Economic burden of systemic lupus erythematosus in Malaysia

Abstract

Introduction

Our cost-of-illness (COI) model adopted the perspective of both payer and society over a time horizon of 5 years to measure the economic burden of systemic lupus erythematosus (SLE) in Malaysia.

Methodology

Our COI model utilized a prevalence-based model to estimate the costs and economic consequences of SLE in Malaysia. The clinical parameters were obtained from published literature and validated using the Delphi panel. Direct and indirect medical costs were measured, including disease management, transient events, and indirect costs. One-way sensitivity analysis was also performed.

Results

The number of target Malaysian patients with SLE in the COI model was 18,121. At diagnosis, the numbers of SLE patients with mild, moderate, and severe phenotypes were 2,582, 13,897, and 1,642, respectively. The total SLE cost in Malaysia over 5 years from both payer and society perspectives was estimated at MYR 678 million and 2 billion, respectively. The results showed a considerable cost burden due to productivity losses resulting from SLE-related morbidity and mortality. Over a 5-year time horizon, the costs per patient per year from the payer and society perspectives were MYR 7,484 ($4766) and 24,281($15,465), respectively.

Conclusion

Our study demonstrated the substantial economic burden of SLE in Malaysia over a time horizon of 5 years. It affects adults of working age, in addition to the costs of SLE management and its consequences, such as flares, infection, and organ damage. Our COI model indicated that disease management costs among patients with higher disease severity were higher than those among patients with a mild phenotype. Hence, more attetion should be paid to limiting the progression of SLE and the occurrence of flares, with the need for further economic evaluation of novel treatments that could lead to better outcomes.

Keywords:

• SLE
• Malaysia
• costs
• consequences
• burden

JEL Classification Codes:

• C51
• C5
• C
• H51
• H5
• H

Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs¹. SLE has a high prevalence of disability and human burden, as it impairs patients’ ability to perform routine daily activities². Furthermore, previous findings highlighted the financial burden and high healthcare resource utilization (HCRU) observed with SLE^3–5.

Notably, there is a variation in SLE-epidemiological data^6,7. In accordance with a recent study that aimed to demonstrate global, regional, and country-specific epidemiological information on SLE, the reported prevalence of SLE among adults in Malaysia was 69.05 per 100,000 persons⁷. Even with progress in SLE management, the mortality risk in patients with SLE is three-fold higher than that in the general population⁸.

Owing to the nature of the disease, SLE can affect different organs such as the kidney, cardiovascular system, and skin⁹, which are associated with poor quality of life (QoL)¹⁰, increased mortality¹¹, and a significant increase in SLE cost¹². Within 5 years of follow-up, 43.4% of patients with SLE develop irreversible organ damage¹³. Organ damage is associated with limited daily activity¹⁰, resulting in patients becoming unemployed¹⁴. Furthermore, a meta-analysis demonstrated that with each 1-unit increase in systemic lupus, international collaborating clinics/American College of Rheumatology Damage Index (SDI) score, a 34% increase in mortality risk was observed¹¹. Chiu et al. assessed the economic impact of SLE and concluded that organ damage represents the highest medical expenditure for patients with SLE¹². Compared to patients without organ damage, the SLE with organ damage cohort incurred a median monthly cost of US$210 per patient¹².

As SLE is a relapsing/remitting disease, its clinical course is characterized by episodes of flares¹⁵. They are known to increase the economic and clinical burden of SLE^16,17. Therefore, they have been perceived as major drivers of direct healthcare costs in cost-of-illness (COI) studies¹⁸. The SLE cost of care in a Greece study, which assessed patients with active SLE allocated to treatment, showed that severe flares contributed to an increase of 123.9% in the annual direct cost¹⁸. The explanation for this increase was due to increased medications, such as increased doses of glucocorticoids (GC) or the initiation of immunosuppressants/biologics to manage flares, and increased hospitalization¹⁸, as patients with flares had 1.72–3.14 fold higher hospitalization rates¹⁷. As the frequency of SLE flares increased, the total work productivity decreased¹⁷. For instance, the mean work-related activity impairment was 12–32% higher in patients with flares than in those without¹⁷.

