Clin Rheumatol DOI 10.1007/s10067-014-2801-1
BRIEF REPORT
The descriptive epidemiology of rheumatoid arthritis in Catalonia: a retrospective study using routinely collected data F. Fina-Aviles & M. Medina-Peralta & L. Mendez-Boo & E. Hermosilla & J. M. Elorza & M. Garcia-Gil & R. Ramos & B. Bolibar & M. K. Javaid & C. J. Edwards & C. Cooper & N. K. Arden & D. Prieto-Alhambra
Received: 19 August 2014 / Revised: 1 October 2014 / Accepted: 12 October 2014 # International League of Associations for Rheumatology (ILAR) 2014
Abstract Information on the epidemiology of rheumatoid arthritis (RA) in Southern Europe is scarce. We estimated the age- and gender-adjusted incidence and prevalence of RA in Catalonia using routinely collected primary care records. We identified incident (2009–2012) and prevalent (on 31 December 2012) cases of RA in the SIDIAP database using ICD-10 codes. SIDIAP contains anonymized data from computerized primary care records for about five million adults (>80 % of the population). We estimated age- (5-year groups) and gender-specific, and directly standardized incidence and F. Fina-Aviles : M. Medina-Peralta : L. Mendez-Boo : M. Garcia-Gil : R. Ramos Primary Care Department, Institut Català de la Salut, Av Gran Via de les Corts Catalanes 587, 3rd floor, 08007 Barcelona, Spain E. Hermosilla : J. M. Elorza : M. Garcia-Gil : R. Ramos : B. Bolibar : D. Prieto-Alhambra IDIAP Jordi Gol Primary Care Research Institute, Universitat Autònoma de Barcelona, Av Gran Via de les Corts Catalanes 587, Atic, 08007 Barcelona, Spain M. K. Javaid : C. Cooper : N. K. Arden : D. Prieto-Alhambra Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, OX3 7LD Oxford, UK M. K. Javaid : C. Cooper : N. K. Arden : D. Prieto-Alhambra MRC Lifecourse Epidemiology Unit, University of Southampton, Tremona Road, SO16 6YD Southampton, UK C. J. Edwards Southampton General Hospital, Tremona Road, SO16 6YD Southampton, UK D. Prieto-Alhambra (*) SIDIAP Database, IDIAP Jordi Gol, Av Gran Via Corts Catalanes, 587, Atic, 08007 Barcelona, Spain e-mail: [email protected]
prevalence of RA and confidence intervals (95% CIs) assuming a Poisson distribution. A total of 20,091 prevalent (among whom 5,796 incident) cases of RA were identified among 4,796,498 study participants observed for up to 4 years. Rates of RA increased with age in both genders, peaking at the age of 65–70 years. Age- and gender-standardized incidence and prevalence rates were 0.20/1,000 person-years (95% CI 0.19– 0.20) and 4.17/1,000 (4.11–4.23) respectively. Rheumatoid factor was positive (≥10 IU/mL) in 1,833 (73.9 %) of 2,482 cases tested in primary care. The incidence and prevalence of RA in Catalonia are similar to those of other Southern European regions, and lower than those of northern areas. This data will inform health care planning and resource allocation. Keywords Arthritis . Electronic health records . Epidemiology . Incidence . Prevalence . Rheumatoid
Introduction Rheumatoid arthritis (RA) is the most common type of inflammatory arthritis [1]. One of its intriguing characteristics is the heterogeneity of its geographical distribution: The prevalence of RA is 4- or 5-fold higher in countries like the USA (1.1 %) [2] or England (8.5/1,000) compared to that in others like Argentina (2/1,000) [3] or South Korea (3/1,000) [4]. In general, countries with Northern European populations have a higher prevalence of RA than those with Southern European populations. However, this is not universally reported: A systematic review on the prevalence of RA [5] revealed almost double the prevalence of RA in a Southern European (Greece) compared to a Northern European Scandinavian (Norway) region. Therefore, accurate descriptions of the epidemiology of RA should be derived for each individual
Clin Rheumatol
country to inform local health care planning and allocation of resources. This is particularly important for Southern European regions, and Spain in particular, where there is a scarcity of high-quality data. In addition to health care planning, knowledge of the epidemiology of RA is also essential for a better understanding of the pathogenesis of the disease. We therefore used data from a large primary care database to calculate population-based age- and gender-specific incidence and prevalence rates of RA in a Southern European region (Catalonia, Spain). Second, we provide updated estimates of age- and gender-standardized incidence and prevalence of RA for the same population.
