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Direct Medical Costs and Healthcare Resource Utilization of Treating Patients With Two Clinical Subtypes of Axial Spondyloarthritis in Colombia

Open AccessPublished:September 21, 2022DOI:https://doi.org/10.1016/j.vhri.2022.08.003

      Highlights

      • This is the first study that evaluated the direct medical costs associated to axial spondyloarthritis (axSpA) in Colombia.
      • Patients with a radiographic spondyloarthritis have 7.2 times the cost of patients with the nonradiographic variant of axSpA.
      • Costs associated to medications accounted for 97.6% of total costs. Comprehensive management of axSpA would be considered for the reduction of costs without compromising quality of care.

      Abstract

      Objectives

      This study aimed to calculate the healthcare resource utilization and direct medical costs in patients with 2 subtypes of axial spondyloarthritis (axSpA) in a rheumatic care center in Colombia.

      Methods

      This is a retrospective cost-of-illness study. Patients with at least 1 medical consultation associated with an axSpA diagnosis between October 2018 and October 2019 were identified. Patients were classified as having radiographic (r-axSpA) or nonradiographic axSpA (nr-axSpA). Direct medical costs were calculated in Colombian pesos and expressed in American dollars using an exchange rate of 3263 Colombian pesos = 1 US dollar ($). Predictors of total direct costs were identified using a generalized linear model with gamma distribution and log-link.

      Results

      A total of 162 patients with a mean age of 49.6 years (± 13.7) were included in the study. Among these, 147 (90.7%) were considered as having r-axSpA and 15 (9.3%) nr-axSpA, with mean costs of $6600 (± 6203) and $843 (± 1135), respectively (P < .001). The total direct mean cost was calculated at $6067 (± 6144) per patient. Medication costs were the main driver of total costs (97.6%, $5921), with biologic disease-modifying antirheumatic drugs accounting for nearly 92.0% ($5582) of these costs. Rheumatologist (100%) and physiatrist (64.2%) visits were the most frequently used medical service.

      Conclusions

      The economic burden associated with axSpA in the Colombian setting is substantial. There is a significant difference in direct medical costs between the r-axSpA and the nr-axSpA. Health policies aimed at the comprehensive management of nr-axSpA would have an important role in the reduction of the associated direct medical costs.

