Clinical and economic burden of systemic lupus erythematosus in Colombia

Abstract

Aims

Our cost-of-illness (COI) model adopted payer and societal perspectives over five years to measure the economic burden of Systemic Lupus Erythematosus (SLE) in Colombia.

Materials and methods

A prevalence-based model was constructed to estimate costs and economic consequences for SLE patients in Colombia. The model included four health states: three phenotypes of SLE representing mild, moderate, and severe states and death. The clinical inputs were captured from the published literature and validated by the Delphi panel. Our model measured direct medical and indirect costs, including disease management, transient events, and indirect costs. One-way sensitivity analysis was also performed.

Results

The number of Colombian SLE patients was 37,498. The number of SLE patients with mild, moderate, and severe phenotypes was 5343, 28757 and 3,397, respectively. SLE-patients with moderate (Colombian pesos; COP 146 billion) and severe phenotypes (COP276 billion) incurred higher costs than those with mild phenotypes (COP2 billion), over 5 years. The total SLE cost in Colombia over five years from the payer and societal perspectives was estimated to be COP 915 billion and 8 trillion, respectively. The costs per patient per year from the payer and societal perspectives were COP 4,881,902 ($3,510) and COP 46,637,054 ($33,528), respectively.

Conclusion

The burden of SLE in Colombia over five years is substantially high, mainly due to the consequences of economic loss because 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. Our COI indicated that disease management costs among patients with moderate and severe SLE were substantially higher than those among patients with a mild phenotype. Therefore, more attention should be paid to limiting the progression of SLE and the occurrence of flares, with the need for further economic evaluation of novel treatment strategies that help in disease control.

Keywords:

• Colombia
• SLE
• costs
• economic burden
• consequences

JEL Classification Codes:

• C51
• C5
• C
• H51
• H5
• H

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease in which autoantibodies and immune complexes damage several body organs¹. SLE is a complex disease characterized by a wide spectrum of clinical manifestations with a relapsing-remitting course². SLE patients live with frequently experienced flares and persistent symptoms. SLE flares are defined as increases in disease activity that cause new or worse clinical symptoms or laboratory measurements in one or more organs over a defined period³. Flares can cause progressive and irreversible damage⁴. The incidence of flares is in 15.3 per 100 patients per year⁵.

SLE causes physical and functional disabilities that affect disease control, leading to high morbidity and mortality rates. The disease also affects the patient’s quality of life (QoL). Frequent physician visits, laboratory tests, hospitalization, side effects of treatment, pain, fatigue, and anxiety put patients in a stressful situation⁶. Depression affects 39% of patients, whereas anxiety impacts 24%⁷.

The World Health Organization ranks Colombia healthcare system as the 22nd most efficient in the world, above Canada, and the United States. Colombia has universal public healthcare funding that covers around 95% of the population⁸. It has one public and many private health insurance plans which improved the treatments access. Colombia spends 8.1% of its gross domestic product on health, compared to 9.2% on average in the Organization for Economic Cooperation and Development (OECD). Colombia performs better than the OECD average on 50% of health indicators⁸.

Globally, SLE is more common in women, with a ratio of 9:1, and mainly affects individuals aged 15–45 years⁹. The global incidence of SLE is estimated as 5.14 per 100,000 person -years, while the annual number of newly diagnosed patients is estimated to be 0.40 million patients¹⁰. Colombia is characterized by high disease prevalence. In 2017, the SLE prevalence in Colombia was 54.47 cases per 100,000⁹. This study also reported that 87.4% of patients were women, and 12.6% were men⁹.

The most common clinical features of SLE include mucocutaneous lesions, renal involvement, arthritis, hematological disorders, fever and serositis². Joint manifestations were found in approximately 80.4% of the patients¹¹. The hematological manifestations include thrombocytopenia, anemia, and leukopenia¹². Among SLE patients, the risk of developing myocardial infarction (MI) is 2–10-folds than that in the general population¹³.

