Buscar en
Revista Colombiana de Reumatología
Toda la web
Inicio Revista Colombiana de Reumatología Systemic lupus erythematosus: Pharmacological differences between women and men ...
Información de la revista
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Visitas
117
Original Investigation
DOI: 10.1016/j.rcreu.2021.05.008
Acceso a texto completo
Disponible online el 20 de Julio de 2021
Systemic lupus erythematosus: Pharmacological differences between women and men and among age groups and geographical regions
Lupus eritematoso sistémico: diferencias farmacológicas entre mujeres y hombres, grupos de edad y regiones geográficas
Visitas
...
Luis Fernando Valladales-Restrepoa,b, Camilo Alexander Constain-Mosquerac, María Clara Mesa-Ardilaa, Jorge Enrique Machado-Albaa,
Autor para correspondencia
machado@utp.edu.co

Corresponding author.
a Grupo de Investigación en Farmacoepidemiología y Farmacovigilancia, Universidad Tecnológica de Pereira-Audifarma SA, Pereira, Colombia
b Grupo de Investigación Biomedicina, Fundación Universitaria Autónoma de las Américas. Pereira, Colombia
c Semillero de Investigación en Farmacología Geriátrica, Grupo de Investigación Biomedicina, Facultad de Medicina, Fundación Universitaria Autónoma de las Américas, Pereira, Colombia
Información del artículo
Resumen
Texto completo
Bibliografía
Descargar PDF
Estadísticas
Tablas (3)
Table 1. Comparison of sociodemographic, clinical and pharmacological variables according to sex for 4307 patients diagnosed with systemic lupus erythematosus in Colombia, 2019–2020.
Table 2. Comparison of sociodemographic, clinical and pharmacological variables according to geographic region for 4307 patients diagnosed with systemic lupus erythematosus in Colombia, 2019–2020.
Table 3. Comparison of sociodemographic, clinical and pharmacological variables according to age group for 4307 patients diagnosed with systemic lupus erythematosus in Colombia, 2019–2020.
Mostrar másMostrar menos
Abstract

Systemic lupus erythematosus (SLE) is a chronic and potentially fatal autoimmune disease. There are clinical differences between women and men and among age groups. Its treatment involves a heterogeneous group of drugs. The objective was to determine the pharmacological treatment patterns in a group of patients with SLE and compare them according to sex, age group and geographic region. This was a cross-sectional study that identified outpatient drugs used in patients with SLE from a population database of Colombians affiliated with the Colombian Health System. Sociodemographic and pharmacological variables were considered. Descriptive and bivariate analyses were performed. A total of 4307 patients with SLE were identified (median age, 44.2 years; 89.4% women). Disease-modifying antirheumatics were the most prescribed drugs (90.5%), especially chloroquine (54.4%), which predominated in all age groups and geographical regions. Hydroxychloroquine and methotrexate were the predominant prescribed drugs for women, while corticosteroids, chloroquine, azathioprine, and mycophenolate were the predominant prescribed drugs for men. The use of corticosteroids (prednisolone and prednisone) decreased with increasing age. Differences were found in the prescription of drugs for patients with SLE between women and men and among geographic regions and age groups. The use of chloroquine predominated over hydroxychloroquine, contrasting with clinical practice guidelines.

Keywords:
Systemic lupus erythematosus
Chloroquine
Women
Adrenal cortex hormones
Pharmacoepidemiology
Colombia
Resumen

El lupus eritematoso sistémico (LES) es una enfermedad autoinmune crónica y potencialmente mortal. Existen diferencias clínicas entre mujeres y hombres, y entre grupos de edad. Su tratamiento involucra un grupo heterogéneo de medicamentos. El objetivo fue determinar los patrones de tratamiento farmacológico de un grupo de pacientes con LES y compararlos según el sexo, los grupos de edad y las regiones geográficas. Estudio de corte transversal que identificó los medicamentos de uso ambulatorio empleados en pacientes con LES, a partir de una base de datos poblacional de colombianos afiliados al Sistema de Salud de Colombia. Se consideraron variables sociodemográficas y farmacológicas. Se realizó un análisis descriptivo y bivariado. Se identificó a 4.307 pacientes con LES, con una mediana de edad 44,2 años y un 89,4% mujeres. Los medicamentos modificadores de enfermedad reumática fueron los más prescritos (90,5%), en especial cloroquina (54,4%), el cual predominó en todos los grupos de edad y las regiones geográficas. La hidroxicloroquina y el metotrexato predominaron en mujeres, mientras que los corticosteroides, la cloroquina, la azatioprina y el micofenolato, en hombres. Con el aumento de la edad disminuyó el uso de corticoides (prednisolona y prednisona). Se encontraron diferencias en la prescripción de los medicamentos empleados en los pacientes con LES entre mujeres y hombres, regiones geográficas y grupos etarios. El uso de cloroquina predominó sobre la hidroxicloroquina, en contraste con lo recomendado por las guías de práctica clínica.