      Keywords

      Introduction

      As the leading cause of disability worldwide, musculoskeletal (MSK) disorders (with low back pain as the first leading cause) contribute considerably to the overall economic burden of noncommunicable diseases.
      • Sebbag E.
      • Felten R.
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      • Sibilia J.
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      • Arnaud L.
      The world-wide burden of musculoskeletal diseases: a systematic analysis of the World Health Organization Burden of Diseases Database.
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      The global burden of rheumatoid arthritis: estimates from the Global Burden of Disease 2010 study.
      GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017 [published correction appears in Lancet. 2019;393(10190):e44].
      Axial spondyloarthritis (axSpA) is a heterogeneous MSK disorder characterized by an inflammation of the axial skeleton.
      • Sieper J.
      • Poddubnyy D.
      Axial spondyloarthritis.
      This chronic condition demands high expenditures in pharmacological treatment and generates a considerable burden to healthcare systems and society due to productivity losses and its impairment in quality of life.
      • Strand V.
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      Patient burden of axial spondyloarthritis.
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      The relationship between demographic- and disease-related variables and health-related quality of life in patients with axial spondyloarthritis.
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      • Molto A.
      Characteristics and burden of disease in patients with radiographic and non-radiographic axial spondyloarthritis: a comparison by systematic literature review and meta-analysis.
      Direct medical costs associated with axSpA are variable across countries. Previous research has reported mean direct costs per patient from US dollar ($) 4669 in 2016 in Brazil to $8565 in 2017 in Singapore.
      • Kwan Y.H.
      • Kwoh S.Y.
      • Phang J.K.
      • et al.
      The direct and indirect costs of axial spondyloarthritis (axSpA) in Singapore.
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      • et al.
      Costs of drug therapy in patients with ankylosing spondylitis in Brazil.
      Most studies have broadly focused on radiographic axSpA (r-axSpA) or ankylosing spondylitis, the most severe form of axSpA.
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      • et al.
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      • et al.
      Direct and indirect costs associated with ankylosing spondylitis and related disease activity scores in Turkey.
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      • Meier F.
      • et al.
      Ankylosing spondylitis causes high burden to patients and the healthcare system: results from a German claims database analysis.
      Medications are considered the major contributor of direct costs as more expensive therapies are currently available for the treatment of axSpA, especially for patients with greater disease severity and those with a poor response to conventional disease-modifying antirheumatic drugs (cDMARDs).
      • Reveille J.D.
      • Ximenes A.
      • Ward M.M.
      Economic considerations of the treatment of ankylosing spondylitis.
      Despite the availability of guidelines for the diagnosis and treatment of axSpA, early disease management is challenging and remains heterogeneous. Two types of axSpA are described: one in which the diagnosis is performed by clinics and conventional X-rays of sacroiliac joints and is called r-axSpA
      • Malaviya A.
      Classification of spondyloarthritis: a journey well worth.
      ; this form of SpA is generally considered to be more rapidly evolving and therefore more costly. The other form of disease diagnosed by clinics and/or using magnetic resonance imaging is called nonradiographic axSpA (nr-axSpA); it is assumed that this presentation is a milder form of disease and does not generate as many costs as the previous one.
      • Malaviya A.
      Classification of spondyloarthritis: a journey well worth.
      An association between delayed axSpA diagnosis and increased clinical, economic, and humanistic burden has been reported.
      • Yi E.
      • Ahuja A.
      • Rajput T.
      • George A.T.
      • Park Y.
      Clinical, economic, and humanistic burden associated with delayed diagnosis of axial spondyloarthritis: a systematic review.
      In Latin America, several other barriers exist for the adequate and opportune treatment of axSpA, including the low supply of rheumatologists and the high cost of biologic disease-modifying antirheumatic drugs (bDMARDs).
      • Rocha F.A.C.
      Latin-American challenges and opportunities in rheumatology.
      ,
      • Brenol C.V.
      • Ivan J.
      • Nava G.
      • Soriano E.R.
      Proper management of rheumatoid arthritis in Latin America. What the guidelines say? [published correction appears in Clin Rheumatol. 2015;34(suppl 1):S57].
      Although cost-of-illness studies are considered relevant inputs for the economic evaluation of novel medical technologies such as bDMARDs, they are scarce in Latin America. The objective of this study was to describe the healthcare resource utilization (HCRU) and costs associated with r-axSpA and nr-axSpA from a rheumatic care center in Colombia.

      Methods

      Analytical Framework

      A retrospective cost-of-illness study was conducted using the healthcare system perspective (ie, third payer perspective). The Colombian healthcare system provides medical attention through 3 different schemes: (1) a subsidized plan to provide health insurance coverage of poor individuals (defined by the Sistema de Identificación de Potenciales Beneficiarios de Programas Sociales [SISBEN], a general-purpose system for selecting beneficiaries for social programs in Colombia) and those outside the formal sector
      Colombia - Régimen subsidiado del sistema general de seguridad social en salud de Colombia - Serie de estudios ÚNICO. Banco Mundial.
      ; (2) a contributive plan for people with formal employment or those who can afford healthcare attention based on a mandatory payroll deduction (∼ 12.5% of the gross income divided between the employee and the employer) or individual out-of-pocket contributions, respectively; and (3) a special plan: for members of the military, teachers, and others.
      • Guerrero M.C., R.
      • Gallego A.I.
      • Becerril-Montekio V.
      • et al.
      Sistema de salud de Colombia.
      ,
      Acceso a servicios de salud en Colombia. Décimo primer Informe Técnico Bogotá. Instituto Nacional de Salud. Observatorio Nacional de Salud.
      These schemes have a standardized benefit plan (Plan de Beneficios en Salud, in Spanish) that covers a package of medical services paid by the Colombian healthcare system through insurance companies in a regulated competence market. Currently nearly 94.6% of the Colombian population have coverage to the Plan de Beneficios en Salud.
      Comportamiento del aseguramiento. Ministerio de Salud y Protección Social.
      Patients remitted from general practitioners of insurance companies with at least 1 outpatient medical consultation associated with an International Classification of Diseases, Tenth Revision (ICD-10) codes M45X or M469
      • Lindström U.
      • Bremander A.
      • Bergman S.
      • Haglund E.
      • Petersson I.F.
      • Jacobsson L.T.
      SAT0253 patients with non-as axial SPA have similar prevalence compared to as, but worse perceived health. Results from a population based study. Ann Rheum Dis. 2013;72(suppl 3):A667-A668.
      from October 2018 to October 2019 were identified in a database of medical records from a rheumatic care center in Bogotá-Colombia (Biomab Institución Prestadora de Servicios de Salud, in Spanish). Biomab is a private healthcare center that provides specialized medical care to patients with rheumatic conditions and is pioneer in the comprehensive treatment of these conditions in Colombia. Patients with an M45X and M46.9 code were considered as having r-axSpA and nr-axSpA, respectively. Routine measurements of the Ankylosing Spondylitis Disease Activity Score, the Bath Ankylosing Spondylitis Disease Activity Index, and Bath Ankylosing Spondylitis Functional Index (BASFI) were available for the study. Medical services and medications prescribed in the study period related to nonrheumatic comorbidities were excluded to describe HCRU and direct medical costs only related to axSpA.

