe phenotypes was 3,914 (29.3%), 8,109 (60.7%), and 1,336 (10%) patients, respectively. Over a period of five years, the disease management costs, including the treatment of each phenotype and disease follow-up, were AED 2 billion, while the costs of transient events (infections, flares, and consequences of SLE-related organ damage) were AED 1 billion. The productivity loss costs among adult-employed patients with SLE in the UAE were estimated at AED 7 billion. The total SLE cost in the UAE over five years from payer and societal perspectives was estimated at AED 3 and 10 billion, respectively (Table 4). The disease management costs were AED 57 million ($25 million) for mild SLE and AED 1 billion ($558 million) and 411 million ($184 million) for moderate and severe SLE, respectively. Additionally, the costs per patient per year from the payer and societal perspectives were AED 45,960 ($20,610) and AED 148,468 ($66,578), respectively. The results showed a huge cost burden due to productivity losses resulting from SLE-related morbidity and mortality (Figure 2).

Figure 2. The cost components of SLE burden from societal perspective. Abbreviations. SLE, systemic lupus erythematosus.

Table 4. The model results of SLE cost over 5 years.

The payer perspective
Total disease cost (AED)	AED 3,069,824,597 ($1,376,602,958)
Cost components	Disease management cost		Transient events cost
	AED 1,817,065,716 ($ 814,827,675)		AED 1,252,758,881 ($ 561,775,283)
The societal perspective
Total disease cost (AED)	AED 9,916,679,512 ($2,549,997,672)
Cost components	Disease management cost	Transient events cost		Indirect cost
	AED 1,817,065,716 ($ 814,827,675)	AED 1,252,758,881 ($ 561,775,283)		AED 6,846,854,915 ($3,070,338,527)

Abbreviations. AED, Arab Emirati Dirham; SLE, Systemic lupus erythematosus; the local currency was converted to international dollar using the 2022 purchasing power parity conversion factor (2.23), sourced from the World Bank.

Extrapolating the time horizon of the analysis to10 years did not alter the conclusions reached on the basis of other analyses.

Sensitivity analysis

One-way sensitivity analysis was performed to test the robustness of the results. Tornado diagrams showed that the number of adult patients with SLE in the UAE was the most sensitive parameter from the payer’s perspective. Further, the number of employed persons in our cohort was the most sensitive parameter from a societal perspective (Figures 3 and 4).

Figure 3. One-way sensitivity analyses for SLE cost from payer perspective over 5 years. The blue color indicates the low value of the results, while the red color indicates the high value of the results. Abbreviations. SLE, Systemic lupus erythematosus; SC, Subcutaneous; Cap, Capsule; ESRD, End stage renal disease; UAE, United Arab Emirates; λ, Lambda.

Figure 4. One-way sensitivity analyses for SLE cost from societal perspective over 5 years. The yellow color indicates the high value of the results, while the blue color indicates the low value of the results. Abbreviations. SLE, Systemic lupus erythematosus; SC, subcutaneous; Cap, Capsule; ESRD, End stage renal disease; UAE, United Arab Emirates.

Discussion

To our knowledge, this study is the first in the UAE to simulate the financial burden of SLE on patients and the healthcare system, which can be used as an evidence-based evaluation for decision-makers to address the unmet needs of patients with SLE in their country. This study used a prevalence-based approach, with data validated by local experts.

The burden of SLE also affects the SLE patients’ caregivers⁴². Among employed caregivers, the missed paid work time for the caregivers was 12.8%⁴². Further, almost half (49.4%) of the caregivers reported that caregiving responsibilities influenced their ability to socialize with friends⁴⁵. Additionally, nearly all the caregivers (97.6%) experienced an increase in stress and anxiety due to their roles as caregivers⁴². We did not measure the caregiver productivity lost in our study due to the lack of local data.

The management of SLE and its related manifestations account for considerable direct and indirect costs⁴³. For instance, the annual direct cost for patients with SLE in the US is $13,735–$20,926⁴⁴. Outside the US, the average annual cost per patient in Taiwan was $1,660⁴⁵, whereas the average annual cost between 2009 and 2014 in Germany for mild, moderate, and severe SLE ranged from €1,890 to 3,010, €4,867 to 5,876, and €8,396 to 10,001, respectively⁴⁶. This highlights the increase in the cost of SLE in the Emirates compared to that in other countries.

Approximately 77% of SLE patients develop organ damage⁴⁷. Therefore, organ damage is a vital aspect in patients with SLE, as it is a prognostic factor for morbidity and mortality^48,49 and an increase in financial burden ^49,50. A systematic review and meta-analysis showed that each 1-unit increase in the damage index score resulted in mortality increase (pooled hazard ratio [HR] = 1.34; 95% confidence interval [CI] = 1.24: 1.44)⁴⁸.