Different studies have demonstrated a significant burden of SLE after diagnosis^19,20. In the United States (US), Jiang et al. assessed 2,227 patients with mild, moderate, and severe SLE 1 year before and after diagnosis¹⁹. The study concluded that HCRU and costs increased the year after diagnosis, regardless of disease activity¹⁹. However, patients with greater disease activity incurred higher costs¹⁹. In the year following diagnosis, patients with mild, moderate, and severe SLE incurred additional costs of US$1,042, US$6,953, and US$28,999, respectively¹⁹. Furthermore, in the first year after diagnosis, hospitalization increased from 13% before diagnosis to 40%²⁰. Thereafter, the mean number of prescribed medications almost tripled after diagnosis (3.4 in 2015 to 9.5 in 2018)²⁰.

Objective

Health organizations and governments must estimate the costs associated with SLE. These estimates could support the efficient planning of care management within the Malaysian population. Therefore, this study aims to estimate the costs associated with SLE management and its consequences in Malaysia from the perspective of both payers and society over a time horizon of 5 years.

Methodology

A state transition model was used to measure the substantial SLE-associated burden after diagnosis in Malaysia. For disease diagnosis, patients with SLE were categorized in accordance with the phenotypes of SLE, that is, mild, moderate, and severe SLE, considering both physician interpretation and the severity of clinical manifestations according to the British Isles Lupus Assessment Group (BILAG)²¹. Our model demonstrated the SLE costs according to disease progression simulated by each health state. Notably, our model was built in accordance with the most standardized local clinical practice in Malaysia and was validated by a local Delphi panel. Our model simulated the results over a 5-year time horizon.

The monetary effect of SLE in our model was quantified according to the most commonly applied method in epidemiological studies, a prevalence-based approach. The prevalence of SLE among the adult Malaysian population was determined in accordance with a comprehensive systematic analysis and modeling study that aimed to demonstrate global, regional, and country-specific SLE-related epidemiological data⁷. The simulated population in our model was an adult Malaysian population aged ≥ 15 years and diagnosed with SLE. The population in our model was extracted from the data most recently published by the World Bank in 2022^22,23. The target Malaysian patients with SLE had an average weight of 70 kg.

In our model, four health states were simulated: three SLE phenotypes (mild, moderate, and severe) and death. In addition, patients with SLE can experience transient events such as infection, flares, and complications due to SLE-related organ damage during the course of the disease. Patients with SLE might transition to a more severe phenotype. Transition to a state of higher disease severity was retrieved from a study that followed 462 patients with SLE for a median of 36 months²⁴. Figure 1 shows the structure of the COI model employed in our study.

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

Our model was reported in accordance with the Consolidated Health Economic Evaluation Reporting Standards statement²⁵. All the parameters included in our model were validated using a Delphi panel. Transitions to a phenotype of higher severity were assumed to occur within a 4-week cycle period. Based on the International Society for Health Economics and Outcomes Research modeling recommendations, a half-cycle correction was utilized to adjust the cost distribution through the model²⁶. Costs were discounted at 3% in the base case, as recommended by other economic evaluations conducted in Malaysia²⁷.

Clinical inputs

At the time of diagnosis, patients were classified according to disease severity into one of the three health states of SLE: mild, moderate, or severe. Due to a lack of data in Malaysia, the percentages of patients with SLE after diagnosis into mild (14.25%) or moderate (76.69%) phenotypes were extracted from an evident study focused on the Colombian contributive health system between 2014 and 2017 conducted on 5527 patients with SLE²⁸.

The transition probabilities from a live health state to a dead health state were retrieved from a prospective study that evaluated 465 hospitalizations of 251 patients with SLE within a five-year period between January 2006 and December 2010 in Sarawak General Hospital in Malaysia⁸. An extrapolation of overall survival (OS) curves of patients with SLE without co-infection was extrapolated to assess lifetime patient-level data based on parametric models⁸. The exponential parametric function provided a plausible fit for the OS curves⁸. Table 1 lists all input parameters of the model.