      HCRU and Direct Medical Costs

      We extracted information from clinical records of patients with a previous diagnosis of r-axSpA and nr-axSpA treated at a rheumatic care center in Bogotá, Colombia, for a year. We analyzed and reported HCRU and costs by the following categories: consultations (rheumatologist, dermatologist, physiatrist, orthopedist, physical therapy, and other consultations), imaging tests, medications (nonsteroidal anti-inflammatory drugs, analgesic drugs, cDMARDs, and bDMARDs), and other health services. Costs resulting of hospitalizations and surgeries were not considered in this study because of the low frequency of these events in axSpA.
      • Jovani V.
      • Loza E.
      • García de Yébenes M.J.
      • et al.
      Variability in resource consumption in patients with spondyloarthritis in Spain. Preliminary descriptive data from the emAR II study.
      Direct medical costs were calculated by multiplying individual cost inputs by the total frequency of each medical service or medication. All cost inputs were obtained from Colombian official databases. For pharmacological treatments, costs inputs were obtained using official information provided by the Drug Price Information System (Sistema de Información de Precios de Medicamentos [SISMED] in Spanish).
      SISMED, Sistema de Información de Precios de Medicamentos. Ministerio de Salud y Protección Social.
      The SISMED reports minimum, average, and maximum prices and the number of units sold for each medication offered in the Colombian market. In this study, each drug price was obtained according to the SISMED reported prices, weighing them by the number of units sold for each presentation in the country.
      Manual para la elaboración de evaluaciones económicas en salud. Instituto de Evaluación Tecnológica en Salud-IETS.
      ,
      • Santos-Moreno P.
      • Gómez-De la Rosa F.
      • Parra-Padilla D.
      • et al.
      Frequency of health care resource utilization and direct medical costs associated with psoriatic arthritis in a Rheumatic Care Center in Colombia.
      Costs of imaging tests, medical consultations, and other health services were calculated using the Instituto de Seguros Sociales price list, adding 30%, as is recommended by the Colombian agency for health technology assessment (Instituto de Evaluación Tecnológica en Salud, in Spanish) in its guideline to conduct economic evaluations.
      Manual para la elaboración de evaluaciones económicas en salud. Instituto de Evaluación Tecnológica en Salud-IETS.
      ,
      Acuerdo No. 256 de 2001 - manual de tarifas de la entidad promotora de salud del seguro social. Ministerio de Salud y Protección Social.
      The total cost per patient was calculated as the sum of all valued healthcare services and medication prescriptions observed in the study period. Mean and median direct costs were calculated only among patients who used the medical service or received the medication prescription. Calculated costs reflect the trends in healthcare utilization paid by the healthcare system resulting from the clinical care provided by physicians and healthcare workers. All costs were displayed in American dollars, using the official exchange rate reported by the Central Bank of Colombia between October 2018 and October 2019 (1 US dollar = 3263 Colombian pesos).
      Tasa representativa del mercado (TRM - Peso por dólar). Banco de la República, Colombia.