A serious infection requires hospitalization or leads to death¹⁴. Serious infections cause approximately one-third of SLE deaths¹⁴. The lower respiratory tract, skin, and urinary systems are the most common sites¹⁵. Further, patients who develop serious infections have a 12 times increase in hospitalization rates than those without SLE¹⁵. Other common manifestations of SLE are neuropsychiatric symptoms such as severe headache, seizure disorder, psychosis, acute confessional state, and cognitive dysfunction². Approximately 80% of patients with SLE develop cognitive impairment¹⁶. These are among the most challenging manifestations of SLE, and their management remains an important and unmet need among patients¹⁴.

Furthermore, SLE significantly affects the renal system¹⁴. It has been estimated that 40–70% of patients with SLE develop lupus nephritis (LN)². LN is one of the most severe clinical manifestations of SLE and is associated with the progression to end-stage renal disease (ESRD), accrual of organ damage, and high mortality¹⁴. Approximately 10–30% of patients with LN progress to ESRD¹⁷. LN continues to be a major cause of morbidity and mortality despite all available treatment options¹⁴. Additionally, LN was compared to other chronic health conditions among patients with SLE and was shown to be the costliest condition¹⁸.

SLE poses a significant economic burden on Colombia⁹. A study conducted in Colombia showed that the total annual direct cost per SLE patient was $2,172⁹.

SLE is associated with significant direct and indirect costs¹⁹. Direct medical costs include medications, follow-up tests, physician visits, and hospitalizations, whereas indirect costs include productivity loss due to the impact of the disease on the physical and mental status of the patients. Early diagnosis of SLE can result in a lower rate of flares, resource utilization, and total healthcare costs²⁰.

Objective

This cost-of-illness (COI) model outlines the state of knowledge with respect to the economic burden and costs of SLE regarding the management of disease, follow-up, and complications in Colombia. We adopt the perspectives of payers and society over five years. To meet the study objectives, our analysis was based on the prevalence of SLE in the Colombian population.

Methodology

This COI model was established using Microsoft Excel® 365 to estimate the costs and economic consequences of SLE for patients after diagnosis in Colombia. Upon SLE diagnosis, patients were categorized as mild, moderate, or severe based on the severity of clinical manifestations according to the British Isles Lupus Assessment Group (BILAG) and physician interpretation²¹. Owing to variations in the severity of SLE, each health state in the model has different costs. Therefore, disease costs were calculated based on SLE progression using a state transition model. The model structure was based on the most standardized local clinical practice in Colombia, as captured by the local Delphi panel. This Delphi panel composed of six experts; four reputable rheumatologists affiliated to the National University of Colombia hospitals and Hospital Italiano de Buenos Aires, Bogota, Colombia and two health economists. We collected insights from experts through three rounds meetings by using the quasi-Delphi panel approach. The experts’ insights included the current local clinical practice and treatment patterns within the Colombian healthcare settings. SLE cost quantification was simulated using the most commonly used approach in COI, which is a prevalence-based approach. Using this method, the estimated disease cost was calculated over five years.

The prevalence of SLE among the Colombian population was extracted from an epidemiological study that utilized data collected by the Integrated Social Protection Information System (SISPRO) to estimate the SLE prevalence in Colombia from 2012 to 2016²². The target population in our model comprised Colombian adults aged 15 years or older who were diagnosed with SLE. The total Colombian population aged 15 years or older was extracted using the most recently published total population data by the World Bank for 2022^23,24.

Our model included four health states: (i) the three phenotypes of SLE representing mild, moderate, and severe SLE and (ii) death. During the course of the disease, SLE patients can experience transient events such as flares, infection, and complications due to SLE-related organ damage. The percentages of SLE patients at mild and moderate states after diagnosis were extracted from a study that utilized patient data through 1,375,863 medical records (SLE population =21,993 individuals) on the Colombian contributive health system between 2014 and 2017⁹. At any time after diagnosis, patients might transition to a health state of higher disease severity (e.g. from mild to moderate/severe or from moderate to severe). The transition to a health state of higher disease severity was extracted from a study that evaluated 462 patients over a median follow-up of 36 months to describe the transition in disease severity²⁵. Figure 1 illustrates the model used in the COI study.

