Paediatric infections in the first 3 years of life after maternal anti-TNF treatment during pregnancy.
Bröms Gabriella,Kieler Helle,Ekbom Anders,Gissler Mika,Hellgren Karin,Leinonen Maarit K,Pedersen Lars,Schmitt-Egenolf Marcus,Toft Sørensen Henrik,Granath Fredrik
Alimentary pharmacology & therapeutics
BACKGROUND:Most anti-tumour necrosis factor (anti-TNF) agents are transferred across the placenta and may increase paediatric susceptibility to infections. AIMS:To assess the risk of paediatric infections after maternal anti-TNF treatment. METHODS:Population-based cohort study in Denmark, Finland and Sweden 2006-2013 in which 1027 children born to women with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis or inflammatory bowel disease, treated with anti-TNF, and 9346 children to women with non-biologic systemic treatment, were compared to 1 617 886 children of the general population. Children were followed for 3 years. RESULTS:Adjusted by maternal age, parity, smoking, body mass index, country and calendar year, the incidence rate ratios with 95% confidence interval (CI) for hospital admissions for infection in the first year were 1.43 (1.23-1.67) for anti-TNF and 1.14 (1.07-1.21) for non-biologic systemic treatment, and 1.29 (1.11-1.50) and 1.09 (1.02-1.15), respectively, when additionally adjusting for adverse birth outcomes. There was a slight increase in antibiotic prescriptions in the second year for anti-TNF, 1.19 (1.11-1.29), and for non-biologic systemic treatment, 1.10 (1.07-1.13). There was no difference among anti-TNF agents, treatment in the third trimester, or between mono/combination therapy with non-biologic systemic treatment. CONCLUSIONS:Both anti-TNF and non-biologic systemic treatment were associated with an increased risk of paediatric infections. However, reassuringly, the increased risks were present regardless of treatment in the third trimester, or with combination treatment, and were not persistent during the first 3 years of life. Our findings may indicate a true risk, but could also be due to unadjusted confounding by disease severity and healthcare-seeking behaviour. This may in turn shift the risk-benefit equation towards continuation of treatment even in the third trimester.
Risk factors for development and persistence of chronic widespread pain in spondyloarthritis: a population-based two-year follow-up study.
Mogard E,Lindqvist E,Bremander A,Bergman S
Scandinavian journal of rheumatology
: To study chronic widespread pain (CWP) over time in patients with spondyloarthritis (SpA), and to identify risk factors for development and persistence of CWP.: In this cohort study with baseline and 2.5 year follow-up postal surveys, patients with ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (USpA) (47% women) answered questions regarding pain, and were categorized as no chronic pain (NCP), chronic regional pain (CRP), or CWP. For each risk factor candidate (disease duration, body mass index, smoking, and patient-reported outcome measures), logistic regression analyses with CWP as the main outcome were performed separately, together with a basic model including age, gender, and SpA subgroup.: Altogether, 644 patients could be categorized at both time-points, yielding similar prevalence estimates at baseline and follow-up, although 38% transitioned between pain groups. Risk factors (odds ratio; 95% confidence interval) for development of CWP included more pain regions (1.36; 1.20‒1.53), higher pain intensity (1.35; 1.20‒1.52), worse fatigue (1.25; 1.13‒1.38), and worse global health (1.35; 1.19‒1.54). Persistent CWP was reported by 72%. In addition to factors predicting development of CWP, higher age (1.02; 1.00‒1.04), female gender (1.82; 1.06‒3.10), and anxiety (1.07; 1.00-1.14) also predicted persistence.: The prevalence of CWP remained high over time, but with individual transitions between the pain groups. The development and persistence of CWP were predicted by more pain and worse health, with the addition of female gender and higher age for persistent CWP. Special attention and treatment alternatives for patients with SpA and concomitant CWP are essential in the clinic.
Increasing proportion of female patients with ankylosing spondylitis: a population-based study of trends in the incidence and prevalence of AS.