Methods Study design Population-based retrospective cohort study. Source of data and study participants The SIDIAP database (www.sidiap.org) contains clinical information as recorded by primary care physicians and nurses in the medical records of >70 % of the population aged 14 years or above of Catalonia, Spain (about 5.4 million people) according to the Spanish National Office of Statistics (www.ine.es). General practitioners and nurses code clinical events using ICD-10 codes, and each participant is assigned a unique anonymous identifier to ensure confidentiality. The data is highly representative for the whole population of the region [6], and it has been widely used to study the epidemiology of a number of musculoskeletal conditions such as osteoporotic fractures [7, 8] and osteoarthritis [9, 10]. In addition, SIDIAP contains all the information on results obtained from blood tests performed in primary care settings, as well as on all the medications dispensed by prescription in community pharmacies for all participants. Medicines data is stored using ATC codes. All participants in the SIDIAP database in the study period (1 January 2009 to 31 December 2012) were included. Identification of RA cases Incident (newly diagnosed in the years 2009–2012 with no prior diagnosis of RA in at least 3 previous years) and prevalent (on 31 December 2012) cases of RA were identified using ICD-10 codes (M05 and M06) as registered in primary care records. Based on a modified algorithm proposed to identify patients with RA in the British GPRD database [11], patients with no prescriptions of disease-modifying anti-rheumatic drugs (DMARDs) and with a potential alternative diagnosis (osteoarthritis, psoriasic arthritis, ankylosing spondylitis, other spondylo-arthropathies, gout, reactive arthritis,
septic arthritis, systemic lupus erytematous, dermato-polymyositis, sclerodermia and fybromyalgia) following the recording of an RA code were re-classified as non-RA patients. Finally, we looked at the results of rheumatoid factor measurements performed in primary care settings in the year prior to an RA diagnosis amongst incident cases, expecting about 75 % of them to be sero-positive (≥10 IU/mL) in an RA population based on previous literature reporting on the prevalence of sero-positivity in a community-based series of RA patients [12]. Statistical analyses Specific incidence and prevalence rates for RA (and 95 % confidence intervals) were calculated for each age (in 5-year groups) and gender strata assuming a Poisson distribution. Age-specific (unadjusted) female-to-male rate ratios (RRs) were then estimated for each of the previously specified 5year groups and plotted against age. We used the direct method to estimate age- and genderstandardized incidence and prevalence rates of RA in the overall study population (using the entire RA-free population registered in SIDIAP in the study period as a reference), as well as age-standardized rates for female and male participants separately. The statistical analyses were carried out using Stata version 12.0 SE for Mac.