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

This manuscript is reported according to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement²⁶. The inputs were obtained from a literature review of all the clinical trials and validated using the Delphi panel. The Delphi consensus included commonly used treatment strategies for SLE patients within the Colombian healthcare system.

Transitions to a health state of higher disease severity were assumed to occur in a four-week cycle period. To adjust the cost distribution through the model, a half-cycle correction was applied based on the International Society for Health Economics and Outcomes Research (ISPOR) modeling recommendations²⁷.

Both the payer and societal perspectives include disease management and transient event costs; the societal perspective also includes indirect costs. Costs were discounted at a rate of 5% in the base case (mean value), as recommended in other economic evaluations conducted in Colombia^28,29.

Clinical inputs

The model simulated Colombian SLE patients at diagnosis over five years. The target Colombian SLE population in our COI study weighed an average of 70 kg, validated from our Delphi panel. The Colombian population aged 15 years or more (40,802,585) was estimated using the most recent published total population data by the World Bank in 2022^23,24. According to the national record report of 41,804 SLE patients in Colombia, the estimated prevalence of SLE in Colombia is 91.9/100,000 subjects²². Therefore, the number of SLE patients among the adult Colombian population ≥ 15 years was 37,498.

Our model represents the different health states of SLE. During disease diagnosis, patients are categorized into one of the three health states of SLE: mild, moderate, or severe SLE. The percentages of Colombian SLE patients after diagnosis into mild (14.25%) or moderate (76.69%) SLE were extracted from a study that assessed databases of the Colombian contributive health system for 2014–2017⁹. The probability of severe SLE during diagnosis was calculated as follows: 1- (sum probabilities of mild and moderate SLE).

The transition probabilities from a living health state (different SLE phenotypes/states) into an absorbing health state were extracted from a case-control study in January 2013 and December 2020 that assessed 72 SLE patients, of which 15 had hematological malignancies, and 57 had no hematological malignancies³⁰. An extrapolation of overall survival (OS) Kaplan–Meier’s (KM) curve of SLE patients without hematological malignancies was performed to evaluate lifetime patient-level data based on parametric models³⁰. Plausible fits for the OS curves were obtained using an exponential parametric function. 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:
Target population ≥ 15 years	40,802,585	32,642,068	48,963,102	^23^,^24
Prevalence of SLE (%)	0.0919%	0.07%	0.11%	^22
Percentage of mild SLE (%)	14%	11%	17%	^9
Percentage of moderate SLE (%)	77%	61%	92%
(B) Baseline patient characteristics:
Weight (Kg)	70	56	84	Delphi panel
Hematologic manifestations (%, anemia)	50%	40%	60%	^31
Joint manifestations (%, arthritis)	80%	64%	96%	^11
Skin manifestations (%)	73%	59%	88%
Cardiovascular manifestations (%)	37%	29%	44%	^32
Renal manifestations (%)	51%	40%	61%	^33
Renal patients progressed into ESRD (%)	14%	11%	16%	^34
(C) Clinical parameters: (1) Transition to more severe state:
Mild to moderate SLE (%)	29.10%	23%	35%	^25
Mild to severe SLE (%)	20.70%	17%	25%
Moderate to severe SLE (%)	29.40%	24%	35%
(2) OS
OS: exponential λ	−0.0036407	−0.0029	−0.0044	^30
(3) Risk of flares
SLE patients experience flares annually (%)	95%	76%	114%	^35
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%	12%	17%	^36
(D) Discount rate:
Discount rate	5%	4%	6%	^28^,^29
(E) Indirect cost parameters:
Labor force among population ≥ 15 years (%)	63.60%	51%	76%	^37
Work productivity impairment among mild-SLE (%)	15%	12%	18%	^38
Work productivity impairment among moderate-SLE (%)	38%	30%	46%
Work productivity impairment among severe-SLE (%)	50%	40%	60%
Mean monthly sick days per patient	2.3	1.8	2.8	^39
Colombian GDP per capita (COP)	18802572	15042058	22563086	^40

Abbreviations. SLE, Systemic lupus erythematosus; ESRD, end stage renal disease; OS, overall survival; GDP, gross domestic product; COP, Colombian pesos; λ, lambda.