Haroon Nisha N,Paterson J Michael,Li Ping,Haroon Nigil
OBJECTIVE:With the introduction of MRI in diagnosis and tumour necrosis factor inhibitors for treatment, the field of ankylosing spondylitis (AS) has undergone significant changes. We carried out a population-based study of the trends in incidence and prevalence of AS over the past 15 years. METHODS:This is a retrospective analysis of provincial health administrative databases. Residents of Ontario, Canada aged 15 years or older diagnosed with AS between 1995 and 2010 were included in the study. Crude as well as age-standardised and sex-standardised incidence and prevalence of AS between 1995 and 2010 were calculated. Trends in prevalence and incidence of male and female patients with AS were separately analysed. RESULTS:We identified 24,976 Ontarians with AS. Age/sex-standardised AS prevalence increased from 79/100,000 in 1995 to 213/100,000 in 2010. Men had higher prevalence than women, but the male/female prevalence ratio decreased from 1.70 in 1995 to 1.21 by 2010. A higher proportion of male compared with female patients with AS were diagnosed in the 15-45 age group. Annual incidence rates revealed increasing diagnosis of AS among women after 2003. CONCLUSIONS:The prevalence of AS in Ontario has nearly tripled over the past two decades. The proportion of women with new diagnosis of AS is increasing, a trend that began around the year 2003. A higher proportion of male compared with female patients with AS are diagnosed at an earlier age.
Costs of Drug Therapy in Patients with Ankylosing Spondylitis in Brazil.
Machado Marina Amaral de Ávila,Ferre Felipe,Moura Cristiano Soares de,Almeida Alessandra Maciel,Andrade Eli Iola Gurgel,Cherchiglia Mariângela Leal,Acurcio Francisco de Assis
Rheumatology and therapy
INTRODUCTION:The Brazilian Public Health System offers free-of-charge drug treatment for ankylosing spondylitis (AS) to all Brazilian citizens. We report here the first population-based cohort study on patients with AS in Brazil. The aim of this study was to evaluate the costs of the tumour necrosis factor (anti-TNF) blockers and disease-modifying antirheumatic drugs (DMARDs) that were used in the treatments of patients with AS in Brazil between March 2010 and September 2013. METHODS:A retrospective cohort study was performed using administrative databases. All patients with a diagnosis of AS who were aged 18 years or older and had been dispensed anti-TNF or DMARDs were included in the analysis. The cost analysis was carried out from the health system perspective, and the results were described as median monthly cost per capita and the annual cost over the study period. RESULTS:A search of the databases identified 1251 patients with AS who were treated during the study period, of whom 63.3% were male; the median age was 41 years. During the study period, 78.0% of patients initiated treatment with anti-TNF drugs and 22.0% with DMARDs. The median monthly cost per capita was US$ 1650 for anti-TNF therapy and US$ 25 for treatment with DMARDs. Among the anti-TNF drugs, therapy with etanercept was associated with the lowest cost per patient, followed by adalimumab and infliximab. No difference in monthly cost was observed in relation to gender and age. CONCLUSION:The cost per patient of treating AS in this study cohort was lower with etanercept than with adalimumab and infliximab. These results highlights the economic burden of treating patients with AS.
Increased risk of ischemic stroke in young patients with ankylosing spondylitis: a population-based longitudinal follow-up study.
Lin Chia-Wei,Huang Ya-Ping,Chiu Yueh-Hsia,Ho Yu-Tsun,Pan Shin-Liang
BACKGROUND:Prospective data on the association between ischemic stroke and ankylosing spondylitis (AS) in the young are sparse. The purpose of this population-based, age- and sex-matched longitudinal follow-up study was to investigate the risk of developing ischemic stroke in young patients with AS. METHODS:A total of 4562 patients aged 18- to 45-year-old with at least two ambulatory visits in 2001 with a principal diagnosis of AS were enrolled in the AS group. The non-AS group consisted of 22810 age- and sex-matched, randomly sampled subjects without AS. The two-year ischemic stroke-free survival rate for each group were calculated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used to estimate the hazard ratio of ischemic stroke after adjusting for demographic and clinical covariates. RESULTS:During follow-up, 21 patients in the AS group and 53 in the non-AS group developed ischemic stroke. The ischemic stroke-free survival rate over the 2 year follow-up was lower in the AS group than the non-AS group (p = 0.0021). The crude hazard ratio of ischemic stroke for the AS group was 1.98 (95% CI, 1.20-3.29; p = 0.0079) and the adjusted hazard ratio after controlling for demographic and comorbid medical disorders was 1.93 (95% CI, 1.16-3.20; p = 0.0110). CONCLUSION:Our study showed an increased risk of developing ischemic stroke in young patients with AS.
Is ankylosing spondylitis a risk factor for cardiovascular disease, and how do these risks compare with those in rheumatoid arthritis?
