Autoimmune Idiopathic Inflammatory Myopathies: Pharmacological Differences and Similarities by Type of Myositis and by Sociodemographic Variables

Objective Autoimmune idiopathic inflammatory myopathies (IIMs) are a group of pathologies that are generally characterized by muscle weakness. Their treatment involves glucocorticoids and immunosuppressants. The aim was to identify differences and similarities in the pharmacological management of a group of patients with autoimmune IIMs according to the type of disease, sex, age group, and city of residence in Colombia from 2020 to 2021. Methods This cross-sectional study identified medication prescription patterns for outpatient use in patients with autoimmune IIMs between 2020 and 2021 based on a population database of 8.5 million Colombians affiliated with the Colombian health system. Sociodemographic and pharmacological variables were considered. Results A total of 671 patients with autoimmune IIMs were identified, with a median age of 57 years, and 70.9% were women. Overlap myositis was the most frequent disease (31.4%). A total of 91.5% of the patients received pharmacological treatment, mainly systemic glucocorticoids (78.5%), conventional disease-modifying antirheumatic drugs (DMARDs) (74.1%), immunosuppressants (9.1%), and biological DMARDs (3.7%). Pharmacological management predominated among patients with overlap myositis, those who lived in cities, and those affiliated with the contributory regime of the Colombian health system. Conventional DMARDs were prescribed mainly to women and to those older than 65 years. Conclusions Patients with autoimmune IIMs are not treated homogeneously. The pattern of drug use varies according to the type of IIM, sex, age group, city, and health system regime affiliation.


Introduction
Autoimmune idiopathic inflammatory myopathies (IIMs) are a group of rare immune-mediated, multisystemic, heterogeneous diseases that mainly affect skeletal muscle and the skin but can also affect many other organs, such as the lungs, heart, joints, and gastrointestinal tract [1][2][3]. They are mainly char-acterized by progressive, symmetrical muscle weakness, and sometimes myalgias, but in addition, heliotrope erythema, Gottron papules, and cutaneous ulcers may appear on the skin. Extramuscular manifestations may also emerge, such as fever, arthralgia, Raynaud's phenomenon, arrhythmias, and dysfunction. Ventricular and pulmonary complications are mainly due to interstitial lung disease [4][5][6]. The prevalence varies between 2.4 and 33.8 per 100,000 inhabitants, and the incidence ranges from 1.16 to 19 per million people per year [7]. In Colombia, the estimated global prevalence is 25.7 cases per 100,000 inhabitants [8].
IIMs traditionally include polymyositis, dermatomyositis, juvenile dermatomyositis, inclusion body myositis, immunemediated necrotizing myopathy, and antisynthetase syndrome [1,3,9]. In addition, inflammation of the skeletal tissue can occur in the context of other connective tissue diseases, such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, and systemic sclerosis, a condition called overlap myositis [3,5]. Its management seeks to control the inflammatory process and prevent damage to skeletal muscle or extramuscular organs [2]. Depending on the type of autoimmune IIM and its severity and complications, systemic glucocorticoids, conventional disease-modifying antirheumatic drugs (DMARDs) (especially azathioprine or methotrexate), or immunosuppressants (primarily cyclophosphamide, cyclosporine, human mycophenolate mofetil, or gamma-globulin) are prescribed. Biological DMARDs (mainly rituximab) [2-4, 6, 10] are given, but the response to treatment varies [3]. The Colombian health system offers universal coverage to the entire population through two regimes, including one contributory (paid by the worker and employer) and another subsidized by the state, and has a benefit plan that includes a heterogeneous group of medications used for the treatment of autoimmune IIMs. Sociodemographic factors such as age, sex, location of residence, and type of health system coverage can influence the use of medications [11][12][13], as well as the type of autoimmune IIM diagnosed [14]. Therefore, we aimed to identify differences and similarities in the pharmacological management of a group of Colombian patients with autoimmune IIMs according to the type of disease, sex, age group, place of residence (capital city vs. smaller city), and system regime affiliation in 2020-2021.

Materials and Methods
An observational cross-sectional study was conducted on the prescription patterns of drugs used in patients diagnosed with autoimmune IIMs based on a population database that collects information from approximately 8.5 million people affiliated with the Colombian health system through six health insurance companies, corresponding to approximately 30.0% of the active affiliated population of the contributory or payment regime and 6.0% of the statesubsidized regime, accounting for 17.3% of the Colombian population.
Patients were identified and classified using International Classification of Diseases (ICD-10) codes, including those for juvenile dermatomyositis (M330), dermatomyositis (M331), polymyositis (M332), and dermatopolymyositis (M339) in the period between January 1, 2020, and December 31, 2021. Patients with a concomitant diagnosis of rheumatoid arthritis (M053, M058-M060, M068, M069, and M080), systemic sclerosis (M340, M348, and M349), systemic lupus erythematosus (M321, M328, and M329), and Sjögren's syndrome (M350) were considered to have overlap myositis. Patients of any age and sex who attended outpa-tient medical consultations were selected. Those with two or more different diagnoses of autoimmune IIMs and those who appeared only once with a considered diagnosis in the study period were excluded.

Associations between the Type of Autoimmune Idiopathic Inflammatory Myositis and Some Sociodemographic
Variables. Systemic glucocorticoids, immunosuppressants, and conventional and biological DMARDs predominated in a statistically significant manner in overlap myositis (Table 1  and Supplementary Table 1). Prednisolone, prednisone, and conventional DMARDs were prescribed significantly more frequently to women ( Table 2). With respect to age, conventional DMARDs were used more often in adults older than 65 years, but chloroquine predominated among those younger than 65 years (Table 3). Significant differences were found between the place of origin and the type of health system regime affiliation, where pharmacological treatment and the use of conventional DMARDs predominated among patients from capital cities and among those affiliated with the contributory regime (Tables 4 and 5, respectively).