According to the Delphi panel and literature review, most Colombian SLE patients suffered from hematologic manifestations (anemia), joint manifestations (arthritis), skin manifestations, cardiovascular disease (CVD), and LN. The percentage of SLE patients with anemia (50%) was extracted from a review of chronic diseases in SLE patients³¹. Joint and skin manifestations were captured from a cross-sectional study that assessed 1,175 Colombian SLE patients and showed that 80.4% and 73.4% of Colombian SLE patients experienced joint and skin manifestations, respectively¹¹. Regarding CVD, a cross-sectional study of 310 Colombian SLE patients and a systematic review of CVD in Latin American SLE patients showed that 36.5% of Colombian SLE patients experience CVD³². The LN estimate (50.5%) was obtained from a cross-sectional multicenter study that followed 467 Colombian SLE patients³³. The number of LN patients who progressed to ESRD within five years (average of 16% and 11%) was extracted from a systematic review and Bayesian meta-analysis that assessed the risk of ESRD in LN adults patients from 1971 to 2015 among 187 studies³⁴. Based on the Delphi panel, we assumed that 25% of ESRD were managed with renal transplantation, while 75% were managed with hemodialysis.

Our model simulates the economic consequences of different types of flares in SLE patients. The annual percentage of SLE patients experiencing flares (95.1%) and the mean annual frequency rates of mild (1.1), moderate (2.2), and severe (0.2) flares per patient were extracted from a retrospective study that evaluated flares among 2,227 newly diagnosed SLE adult patients in the United States (US) from 2005 to 2014 to demonstrate flare frequency and severity³⁵. The risk of serious infection (14.5%) among SLE patients was extracted from a time-to-event analysis that evaluated 346 SLE patients with SLE over a follow-up of 6.6 years³⁶.

Costs

The costs measured in our model are disease management, transient events, and indirect costs. Disease management costs included treatments used for different SLE health states and disease follow-up, whereas transient event costs included the management of flares, infections, and SLE-related organ damage. Total healthcare costs were measured by multiplying resource use by the unit costs of each component. Resource use during routine follow-ups was informed by the Delphi panel and was based on local clinical practice in Colombian healthcare settings. Transient event costs were calculated based on the average resources used and the length of hospital stay, if needed, to treat a single event. All unit costs measured in Colombian pesos (COP) were obtained from the Colombian hospital system based on the financial year 2023. Local currency conversions to international dollar were performed for comparability of results among countries using the purchasing power parity rate, sourced from the World Bank. Table 2 includes all the unit costs used in our model.

Table 2. The model unit costs.