Palabras clave:
Lupus eritematoso sistémico
Cloroquina
Mujeres
Corticosteroides
Farmacoepidemiología
Colombia
Texto completo
Introduction

Systemic lupus erythematosus (SLE) is a chronic and life-threatening autoimmune disease that can affect any organ, such as the skin, kidneys, joints, central nervous system and cardiovascular system.1 Its global prevalence has been estimated at 9–241 per 100,000 person-years, with an incidence of 0.3–23.2 per 100,000 person-years, ranging from 2.4 to 7.4 in Europe to 7.9 in Central and South America and 8.1 in Asia.2 It is more common in women, with a ratio of women to men of 7–15:1 for adults and 3–5:1 for pediatric patients.2 However, in the latter group and in men, SLE appears to be much more aggressive, with a greater presence of clinical manifestations and higher severity.3,4

In Colombia, between 2012 and 2016, 431,834 cases of SLE were identified, with an unadjusted prevalence of 91.9 cases per 100,000 inhabitants; in those over 18 years of age, the prevalence was 126.3 per 100,000 inhabitants.5 There is evidence of greater aggressiveness in the clinical presentation of SLE in men, who present with greater lung involvement, longer hospital stays and high readmission and lethality rates.6

In the pharmacological treatment of SLE, antimalarials, corticosteroids, immunosuppressants and biotech drugs stand out; these drugs are used to induce remission or reduce disease activity and prevent flare-ups and target organ damage.7 Management is individualized and must take into account the clinical manifestations, complications, severity and degree of disease activity.7–9 However, these drugs are not innocuous and may be associated with adverse reactions, such as increased susceptibility to infections, increased risk of cardiovascular diseases, diabetes and cancer, and decreased bone density.1,10

The existing information on the prescription patterns of drugs used in rheumatological diseases is scarce in Colombia, and an understanding of these patterns can help direct informed interventions that focus on the appropriate use of these drugs. Such prescription patterns vary among countries and may also differ among their different regions; therefore, we sought to determine the pharmacological management of patients with SLE and to identify the differences between women and men and among age groups and geographical regions in Colombia.

Materials and methods

This was a cross-sectional study on the prescription patterns of drugs used for patients diagnosed with SLE; the data were obtained from a population database for drug dispensing that collects information from approximately 8.5 million people affiliated with the Colombian Health System in six health insurance companies, corresponding to approximately 30.0% of the active population covered by the contributory or paid regime and 6.0% covered by the state-subsidized regime, which together comprise 17.3% of the Colombian population.

Patients were identified using International Classification of Diseases (ICD-10) codes related to SLE (M321, M328, M329) in the period from July 1, 2019, to June 30, 2020. Patients of any age and sex who were seen as outpatients and were under pharmacological management for SLE were selected. Patients with a concomitant diagnosis of cutaneous lupus erythematosus or drug-induced lupus and those diagnosed with SLE without pharmacological treatment were excluded.

Based on the information on the prescription of drugs to the affiliated population, systematically obtained by a dispensing company (Audifarma SA), a database was designed that allowed the collection of the following groups of patient variables:

  • 1.

    Sociodemographic: sex, age (groups: <20 years, 20–39 years, 40–64 years and ≥65 years), health system regime affiliation (contributory or subsidized) and city of dispensation;

    • Geographical areas: The place of residence was categorized by department according to the regions of Colombia and considering the classification of the National Administrative Department of Statistics (DANE) of Colombia, as follows:

    • Caribbean region: Atlántico, Bolívar, Cesar, Córdoba, La Guajira, Magdalena, Sucre, San Andrés, Providencia and Santa Catalina.

    • Central region: Antioquia, Caldas, Quindío, Risaralda, Caquetá, Huila and Tolima.

    • Bogotá-Cundinamarca region.

    • Eastern region: Boyacá, Meta, Norte de Santander, Santander, Arauca and Casanare.

    • Pacific region: Cauca, Chocó, Nariño, Valle del Cauca, and

    • Amazon-Orinoco Region: Amazonas, Guaviare, Guainía, Vaupés, Vichada and Putumayo.

  • 2.

    Drugs for SLE management:

    • Corticosteroids: prednisolone, prednisone, deflazacort, and methylprednisolone;

    • Synthetic disease-modifying antirheumatic drugs (DMARDs): methotrexate, azathioprine, leflunomide, chloroquine, hydroxychloroquine, and sulfasalazine;

    • Immunosuppressants: cyclophosphamide, cyclosporine, mycophenolate, and tacrolimus; and

    • Biologic disease-modifying antirheumatic drugs (DMARDb): rituximab, belimumab, and adalimumab; and

  • 3.

    Comedications (grouped into the following categories): (a) antidiabetics (oral and subcutaneous), (b) antihypertensives and diuretics, (c) lipid-lowering drugs; (d) antiulcers, (e) antidepressants, (f) anxiolytics and hypnotics (benzodiazepines and Z-drugs), (g) thyroid hormone, (h) antipsychotics (typical and atypical), (i) antiepileptics, (j) antiarrhythmics, (k) antihistamines, (l) antidementia drugs, (m) opioid analgesics, (n) nonopioid analgesics, (o) bronchodilators and inhaled corticosteroids, (p) antiplatelet agents, (q) anticoagulants (oral and parenteral), (r) antipsychotics, and (s) hormonal contraceptives.

  • 4.

    Comorbidities: The main cardiovascular, endocrine, rheumatic, urological, kidney, psychiatric, neurological, digestive, respiratory and neoplastic diseases were identified from the reported ICD-10 diagnostic codes. Autoimmune rheumatological diseases (rheumatoid arthritis, Sjogren's syndrome, vasculitis, polymyalgia rheumatica, psoriatic arthritis, ankylosing spondylitis and systemic sclerosis) and non-immune diseases (fibromyalgia, osteoatrosis, osteoporosis and gout) were included.

The protocol was approved by the Bioethics Committee of Universidad Tecnológica de Pereira in the “research without risk” category (approval number: 02-051020). The principles established by the Declaration of Helsinki were respected.