Eriksson Jonas K,Jacobsson Lennart,Bengtsson Karin,Askling Johan
Annals of the rheumatic diseases
AIMS:To assess and compare the incidence of cardiovascular (CV) events, by CV phenotype, between patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA) and the general population. METHODS:Using linkages of national and population-based registers, we identified one cohort of prevalent patients with AS (n=5358), one with RA (n=37 245) and one with matched general population subjects (n=25 006). These cohorts were identified in 2006 through 2011 and were followed in 31 December 2012, for first ever occurrence of acute coronary syndromes (ACS), deep venous thromboembolism, pulmonary embolism and stroke, respectively. For each outcome, we calculated incidence rates standardised to the age and sex distribution of the AS cohort, as well as relative risks using Cox proportional hazards models. RESULTS:Based on 69 ACS events during 20 251 person-years of follow-up of the patients with AS, and 966 events during 127 014 person-years in the RA cohort, the age/sex-adjusted relative risks for ACS compared with the general population was 1.3 (95% CI 1.0 to 1.7) for AS and 1.7 (1.4 to 2.0) for RA. For thromboembolic events, the corresponding risks were 1.4 (1.1 to 1.9) in AS and 1.8 (1.5 to 2.1) in RA. Finally, for stroke, the relative risks were 1.5 (1.1 to 2.0) in AS and 1.5 (1.2 to 1.8) in RA, compared with the general population. CONCLUSIONS:Prevalent patients with AS are at a 30%-50% increased risk of incident CV events. When compared with patients with RA, this level of increase was similar for stroke, but only half as high for ACS and thrombotic events.
Patients With Ankylosing Spondylitis Have Increased Cardiovascular and Cerebrovascular Mortality: A Population-Based Study.
Haroon Nisha Nigil,Paterson J Michael,Li Ping,Inman Robert D,Haroon Nigil
Annals of internal medicine
BACKGROUND:Ankylosing spondylitis (AS) is a chronic inflammatory arthritis affecting the spine in young adults. It is associated with excess cardiovascular and cerebrovascular morbidity. OBJECTIVE:To determine whether patients with AS are at increased risk for cardiovascular and cerebrovascular mortality. DESIGN:Population-based retrospective cohort study using administrative health data. SETTING:Ontario, Canada. PATIENTS:21 473 patients with AS aged 15 years or older and 86 606 comparators without AS, matched for age, sex, and location of residence. MEASUREMENTS:The primary outcome was a composite of cardiovascular and cerebrovascular death. Hazard ratios (HRs) for vascular death were calculated; adjusted for history of cancer, diabetes, dementia, inflammatory bowel disease, hypertension, chronic kidney disease, and peripheral vascular disease; and, among those aged 66 years or older, relevant drug therapies. Independent risk factors for vascular mortality were identified in patients with AS. RESULTS:The mean age of patients with AS was 46 years, and 53% were male. Patients and comparators were followed for 166 920 and 686 461 patient-years, respectively. Adjusted HRs for vascular death in AS were 1.36 (95% CI, 1.13 to 1.65) overall, 1.46 (CI, 1.13 to 1.87) in men, and 1.24 (CI, 0.92 to 1.67) in women. Significant risk factors for vascular death were age; male sex; lower income; dementia; chronic kidney disease; peripheral vascular disease; and, among patients aged 65 years or older, lack of exposure to nonsteroidal anti-inflammatory drugs and statins. LIMITATION:Diagnosis codes for AS were not validated in Ontario. CONCLUSION:Ankylosing spondylitis is associated with increased risk for vascular mortality. A comprehensive strategy to screen and treat modifiable vascular risk factors in AS is needed. PRIMARY FUNDING SOURCE:The Arthritis Program, University Health Network, Toronto; and The Arthritis Society, Canada.
The risk of depression, suicidal ideation and suicide attempt in patients with psoriasis, psoriatic arthritis or ankylosing spondylitis.
Wu J J,Penfold R B,Primatesta P,Fox T K,Stewart C,Reddy S P,Egeberg A,Liu J,Simon G
Journal of the European Academy of Dermatology and Venereology : JEADV
BACKGROUND:Sparse information is available concerning mental health issues in psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients. OBJECTIVE:To estimate risk of depression, suicidal ideation and suicide attempt in patients with psoriasis, PsA and AS, respectively, compared with the general population. METHODS:This population-based cohort study analysed 36 214 psoriasis patients, 5138 PsA patients and 1878 AS patients who were frequency-matched with a general population cohort. Annual incidence rate of depression, suicidal ideation and suicide attempt was calculated separately for psoriasis, PsA and AS. RESULTS:There was an increased risk of depression in the three cohorts; adjusted IRR: psoriasis, 1.14 (95% CI, 1.11, 1.17); PsA, 1.22 (95% CI, 1.16, 1.29); AS, 1.34 (95% CI, 1.23, 1.47). There was no significantly increased risk for suicidal ideations or suicide attempt among psoriasis, PsA or AS patients. LIMITATIONS:Patients were not excluded if previously diagnosed with depression, suicidal ideation or suicide attempt. Suicide attempt and completed suicide analyses were not adjusted for presence of depression. Use of systemic psoriasis treatment to measure severe psoriasis could lead to psoriasis severity misclassification. CONCLUSION:The risk of depression, but not suicidal ideation or suicide attempt, was significantly increased in patients with psoriasis, PsA and AS.