Cost parameters
	Base case	Low value	High value	References
(1) Disease management
Hydroxychloroquine 200 mg	COP 496	397	595	Colombian healthcare system
Methotrexate 10 mg	COP 2,604	2,083	3,125
Folic acid 1mg	COP 1,080	864	1,296
Cyclosporine 100 mg	COP 8,600	6,880	10,320
Cyclosporine 50 mg	COP 3,639	2,911	4,366
Cyclosporine 25 mg	COP 1,863	1,490	2,236
Azathioprine 100 mg	COP 2,250	1,800	2,700
Azathioprine 50 mg	COP 1,125	900	1,350
MMF 500 mg	COP 2,400	1,920	2,880
Herpes vaccination	COP 400,000	320,000	480,000
Covid 19 vaccination	COP 44,654	35,723	53,585
Hepatitis B vaccination	COP 35,500	28,400	42,600
Influenza vaccination	COP 48,800	39,040	58,560
Rituximab 500 mg/50 mL	COP 2,369,920	1,895,936	2,843,904
(2) Disease follow-up
KFT	COP 21,000	16,800	25,200
CBC	COP 5,000	4,000	6,000
C3 and C4	COP 47,000	37,600	56,400
Anti-dsDNA antibodies	COP 59,000	47,200	70,800
ESR	COP 21,000	16,800	25,200
CRP	COP 21,000	16,800	25,200
Ophthalmologist visit	COP 50,000	40,000	60,000
Rheumatologist visit	COP 170,000	136,000	204,000
Dermatologist visit	COP 110,000	88,000	132,000
Hematologist visit	COP 70,000	56,000	84,000
Nephrologist visit	COP 150,000	120000	180,000
Cardiologist visit	COP 65,000	52,000	78,000
(3) Flares management
Prednisone 10 mg	COP 467	374	561
Prednisone 20 mg	COP 934	747	1,121
Prednisone 5 mg	COP 234	187	280
Methylprednisolone 1 g	COP 26,478	21,182	31,774
ICU day	COP 2,458,848	1,967,078	2,950,618
Ward day	COP 150,000	120,000	180,000
Lipid profile	COP 68,000	54,400	81,600
Calcium salts with vitamin D3 oral supplement	COP 471	377	565
Densitometry	COP 100,000	80,000	120,000
Blood glucose test	COP 4,900	3,920	5,880
(4) Infection management
Piperacillin tazobactam 4.5 g	COP 21,438	17,150	25,726
(5) Organ complications	Base case	Low value	High value
X-ray for joint	COP 36,000	28,800	43,200
Topical retinoids	COP 7,660	6,128	9,192
Ferrous sulphate 100 mg oral	COP 2,298	1,838	2,757
Renal biopsy	COP 500,000	400,000	600,000
Hemodialysis session	COP 400,000	320,000	480,000
Enalapril 5 mg tab.	COP 43	34	52
ECHO	COP 250,000	200,000	300,000
Renal transplantation cost	COP 35,000,000	28,000,000	42,000,000
Aspirin 100 mg tab.	COP 259	207	311

Abbreviations. MMF, Mycophenolate mofetil; ECHO, echocardiogram; ICU, intensive care unit; KFT, kidney function test; CBC, complete blood test; C3, Complement component 3; C4, Complement component; ESR, erythrocyte sedimentation rate; CRP, c-reactive protein; Anti-d DNA, Anti-double stranded DNA.

The indirect costs were measured in terms of productivity losses. The average labor force among the Colombian population aged 15 years and older (63.6%) was published by the World Bank in 2022³⁷. We assumed that most patients are in the productive age (18–52 years) while the retirement age for men in Colombia is 62, and for women, it is 57 according to our Delphi panel. The percentage of mild, moderate, and severe SLE patients who experienced work impairment was extracted from a study conducted in the US to assess 689 SLE patients to determine SLE-burden on work productivity³⁸. The mean monthly sick days per patient were extracted from a study that evaluated work disability and lost productivity in 344 SLE patients and 322 matched controls using a questionnaire³⁹. The Colombian average wage per hour was estimated using the most recently published gross domestic product (GDP) published by the World Bank for 2022⁴⁰. We used the equation below:

Work productivity lost per month = number of employed persons in Colombia X percentage of mild, moderate, or severe SLE in patients who experienced work impairment X number of mean monthly sick days per patient X monthly patient wages.