Results Data was available for 4,895,307 patients: 2,423,177 (49.5 %) men and 2,472,130 (50.5 %) women, with a mean (standard deviation) age of 46.9 (19.1) years. Amongst these, 5,796 (0.12 %) incident and 20,091 (0.41 %) prevalent cases of RA were identified. The age- and gender-specific incidence rates of RA are represented in Fig. 1 and reported in detail in Table 1. These were always higher among women at all ages and peaked for both genders at a similar age of 65–70 years with incidence rates of 0.51/1,000 person-years in women compared to 0.31/ 1,000 in men. Interestingly, we observed a first incidence peak in women aged 50–55 years, which was not apparent in the male population. The gender-related excess risk was highest in younger ages, with a maximum female/male rate ratio of 4.18 amongst participants aged 25–30 years, and then decreased reaching a trough in the sixth and seventh decades of life (Fig. 1). The age- and gender-standardized incidence of RA was 0.20/1,000 person-years (0.19 to 0.20), with agestandardized rates of 0.28 (0.27 to 0.29) in women and 0.12 (0.11 to 0.12) in men (female-to-male RR 2.44). Out of 5,796 incident cases of RA, 2,482(42.8 %) had a rheumatoid factor test in primary care in the year before the
Clin Rheumatol Fig. 1 Age- and gender-specific incidence rates (per 100,000 person-years at risk) and age-specific female-to-male rate ratios (F:M RRs) of RA in Catalonia, Spain
date of their diagnosis, and 1,833 (73.9 %) of these were seropositive (≥10 IU/mL). The prevalence of RA was higher in women at all ages compared to that in men of a similar age (Table 2). The proportion of affected patients increased with age for both genders, peaking in the seventh decade of life, with a top prevalence of 11.77/1,000 and 6.72/1,000 in women and men respectively (Fig. 2). The crude prevalence of RA in the population aged ≥15 years old was of 4.1/1,000, and age- and gender-standardized prevalence was 4.17/1,000 (95 % confidence interval 4.11 to 4.23). Corresponding age-standardized prevalence rates were 5.80/1,000 (5.70 to 5.89) in women and 2.50/1,000 (2.44 to 2.56) in men.
Discussion We report the first population-based estimates of age- and gender-adjusted incidence and prevalence rates of RA in Catalonia, Spain. The sample size available, including almost five million participants and up to 4 years of follow-up, allows us to accurately characterize the effect of age and gender on the risk of RA in the community. In our data, the proportion of the population affected with RA increases with age in both men and women, peaking at the age of 65–70 years, with women having always a higher prevalence of disease at all ages. The age- and genderstandardized prevalence of RA in our data (4.2/1,000 in the overall study population) overlaps with that published by Carmona et al. [13] in the only population-based prevalence study performed in Spain to date, which reported a crude prevalence of 5/1,000 (95 % CI 3 to 9/1,000). That study recruited a representative sample of 2,192 participants aged
20 years or above, including only 11 prevalent cases of RA compared to >20,000 affected patients in our current report. Only one previous study has estimated the incidence of RA in Spain [14]: A nationwide clinical cohort reported crude rates of “early arthritis” of 0.25/1,000 cases, but a short follow-up of only 6 months led to a confirmed diagnosis of RA in only 1 in 3 of these (0.083/1,000). In our study, age- and gender-standardized rates were higher at almost 0.20/ 1,000 person-years. A longer follow-up of up to 4 years for confirmation of incident diagnoses might partially explain the observed differences. Geographical variation within Spain, with northern areas such as Catalonia having higher rates of RA disease, as has been observed worldwide [5], might also contribute to the observed disparity. In an international context, our data position Catalonia (northeast Spain) as a region with an incidence and prevalence of RA in the lower range, similar to other countries in Southern Europe such as France [15, 16] (prevalence 5/1,000, incidence 0.10/1,000), Italy (prevalence 5.1/1,000 in Tuscany) [17], Turkey (prevalence 4.9/1,000) [18] or Greece [19, 20] (prevalence 7/1,000, incidence 0.20/1,000). In comparison, studies have shown the highest prevalence rates in northern populations including the USA (prevalence 10.7/1,000) [21], England (prevalence 8.5/1,000) [22] or Finland (prevalence 8/1,000) [23], and lowest prevalence in southern (prevalence 3.6/1,000 in Oman) [24] and western (prevalence 2.8/1,000 in China) [25] populations. One interesting finding in our data is the peak in age- and gender-specific incidence rates of RA observed among women (and not among men) aged 50 to 54 years old. We speculate that this finding may be due to the effects of oestrogen depletion related to the menopause on the onset of RA: Previous data has suggested an association between early menopause and an increased risk of RA [26], with hormone