      Statistical Analysis

      Categorical and continuous variables were described with means and standard deviations and absolute (N) and relative frequencies (%). Direct medical costs were reported both as arithmetic means with standard deviations and medians. Differences in costs and HCRU between r-axSpA and nr-axSpA were evaluated using t test and Pearson chi-square test. The ISPOR good research practice guidelines were used for cost data analysis.
      • Ramsey S.D.
      • Willke R.J.
      • Glick H.
      • et al.
      Cost-effectiveness analysis alongside clinical trials II—an ISPOR good research practices task force report.
      We performed a one-part generalized linear model with gamma distribution, log-link function, and robust standard errors to identify direct medical costs key drivers.
      • Mihaylova B.
      • Briggs A.
      • O’Hagan A.
      • Thompson S.G.
      Review of statistical methods for analysing healthcare resources and costs.
      Bivariate logistic regression models were used to evaluate the association between patient characteristics (demographic and clinical variables) and axSpA-related costs. Predictors with a P value < .25 were included in a multivariate regression model. The resulting coefficients were presented in their exponentiated form, indicating a ratio of costs between a category of interest and a category of reference for categorical predictors or as the percentage of increase in the mean cost per unit increase for a continuous predictor.
      • Barber J.
      • Thompson S.
      Multiple regression of cost data: use of generalised linear models.
      Data analysis was performed in R: A language and environment for statistical computing version 3.3.6 (R Foundation for Statistical Computing, Vienna, Austria). A 2-sided P < .05 was considered statistically significant.

      Results

      Sample Characteristics

      Table 1 depicts the baseline sociodemographic characteristics of the study sample. A final sample of 162 patients was analyzed. Among these, 147 (90.7%) were considered as having r-axSpA and 15 (9.3%) nr-axSpA. Patients had a mean age of 49.6 years (± 13.7) and 138 (85.2%) were younger than 65 years. A higher proportion of male patients was observed among the r-axSpA group compared with nr-axSpA group (P < .001). Although we found higher baseline values of the Bath Ankylosing Spondylitis Disease Activity Index and Ankylosing Spondylitis Disease Activity Scores among the r-axSpA group, no statistically significant differences were found compared with the nr-axSpA group (P > .050). Only the BASFI score showed a significantly higher mean value among patients with r-axSpA (P = .048), indicating a higher disability than the nr-axSpA group. Regarding comorbidities, primary osteoarthritis and fibromyalgia were the most frequent comorbid conditions.
      Table 1Baseline characteristics of the study sample.
      CharacteristicOverall samplenr-axSpAr-axSpAP value
      Number of patients16215147
      Sex
       Men106 (65.4)4 (26.7)102 (69.4).003
      Age in years, mean (SD)49.6 (13.7)43.6 (13.3)50.2 (13.6).086
      Clinimetrics, mean (SD)
       BASDAI (0-10)
      Estimated for 156 patients.
      2.3 (2.1)1.5 (1.9)2.4 (2.1).167
       BASFI (0-10)
      Estimated for 153 patients.
      2.4 (2.3)1.2 (1.9)2.5 (2.3).048
       ASDAS (0-10)
      Estimated for 145 patients.
      1.5 (1)1.2 (1)1.5 (1).402
      Comorbidities
       Primary osteoarthritis45 (27.8)3 (20.0)42 (28.6).562
       Fibromyalgia11 (6.8)0 (0)11 (7.5).601
       Intervertebral disk disorder6 (3.7)1 (6.7)5 (3.4).447
       Uveitis8 (4.9)3 (20.0)5 (3.4).027
       Primary hypertension7 (4.3)0 (0)7 (4.8).999
      ASDAS indicates Ankylosing Spondylitis Disease Activity Score; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functioning Index; nr-axSpA, nonradiographic spondyloarthritis; r-axSpA, radiographic spondyloarthritis.
      Estimated for 156 patients.
      Estimated for 153 patients.
      Estimated for 145 patients.