Sick leave in patients with ankylosing spondylitis before and after anti-TNF therapy: a population-based cohort study.
Kristensen Lars E,Petersson Ingemar F,Geborek Pierre,Jöud Anna,Saxne Tore,Jacobsson Lennart T H,Englund Martin
Rheumatology (Oxford, England)
OBJECTIVE:To study levels of sick leave and disability pension before and after TNF-antagonist therapy in AS patients. METHODS:Using the population-based South Swedish Arthritis Treatment Group register, we identified 139 AS patients (aged 18-58 years, 78% men), who between January 2002 and December 2008 started their first treatment with adalimumab, etanercept or infliximab. We linked data to the payment register by the Swedish Social Insurance Agency and calculated the proportion on sick leave in 30-day intervals from 12 months before treatment start until 12 months after. For each AS patient, we randomly selected four subjects from the general population matched for age, sex and area of residence. RESULTS:One to 3 months before treatment, an average of 24% of AS patients were on sick leave. During the first 6 months after treatment start, this fraction dropped to 15%, and further declined to 12% at 12 months (P < 0.001). Comparing AS patients with the general population, the relative risk of being on sick leave 3 months before treatment, treatment start and 12 months after treatment start was 8.0 (95% CI 4.6, 13.9), 9.2 (95% CI 5.4, 15.7) and 4.0 (95% CI 2.1, 6.3), respectively. The decrease in sick leave was not substantially offset by changes in disability pension. CONCLUSION:There is a decline in sick leave during the first 12 months after initiation of TNF-antagonist treatment in AS patients not explained by societal factors or secular trends. The proportion of AS patients on disability pension remained unchanged during the observation period.
Ankylosing spondylitis: A novel risk factor for atrial fibrillation - A nationwide population-based study.
Moon Inki,Choi Eue-Keun,Jung Jin-Hyung,Han Kyung-Do,Choi You-Jung,Park Jiesuck,Cho Jun Hwan,Lee Euijae,Choe Wonseok,Lee So-Ryoung,Cha Myung-Jin,Lim Woo-Hyun,Oh Seil
International journal of cardiology
BACKGROUND:Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease, associated with a number of cardiovascular diseases. We sought to investigate whether AS increases the risk of atrial fibrillation (AF) in a nationwide population-based study. METHODS:A total of 14,129 patients newly diagnosed with AS (mean age 41.8 ± 15.3 years, 72% male) were recruited from the Korean National Health Insurance Service database between 2010 and 2014 and followed up for new onset AF. Age- and sex-matched non-AS subjects (1:5, n = 70,645) were selected and compared with the AS patients. RESULTS:During a mean follow-up of 3.5 years, AF was newly diagnosed in 486 patients (114 patients of the AS group). The AS patients developed AF more frequently than the non-AS subjects (2.32 vs. 1.51 per 1000 person-years). In multivariate Cox regression analysis, AS was an independent risk factor for AF (Hazard ratio [HR] 1.28, 95% confidence interval [1.03-1.58]). The AS with tumor necrosis factor inhibitor (TNFi) therapy group showed higher risk for AF (HR 1.60 [1.02-2.39]). In younger patients of the AS group (patients <40 years old), the risk for AF was three times higher than patients at same age in the non-AS group. AS was an independent risk factor for AF in men, but not in women (HR 1.53 [1.18-1.95]; HR 1.42 [0.94-2.08], respectively). CONCLUSIONS:AS was an independent risk factor for AF, especially in those under 40 years of age and those administered TNFi. It would be reasonable to screen for AF and stroke prevention in these high-risk patients.
Mortality in ankylosing spondylitis: results from a nationwide population-based study.