The data were analyzed with the statistical package SPSS Statistics, version 26.0 for Windows (IBM, USA). A descriptive analysis was performed; qualitative variables are presented as frequencies and proportions, and quantitative variables are presented as measures of central tendency and dispersion, depending on the normality of the data, as established by the Kolmogorov–Smirnov test. Quantitative variables were compared using Student's t-test or the Mann–Whitney U test, and categorical variables were compared using the X2 test or Fisher's exact test. A statistical significance level of p<0.05 was adopted.

Results

A total of 4307 patients with a diagnosis of SLE were identified, distributed in 135 different cities or municipalities. Of these, 89.4% (n=3851) were women, and the median age was 44.2 years (interquartile range: 32.4–55.8 years; range:6.7–90.8 years); the age group distributions were as follows: <20 years (n=198; 4.6%), 20–39 years (n=1560; 36.2%), 40–64 years (n=2120; 49.2%) and ≥65 years (n=429; 10.0%). Most patients lived in the Bogotá-Cundinamarca Region (n=1491; 34.6%), followed by the Caribbean Region (n=1036; 24.1%), Central Region (n=878; 20.4%), Pacific Region (n=753; 17.5%), and Eastern Region and Amazonia (n=149; 3.5%). A total of 91.2% (n=3926) of the patients participated in the contributory regime, and 8.8% (n=381) belonged to the subsidized regime.

Most patients with SLE were treated with DMARDs (n=3901; 90.5%), with a predominance of chloroquine (n=2343; 54.4%), azathioprine (n=1579; 36.6%), hydroxychloroquine (n=1267; 29.4%) and methotrexate (n=758; 17.6%). Corticosteroids, especially prednisolone (n=2915; 67.6%), were prescribed to 76.1% (n=3278) of patients; among immunosuppressants, mycophenolate was the most prescribed (n=719; 16.7%). The cyclophosphamide was prescribed to 36 patients (0.8%) while DMARDb were prescribed to 11 patients (0.3%).

A total of 71.4% (n=3076) of all patients had some chronic disease. Of these, 67.8% (n=2084) had one or two diseases, 23.6% (n=726) had three or four diseases, and 8.6% (n=266) had five or more diseases. The 10 most common comorbidities were hypertension (n=2012; 46.7%), rheumatoid arthritis (n=532; 12.4%), hypothyroidism (n=513; 11.9%), Sjögren's syndrome (n=489; 11.4%); diabetes (n=383; 8.9%); chronic kidney disease (n=277; 6.4%); depressive disorders (n=226; 5.2%); chronic pain (n=207; 4.8%); anxiety disorders (n=179; 4.2%) and fibromyalgia (n=157; 3.6%). Polyautoimmunity (systemic lupus erythematosus and rheumatoid arthritis and Sjogren's syndrome) occurred in 21.6% (n=932) of patients. In addition, of all patients, 2.7% (n=115) had a diagnosis related to thrombosis. A total of 18.4% (n=792) of the patients had an infection-related diagnosis, including urinary tract infection (n=189; 4.4%), tuberculosis (n=47; 1.1%), pneumonia (n=39; 0.9%), meningitis (n=7; 0.2%) and sepsis (n=7; 0.2%).

The most common comedications were nonopioid analgesics (n=2854; 66.3%), followed by antiulcers (n=2391; 55.5%), antihypertensives and diuretics (n=2234; 51.9%), antiplatelet agents (n=1210; 28.1%), lipid-lowering drugs (n=1078; 25.0); antidepressants (n=1017; 23.5%), antihistamines (n=1002; 23.3%), opioid analgesics (n=949; 22.0%), thyroid hormone (n=922; 21.4%), antiepileptics (n=621; 14.4%), anticoagulants (n=525; 12.2%), bronchodilators and inhaled corticosteroids (n=382; 8.9%), antidiabetics (n=262; 6.1%)), antipsychotics (n=68; 3.9%) and hormonal contraceptives (n=97; 2.3%).

Comparison between women and men

Significant differences were found in some variables between women and men. It was found that cardiovascular, renal and urological comorbidities were more frequent in men, whereas rheumatologic comorbidities (immune and non-immune) were more frequent in women. Regarding pharmacological management, corticosteroids, chloroquine, azathioprine and mycophenolate were prescribed more to men, whereas hydroxychloroquine, methotrexate and leflunomide were prescribed more to women. Regarding comedications, analgesics were prescribed more to women, whereas antihypertensives, lipid-lowering drugs and anticoagulants were prescribed more to men (Table 1).

Table 1.

Comparison of sociodemographic, clinical and pharmacological variables according to sex for 4307 patients diagnosed with systemic lupus erythematosus in Colombia, 2019–2020.