Treatment regimens and follow up

Hydroxychloroquine is the cornerstone for managing SLE in Colombian patients, regardless of disease severity. In patients with moderate or severe SLE, immunosuppressants are added to hydroxychloroquine to prevent organ damage. After prolonged therapy, some patients may experience slow tapering of immunosuppressants⁴¹. Furthermore, severe SLE patients received biological medications (rituximab), hydroxychloroquine, and immunosuppressants. At the time of diagnosis, the patient received only one immunosuppressant. As the choice of immunosuppressant was based on disease manifestations, we considered the average cost of commonly used immunosuppressants (methotrexate, cyclosporine, azathioprine, and mycophenolate mofetil [MMF]) in our model. Before the initiation of immunosuppressant therapy, patients were vaccinated against seasonal influenza (annually), herpes, COVID-19 and hepatitis B. Table 3 shows the treatment doses used in our model (some treatments are based on patient weight).

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 with methotrexate to decrease the risk for side effects
Cyclosporine^a	2.5mg/kg/d (175 mg daily)
Azathioprine^a	2 mg/kg/d (140 mg daily)
MMF	2 g daily
Rituximab	0.5 to 1.0 g at days 1 and 15, then repeat course q24weeks (2 infusion per year)
Piperacillin tazobactam	4.5 g q6hr
Prednisolone^a	0.2 − 0.4 mg/kg (Mild flares) 0.4 − 0.7 mg/kg (Moderate flares) 0.8 mg/kg (Severe flares)
Methylprednisolone	1 g daily
Calcium/vitamin D	1 tablet twice daily
Aspirin	100 mg once a day
Enalapril	5 mg once daily
Ferrous sulfate	100 mg once daily

Abbreviation. MMF, mycophenolate mofetil.

^a Some treatments are based on patient weight.

According to the Delphi panel, SLE patients must be followed up frequently. Disease follow-up depends on the severity of SLE. An annual ophthalmologist visit is required for hydroxychloroquine treatment. Regular follow-up (complete blood count [CBC], kidney function test [KFT], erythrocyte sedimentation rate [ESR], and C-reactive protein [C-RP]) for patients with mild, moderate, and severe SLE was performed every 6, 3, and 1 month, respectively. The most common type of infection in Colombia was pneumonia, which required hospitalization and treatment with piperacillin-tazobactam for an average of 10 d.

In the case of flares, patients were managed according to flare severity by glucocorticoid (GC; prednisone) and tapered to the least allowed daily dose to avoid adverse events (AEs) of GC^42,43. The duration of the initial prednisone dose was 2 weeks and tapered once every 2 weeks (5 mg decrement)⁴⁴. Furthermore, mild and moderate flares required follow-up with complement component 3 (C3), complement component 4 (C4), anti-double stranded DNA (anti-dsDNA), and rheumatology visits every month and every other week, respectively. Severe flares required hospitalization (2 weeks in the intensive care unit and 2 weeks in the general ward). During severe flares, patients were followed-up weekly using C3/C4 and anti-dsDNA. Concomitant medications (calcium/vitamin D supplements) were administered as protection against GC AEs with annual assessment by densitometry, lipid profile, and blood glucose.

Owing to disease heterogeneity and non-specific symptoms, the interval between the onset of symptoms and the time to diagnosis is long (mean duration = 47 months)⁴⁵. Therefore, most SLE patients experience signs of acute organ damage at diagnosis. Our model utilized SLE-related organ complications that occurred during the first cycle. The most common SLE-related organ damages were arthritis, CVD, cutaneous manifestations, LN, and anemia. For SLE-related arthritis, patients required an assessment conducted once at baseline using radiography. Manifestations of CVD were controlled by the administration of aspirin, with a cardiologist’s follow-up every four months, and an echocardiogram (ECHO) was performed annually. SLE-related cutaneous manifestations were controlled using topical retinoids, with dermatological follow-up once every four months. Patients with LN underwent renal biopsy to confirm the diagnosis; subsequently, case assessment by a nephrologist at follow-up was performed once every four months. For LN patients without ESRD, enalapril was administered. For those who developed SLE-related anemia, ferrous sulfate was administered with hematological follow-up once every four months.