Table 1. The input parameters of the model.

	Base case	Low value	High value	References
(A) Eligible patients
Number of Malaysian populations ≥ 15 years	26,243,456	20994765	31492147	22,23
Prevalence of SLE in Malaysia (%)	0.07%	0.0006	0.0008	7
Mild SLE (%)	14%	0.11	0.17	28
Moderate SLE (%)	77%	0.61	0.92
(B) Baseline patient characteristics:
Weight	70	56	84	Delphi panel
Hematologic manifestations (anemia)	50%	0.4	0.6	29
Joint manifestations (arthritis)	52%	0.4	0.6	30
Skin manifestations	45%	0.4	0.5	31
CV (hypercholesterolemia)	36%	0.3	0.4	32
Renal manifestations	65%	0.5	0.8	31
Renal patients progressed into ESRD (5 years)	14%	0.1	0.2	33
ESRD managed by hemodialysis	75%	0.6	0.9	Assumption
(C) Clinical parameters: (1) Transition to severe state:
Mild to moderate SLE (%)	29.10%	0.23	0.35	24
Mild to severe SLE (%)	20.70%	0.17	0.25
Moderate to severe SLE (%)	29.40%	0.24	0.35
(2) OS
OS: exponential λ	−0.0018486	−0.0015	−0.0022	8
(3) Risk of flares
SLE patients experience flares annually (%)	95%	0.8	1	34
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	35
Effectiveness of pneumococcal vaccines	0.255	0.204	0.306	36
(D) Discount rate:
Discount rate	3%	0.024	0.036	27
(E) Indirect cost parameters:
Labor force among population ≥ 15 years (%)	65.7%	0.5	0.8	37
Work productivity impairment among mild-SLE (%)	15%	0.1	0.2	38
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	39
Malaysia GDP per capita (MYR)	44,413	35530	53296	40

Abbreviations. SLE, Systemic lupus erythematosus; ESRD, end stage renal disease; OS, overall survival; CV, Cardiovascular; GDP, gross domestic product; MYR, Malaysian Ringgit.

Most Malaysian patients with SLE developed the following SLE-related complications: hematological manifestations (anemia), joint manifestations (arthritis), skin manifestations, cardiovascular disease, and lupus nephritis (LN). The proportion of SLE patients with anemia was obtained from a review of anemia in patients with SLE²⁹. In accordance with an evaluation of 155 patients with SLE in 2011, the percentage of patients with SLE and arthritis was 52.3%³⁰. Regarding SLE-related skin manifestations and LN, a cross-sectional study on 424 Malaysian patients with SLE showed that 64.5% and 44.5% of patients with SLE developed LN and mucocutaneous manifestations, respectively³¹. The proportion of patients with LN who progressed to end-stage renal disease (ESRD) over 5 years was obtained from a systematic review and Bayesian meta-analysis of 187 studies³³. It was assumed that 25% of the patients with ESRD were controlled by renal transplantation, whereas the remaining (75%) were managed by hemodialysis. A study of 918 patients with SLE demonstrated that 36% developed hypercholesterolemia as a risk factor for coronary artery disease³².

Five years’ time horizon was chosen as the end stage renal disease and most complications developed within 5 years³³.Our COI model included the economic consequences of infection risk and different types of flares within the SLE cohort. The annual proportion of patients with SLE developing flares and the average annual rates of mild, moderate, and severe flares per patient were retrieved from a real-world study of 2,227 newly diagnosed adult patients with SLE in the US³⁴. Based on a time-to-event analysis of 346 patients with SLE over 6.6 years, the risk of serious infection was 14.5%³⁵.

The adjusted effectiveness of pneumococcal vaccination due to the high risk of developing pneumonia from treatment with immunosuppressants was captured from a prospective multicenter study that aimed to assess its effectiveness among older adults³⁶.