Variables  WomenMenp 
  n=3851  n=456   
Age (median; IQR)  44.2 (32.6–55.7)44.3 (31.2–57.2)0.872 
No chronic comorbidities  1095  28.4  136  29.8  0.534 
With chronic comorbidities  2756  71.6  320  70.2   
Cardiovascular  1807  46.9  241  52.6  0.021 
Rheumatological  1124  29.2  74  16.2  <0.001 
Inmune  933  24.2  57  12.5  <0.001 
Non-inmune  328  8.5  20  4.4  <0.001 
Endocrine  893  23.2  89  19.4  0.070 
Neurological  533  13.8  52  11.4  0.142 
Psychiatric  359  9.3  31  6.8  0.072 
Renal  269  7.0  49  10.7  0.004 
Gastrointestinal  257  6.7  21  4.6  0.085 
Respiratory  99  2.6  13  2.8  0.734 
Cancer  91  2.4  2.0  0.593 
Urinary  36  0.9  24  5.2  <0.001 
Pharmacological management  –  –  –  –  – 
DMARDs  3498  90.8  403  88.0  0.050 
Chloroquine  2065  53.6  278  60.7  0.004 
Azathioprine  1390  36.1  189  41.3  0.030 
Hydroxychloroquine  1161  30.1  106  23.1  0.002 
Methotrexate  694  18.0  64  14.0  0.031 
Leflunomide  94  2.4  0.7  0.011* 
Sulfasalazine  52  1.4  0.9  0.515* 
Corticosteroids  2910  75.6  368  80.3  0.023 
Prednisolone  2578  66.9  337  73.6  0.004 
Prednisone  464  12.0  91  19.9  <0.001 
Deflazacort  246  6.4  15  3.3  0.008 
Methylprednisolone  144  3.7  12  2.6  0.225 
Other immunosuppressants  716  18.6  121  26.4  <0.001 
Mycophenolate  609  15.8  110  24.0  <0.001 
Cyclosporine  104  2.7  10  2.2  0.514 
Cyclophosphamide  30  0.8  1.3  0.269* 
Tacrolimus  13  0.3  0.4  0.669* 
DMARDb  11  0.3  0.0  0.620* 
Belimumab  0.2  0.0  1.000* 
Rituximab  0.1  0.0  1.000* 
Adalimumab  0.1  0.0  1.000* 
Comedications  3643  94.6  418  91.7  0.011 
Non-opioid pain medications  2626  68.2  228  50.0  <0.001 
Antiulcer  2172  56.4  219  48.0  0.001 
Antihypertensives and diuretics  1961  50.9  273  59.9  <0.001 
Platelet antiaggregants  1087  28.2  123  27.0  0.574 
Lipid-lowering  917  23.8  161  35.3  <0.001 
Antidepressants  934  24.3  83  18.2  0.004 
Antihistamines  936  24.3  66  14.5  <0.001 
Opioid pain medications  881  22.9  68  14.9  <0.001 
Thyroid hormone  857  22.3  65  14.3  <0.001 
Antiepileptic drugs  563  14.6  58  12.7  0.275 
Anticoagulants  442  11.5  83  18.2  <0.001 
Inhaled bronchodilators and corticosteroids  336  8.7  46  10.1  0.333 
Antidiabetic  232  6.0  30  6.6  0.639 
Antipsychotics  151  3.9  17  3.7  0.840 

IQR: Interquartile range. DMARDs: synthetic disease-modifying antirheumatic drugs. DMARDb: biological disease-modifying antirheumatic drugs.

*

Fisher's exact test.

Comparison among geographical regions

The median age was higher in the Pacific Region than in the other regions. The proportion of patients with chronic comorbidities was lowest in the Caribbean Region, and cardiovascular diseases predominated in all regions. Patients in the Pacific Region had fewer prescriptions for corticosteroids and mycophenolate but more prescriptions for chloroquine, azathioprine and methotrexate than did the other regions. Deflazacort was widely used in the Central Region. The use of anticoagulants was predominant in the Bogotá-Cundinamarca Region (Table 2).

Table 2.

Comparison of sociodemographic, clinical and pharmacological variables according to geographic region for 4307 patients diagnosed with systemic lupus erythematosus in Colombia, 2019–2020.