Sensitivity analysis

One-way sensitivity analysis was performed to ensure the robustness of the results. The various parameters were varied by 10–20% above or below their base-case values. The parameters tested were epidemiological data, clinical parameters, and unit cost data for all treatments.

Results

The number of target Colombian SLE patients with SLE in our COI was 37,498. At diagnosis, the number of SLE patients with mild, moderate, and severe phenotypes was 5,343, 28,757 and 3,397, respectively. Over a period of five years, the disease management costs, including treatment of each phenotype and disease follow-up, were COP 495 billion, while the costs of transient events (infections, flares, and consequences of SLE-related organ damage) were 420 billion (Table 4). 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 COP 2 billion ($1,935,136), while those for moderate and severe SLE were COP 146 billion ($105,645,004) and 276 billion ($198,440,266), respectively, over 5 years. The annual costs per patient from the payer and societal perspectives were COP 4,881,902 ($3,510) and COP 46,637,054 ($33,528), respectively.

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

The payer perspective (indirect cost is not covered)
Total disease cost (COP)	COP 915,297,518,773 (US$ 658,014,032)
Cost components	Disease management cost		Transient events cost
	COP 495,461,850,539 (US$ 356,191,122)		COP 419,835,668,234 (US$ 301,822,910)
The societal perspective
Total disease cost (COP)	COP 8,743,882,385,893 (US$ 6,286,040,536)
Cost components	Disease management cost	Transient events cost		Indirect cost
	COP 495,461,850,539 (US$ 356,191,122)	COP 419,835,668,234 (US$301,822,910)		COP 7,828,584,867,120 (US$ 5,628,026,504)

Abbreviations. COP, Colombian Peso; SLE, Systemic lupus erythematosus; US$, united states or international dollar.

Productivity loss costs among adult-employed Colombian SLE patients were estimated at COP 7.8 trillion. The total SLE cost in Colombia over five years from both payer and societal perspectives was estimated to be COP 915 billion and 8 trillion, respectively (Table 4). The results showed a huge cost burden due to productivity losses resulting from SLE-related morbidity and mortality (Figure 2). Extrapolating the time horizon of the analysis to10 years did not alter the conclusions reached on the basis of other analyses. Figure 3 shows that moderate SLE employed patients have increased costs than the other types of severity in the first months of the patient journey.

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

Figure 3. One-way sensitivity analyses for SLE cost from payer perspective over 5 years. Abbreviations. OS: overall survival, ESRD: end stage renal disease, SLE: Systemic lupus erythematosus.

Sensitivity analysis

One-way sensitivity analysis was conducted to test the uncertainty of the results. Tornado diagrams showed that the number of SLE patients in Colombia and the number of employed persons were the most sensitive parameters that could have affected the results (Figures 4 and 5).

Figure 4. One-way sensitivity analyses for SLE cost from societal perspective over 5 years. Abbreviations. OS, overall survival; ESRD, end stage renal disease; SLE, Systemic lupus erythematosus.

Figure 5. The productivity lost costs among SLE employed patients over 5 years.

Discussion

The economic burden of SLE ranges from the management of the disease to that of transient events, such as flares, infections, and consequences of organ damage up to the end of life. Our results simulated the total cost of SLE over 5 years in Colombia from payer and societal perspectives. The results indicated that the highest burden of SLE lies in productivity loss, followed by disease management and transient event costs, reflecting the urgent need for novel therapeutic strategies to improve patients’ QoL and decrease the total SLE burden on patients, society, and the economy in Colombia.

SLE is associated with a significant burden related to the frequent use of medical resources and loss of productivity for patients and their caregivers⁴⁶. A Canadian study conducted to estimate the economic burden of the disease showed that the mean annual costs of SLE and non-SLE per case were $7,740 and $2,479 respectively⁴⁷. Compared to non-SLE, SLE patients frequently utilize resources⁴⁷. For instance, the average costs per case of inpatient hospital services and emergency department services were 2.3 and 2.1 folds higher than those of non-SLE, respectively⁴⁷. The economic burden of SLE has been assessed in several countries. A tri-national study surveyed 715 SLE patients (from the US, Canada, and the UK) and showed that cumulative indirect costs accounted for almost 74% of the total costs⁴⁸. Thus, the indirect cost of SLE is a major component of the economic burden of the disease in many countries.