Costs

The costs simulated in our model were (i) disease management costs, (ii) transient event costs, and (iii) indirect costs. Disease management costs represented treatments used for different SLE health states and disease follow-ups, whereas transient event costs included infection, management of flares, and SLE-related organ complications. Total healthcare costs were calculated by multiplying the resource use by the unit costs of each component. The resource use applied in our model was informed by the Delphi panel and based on local clinical practice in Malaysian healthcare settings. The costs of transient events were measured based on the mean resources used and the length of hospital stay, if needed, to manage a single event. All unit costs measured in Malaysian Ringgit (MYR) were retrieved from the Malaysian hospital system based on the financial year 2023. Local currency conversions to international dollar were performed using the purchasing power parity rate, sourced from the World Bank. Table 2 lists all the unit costs used in our model.

Table 2. The unit costs used in our model.

Cost parameters
	Base case	Low value	High value	References
(1) Disease management
Hydroxychloroquine 200 mg	MYR 0.5	0.4	1	Malaysian healthcare system
Methotrexate 2.5 mg	MYR 0.54	0.4	1
Folic acid 1 mg	MYR 0.004	0.0	0
Cyclosporine 100 mg	MYR 15.01	12	18
Cyclosporine 25 mg	MYR 3.74	3	4
Azathioprine 50 mg oral	MYR 0.87	1	1
MMF 500 mg oral	MYR 0.84	1	1
Cyclophosphamide 1 g vial	MYR 46.93	38	56
Quanti FERON	MYR 87	69	104
Vaccination against pneumococcus	MYR 120.75	97	145
Rituximab 500 mg/50 mL	MYR 3,402	2,722	4,082
Consultation	MYR 85	68	102
(2) Disease follow-up
KFT	MYR 80	64	96
LFT	MYR 100	80	120
Physician follow-up	MYR 83	67	100
CBC	MYR 58	46	69
C3 and C4	MYR 100	80	120
ESR	MYR 20	16	24
CRP	MYR 60	48	72
(3) Flares management
Prednisolone 20 mg	MYR 0.45	0	1
Prednisolone 5 mg	MYR 0.11	0	0
Methylprednisolone 500 mg iv.	MYR 46.90	38	56
Calcium carbonate	MYR 0.03	0.024	0.036
Cholecalciferol 800 iu (vitamin D)	MYR 0.89	0.712	1.068
(4) Infection management
Amoxicillin/clavulanate 500/125 mg	MYR 3.75	3	4
Chest radiograph	MYR 26.25	21	32
Hospital Ward	MYR 168	134	201
(5) Organ complications	Base case	Low value	High value
Celecoxib 200 mg	MYR 0.28	0	0
Lipid profile test	MYR 40.00	32	48
Mometasone 15 g	MYR 3.05	2	4
Ferrous sulphate 200 mg	MYR 0.21	0.2	0.3
Renal biopsy	MYR 2,725	2,180	3,270
Hemodialysis session	MYR 245	196	294
Perindopril 4 mg	MYR 0.06	0.05	0.07
Renal transplantation	MYR 7,250	5,800	8,700

Abbreviations. MMF, Mycophenolate mofetil; KFT, kidney function test; CBC, complete blood test; C3, Complement component 3; C4, Complement component; ESR, erythrocyte sedimentation rate; CRP, c-reactive protein; LFT, liver function test.

Indirect costs were measured with respect to productivity loss among living and deceased Malaysian patients with SLE. The average labor force among the Malaysian population in 2022 was reported by the World Bank³⁷. The proportion of patients with mild, moderate, and severe SLE who developed work impairment was obtained from a study of 689 patients with SLE in the US to evaluate the SLE-related burden on work productivity³⁸. The average monthly sick days per patient in our model were used in accordance with a study that evaluated productivity loss and work disability in 344 patients with SLE and 322 matched controls³⁹. The Malaysian patients’ average wage/hour was estimated from the gross domestic product published by the World Bank in 2022⁴⁰.

Treatment regimens and follow-up

According to the Delphi panel, the cornerstone for managing SLE in Malaysian patients, regardless of disease severity, was hydroxychloroquine. For patients with moderate and severe SLE phenotypes, immunosuppressants were added to hydroxychloroquine and oral corticosteroids to prevent SLE-related organ damage. However, patients with severe SLE received biologic medication (rituximab) in addition to hydroxychloroquine, immunosuppressants, and oral corticosteroids. Table 3 lists the treatment doses used in the model.