Clin Rheumatol Table 1 Incidence rates of rheumatoid arthritis according to age (5-year groups) and gender in the period 2009–2012 Women Age
No. of incident RA cases
Person-years (denominator)
IR/1,000 person-years
15 to
BRIEF REPORT
The descriptive epidemiology of rheumatoid arthritis in Catalonia: a retrospective study using routinely collected data F. Fina-Aviles & M. Medina-Peralta & L. Mendez-Boo & E. Hermosilla & J. M. Elorza & M. Garcia-Gil & R. Ramos & B. Bolibar & M. K. Javaid & C. J. Edwards & C. Cooper & N. K. Arden & D. Prieto-Alhambra
Received: 19 August 2014 / Revised: 1 October 2014 / Accepted: 12 October 2014 # International League of Associations for Rheumatology (ILAR) 2014
Abstract Information on the epidemiology of rheumatoid arthritis (RA) in Southern Europe is scarce. We estimated the age- and gender-adjusted incidence and prevalence of RA in Catalonia using routinely collected primary care records. We identified incident (2009–2012) and prevalent (on 31 December 2012) cases of RA in the SIDIAP database using ICD-10 codes. SIDIAP contains anonymized data from computerized primary care records for about five million adults (>80 % of the population). We estimated age- (5-year groups) and gender-specific, and directly standardized incidence and F. Fina-Aviles : M. Medina-Peralta : L. Mendez-Boo : M. Garcia-Gil : R. Ramos Primary Care Department, Institut Català de la Salut, Av Gran Via de les Corts Catalanes 587, 3rd floor, 08007 Barcelona, Spain E. Hermosilla : J. M. Elorza : M. Garcia-Gil : R. Ramos : B. Bolibar : D. Prieto-Alhambra IDIAP Jordi Gol Primary Care Research Institute, Universitat Autònoma de Barcelona, Av Gran Via de les Corts Catalanes 587, Atic, 08007 Barcelona, Spain M. K. Javaid : C. Cooper : N. K. Arden : D. Prieto-Alhambra Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, OX3 7LD Oxford, UK M. K. Javaid : C. Cooper : N. K. Arden : D. Prieto-Alhambra MRC Lifecourse Epidemiology Unit, University of Southampton, Tremona Road, SO16 6YD Southampton, UK C. J. Edwards Southampton General Hospital, Tremona Road, SO16 6YD Southampton, UK D. Prieto-Alhambra (*) SIDIAP Database, IDIAP Jordi Gol, Av Gran Via Corts Catalanes, 587, Atic, 08007 Barcelona, Spain e-mail: [email protected]
prevalence of RA and confidence intervals (95% CIs) assuming a Poisson distribution. A total of 20,091 prevalent (among whom 5,796 incident) cases of RA were identified among 4,796,498 study participants observed for up to 4 years. Rates of RA increased with age in both genders, peaking at the age of 65–70 years. Age- and gender-standardized incidence and prevalence rates were 0.20/1,000 person-years (95% CI 0.19– 0.20) and 4.17/1,000 (4.11–4.23) respectively. Rheumatoid factor was positive (≥10 IU/mL) in 1,833 (73.9 %) of 2,482 cases tested in primary care. The incidence and prevalence of RA in Catalonia are similar to those of other Southern European regions, and lower than those of northern areas. This data will inform health care planning and resource allocation. Keywords Arthritis . Electronic health records . Epidemiology . Incidence . Prevalence . Rheumatoid
Introduction Rheumatoid arthritis (RA) is the most common type of inflammatory arthritis [1]. One of its intriguing characteristics is the heterogeneity of its geographical distribution: The prevalence of RA is 4- or 5-fold higher in countries like the USA (1.1 %) [2] or England (8.5/1,000) compared to that in others like Argentina (2/1,000) [3] or South Korea (3/1,000) [4]. In general, countries with Northern European populations have a higher prevalence of RA than those with Southern European populations. However, this is not universally reported: A systematic review on the prevalence of RA [5] revealed almost double the prevalence of RA in a Southern European (Greece) compared to a Northern European Scandinavian (Norway) region. Therefore, accurate descriptions of the epidemiology of RA should be derived for each individual
Clin Rheumatol
country to inform local health care planning and allocation of resources. This is particularly important for Southern European regions, and Spain in particular, where there is a scarcity of high-quality data. In addition to health care planning, knowledge of the epidemiology of RA is also essential for a better understanding of the pathogenesis of the disease. We therefore used data from a large primary care database to calculate population-based age- and gender-specific incidence and prevalence rates of RA in a Southern European region (Catalonia, Spain). Second, we provide updated estimates of age- and gender-standardized incidence and prevalence of RA for the same population.