Increased disease severity and the development of relapses or flares have a significant direct impact on total costs. A study conducted at the Japan Medical Data Center over three years showed that the cost for SLE patients increased as the severity of SLE increased⁴⁹. For mild SLE patients, the total medical cost over three years was $5,549; for moderate and severe SLE, the costs were estimated as $15,290 and $43,322, respectively⁴⁹.

The presence of ESRD in SLE is a major risk factor for increased resource utilization, morbidity, and mortality⁵⁰. A study of SLE patients with renal complications showed that the total annual medical expenditure for patients with SLE with renal insufficiency (nephritis) was $58,389 for SLE with nephritis, while it was $11,527 for non-SLE (difference: $46,862)¹⁸. Furthermore, developing LN was associated with a 7.5 folds increase in the annual direct costs per patient compared to SLE patients without LN⁵¹.

Almost all patients with SLE (95.6%) develop at least one flare episode⁴⁹. A US study was conducted to estimate the costs associated with different flare severities in SLE patients⁵². The results showed that the annual medical costs were $6,607 for SLE patients without flares and $7,079, $10,471, and $25,118, respectively, for SLE patients with mild, moderate, and severe flares⁵².

SLE negatively affects patient productivity. A study conducted among US patients with SLE showed that within an average disease duration of 13 years, 49% of employed patients experienced work loss³⁸. A Swedish study was conducted to compare the cost of SLE patients to that of a control group over eight years⁵³. The results showed that the number of annual sick leaves (i.e. one leave lasting 5 d) was 100 for SLE patients but 36 for the control group⁵³. Therefore, it resulted in an increased productivity loss cost of $ 18,000 for SLE patients compared to $7,000 for the control group⁵³.

SLE mortality is unacceptably high, being 2.6-fold higher than that in the general population⁵⁴. This increase in mortality rate is associated with disease complications, comorbidities, and infections⁵⁵. A study conducted among adults and children with SLE showed that infection was the main cause of death in these patients⁵⁶. Deaths due to infections in high- and low/middle-income countries were 15.1% and 37.5%, respectively⁵⁶. Furthermore, CVD accounts for 11.3% of deaths in high-income countries and 10.6% in low/middle-income countries⁵⁶.

To our knowledge, this is the first prevalence-based COI study in Colombia to simulate the real burden of SLE from a payer and societal perspective, which aimed to inform decision-makers about the unmet needs of SLE and the urgent need for novel SLE medications. Our study has several strengths and limitations. The strengths of this study include the fact that the prevalence of SLE in Colombia was extracted from an epidemiological study that utilized data from a Colombian population. Moreover, the results of our study could be generalized to Colombia, as we included the consensus of the reputable Delphi Panel in Colombia to ensure that it simulates local practice and the patient’s journey in the healthcare system. Our study has some limitations. Local data regarding the estimation of the percentage of flares in SLE patients, the percentage of mild, moderate, and severe SLE patients who experienced work impairment and the mean monthly sick days per patient are lacking. Therefore, we relied on international credible evident data and validated these parameters using a Delphi Panel.

Conclusion

The burden of SLE in Colombia over five years is substantially high, mainly due to the consequences of economic loss because 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. Our COI indicated that disease manage-ment costs among patients with moderate and severe SLE were substantially higher than those among patients with a mild phenotype. Therefore, more attention should be paid to limiting the progression of SLE and the occurrence of flares, with the need for further economic evaluation of novel treatment strategies that help in disease control.

Transparency

Author contributions

GE, GQ involved in conception and design, PS involved in interpretation of the data; GE draft the paper, DF, GQ 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 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.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.