Table 3. The treatments doses and regimens.

Medication	Doses
Hydroxychloroquine	200 mg daily dose
Methotrexate	A single dose not to exceed 20 mg/week orally
Folic acid	1 mg oral everyday with methotrexate to decrease the risk for side effects
Cyclosporine	2.5 mg/kg/d (175 mg daily)
Azathioprine	2 mg/kg/d (140 mg daily)
MMF	2 g daily
Cyclophosphamide	500 mg IV every 2 weeks for 6 doses (3mos)
Rituximab	A course of 1,000 mg infusion and repeat after 2 weeks (course repeated every 24 weeks)
Amoxicillin/clavulanate	500/125 mg PO q12hr for 10 days
Prednisolone	0.25 mg/kg (Mild flares) 0.4–0.7 mg/kg (Moderate flares) 0.8 mg/kg (Severe flares)
Methylprednisolone	500 mg daily
Calcium/vitamin D supplement	1 tablet twice daily
Celecoxib	100 mg q12hr for 6 months
Perindopril	4 mg once daily
Ferrous sulfate	200 mg once daily

Abbreviation. MMF, mycophenolate mofetil.

The management of flares was dependent on its severity by GC; prednisone, then tapered to the least allowed daily dose to avoid the GC-related adverse events (AEs)^41–43. Furthermore, all flares were assessed by a rheumatologist. During severe flares, patients required a 3-day hospitalization as inpatients. Concomitant medications (calcium and vitamin D supplements) were administered to prevent GC-related AE.

Owing to nonspecific symptoms and the complexity of the disease, the interval between the onset of symptoms and the time to diagnosis is long (47 months)⁴⁴. Consequently, most patients with SLE develop signs of accrual-based organ damage at diagnosis. Therefore, SLE-related organ complications were simulated in our model from the 1st cycle. According to our Delphi panel, the most common types of SLE-related organ damage were arthritis, dyslipidemia, skin manifestations, LN, and anemia. The SLE-related arthritis was treated with celecoxib. As patients with SLE were at a high risk of developing renal and cardiac problems, the lowest dose of celecoxib was administered for the least duration (6 months)⁴⁵. Dyslipidemia among Malaysian patients with SLE required a cardiologist assessment every 6 months based on the lipid profile. Regarding SLE-related cutaneous manifestations, patients received topical steroids with dermatological follow-up once every 6 months. For patients with LN, a renal biopsy was conducted, followed by a case assessment by a nephrologist once every 6 months. Perindopril was administered to LN patients without ESRD. Ferrous sulfate was administered to patients who developed SLE-related anemia.

Sensitivity analyses

One-way sensitivity analysis was performed to ensure the robustness of the results. Various parameters were varied, with plausible values above or below the base-case values. The parameters tested were epidemiological, clinical, and unit cost data.

Results

The number of target Malaysian patients with SLE in the COI was 18,121. The numbers of SLE patients with mild, moderate, and severe phenotypes were 2,582, 13,897, and 1,642, respectively. Over a time horizon of 5 years, the disease management costs, including treatment of each phenotype and disease follow-up, were MYR 522 million, whereas the costs of transient events (infections, flares, and consequences of SLE-related organ damage) were MYR 155 million. Regarding disease management costs, SLE patients with moderate and severe phenotypes incurred higher costs than those with mild phenotypes. For instance, the disease management costs for mild SLE were MYR 9 million ($5,890,222), whereas they were MYR 137 million ($87,759,539) and 327 million ($208,812,542) for moderate and severe SLE, respectively.

The productivity loss costs among adult-employed Malaysian patients with SLE were estimated at MYR 1 billion. The total SLE cost in Malaysia over 5 years from both payer and society perspectives was estimated at MYR 678 million and 2 billion, respectively (Tables 4 and 5). The results showed a considerable cost burden due to productivity losses resulting from SLE-related morbidity and mortality (Figure 2). Over a 5-year time horizon, the costs per patient per year from the payer and society perspectives were 7,484 ($4,766) and 24,281($15,465), respectively.