Methods Study design Population-based retrospective cohort study. Source of data and study participants The SIDIAP database (www.sidiap.org) contains clinical information as recorded by primary care physicians and nurses in the medical records of >70 % of the population aged 14 years or above of Catalonia, Spain (about 5.4 million people) according to the Spanish National Office of Statistics (www.ine.es). General practitioners and nurses code clinical events using ICD-10 codes, and each participant is assigned a unique anonymous identifier to ensure confidentiality. The data is highly representative for the whole population of the region [6], and it has been widely used to study the epidemiology of a number of musculoskeletal conditions such as osteoporotic fractures [7, 8] and osteoarthritis [9, 10]. In addition, SIDIAP contains all the information on results obtained from blood tests performed in primary care settings, as well as on all the medications dispensed by prescription in community pharmacies for all participants. Medicines data is stored using ATC codes. All participants in the SIDIAP database in the study period (1 January 2009 to 31 December 2012) were included. Identification of RA cases Incident (newly diagnosed in the years 2009–2012 with no prior diagnosis of RA in at least 3 previous years) and prevalent (on 31 December 2012) cases of RA were identified using ICD-10 codes (M05 and M06) as registered in primary care records. Based on a modified algorithm proposed to identify patients with RA in the British GPRD database [11], patients with no prescriptions of disease-modifying anti-rheumatic drugs (DMARDs) and with a potential alternative diagnosis (osteoarthritis, psoriasic arthritis, ankylosing spondylitis, other spondylo-arthropathies, gout, reactive arthritis,
septic arthritis, systemic lupus erytematous, dermato-polymyositis, sclerodermia and fybromyalgia) following the recording of an RA code were re-classified as non-RA patients. Finally, we looked at the results of rheumatoid factor measurements performed in primary care settings in the year prior to an RA diagnosis amongst incident cases, expecting about 75 % of them to be sero-positive (≥10 IU/mL) in an RA population based on previous literature reporting on the prevalence of sero-positivity in a community-based series of RA patients [12]. Statistical analyses Specific incidence and prevalence rates for RA (and 95 % confidence intervals) were calculated for each age (in 5-year groups) and gender strata assuming a Poisson distribution. Age-specific (unadjusted) female-to-male rate ratios (RRs) were then estimated for each of the previously specified 5year groups and plotted against age. We used the direct method to estimate age- and genderstandardized incidence and prevalence rates of RA in the overall study population (using the entire RA-free population registered in SIDIAP in the study period as a reference), as well as age-standardized rates for female and male participants separately. The statistical analyses were carried out using Stata version 12.0 SE for Mac.