Discussion
This study allowed us to identify the pattern of prescription medications taken by patients with autoimmune IIMs as evidence of the use of medications in the real world in a group of people affiliated with the Colombian health system. To the best of our knowledge, this is the largest study of patients with these pathologies in Colombia or Latin America. The median age of the patients was higher than that found in other studies (34.3-52.5 years) [9,[14][15][16][17][18], although a predominance of women was found in all such studies (63.3-69.0-82.7%) [9,[14][15][16][17][18][19][20]. On the other hand, the characterization of the main comorbidities was also consistent with that found in other publications [12,14,17,18,21].
In this analysis, most patients were diagnosed with overlap myositis, which is consistent with observations reported by Chinniah and Mody in a cohort from South Africa (39.4%) [19] but is not consistent with observations found in the European registry of inflammatory myopathies (Euro-Myositis Registry), where dermatomyositis predominated (31.0%) [9], as in Asia (42.0-63.3%) [15,16,22] and South America (43.9-62.9%) [17,21], while in Spain, cases of polymyositis prevailed (29.0-40.1%) [14,18]. These differences may be methodological in nature, deriving from the type of study, the inclusion and exclusion criteria, the method of identifying the patients, the source of information, the diagnostic criteria used, and the period during which the cases were identified, as well as the different geographical regions where the research was conducted [8, 9, 14-19, 21, 22]. In this study, the patients were identified by their ICD-10 codes, but the ICD-10 does not have an exact diagnosis for some autoimmune IIMs, such as antisynthetase syndrome, immune-mediated necrotizing myopathy, and inclusion body myositis [23], which leads to the available codes being used to cover different types of myositis [3].
Most patients received some medication for their autoimmune IIMs in contrast to data found in the EuroMyositis Registry, where only one-third of patients were receiving treatment at the time of publication [9]. The proportion of  [12] but was higher than that found in the EuroMyositis Registry (31.6%) [9] and in the last consultation of the Myopathies Registry of the Community of Madrid (REMICAM Cohort) (56.6%) [14]. Among the conventional DMARDs, azathioprine and methotrexate were  International Journal of Rheumatology the most commonly used, which is consistent with other reports [9,[14][15][16][17][18]22]. Among the biological DMARDs, rituximab was the most commonly used, which is also con-sistent with the literature [9,12,14,17,18,22]. On the other hand, among the immunosuppressants, a predominance of mycophenolate mofetil was found, which is consistent with   International Journal of Rheumatology   International Journal of Rheumatology findings in India [22] and the USA [12] but not with findings in other countries, where cyclophosphamide prevailed [14,15,17,18]. The differences in drug use patterns may be due to the characteristics of health systems, the accessibility and availability of drugs in each country, the management guidelines followed, the preferences of the prescriber, the marketing strategies of the pharmaceutical industry, the disease severity and complications, the type of myopathy, the disease course, and the patient tolerability to these drugs [6,11,24]. In general, most patients with autoimmune IIMs were treated with the medications indicated by guidelines [3][4][5][6]10], but notably, the management of IIMs is challenging due to the heterogeneous behavior of the different entities and the absence of multidisciplinary and comprehensive management guidelines [3,6] and evidence-based recommendations for the management of patients with extramuscular conditions, comorbidities, and severe manifestations [6]. In this study, differences were found in the pattern of drug use according to the type of autoimmune IIM, which is consistent with other reports [9,17,22]. The predominance of different therapeutic groups among patients with overlap myositis is notable, as described in Spain, where Nuño-Nuño et al. found that these patients had more prescriptions for glucocorticoids, methotrexate, mycophenolate, and cyclophosphamide than those who diagnosed with dermatomyositis or polymyositis [14]. In China, Xiao et al. found sociodemographic, clinical, and paraclinical differences between these patients, but their pharmacological treatments were not evaluated [25]. The greater use of medications in this group of patients is due to the concomitant presence of other connective tissue diseases [14,15,21,26,27]. On the other hand, patients with inclusion body myositis do not usually respond to the therapies recommended for other autoimmune IIMs [3][4][5]10]. However, these cases could not be identified due to the methodological limitations of our study.
Drug prescriptions were not homogeneous with respect to certain sociodemographic variables. Prednisolone/prednisone and conventional DMARDs prevailed among women. Such differences between sexes have also been documented in studies involving other rheumatological diseases [11,28,29]. Thus, among patients with systemic lupus erythematosus, glucocorticoids, immunosuppressants, chloroquine, and azathioprine predominate for men [11]. In patients with axial spondyloarthropathies, prednisone and conventional DMARDs prevail for women [28], and among patients with ankylosing spondylitis, glucocorticoids and methotrexate predominate for women, while biological DMARDs predominate for men [29]. These differences in treatment, rather than being due to health inequalities due to sex, are better explained by genetic and hormonal differences between men and women, the greater burden of autoimmune morbidity in women-which affects the degree of activity, the progression, the severity, and the prognosis of rheumatological diseases-and the effectiveness of pharmacological therapy [11,[28][29][30].
In general, treatment with conventional DMARDs strongly predominated among older adults, which differs from observations in patients with systemic lupus erythematosus, where pharmacological therapy with conventional