Figure 2. The cost components of SLE burden from societal perspective.

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

The payer perspective
Total disease cost (MYR)	MYR 678,071,796 ($431,892,864)
Cost components	Disease management cost		Transient events cost
	MYR 522,892,350 ($ 333,052,451)		MYR 155,179,447 ($98,840,411)
The societal perspective
Total disease cost (MYR)	MYR 2,199,970,756 ($1,401,255,258)
Cost components	Disease management cost	Transient events cost		Indirect cost
	MYR 522,892,350 ($ 333,052,451)	MYR 155,179,447 ($98,840,411)		MYR 1,521,898,959 ($969,362,395)

Abbreviations. MYR, Malaysian Ringgit; SLE, Systemic lupus erythematosus.

Table 5. The components of the transient events cost over 5 years.

Transient events cost (MYR)
Infection	Mild-flares	Moderate flares	Severe flares	Organ damage	Total discounted Cost
926,890	843,787	1,836,006	1,364,646	153,480,601	155,179,447

Extrapolating the time horizon of the analysis to 10 years did not alter the conclusions reached on the basis of other analyses.

Sensitivity analyses

Deterministic sensitivity analyses were performed to test the robustness of the results. Tornado diagrams showed that the probability of moderate SLE in Malaysia was the most sensitive parameter that could affect the results from the payer’s perspective, whereas GDP per capita in Malaysia was the most sensitive parameter that could affect the results from a society perspective (Figures 3 and 4).

Figure 3. DSA of SLE burden from the payer perspective. The dark red color indicates low value of the output while the light grey color indicates the high value of the output. Abbreviations. DSA, deterministic sensitivity analysis; OS, overall survival; ESRD, end stage renal disease; SLE, Systemic lupus erythematosus.

Figure 4. DSA of SLE burden from the societal perspective. The dark blue color indicates high value of the output while the light grey color indicates the low value of the output. Abbreviations. DSA, deterministic sensitivity analysis; OS, overall survival; ESRD, end stage renal disease; SLE, Systemic lupus erythematosus.

Discussion

This study provides insights into the SLE-related financial burden on patients and the healthcare system, which can be used as an informative tool by policymakers regarding SLE and its related complications in the Malaysian population. Work impairment and loss of productivity are fundamental consequences of SLE⁴⁶. Bakar et al. evaluated the effects of SLE on daily life and work in 167 patients in Malaysia⁴⁶. Due to SLE, more than two-thirds of Malaysian patients reported impairments in their work and non-work daily life activities⁴⁶. Over 1 week, the rate of absenteeism was 10.4% (17 patients), accounting for an indirect cost of MYR 2,875.17⁴⁶. The study showed that SLE leads to impairment in all health-related QoL domains, especially the limitation of the physical health of Malaysian patients⁴⁶.

Outside Malaysia, various studies have examined the influence of SLE on productivity^47,48. A COI study by Jönsen et al. conducted in Sweden on 1,029 patients with SLE concluded that the total annual cost of SLE was $188 million, of which 70% and 30% were indirect and direct costs, respectively⁴⁷. These results are similar to those of another study in Sweden, which stated that indirect costs accounted for 72% of the total cost of SLE⁴⁸.

The severity of SLE is a crucial factor in determining disease cost⁴⁹. The risk of developing flares increases among patients with SLE with a high disease activity status, which leads to the addition of other medications to control disease activity⁴⁹. In Malaysia, higher disease activity, flares, and SLE-related complications such as LN were among the significant predictors of impairment in work and non-work activities⁴⁶. In Sweden, higher disease activity was a cost driver for patients with SLE⁴⁷. For instance, higher disease activity resulted in a 50% increase in direct and indirect costs⁴⁷. The annual cost for patients with severe SLE in the US from 2012 to 2015 was $52,951, whereas the mean annual cost for patients with moderate and mild SLE was $28,936 and $21,052, respectively⁵⁰.