      Healthcare Resource Utilization

      The HCRU owing to the attention of patients with axSpA is presented in Table 2. Rheumatologist (100%) and physiatrist visits (64.2%) were the most frequently used medical service. On average, a patient with r-axSpA was seen by a rheumatologist ∼ 4 times per year. Patients with r-axSpA had a mean higher frequency of consultations to the rheumatologist and other medical services (P = .001 and P = .009, respectively). Regarding medication utilization, 95.3% of patients had at least 1 prescription of any axSpA-related medication. bDMARDs (69.1%) were the most commonly prescribed medication and analgesic drugs the least (29.6%). Among patients with a prescription of bDMARDs, 60.7% had at least 1 prescription of a cDMARD. Compared with the nr-axSpA group, patients in the r-axSpA group had a higher relative frequency of prescriptions of any bDMARD in the study period (6.7% vs 75.5%) (P = .001). Adalimumab (23.5%) and etanercept (17.9%) were the most frequently prescribed biologics. Among cDMARDs, sulfasalazine (46.6%) and methotrexate (21.6%) were the most frequently prescribed drugs.
      Table 2Healthcare services and medication utilization related to axSpA type in the study period.
      Medical service/medication
      The number of patients using each medical service/medication is reported. Relative frequencies were calculated using the total number of subjects for each column as denominator. Patients may have used more than one service/medication in the study period.
      Overall samplenr-axSpAr-axSpAP value
      Number of patients16215147
      Consultations, n (%)
       Rheumatologist162 (100)15 (100)147 (100)-
       Mean (SD)3.7 (1.3)2.5 (1.2)3.9 (1.3)< .001
      Dermatologist15 (9.3)2 (13.3)13 (8.8).633
       Mean (SD)1.7 (0.9)2.5 (0.7)1.5 (0.9).263
      Physiatrist104 (64.2)10 (66.7)94 (63.9).999
       Mean (SD)1.7 (0.9)1.6 (1.3)1.7 (0.9).809
      Orthopedist9 (5.6)1 (6.7)8 (5.4).593
       Mean (SD)1.2 (0.4)2 (-)1.1 (0.4)-
      Other consultations
      Includes outpatient visits to the nutritionist, palliative care specialist, infectologist, psychologist, and psychiatrist.
      63 (38.9)5 (33.3)58 (39.5).784
       Mean (SD)1.8 (1.5)2 (1.7)1.8 (1.4).807
      Physical therapy74 (45.7)6 (40)68 (46.3).788
       Mean (SD)1.9 (1.8)2.8 (3.5)1.9 (1.5).531
      Medical imaging71 (43.8)6 (40)65 (44.2).792
       Mean (SD)1.7 (0.9)2 (1)1.7 (0.9).457
      Other services
      Includes infusion therapy and pharmacovigilance.
      0.4 (0.5)0.2 (0.4)0.4 (0.5).103
       Mean (SD)6.7 (5.4)2.3 (1.5)6.9 (5.4).009
      Total frequency of any medical service162 (100)15 (100)147 (100)-
       Mean (SD)10.1 (6.3)7.3 (5.4)10.4 (6.4).053
      Medications, n (%)
       NSAIDs91 (56.2)11 (73.3)80 (54.4).183
       Mean (SD)2.5 (1.3)2.1 (1.1)2.5 (1.4).263
      Analgesic drugs48 (29.6)3 (20)45 (30.6).556
       Mean (SD)3 (1.4)1.5 (0.7)3.1 (1.4).151
      Conventional DMARDs
      Includes leflunomide, cyclosporine, methotrexate, and sulfasalazine.
      93 (57.4)12 (80)81 (55.1).098
       Mean (SD)3.9 (2.4)3.8 (2.5)4 (2.4).771
      Biologic DMARDs
      Includes golimumab, adalimumab, secukinumab, certolizumab, infliximab, etanercept, and ustekinumab.
      112 (69.1)1 (6.7)111 (75.5)< .001
       Mean (SD)3.9 (1.2)1.5 (0.7)4 (1.2).113
      Total frequency of any medication155 (95.7)15 (100)140 (95.2).990
       Mean (SD)7.4 (4.3)4.8 (3.9)7.7 (4.2).013
      axSpA indicates axial spondyloarthritis; DMARD, disease-modifying antirheumatic drug; nr-axSpA, nonradiographic spondyloarthritis; NSAID, nonsteroidal anti-inflammatory drug; r-axSpA, radiographic spondyloarthritis.
      The number of patients using each medical service/medication is reported. Relative frequencies were calculated using the total number of subjects for each column as denominator. Patients may have used more than one service/medication in the study period.
      Includes outpatient visits to the nutritionist, palliative care specialist, infectologist, psychologist, and psychiatrist.
      Includes infusion therapy and pharmacovigilance.
      § Includes leflunomide, cyclosporine, methotrexate, and sulfasalazine.
      ǁ Includes golimumab, adalimumab, secukinumab, certolizumab, infliximab, etanercept, and ustekinumab.