Variables  Bogota-CundinamarcaCaribbean RegionCentral RegionPacific RegionAmazon-Orinoco and Eastern Region
  n=1491  n=1036  n=878  n=753  n=149 
Woman  1288  86.4  940  90.7  806  91.8  684  90.8  133  89.3 
Man  203  13.6  96  9.3  72  8.2  69  9.2  16  10.7 
Age (median; IQR)  43.4 (31.2–56.2)42.0 (32.4–51.4)45.1 (33.1–56.5)49.3 (35.3–60.3)41.0 (30.5–54.8)
No chronic comorbidities  332  22.3  427  41.2  197  22.4  243  32.3  32  21.5 
With chronic comorbidities  1159  77.7  609  58.8  681  77.6  510  67.7  117  78.5 
Cardiovascular  865  58.0  332  32.0  498  56.7  287  38.1  66  44.3 
Rheumatological  376  25.2  236  22.8  299  34.1  253  33.6  34  22.8 
Endocrine  419  28.1  160  15.4  208  23.7  132  17.5  63  42.3 
Neurological  210  14.1  113  10.9  163  18.6  78  10.4  21  14.1 
Psychiatric  118  7.9  51  4.9  138  15.7  59  7.8  24  16.1 
Renal  131  8.8  59  5.7  61  6.9  55  7.3  12  8.1 
Gastrointestinal  112  7.5  48  4.6  66  7.5  45  6.0  4.7 
Respiratory  35  2.3  23  2.2  23  2.6  26  3.5  3.4 
Cancer  34  2.3  19  1.8  26  3.0  14  1.9  4.7 
Urinary  27  1.8  0.9  13  1.5  1.1  2.0 
Pharmacological management  –  –  –  –  –  –  –  –  –  – 
DMARDs  1369  91.8  915  88.3  795  90.5  684  90.8  138  92.6 
Chloroquine  830  55.7  538  51.9  412  46.9  499  66.3  64  43.0 
Azathioprine  570  38.2  373  36.0  299  34.1  295  39.2  42  28.2 
Hydroxychloroquine  469  31.5  331  31.9  332  37.8  86  11.4  49  32.9 
Methotrexate  287  19.2  119  11.5  168  19.1  159  21.1  25  16.8 
Leflunomide  21  1.4  18  1.7  41  4.7  13  1.7  2.7 
Sulfasalazine  16  1.1  0.8  18  2.1  14  1.9  0.0 
Corticosteroids  1184  79.4  838  80.9  632  72.0  507  67.3  117  78.5 
Prednisolone  1129  75.7  709  68.4  521  59.3  449  59.6  107  71.8 
Prednisone  200  13.4  146  14.1  74  8.4  121  16.1  14  9.4 
Deflazacort  46  3.1  57  5.5  120  13.7  27  3.6  11  7.4 
Methylprednisolone  28  1.9  84  8.1  21  2.4  19  2.5  2.7 
Other immunosuppressants  298  20.0  205  19.8  176  20.0  136  18.1  22  14.8 
Mycophenolate  260  17.4  194  18.7  164  18.7  83  11.0  18  12.1 
Cyclosporine  42  2.8  0.4  11  1.3  54  7.2  2.0 
Cyclophosphamide  0.3  17  1.6  0.6  1.1  0.7 
Tacrolimus  0.3  0.2  0.5  0.5  0.0 
DMARDb  0.0  0.5  0.1  0.5  0.7 
Belimumab  0.0  0.2  0.1  0.4  0.0 
Rituximab  0.0  0.2  0.0  0.0  0.7 
Adalimumab  0.0  0.1  0.0  0.1  0.0 
Comedications  1433  96.1  965  93.1  808  92.0  712  94.6  143  96.0 
Non-opioid pain medications  1014  68.0  699  67.5  548  62.4  486  64.5  107  71.8 
Antiulcer  721  48.4  657  63.4  486  55.4  441  58.6  86  57.7 
Antihypertensives and diuretics  840  56.3  493  47.6  451  51.4  377  50.1  73  49.0 
Platelet antiaggregants  463  31.1  249  24.0  237  27.0  227  30.1  34  22.8 
Lipid-lowering  352  23.6  245  23.6  238  27.1  211  28.0  32  21.5 
Antidepressants  306  20.5  205  19.8  266  30.3  185  24.6  55  36.9 
Antihistamines  328  22.0  276  26.6  212  24.1  157  20.8  29  19.5 
Opioid pain medications  312  20.9  225  21.7  262  29.8  107  14.2  43  28.9 
Thyroid hormone  396  26.6  123  11.9  181  20.6  182  24.2  40  26.8 
Anticonvulsants drugs  197  13.2  136  13.1  173  19.7  91  12.1  24  16.1 
Anticoagulants  269  18.0  73  7.0  93  10.6  68  9.0  22  14.8 
Inhaled bronchodilators and corticosteroids  145  9.7  114  11.0  56  6.4  57  7.6  10  6.7 
Antidiabetic  82  5.5  67  6.5  58  6.6  47  6.2  5.4 
Antipsychotics  34  2.3  30  2.9  55  6.3  38  5.0  11  7.4 

IQR: Interquartile range. DMARDs: synthetic disease-modifying antirheumatic drugs. DMARDb: biological disease-modifying antirheumatic drugs.

Comparison among age groups

Women represented the majority in all age groups. The proportion of comorbidities increased with increasing age. Cardiovascular diseases were predominant in all groups, but their frequency was higher in people older than 65 years. Prescriptions for corticosteroids decreased with increasing age, a trend that was observed with prednisolone and prednisone; for deflazacort, prescriptions increased with age. Chloroquine was predominant for those under 20 years of age, hydroxychloroquine was predominant for those between 20 and 39 years of age, and methotrexate was predominant for those over 40 years of age. Mycophenolate and cyclosporine were prescribed more frequently for children under 20 years of age. Anticoagulants and antiplatelet agents were prescribed more often for patients older than 65 years (Table 3).

Table 3.

Comparison of sociodemographic, clinical and pharmacological variables according to age group for 4307 patients diagnosed with systemic lupus erythematosus in Colombia, 2019–2020.