As LN is the most common manifestation of SLE⁵¹, it accounts for a high economic burden and HCRU⁵². Bell et al. evaluated the LN-related costs in the US⁵³. Compared with SLE without LN, the LN cohort incurred a higher all-cause HCRU⁵³. For instance, the mean numbers of ambulatory and emergency room visits for the LN cohort were 53.9 and 2.9, respectively, and 33 and 1.6, respectively, for the non-LN cohort⁵³. Therefore, the all-cause cost of LN ($50,975) was higher compared to SLE without LN ($26,262)⁵³.

Due to the clinical course of the disease, the psychological effect of SLE on both patients and caregivers is an important aspect to consider⁵⁴. Patients diagnosed with SLE experience pain, anxiety, or stress, and may need psychosocial support for their health complains⁵⁴. It was also reported that any increase in disease activity is associated with an increase in productivity loss for patients with SLE and their caregivers⁵⁵. Social and financial factors affect the caregivers of patients with SLE⁵⁵. It was shown that SLE had an impact on patients’ caregiver working hours. Owing to caregiver responsibility, employed caregivers reported that they missed 12.8% of their paid work time⁵⁵, whereas almost half (49.4%) experienced an inability to socialize with friends⁵⁵. In addition, 97.6% of the caregivers reported stress and anxiety related to their responsibilities as caregivers⁵⁵.

Owing to the clinical course of the disease, organ damage is inevitable in patients with SLE⁵⁶. Organ damage is considered a significant parameter for poor health outcomes and increased financial burden^11,57. For instance, the 10-year cumulative costs of SLE patients with high organ damage (SDI scores ≥5) were approximately nine times higher compared to patients with the least organ damage (SDI scores of 0)⁵⁷. A population-based study conducted in Taiwan demonstrated that patients with renal, neuropsychiatric, and pulmonary system damage had the highest annual medical spending of US$15,750, US$31,894, and US$24,839, respectively¹².

To our knowledge, this is the first prevalence-based COI study in Malaysia to demonstrate the real burden of SLE from a payer and society perspective, which aimed to inform decision-makers about the unmet needs of patients with SLE and the urgent need for novel SLE medications. In comparison with other upper middle income countries (under publication), the total disease cost per malaysian patient per year in our study is US$15,465 (less than US$33,528 in Colombia and higher than US$8,831 in Mexico), this is due to the government health care reforms planned recently⁵⁸. Our study has several strengths and limitations. The strengths include the fact that we utilized local data on Malaysia from the literature. Furthermore, all inputs were validated using our Delphi panel. Therefore, the results of our study could be generalized to Malaysia, as we included the consensus of the reputable Delphi Panel in Malaysia to ensure that it simulates local practice and the patient’s journey in the healthcare system. However, data regarding the percentage of patients with mild, moderate, and severe SLE who experienced work impairments were lacking. Therefore, we relied on international data validated by a Delphi panel. In addition, the estimation of the annual proportion of patients with SLE developing flares and the average annual rates of mild, moderate, and severe flares per patient are also lacking in Malaysia. Therefore, we relied on a real-world study of 2,227 newly diagnosed adult patients with SLE and validated these parameters using a Delphi panel.

Conclusion

Our study demonstrated the substantial economic consequences of SLE in Malaysia over a time horizon of 5 years. The reason behind this was the consequences of economic loss, as it affects women and men of working age, in addition to the costs of SLE management and its consequences, such as flares, infection, and organ damage. Furthermore, our COI indicated that disease management costs among patients with higher disease severity were higher than those among patients with a mild phenotype. Hence, more attention should be paid to limiting the progression of SLE and the occurrence of flares, with the need for further economic evaluations of novel treatment strategies that could help in disease control.

Transparency

Author contributions

GE, KT involved in building the concept and design, AJ, MZ, HY, LI involved in analysis and interpretation of the data; GE draft the paper, AJ, MZ, HY, LI, AM, TL, KT revised it critically for intellectual content; and the final approval of the version to be published; and that all authors agree to be accountable for all aspects of the work.

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.

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.

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.