      Direct Medical Costs

      Table 3 gives a breakdown of the direct medical costs of patients with axSpA. The calculated mean annual cost per patient was $6067 (± 6144). Mean total costs for r-axSpA and nr-axSpA were $6600 (± 6203) and $843 (± 1135) (P < .001). No statistically significant differences were observed in mean total costs between males ($6160 [± 5959]) and females ($5893 [± 6545]) (P = .799). Similar results were obtained regarding age groups (P = .151) despite a higher mean cost for patients younger than 65 years ($6344 [± 6207]) than those at the age of 65 years or older ($4478 [± 5664]). The overall economic burden from the health system perspective for all treated patients was $982 973 per year. Medication costs were the main driver of total costs (97.6%), corresponding to $959 554. bDMARDs accounted for nearly 92.0% of these costs ($881 286). With regard to the distribution of total costs by type of axSpA and cost component, patients in the r-axSpA group accounted for 98.7% of total costs ($970 319), and medication costs were more concentrated among these patients (97.7% vs 88.4% for patients with nr-axSpA).
      Table 3Direct medical costs related to axial spondyloarthritis type.
      Medical service/medication
      Mean and median costs were calculated only among patients who used the medical service or received the medication prescription.
      Overall samplenr-axSpAr-axSpAP value
      Mean (SD)MedianMean (SD)MedianMean (SD)Median
      Consultations
       Rheumatologist52.6 (18.4)56.435.7 (17.6)42.354.3 (17.6)56.4< .001
       Dermatologist14.5 (7.8)8.721.7 (6.1)21.713.4  (7.6)8.7.263
       Physiatrist14.7 (8)8.713.9 (11)8.714.8 (7.7)13.809
       Orthopedist10.6 (3.8)8.717.4 (-)17.49.8 (3.1)8.7
       Other medical visits
      Includes outpatient visits to the nutritionist, palliative care specialist, infectologist, psychologist, and psychiatrist.
      7.7 (7.2)5.75.8 (5.2)2.97.9 (7.3)5.7.442
       Physical therapy5.9 (5.4)3.18.7 (10.9)4.65.7 (4.7)3.1.529
      Medical imaging53.2 (71.8)18.975.5 (112.8)16.450.7 (66.5)18.9.587
      Other services
      Includes infusion therapy and pharmacovigilance.
      129.1 (108.4)119.540.9 (21.5)39.8133.3 (109.2)119.5< .001
      Any medical service6190.7 (6157.1)144.6745.8 (1058.1)97.96774.1 (6192.5)149.3< .001
      Medications
       NSAIDs72 (92.1)33.861.4 (74.5)25.373.5 (94.6)33.8.652
       Analgesic drugs100.5 (122.8)30.3130.8 (180.1)130.899.1 (122.4)30.3.845
       Conventional DMARDs
      Includes leflunomide, cyclosporine, methotrexate, and sulfasalazine.
      728.7 (1019.4)157.3572.4 (878.9)157.3751.9 (1041.5)157.3.529
       Biologic DMARDs
      Includes golimumab, adalimumab, secukinumab, certolizumab, infliximab, etanercept, and ustekinumab.
      7799 (5538.2)6838.31721.3 (466.9)1721.37908.5 (5526.6)6956< .001
      Any medication144.6 (122.6)6190.797.9 (106.5)745.8149.3 (123.5)6774.1.096
      Total costs6067.7 (6148.8)4334.4843.7 (1135.9)250.96600.8 (6203.1)4897.2< .001
      axSpA indicates axial spondyloarthritis; DMARD, disease-modifying antirheumatic drug; nr-axSpA, nonradiographic spondyloarthritis; NSAID, nonsteroidal anti-inflammatory drug; r-axSpA, radiographic spondyloarthritis.
      Mean and median costs were calculated only among patients who used the medical service or received the medication prescription.
      Includes outpatient visits to the nutritionist, palliative care specialist, infectologist, psychologist, and psychiatrist.
      Includes infusion therapy and pharmacovigilance.
      § Includes leflunomide, cyclosporine, methotrexate, and sulfasalazine.
      ǁ Includes golimumab, adalimumab, secukinumab, certolizumab, infliximab, etanercept, and ustekinumab.
      A comparison of mean direct medical costs according to age (≥ 65 vs < 65 years), sex, and prescription of any bDMARD is presented in Figure 1.
      Figure thumbnail gr1
      Figure 1Mean total costs according with age group, sex, and prescription of biologic disease modifying antirheumatic drugs. Error bars indicate 95% confidence intervals.
      DMARD indicates disease-modifying antirheumatic drug.