Results Data was available for 4,895,307 patients: 2,423,177 (49.5 %) men and 2,472,130 (50.5 %) women, with a mean (standard deviation) age of 46.9 (19.1) years. Amongst these, 5,796 (0.12 %) incident and 20,091 (0.41 %) prevalent cases of RA were identified. The age- and gender-specific incidence rates of RA are represented in Fig. 1 and reported in detail in Table 1. These were always higher among women at all ages and peaked for both genders at a similar age of 65–70 years with incidence rates of 0.51/1,000 person-years in women compared to 0.31/ 1,000 in men. Interestingly, we observed a first incidence peak in women aged 50–55 years, which was not apparent in the male population. The gender-related excess risk was highest in younger ages, with a maximum female/male rate ratio of 4.18 amongst participants aged 25–30 years, and then decreased reaching a trough in the sixth and seventh decades of life (Fig. 1). The age- and gender-standardized incidence of RA was 0.20/1,000 person-years (0.19 to 0.20), with agestandardized rates of 0.28 (0.27 to 0.29) in women and 0.12 (0.11 to 0.12) in men (female-to-male RR 2.44). Out of 5,796 incident cases of RA, 2,482(42.8 %) had a rheumatoid factor test in primary care in the year before the
Clin Rheumatol Fig. 1 Age- and gender-specific incidence rates (per 100,000 person-years at risk) and age-specific female-to-male rate ratios (F:M RRs) of RA in Catalonia, Spain
date of their diagnosis, and 1,833 (73.9 %) of these were seropositive (≥10 IU/mL). The prevalence of RA was higher in women at all ages compared to that in men of a similar age (Table 2). The proportion of affected patients increased with age for both genders, peaking in the seventh decade of life, with a top prevalence of 11.77/1,000 and 6.72/1,000 in women and men respectively (Fig. 2). The crude prevalence of RA in the population aged ≥15 years old was of 4.1/1,000, and age- and gender-standardized prevalence was 4.17/1,000 (95 % confidence interval 4.11 to 4.23). Corresponding age-standardized prevalence rates were 5.80/1,000 (5.70 to 5.89) in women and 2.50/1,000 (2.44 to 2.56) in men.
Discussion We report the first population-based estimates of age- and gender-adjusted incidence and prevalence rates of RA in Catalonia, Spain. The sample size available, including almost five million participants and up to 4 years of follow-up, allows us to accurately characterize the effect of age and gender on the risk of RA in the community. In our data, the proportion of the population affected with RA increases with age in both men and women, peaking at the age of 65–70 years, with women having always a higher prevalence of disease at all ages. The age- and genderstandardized prevalence of RA in our data (4.2/1,000 in the overall study population) overlaps with that published by Carmona et al. [13] in the only population-based prevalence study performed in Spain to date, which reported a crude prevalence of 5/1,000 (95 % CI 3 to 9/1,000). That study recruited a representative sample of 2,192 participants aged
20 years or above, including only 11 prevalent cases of RA compared to >20,000 affected patients in our current report. Only one previous study has estimated the incidence of RA in Spain [14]: A nationwide clinical cohort reported crude rates of “early arthritis” of 0.25/1,000 cases, but a short follow-up of only 6 months led to a confirmed diagnosis of RA in only 1 in 3 of these (0.083/1,000). In our study, age- and gender-standardized rates were higher at almost 0.20/ 1,000 person-years. A longer follow-up of up to 4 years for confirmation of incident diagnoses might partially explain the observed differences. Geographical variation within Spain, with northern areas such as Catalonia having higher rates of RA disease, as has been observed worldwide [5], might also contribute to the observed disparity. In an international context, our data position Catalonia (northeast Spain) as a region with an incidence and prevalence of RA in the lower range, similar to other countries in Southern Europe such as France [15, 16] (prevalence 5/1,000, incidence 0.10/1,000), Italy (prevalence 5.1/1,000 in Tuscany) [17], Turkey (prevalence 4.9/1,000) [18] or Greece [19, 20] (prevalence 7/1,000, incidence 0.20/1,000). In comparison, studies have shown the highest prevalence rates in northern populations including the USA (prevalence 10.7/1,000) [21], England (prevalence 8.5/1,000) [22] or Finland (prevalence 8/1,000) [23], and lowest prevalence in southern (prevalence 3.6/1,000 in Oman) [24] and western (prevalence 2.8/1,000 in China) [25] populations. One interesting finding in our data is the peak in age- and gender-specific incidence rates of RA observed among women (and not among men) aged 50 to 54 years old. We speculate that this finding may be due to the effects of oestrogen depletion related to the menopause on the onset of RA: Previous data has suggested an association between early menopause and an increased risk of RA [26], with hormone
Clin Rheumatol Table 1 Incidence rates of rheumatoid arthritis according to age (5-year groups) and gender in the period 2009–2012 Women Age
No. of incident RA cases
Person-years (denominator)
IR/1,000 person-years
15 to