Exarchou Sofia,Lie Elisabeth,Lindström Ulf,Askling Johan,Forsblad-d'Elia Helena,Turesson Carl,Kristensen Lars Erik,Jacobsson Lennart Th
Annals of the rheumatic diseases
OBJECTIVES:Information on mortality in ankylosing spondylitis (AS) is scarce. Our study therefore aimed to assess: (1) mortality in AS versus the general population, and (2) predictors of death in the AS population. METHODS:Nationwide cohorts of patients with AS diagnosed at rheumatology or internal medicine outpatient clinics (n=8600) and age-matched, sex-matched and county-matched general population comparators (n=40 460) were identified from the National Patient Register and the census register, respectively. The follow-up period began on 1 January 2006 or at the first date of registered diagnosis thereafter and extended until death, emigration or 31 December 2012, whichever occurred first. Socioeconomic variables, AS-related clinical manifestations, joint surgery, comorbidities and medication were identified from other national registers. Cox regression models were used to determine mortality and predictors for death in the AS cohort. RESULTS:There were 496 deaths in the AS cohort and 1533 deaths in the control cohort resulting in an age-adjusted and sex-adjusted HR of 1.60 (95% CI 1.44 to 1.77), with increased mortality for men (age-adjusted HR=1.53, 95% CI 1.36 to 1.72) and women (age-adjusted HR=1.83, 95% CI 1.50 to 2.22). Within the AS cohort, statistically significant predictors for death were a lower level of education, general comorbidities (diabetes, infections, cardiovascular, pulmonary and malignant diseases) and previous hip replacement surgery. CONCLUSIONS:Mortality was increased for male and female patients with AS. Predictors of death within the AS cohort included socioeconomic status, general comorbidities and hip replacement surgery.
The risk for depression in patients with ankylosing spondylitis: a population-based cohort study.
Meesters Jorit J L,Bremander Ann,Bergman Stefan,Petersson Ingemar F,Turkiewicz Aleksandra,Englund Martin
Arthritis research & therapy
INTRODUCTION:Depression is frequent in ankylosing spondylitis (AS) patients. However, epidemiological data about the potential increase in risk are lacking. This study compares the rate of doctor-diagnosed depression in a well defined cohort of AS patients to the general population seeking care. METHODS:The Skåne Healthcare Register comprises healthcare data of each resident in Region Skåne, Sweden (population 1.2 million), including ICD-10 diagnoses. Using physician coded consultation data from years 1999 to 2011, we calculated depression consultation rates for all AS patients. We obtained standardized depression-rate ratios by dividing the observed depression rate in AS patients by the expected rate based on the corresponding age- and sex-specific rates of depression in the general population seeking care. A ratio > 1 equals a higher rate of depression among AS patients. RESULTS:The AS cohort consisted of 1738 subjects (65% men) with a mean age of 54 years. The reference population consisted of 967,012 subjects. During the 13-year observation period 10% (n = 172) of the AS cohort had a doctor-diagnosed depression compared to 6% (n = 105) to be expected. The standardized estimate of depression-rate ratio was 1.81 (95% confidence interval 1.44 to 2.24) in women men and 1.49 (1.20 to 1.89) in men. CONCLUSIONS:The rate of doctor-diagnosed depression is increased about 80% in female and 50% in male AS patients. Future challenges are to timely identify and treat the AS patients who suffer from depression.
Increased risk of cancer for patients with ankylosing spondylitis: a nationwide population-based retrospective cohort study.
Sun L-M,Muo C-H,Liang J-A,Chang S-N,Sung F-C,Kao C-H
Scandinavian journal of rheumatology
OBJECTIVES:Few studies have investigated the relationship between ankylosing spondylitis (AS) and other inflammatory spondyloarthritis and subsequent cancer. The aim of this study was to determine whether AS is associated with cancer risk. METHOD:We used data from the National Health Insurance (NHI) system of Taiwan to investigate this association. The AS cohort included 4133 patients, and each patient was randomly frequency matched with four persons without AS based on sex, age, and entry year (control cohort). We conducted a Cox proportional hazards regression analysis to estimate the influence of AS on cancer risk. RESULTS:Among patients with AS, the overall risk of developing cancer was 38% higher than that of people without AS, and the difference was significant [adjusted hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.18-1.60]. This phenomenon held true even when we analysed males and females separately. The risk of developing lung or head and neck cancer among patients with AS was significantly higher; and risks for liver, bladder, and uterus cancers were marginally significantly higher. CONCLUSIONS:This nationwide population-based cohort study shows that Taiwanese patients with AS have a higher risk of developing cancer, particularly lung or head and neck cancer.
The epidemiology of extra-articular manifestations in ankylosing spondylitis: a population-based matched cohort study.