Variables  <20 years20–39 years40–64 years≥65 years
  n=198  n=1560  n=2120  n=429 
Woman  168  84.8  1396  89.5  1906  89.9  381  88.8 
Man  30  15.2  164  10.5  214  10.1  48  11.2 
No chronic comorbidities  94  47.5  592  37.9  487  23.0  58  13.5 
With chronic comorbidities  104  52.5  968  62.1  1633  77.0  371  86.5 
Cardiovascular  68  34.3  621  39.8  1080  50.9  279  65.0 
Rheumatological  18  9.1  298  19.1  694  32.7  188  43.8 
Endocrine  25  12.6  238  15.3  580  27.4  139  32.4 
Neurological  14  7.1  164  10.5  331  15.6  76  17.7 
Psychiatric  2.5  100  6.4  237  11.2  48  11.2 
Renal  4.5  114  7.3  148  7.0  47  11.0 
Gastrointestinal  3.0  62  4.0  164  7.7  46  10.7 
Respiratory  1.5  11  0.7  62  2.9  36  8.4 
Cancer  1.5  26  1.7  57  2.7  14  3.3 
Urinary  0.5  0.4  33  1.6  19  4.4 
Pharmacological management  –  –  –  –  –  –  –  – 
DMARDs  185  93.4  1437  92.1  1919  90.5  360  83.9 
Chloroquine  149  75.3  877  56.2  1134  53.5  183  42.7 
Azathioprine  78  39.4  612  39.2  747  35.2  142  33.1 
Hydroxychloroquine  33  16.7  566  36.3  563  26.6  105  24.5 
Methotrexate  23  11.6  250  16.0  400  18.9  85  19.8 
Leflunomide  0.0  28  1.8  62  2.9  1.6 
Sulfasalazine  0.0  14  0.9  34  1.6  1.9 
Corticosteroids  172  86.9  1262  80.9  1549  73.1  295  68.8 
Prednisolone  159  80.3  1140  73.1  1371  64.7  245  57.1 
Prednisone  55  27.8  268  17.2  206  9.7  26  6.1 
Deflazacort  2.0  86  5.5  130  6.1  41  9.6 
Methylprednisolone  3.5  57  3.7  77  3.6  15  3.5 
Other immunosuppressants  83  41.9  391  25.1  317  15.0  46  10.7 
Mycophenolate  72  36.4  343  22.0  268  12.6  36  8.4 
Cyclosporine  15  7.6  41  2.6  48  2.3  10  2.3 
Cyclophosphamide  0.0  25  1.6  10  0.5  0.2 
Tacrolimus  0.0  0.4  0.4  0.0 
DMARDb  0.0  0.4  0.1  0.5 
Belimumab  0.0  0.3  0.0  0.2 
Rituximab  0.0  0.1  0.1  0.0 
Adalimumab  0.0  0.1  0.0  0.2 
Comedications  179  90.4  1454  93.2  2010  94.8  418  97.4 
Non-opioid pain medications  84  42.4  991  63.5  1467  69.2  312  72.7 
Antiulcer  98  49.5  762  48.8  1258  59.3  273  63.6 
Antihypertensives and diuretics  107  54.0  725  46.5  1114  52.5  288  67.1 
Platelet antiaggregants  45  22.7  416  26.7  594  28.0  155  36.1 
Lipid-lowering  15  7.6  271  17.4  620  29.2  172  40.1 
Antidepressants  14  7.1  282  18.1  597  28.2  124  28.9 
Antihistamines  36  18.2  359  23.0  501  23.6  106  24.7 
Opioid pain medications  12  6.1  306  19.6  528  24.9  103  24.0 
Thyroid hormone  15  7.6  208  13.3  533  25.1  166  38.7 
Anticonvulsants drugs  17  8.6  164  10.5  373  17.6  67  15.6 
Anticoagulants  11  5.6  209  13.4  240  11.3  65  15.2 
Inhaled bronchodilators and corticosteroids  4.5  104  6.7  187  8.8  82  19.1 
Antidiabetic  1.0  37  2.4  171  8.1  52  12.1 
Antipsychotics  1.0  49  3.1  96  4.5  21  4.9 

DMARDs: synthetic disease-modifying antirheumatic drugs. DMARDb: biological disease-modifying antirheumatic drugs.

Discussion

The prescription patterns of drugs used for patients diagnosed with SLE of any age and sex in a group of Colombian patients were identified, with characterizations of the differences or similarities in treatment according to age group, sex, and geographical region. SLE occurred more frequently in women, consistent with what is widely documented in other studies,11–15 and the mean age (44.2 years) was in agreement with what was found in the United States (44.5–46.0 years)12,16 Switzerland (44.8 years)13 and Jamaica (45.1 years)17 but higher than previously described in Canada (40.6 years)18 and Colombia (38.4 years).6

Overall, corticosteroids were prescribed to 76.1% of patients, a similar rate to that found in the United States (78.8%)16 but much more frequent than that reported for Canada (53.2%),18 Puerto Rico (50.9%)14 and Switzerland (48.0%).13 Among DMARDs, the use of chloroquine stood out, differing markedly from reports in other studies where the use of hydroxychloroquine was predominant (43.4–91.3%).11,13,16,17 The probable explanation for this result is that in Colombia, hydroxychloroquine is not included in the health benefits plan and has a higher cost compared to chloroquine, which can make access to it difficult.19 However, chloroquine has been associated with greater adverse drug reactions and a worse safety profile, especially regarding the risk of retinopathy.20 It was found that mycophenolate was prescribed more frequently in Colombia than in countries such as Korea (2.2%)21 and the United States (3.3%),11 whereas DMARDb were rarely used, similar to what has been reported in the literature.11,21 In general, our hypothesis is that the differences and similarities found could be explained by the degree of activity and severity of SLE because in mild and moderate cases, antimalarials and corticosteroids are the recommended drugs, whereas when the disease progresses or is refractory, higher doses of corticosteroids, immunosuppressants or DMARDb are necessary7–9; however, we do not know the degree of disease activity in this cohort.

In addition to the above, cyclophosphamide that is indicated in patients with lupus nephritis22 has been prescribed in 10.5% of patients in a Colombian cohort6 and in 29.2% of patients in a Latin American cohort,23 in marked contrast to the minimum proportion of patients who had it prescribed in this study. This is probably because cyclophosphamide when administered intravenously will require it to be performed in the hospital, and as the drug dispensing information used in this research only involves outpatient medications, it is highly likely that the patients who received this medication have not been fully identify them.

The prescription pattern for these drugs showed important differences when comparing women and men. There is limited information available in this regard; however, a study by Santamaría-Alza et al. that included 200 patients with SLE found significant differences in the use of cyclophosphamide between women and men (8.3% vs. 22.6%, respectively, p=0.017),6 a result that was not found in this study. In addition, they found no differences in the proportion of use of other drugs used to manage SLE,6 which contrasts with the results found in the present study, i.e., corticosteroid, chloroquine, azathioprine and mycophenolate prescriptions were predominant for men, whereas azathioprine and hydroxychloroquine prescription were predominant for women. These findings are related to the clinical differences and the frequency of complications between women and men; renal disease, serositis and thrombocytopenia are predominant in the latter.24 In the United States, Pelletier et al. compared patients with and without lupus nephritis and found that the use of corticosteroids, immunosuppressants and antimalarials was more frequent in patients with kidney disease.25