      Direct Cost Predictors

      Results of the multivariate regression analysis are presented in Table 4. Having < 65 years of age and a diagnosis of r-axSpA were significant predictors of greater direct medical costs. No association was found between male sex and direct medical costs. Neither primary osteoarthritis as comorbid condition nor baseline BASFI score was significantly associated with direct medical costs (P = .670 and P = .075, respectively).
      Table 4Generalized linear model of total direct costs.
      CharacteristicCoefficient95% CIP value
      Intercept564287-1199< .001
      Men vs women0.850.59-1.20.360
      Age < 651.631.03-2.48.031
      r-axSpA vs nr-axSpA7.263.85-12.6< .001
      BASFI score1.070.99-1.15.075
      Primary osteoarthritis1.080.75-1.59.670
      Note: Akaike Information Criteria: 2959
      BASFI indicates Bath Ankylosing Spondylitis Functioning Index; CI, confidence interval; nr-axSpA, nonradiographic spondyloarthritis; r-axSpA, radiographic spondyloarthritis.

      Discussion

      To the best of our knowledge, this is the first study that calculated the HCRU and direct medical costs due to axSpA for different disease categories in a real-world setting in Colombia. Our results suggest that patients with a radiographic phenotype are associated with a higher cost than patients with the nonradiographic variant of axSpA ($6600 vs $843). We consider that these results were obtained mainly due to the high proportion of patients with r-axSpA under treatment with bDMARDs (75.5%). Medications accounted for 97.6% of total costs.
      Our results are in line with those previously published in Latin America. We observed a similar distribution of our sample according to age and sex to those reported by Machado et al
      • Machado M.A.d.Á.
      • Ferre F.
      • de Moura C.S.
      • et al.
      Costs of drug therapy in patients with ankylosing spondylitis in Brazil.
      and Azevedo et al
      • Azevedo V.F.
      • Rossetto C.N.
      • Lorencetti P.G.
      • Tramontin M.Y.
      • Fornazari B.
      • Araújo D.V.
      Indirect and direct costs of treating patients with ankylosing spondylitis in the Brazilian public health system.
      in Brazil. Mean age was reported to be between 41.0 and 43.9 years, and male patients were between 65.3% and 75.2% of total patients. In our sample, we found a mean age of 49.6 years and a frequency of 65.4% of the male sex. In addition, primary osteoarthritis and fibromyalgia were the most frequent comorbid conditions reported in the clinical records of the studied patients with axSpA; similar findings were described in previous studies.
      • Fitzgerald G.E.
      • Maguire S.
      • Lopez-Medina C.
      • Dougados M.
      • O’Shea F.D.
      • Haroon N.
      Tender to touch - prevalence and impact of concomitant fibromyalgia and enthesitis in spondyloarthritis: an ancillary analysis of the ASAS PerSpA study.
      • Zhao S.S.
      • Robertson S.
      • Reich T.
      • Harrison N.L.
      • Moots R.J.
      • Goodson N.J.
      Prevalence and impact of comorbidities in axial spondyloarthritis: systematic review and meta-analysis.
      • Puche-Larrubia M.Á.
      • Ladehesa-Pineda L.
      • Font-Ugalde P.
      • et al.
      Distribution of comorbidities in spondyloarthritis with regard to the phenotype and psoriasis: data from the ASAS-COMOSPA study.
      Regarding costs and HCRU, the retrospective study by Azevedo et al
      • Azevedo V.F.
      • Rossetto C.N.
      • Lorencetti P.G.
      • Tramontin M.Y.
      • Fornazari B.
      • Araújo D.V.
      Indirect and direct costs of treating patients with ankylosing spondylitis in the Brazilian public health system.
      calculated costs related to the treatment of ankylosing spondylitis in a tertiary hospital in Brazil and found that 63.4% of patients were prescribed an anti–tumor necrosis factor medication. The associated costs accounted for 97.9% of total direct medical costs ($2.1 million of 2012) and 96.2% of medication costs ($1.8 million of 2012). In our study, we obtained a similar prescription frequency of biologics (69.1%) and a comparable participation of their cost in those related to the overall sample (92.0%). Although the authors only included patients with r-axSpA, these similarities may be associated with the high frequency of patients with r-axSpA in our sample (89.1%), but it is important to emphasize that our study is one of the first in Latin America to discriminate the costs between r-axSpA and nr-axSpA.
      A previous study by Machado et al
      • Machado M.A.d.Á.
      • Ferre F.
      • de Moura C.S.
      • et al.
      Costs of drug therapy in patients with ankylosing spondylitis in Brazil.
      in Brazil that estimated cost related to medications in a sample of 1251 patients with axSpA (ICD-10 codes M45, M46.9, and M46.8) reported that 78.0% of patients were treated with either adalimumab (41.0%), etanercept (20.4%), or infliximab (5.2%). Approximately 94% of medication costs were owing to adalimumab (52.1%) and etanercept (41.6%) prescriptions. These results indicate a trend toward a similar prescription pattern and high access to these medications in Colombia and Brazil.
      Our results underline the high economic burden of axSpA to the health system in a middle-income setting and highlight the necessity of comprehensive management of this disease, focused on the achievement of the highest quality of care at the lowest possible cost.
      • Westhovens R.
      • Annemans L.
      Costs of drugs for treatment of rheumatic diseases.
      In addition, this study filled a gap regarding the direct medical costs of axSpA in Colombia. Then, our findings offer useful inputs to conduct cost-effectiveness analyses of new technologies to treat this MSK disorder.
      Our study has limitations. We were unable to calculate indirect costs, and thus, our calculations may underestimate the total economic burden associated with axSpA in our sample. Regarding disease classification, we could not have access to other relevant clinical variables such as magnetic resonance imaging reports for a more exhaustive assessment of the radiographic nature of the patients with axSpA. We classified patients based on their ICD-10 codes, and this may lead to an inaccurate distinction between patients with nr-axSpA and r-axSpA. Nevertheless, the distribution of our sample among the 2 disease categories is similar to the frequency distribution reported by Kwan et al
      • Kwan Y.H.
      • Kwoh S.Y.
      • Phang J.K.
      • et al.
      The direct and indirect costs of axial spondyloarthritis (axSpA) in Singapore.
      in a cost-of-illness study in Singapore that used the Assessment of Spondyloarthritis International Society classification criteria (11.8% and 88.2% in the nr-axSpA and r-axSpA groups, respectively). In addition, the authors reported no statistically significant differences in the utilization of medical services between patients with r-axSpA and nr-axSpA. In our study, we only found differences in the frequency of medical consultations to the rheumatologist, other medical services (ie, infusion therapy and pharmacovigilance), and the prescription of bDMARDs, with 75.5% of patients in the r-axSpA group with at least 1 prescription of these medications. Furthermore, were analyzed data from a single healthcare center, and our results might not be generalizable to the overall population of patients with axSpA in Colombia. These limitations can be overcome with the availability of more exhaustive data sources.