Stolwijk Carmen,Essers Ivette,van Tubergen Astrid,Boonen Annelies,Bazelier Marloes T,De Bruin Marie L,de Vries Frank
Annals of the rheumatic diseases
OBJECTIVE:To assess the incidence and risks of common extra-articular manifestations (EAMs), that is, acute anterior uveitis (AAU), psoriasis and inflammatory bowel disease (IBD), in patients with ankylosing spondylitis (AS) compared with population-based controls. METHODS:All incident patients with AS (n=4101) from the UK Clinical Practice Research Datalink (1987-2012) were matched with up to seven control subjects without AS by year of birth, sex and practice (n=28,591). Incidence rates, cumulative incidence rates and adjusted (adj) HRs for the development of EAMs were calculated, with time-dependent adjustments for age, sex, comorbidity and medication use. RESULTS:At diagnosis of AS, the proportion of patients with an EAM was 11.4% for AAU, 4.4% for psoriasis and 3.7% for IBD. Incidence rates of EAMs were 8.9/1000 person-years for AAU, 3.4/1000 person-years for psoriasis and 2.4 /1000 person-years for IBD in AS. The 20-year cumulative incidence was 24.5%, 10.1% and 7.5%, respectively. Risks of EAMs were 1.5-fold to 16-fold increased versus controls, with an adj HR of 15.5 (95% CI 11.6 to 20.7) for AAU, adj HR of 1.5 (95% CI 1.1 to 1.9) for psoriasis and adj HR of 3.3 (95% CI 2.3 to 4.8) for IBD. For psoriasis and IBD, the highest risks were found in the 1st years after diagnosis, while developing AAU continued to be increased also 10 years after diagnosis of AS. CONCLUSIONS:The risk of, in particular AAU, but also of psoriasis and IBD, is significantly increased in patients with AS compared with controls. Hazard patterns are different for each of the EAMs.
A nationwide population-based retrospective cohort study: increased risk of acute coronary syndrome in patients with ankylosing spondylitis.
Chou C-H,Lin M-C,Peng C-L,Wu Y-C,Sung F-C,Kao C-H,Liu S-H
Scandinavian journal of rheumatology
OBJECTIVES:To compare the risk of acute coronary syndrome (ACS) between patients with and without ankylosing spondylitis (AS). METHOD:This retrospective cohort study identified all patients with AS aged ≥ 18 years newly diagnosed from 2000 to 2009, registered in the National Health Insurance Research Database (NHIRD) in Taiwan. The non-AS cohort consisted of fourfold randomly selected control patients free of AS, frequency matched by age, sex, and diagnosis year. The incidence of ACS was determined for both AS and non-AS cohorts. RESULTS:We selected 6262 patients with AS and 25 048 patients without AS. The patients with AS were more prevalent than those without, with co-morbidities of hypertension, diabetes mellitus (DM), hyperlipidaemia, stroke, and peripheral vascular diseases. The overall incidence rate of ACS was higher in the AS cohort than in the non-AS cohort (4.4 vs. 2.9 per 1000 person-years), with an adjusted hazard ratio (aHR) of 1.36 [95% confidence interval (CI) 1.16-1.59]. AS patients with co-morbidities of hypertension, DM, and cancer had an aHR of 7.74 for ACS, compared to those without these co-morbidities. CONCLUSIONS:AS patients are at higher risk of ACS compared with non-AS subjects. Management of CV risk factors should be taken into account for the treatment of patients with AS, especially for patients with co-morbidities of hypertension, DM, and cancer.
The risk of asthma in patients with ankylosing spondylitis: a population-based cohort study.
Shen Te-Chun,Lin Cheng-Li,Wei Chang-Ching,Chen Chia-Hung,Tu Chih-Yen,Hsia Te-Chun,Shih Chuen-Ming,Hsu Wu-Huei,Sung Fung-Chang
BACKGROUND:The relationship between asthma and ankylosing spondylitis (AS) is controversial. We examined the risk of asthma among AS patients in a nationwide population. METHODS:We conducted a retrospective cohort study using data from the National Health Insurance (NHI) system of Taiwan. The cohort included 5,974 patients newly diagnosed with AS from 2000 to 2010. The date of diagnosis was defined as the index date. A 4-fold of general population without AS was randomly selected frequency matched by age, gender and the index year. The occurrence and hazard ratio (HR) of asthma were estimated by the end of 2011. RESULTS:The overall incidence of asthma was 1.74 folds greater in the AS cohort than in the non-AS cohort (8.26 versus 4.74 per 1000 person-years) with a multivariable Cox method measured adjusted HR of 1.54 (95% confidence interval (CI), 1.34-1.76). The adjusted HR of asthma associated with AS was higher in women (1.59; 95% CI, 1.33-1.90), those aged 50-64 years (1.66; 95% CI, 1.31-2.09), or those without comorbidities (1.82; 95% CI, 1.54-2.13). CONCLUSION:Patients with AS are at a higher risk of developing asthma than the general population, regardless of gender and age. The pathophysiology needs further investigation.