Different clinical pictures of SLE have been observed in children and adults. In children, the disease is more active, with a much more aggressive progression and with more complications, which affects the type of treatment used.3,15,26 In this analysis, prescription patterns were investigated according to age group, showing greater use of chloroquine, immunosuppressants and corticosteroids in patients under 20 years of age. A study conducted in Canada compared pediatric and adult patients with SLE and reported similar findings; i.e., corticosteroids (97.0% vs. 70.0%; p<0.0001) and immunosuppressants (66.0% vs. 37.0%; p=0.0001) were prescribed more to children, whereas methotrexate was prescribed more to adults (31.0% vs. 9.0%; p=0.009).15 In Hungary, it was found that mycophenolate was prescribed much more frequently to children than to adults (15.2% vs. 5.3%; p=0.0056),26 results that are similar to those for the United States (28.1 vs. 13.0; p<0.001)27 and in agreement with our results.

The drugs used for the management of SLE were prescribed differently among the different geographical regions of Colombia. This pattern had already been evidenced in another pharmacoepidemiological study that compared the prescription of ambulatory antibiotics in the different regions of the country28 and is probably due to the prescribing habits of physicians, to the academic training of physicians, to the variability in the availability of drugs, to the influence of the pharmaceutical industry and to the health system affiliation regime. Thus, for example, in Argentina, cyclophosphamide was administered more frequently in the public health system than in the private system, while the use of corticosteroids, antimalarials and immunosuppressants was similar between the two systems.29

Finally, it is important to highlight that, during the study period, the first months of the mandatory preventive isolation (confinement) caused by the pandemic of Coronavirus Disease 2019 (COVID-19) in Colombia were included, without affecting the dispensing of drugs in patients with systemic lupus erythematosus present in the study.

Some limitations in the interpretation of the results are recognized because access to medical records was not obtained to verify the patients’ diagnoses and their hospitalizations and the activity, severity and complications of the disease or comorbidity such as antiphospholipid antibody syndrome. In addition, the drugs prescribed outside the health system or that were not delivered by the dispensing company and the drug induction cycles that the patients may have received are unknown. However, the sample included many patients distributed throughout most of the Colombian territory and both the contributory and subsidized regimes.

Conclusions

Given the above findings, it can be concluded that there are differences in the prescription of drugs used for patients with SLE according to age group, sex and geographical regions of the country. Patients with SLE in Colombia are treated with DMARDs, especially chloroquine and azathioprine, with corticosteroids, particularly prednisolone, and with immunosuppressants such as mycophenolate, and infrequently receive DMARDb. In addition, they frequently have cardiovascular, rheumatologic and endocrine comorbidities and, in addition to drugs for the management of SLE, are prescribed nonopioid analgesics, antiulcers and antihypertensives. Knowledge of the differences in management found can be useful to guide treating physicians and health plan administrators to manage the resources necessary to meet the needs of this important group of patients.

Sources of funding

The present study did not receive funding.

Conflict of interest

The authors declare no conflict of interest.

Acknowledgments

The authors acknowledge Soffy Claritza López for her work in obtaining the database.