      Conclusions

      The economic burden associated to axSpA in the Colombian setting is substantial. Health policies aimed at the comprehensive management of nr-axSpA would have an important role in reducing the associated direct medical costs.

      Article and Author Information

      Author Contributions: Concept and design: Santos-Moreno, Alvis-Zakzuk
      Acquisition of data: Santos-Moreno, Parra-Padilla, Gómez-De la Rosa, Carrasquilla-Sotomayor, Villarreal, Jervis-Jálabe, Alvis-Zakzuk
      Analysis and interpretation of data: Santos-Moreno, Parra-Padilla, Gómez-De la Rosa, Carrasquilla-Sotomayor, Villarreal, Jervis-Jálabe, Alvis-Zakzuk
      Drafting of the manuscript: Santos-Moreno, Parra-Padilla, Gómez-De la Rosa, Carrasquilla-Sotomayor, Villarreal, Jervis-Jálabe, Alvis-Zakzuk
      Critical revision of the paper for important intellectual content: Santos-Moreno, Parra-Padilla, Gómez-De la Rosa, Carrasquilla-Sotomayor, Villarreal, Jervis-Jálabe, Alvis-Zakzuk
      Statistical analysis: Parra-Padilla, Gómez-De la Rosa
      Provision of study materials or patients: Santos-Moreno
      Conflict of Interest Disclosures: Mr Santos-Moreno reported receiving research grants from Pfizer, Novartis, Abbvie, Janssen, UCB-Biopas, and Procaps; receiving consulting fees and speaker fees from Pfizer, Amgen, Eli Lilly, Janssen, Novartis, and UCB-Biopas; and receiving support for attending academic meetings from Pfizer, Amgen, Janssen, Novartis, and UCB-Biopas. No other disclosures were reported.
      Funding/Support: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

      Acknowledgment

      The authors thank Biomab Health Care Center for the administrative data provided for this study.

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