Increased risk of stroke among patients with ankylosing spondylitis: a population-based matched-cohort study.
Keller Joseph J,Hsu Jung-Lung,Lin Shiue-Ming,Chou Chia-Chi,Wang Li-Hsuan,Wang Jui,Bai Chyi-Huey,Chiou Hung-Yi
Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease. Although two prior studies detected increased prevalence ratios of cerebrovascular disease among AS patients, the results of the two studies investigating AS and stroke are in conflict. Therefore, the present cohort study set out to estimate the risk of subsequent stroke in AS patients compared with matched controls using a population-based dataset in Taiwan. This investigation analyzed administrative claims data sourced from the Taiwan National Health Insurance Database. Our study consisted of a study cohort comprising 1,479 AS patients and a comparison cohort of 5,916 subjects without AS. Cox proportional hazards regressions were performed to estimate the risk of subsequent stroke during the follow-up period. We also conducted additional analyses investigating the risk of subsequent stroke by gender and pharmaceutical prescription. After adjusting for chronic lower respiratory diseases, type 2 diabetes mellitus, hypertension, hyperlipidemia, renal disease, coronary heart disease, atrial fibrillation, income, and urbanization, compared with comparison patients, the hazard ratio for subsequent stroke among patients with AS was 2.3 (95 % CI 1.9-2.8). We also stratified our results by both gender and pharmaceutical prescription, but did not find a statistically significant difference for the risk of subsequent stroke either between men and women, or between AS patients taking various pharmaceutical regimens and the overall AS population. This is the first study to report an increased hazard ratio for subsequent stroke among AS patients when compared with matched comparison patients without AS.
Risk of venous thromboembolism in ankylosing spondylitis: a general population-based study.
Aviña-Zubieta Juan Antonio,Chan Jonathan,De Vera Mary,Sayre Eric C,Choi Hyon,Esdaile John
Annals of the rheumatic diseases
BACKGROUND:Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep venous thrombosis (DVT), can be life threatening. An increased frequency of VTE has been found in inflammatory conditions. To date, evidence assessing whether this risk is also greater in patients with ankylosing spondylitis (AS) is scarce. METHODS:Using the provincial British Columbia, Canada healthcare database that encompasses all residents within the province, we conducted matched cohort analyses of incident PE, DVT and overall VTE among incident cases of AS and compared them with individuals randomly selected from the general population without AS. We calculated incidence rates (IRs) of VTE and multivariable analyses after adjusting for traditional risk factors using Cox models. RESULTS:Among 7190 incident cases of AS, 35 developed PE and 47 developed DVT. IRs of PE, DVT and overall VTE per 1000 person-years for patients with AS were 0.79, 1.06, 1.56 compared with 0.40, 0.50, 0.77 in the control cohort. Corresponding fully adjusted HRs (95% CI) of PE, DVT and VTE were 1.36 (0.92 to 1.99), 1.62 (1.16 to 2.26) and 1.53 (1.16 to 2.01), respectively. The risks of PE, DVT and VTE were highest in the first year of diagnosis with HR (95% CI) of 2.88 (0.87 to 9.62), 2.20 (0.80 to 6.03) and 2.10 (0.88 to 4.99), respectively. CONCLUSIONS:These findings demonstrate an increased risk of VTE in the general AS population. This risk appears the most prominent in the first year after diagnosis.
Impact of ankylosing spondylitis on depression: a nationwide cohort study.