References
[1]
A. Kaul, C. Gordon, M.K. Crow, Z. Touma, M.B. Urowitz, R. van Vollenhoven, et al.
Systemic lupus erythematosus.
Nat Rev Dis Primers, 2 (2016), pp. 16039
[2]
I. Gergianaki, A. Bortoluzzi, G. Bertsias.
Update on the epidemiology, risk factors, and disease outcomes of systemic lupus erythematosus.
Best Pract Res Clin Rheumatol, 32 (2018), pp. 188-205
[3]
P.K. Bundhun, A. Kumari, F. Huang.
Differences in clinical features observed between childhood-onset versus adult-onset systemic lupus erythematosus: a systematic review and meta-analysis.
Medicine (Baltimore), 96 (2017), pp. e8086
[4]
S. Stefanidou, A. Benos, V. Galanopoulou, I. Chatziyannis, F. Kanakoudi, S. Aslanidis, et al.
Clinical expression and morbidity of systemic lupus erythematosus during a post-diagnostic 5-year follow-up: a male:female comparison.
Lupus, 20 (2011), pp. 1090-1094
[5]
D.G. Fernández-Ávila, S. Bernal-Macías, D.N. Rincón-Riaño, J.M. Gutiérrez Dávila, D. Rosselli.
Prevalence of systemic lupus erythematosus in Colombia: data from the national health registry 2012–2016.
Lupus, 28 (2019), pp. 1273-1278
[6]
Y. Santamaría-Alza, J.Z.N. Motta, J.E. Fajardo-Rivero, C.L.F. Pineda.
Systemic lupus erythematosus, gender differences in Colombian patients.
Clin Rheumatol, 37 (2018), pp. 2423-2428
[7]
A. Fanouriakis, M. Kostopoulou, A. Alunno, M. Aringer, I. Bajema, J.N. Boletis, et al.
2019 update of the EULAR recommendations for the management of systemic lupus erythematosus.
Ann Rheum Dis, 78 (2019), pp. 736-745
[8]
C. Gordon, M.B. Amissah-Arthur, M. Gayed, S. Brown, I.N. Bruce, D. D’Cruz, et al.
The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults: executive summary.
Rheumatology (Oxford), 57 (2018), pp. 14-18
[9]
B.A. Pons-Estel, E. Bonfa, E.R. Soriano, M.H. Cardiel, A. Izcovich, F. Popoff, et al.
First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)-Pan-American League of Associations of Rheumatology (PANLAR).
Ann Rheum Dis, 77 (2018), pp. 1549-1557
[10]
J.A. Singh, A. Hossain, A. Kotb, G. Wells.
Risk of serious infections with immunosuppressive drugs and glucocorticoids for lupus nephritis: a systematic review and network meta-analysis.
[11]
F. Kariburyo, L. Xie, J. Sah, N. Li, J.H. Lofland.
Real-world medication use and economic outcomes in incident systemic lupus erythematosus patients in the United States.
[12]
H. Kan, S. Nagar, J. Patel, D.J. Wallace, C. Molta, D.J. Chang.
Longitudinal treatment patterns and associated outcomes in patients with newly diagnosed systemic lupus erythematosus.
[13]
C. Ribi, M. Trendelenburg, A. Gayet-Ageron, C. Cohen, E. Dayer, U. Eisenberger, et al.
The Swiss Systemic lupus erythematosus Cohort Study (SSCS) – cross-sectional analysis of clinical characteristics and treatments across different medical disciplines in Switzerland.
Swiss Med Wkly, 144 (2014), pp. w13990
[14]
M.J. Molina, A.M. Mayor, A.E. Franco, C.A. Morell, M.A. López, L.M. Vilá.
Utilization of health services and prescription patterns among lupus patients followed by primary care physicians and rheumatologists in Puerto Rico.
Ethn Dis, 182 (2008), pp. S2-S205
[15]
H.I. Brunner, D.D. Gladman, D. Ibañez, M.D. Urowitz, E.D. Silverman.
Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus.
Arthritis Rheum, 58 (2008), pp. 556-562
[16]
E. Nyman, T. Vaughan, B. Desta, X. Wang, V. Barut, C. Emmas.
Characteristics and symptom severity of patients reporting systemic lupus erythematosus in the patientslikeme online health community: a retrospective observational study.
Rheumatol Ther, 7 (2020), pp. 201-213
[17]
K.C. Maloney, T.S. Ferguson, H.D. Stewart, A.A. Myers, K. De Ceulaer.
Clinical and immunological characteristics of 150 systemic lupus erythematosus patients in Jamaica: a comparative analysis.
Lupus, 26 (2017), pp. 1448-1456
[18]
J.G. Hanly, A. Sayani, S. Doucette, S. Iczkovitz, J.A.R. Terres.
Treatment pathways in an inception lupus cohort over the first three years.
Lupus, 26 (2017), pp. 119-124
[19]
Ministerio de Salud y Protección Social. Resolución número 0003512 de 2019. Available from: https://www.minsalud.gov.co/salud/POS/Paginas/plan-obligatorio-de-salud-pos.aspx [accessed 21.9.20].
[20]
E.T. Dos Reis Neto, A.M. Kakehasi, M. de Medeiros Pinheiro, G.A. Ferreira, C.D.L. Marques, L.M.H. da Mota, et al.
Revisiting hydroxychloroquine and chloroquine for patients with chronic immunity-mediated inflammatory rheumatic diseases.
Adv Rheumatol, 60 (2020), pp. 32
[21]
S. Shin.
Drug utilization and therapy provision patterns by prescriber types among patients with systemic lupus erythematosus in Korea.
Patient Prefer Adherence, 11 (2017), pp. 1779-1787
[22]
Cyclophosphamide. In: Drug Point Summary [database on the Internet]. Greenwood Village (CO): IBM Corporation; 2021. Available from: www.micromedexsolutions.com [cited 19.5.21]. Subscription required to view.
[23]
G.J. Pons-Estel, L.J. Catoggio, M.H. Cardiel, E. Bonfa, F. Caeiro, E. Sato, et al.
Lupus in Latin-American patients: lessons from the GLADEL cohort.
Lupus, 24 (2015), pp. 536-545
[24]
K.D. Boodhoo, S. Liu, X. Zuo.
Impact of sex disparities on the clinical manifestations in patients with systemic lupus erythematosus: a systematic review and meta-analysis.
Medicine (Baltimore), 95 (2016), pp. e4272
[25]
E.M. Pelletier, S. Ogale, E. Yu, P. Brunetta, J. Garg.
Economic outcomes in patients diagnosed with systemic lupus erythematosus with versus without nephritis: results from an analysis of data from a US claims database.
Clin Ther, 31 (2009), pp. 2653-2664
[26]
T. Tarr, B. Dérfalvi, N. Győri, A. Szántó, Z. Siminszky, A. Malik, et al.
Similarities and differences between pediatric and adult patients with systemic lupus erythematosus.
Lupus, 24 (2015), pp. 796-803
[27]
A.O. Hersh, E. von Scheven, J. Yazdany, P. Panopalis, L. Trupin, L. Julian, et al.
Differences in long-term disease activity and treatment of adult patients with childhood- and adult-onset systemic lupus erythematosus.
Arthritis Rheum, 61 (2009), pp. 13-20
[28]
J.E. Machado-Alba, L.F. Valladales-Restrepo, A. Gaviria-Mendoza, M.E. Machado-Duque, A. Figueras.
Patterns of antibiotic prescription in Colombia: are there differences between capital cities and municipalities?.
Antibiotics (Basel), 9 (2020), pp. 389
[29]
M.M. Schmid, S.G. Roverano, S.O. Paira.
Comparing demographics, clinical presentation, treatments and outcome between systemic lupus erythematosus patients treated in a public and private health system in Santa Fe, Argentina.
Reumatol Clin, 10 (2014), pp. 294-298
Copyright © 2021. Asociación Colombiana de Reumatología
Opciones de artículo
Herramientas