Different studies have reflected the economic burden of SLE-related organ damage^49,50. For example, Barber et al. concluded that SLE patients with more organ damage had higher healthcare costs⁴⁹. In fact, the annual cost of SLE patients with high organ damage index scores (SDI score ≥5) was 12-fold higher than that of those with the lowest organ damage index scores (SDI score =0)⁴⁹.

As LN is one of the most common manifestations of SLE⁵¹, it imposes a high economic burden and HCRU⁵⁰. In the US, Bell et al. (2022) assessed the data of 2,916 LN patients and 8,747 non-LN patients⁵⁰. The study demonstrated that the inpatient stays for LN and non-LN patients were 41% and 17%, respectively⁵⁰. Furthermore, patients in the LN cohort experienced more severe, frequent, and costly flares⁵⁰. For example, the rates of moderate and severe flares were 61.2% and 10.6%, respectively, in the LN cohort and 53.6% and 5.4%, respectively, in the non-LN cohort⁵⁰. Therefore, the mean healthcare cost/flare of any severity in the LN cohort ($5,842) was 2.2 times higher than that in the non-LN cohort ($2,600)⁵⁰.

We compared the total cost of SLE per patient per year in UAE ($ 20,610) vs Mexico ($ 3,096), Colombia ($ 3,510), Taiwan ($ 2,758), and Malaysia ($ 4,767) from payer perspective⁵². The highest SLE burden was in UAE⁵². To our knowledge, this is the first prevalence-based COI study among Emirati SLE patients to demonstrate the real burden of SLE from a payer and societal perspective, which aimed to inform policymakers in the UAE of the unmet needs of SLE and the urgent need for novel SLE medications that reduce the occurrence of flares and organ damage.

Our study has several strengths and limitations. Strengths include the fact that the prevalence of SLE in the UAE was retrieved from the most recent data in the literature. Moreover, the results can be generalized to the UAE, as it represents the most common local clinical practice within the Emirati healthcare system.

The study’s limitations include a lack of local data regarding the following: i) the proportion of SLE patients with each phenotype after diagnosis; ii) the estimation of the percentage of mild, moderate, and severe SLE patients who experienced work impairment; iii) the mean monthly sick days per patient. Consequently, we depend on international data and validate these parameters using a Delphi Panel. In addition, we relied on retrospective study conducted on 72 SLE patients to capture the probability of death from different SLE phenotypes as there was no other reliable studies to inform this parameter, but we validated it from our Delphi panel. Another limitation, we did not include informal care cost in cost calculation due to the paucity of local data. A potential limitation, we included the adult population aged ≥ 15 years in our target population to align with the defined World Bank age category to get the total number of SLE patients in Emirates.

Conclusion

Our findings demonstrate that the burden of SLE in the UAE is enormous, mainly because of the costly complications and productivity loss, as SLE mostly affects the productive age. More awareness should be created to limit the progression of SLE and reduce the occurrence of flares, necessitating further economic evaluations of novel treatments that could help reduce the economic consequences of SLE in the UAE.

Transparency

Reviewer disclosures

Peer reviewers on this manuscript have received an honorarium from JME for their review work but have no other relevant financial relationships to disclose.

Author contributions

GE: conducting the analysis and writing the manuscript. SA, WA, and MF: interpretation of data, and revision of manuscript. AA, SH, NZ, SA, WA, and MF: retrieving data, local clinical practice validation. All authors contributed to the article and approved the submitted version.

Supplement statement

This article is part of a supplement sponsored by AstraZeneca. All articles within this supplement have been rigorously peer reviewed by experts in the field, as per Journal of Medical Economic’s peer review policy. Any conflicts of interest are stated in the “Declaration of financial/other relationships” section.

Acknowledgements

The authors gratefully acknowledge Mariam Elattar for the writing assistance utilized in the production of this manuscript and Neveen Kandil for her efforts in organizing the Delphi panel.

Declaration of funding

This study was funded by AstraZeneca, who had no involvement in the study design, analysis, interpretation of results or manuscript writing.

The funding received was used to pay for the submission and the open access publication fees.

Declaration of financial/other relationships

GE was employed by HTA Office, LLC. GE is a speaker for Janssen, Merck, Novartis, AstraZeneca, Roche, Eva pharma and Pfizer. The authors have no other financial relationships to disclose.

The experts did not receive any compensation for their participation in the Delphi panel.