Park Jin-Sung,Jang Hae-Dong,Hong Jae-Young,Park Ye-Soo,Han Kyungdo,Suh Seung-Woo,Park Si-Yong,Kim Bo-Taek
The aim of this study is to determine the relationship between AS and subsequent depression. This study was conducted using a nationwide dataset available in Korean National Health Insurance System (KNHIS). We identified 11,465 newly diagnosed AS patients and 57,325 patients without AS in the ratio of 1:5 matched by sex, age, and index date, between 2010 and 2014. We investigated any latent characteristics in the patients' demographic information and chronic comorbidities that could trigger a depression when diagnosed with AS. By comparing the cohort data, the hazard ratio of developing subsequent depression in AS patients was calculated and adjusted based on several risk factors. Despite the adjustment of demographic variables and chronic comorbidities, the risk of depression was 2.21 times higher in the AS cohort than in the control group. Multivariate analysis showed that AS patients with female gender, old age and low-income status showed higher risks of developing depression. Additionally, the presence of chronic comorbidities including diabetes mellitus, hypertension, hyperlipidemia, cancer, stroke, and chronic kidney disease increased the patients' risk of depression. The AS patients with stroke were reported to have the highest risk of depression. This population-based cohort study showed that AS significantly increased the subsequent risk of developing depression. Moreover, the development of a depression is influenced by certain demographic variables and different chronic comorbidities.
Ankylosing spondylitis and risk of ischaemic heart disease: a population-based cohort study.
Essers Ivette,Stolwijk Carmen,Boonen Annelies,De Bruin Marie L,Bazelier Marloes T,de Vries Frank,van Tubergen Astrid
Annals of the rheumatic diseases
OBJECTIVE:To investigate the incidence and risk of ischaemic heart disease (IHD) and acute myocardial infarction (AMI), including the role of non-steroidal anti-inflammatory drugs (NSAID), in patients with ankylosing spondylitis (AS) compared with population controls. METHODS:All patients with newly diagnosed AS (n=3809) from the British Clinical Practice Research Datalink (1987-2012) were matched with up to seven persons without AS by year of birth, gender and practice (n=26 197). Incidence rate ratios (IRR) and HRs for development of IHD and AMI were calculated. Stepwise analyses were performed adjusting for age, gender, comorbidity and drug use, including NSAIDs. RESULTS:At baseline, 4.3% of the patients had IHD and 1.8% had AMI compared with 3.4% and 1.4% of the controls, respectively. After exclusion of pre-existing IHD or AMI, the IRRs were 1.18 (95% CI 0.96 to 1.46) and 0.91 (95% CI 0.65 to 1.27) for IHD and AMI, respectively. Compared with controls, the age-gender adjusted HR for developing IHD was 1.20 (95% CI 0.97 to 1.48), and for AMI 0.91 (95% CI 0.65 to 1.28). In female patients, the risk of developing IHD was increased (HR 1.88, 95% CI 1.22 to 2.90), but after adjustment for all possible risk factors only a non-significant trend was found (HR 1.31, 95% CI 0.83 to 2.08). In particular, NSAID use explained this change (HR IHD adjusted for age-gender-NSAID use 1.57, 95% CI 0.99 to 2.48). CONCLUSIONS:Female patients with AS had an increased age-adjusted risk of developing IHD, but after adjustment for NSAID use only a non-significant trend towards increased risk was found.
Increased Risk of Inflammatory Bowel Disease Among Patients With Ankylosing Spondylitis: A 13-Year Population-Based Cohort Study.
Wang Shuya,Tsou Hsi-Kai,Chiou Jeng-Yuan,Wang Yu-Hsun,Zhang Zhiyi,Wei James Cheng-Chung
Frontiers in immunology
Aim:Ankylosing spondylitis (AS) primarily affects the axial skeleton and extraarticular structures. Small-scaled studies have reported that the incidence and prevalence of inﬂammatory bowel disease (IBD) are higher in patients with AS than in the general population. This study determined the incidence of IBD in patients with AS using a large scale population-based cohort dataset. Methods:This was a retrospective cohort study. Patient data were collected from the Taiwan National Health Insurance Research Database from 2000 to 2012. We enrolled 3,804 patients with AS and 7,608 non-AS patients. The endpoint was IBD diagnosis by using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) coding 555 and 556 after at least three outpatient visits or one hospital admission, until the end of 2012. The Kaplan-Meier performed to discriminate IBD Cox proportional hazard model was used to estimate the hazard ratio (HR) for IBD between the AS and non-AS groups. Results:Among the population as a whole the Cox proportional hazard regression indicated that patients aged ≥65 years [adjusted HR (aHR): 2.48, 95% confidence interval (CI): 1.38-4.47] or with comorbidity of cancer (aHR: 3.51, 95% CI: 1.40-8.80) had a higher HR for IBD. Kaplan-Meier curves of cumulative incidence proportion of IBD indicated that patients with AS had a higher risk of IBD than the non-AS group in the subgroup aged <40 years (HR: 2.85, 95% CI: 1.51-5.40, p = 0.001). Conclusions:Patients with AS aged <40 years had a higher IBD risk than did those without AS in Taiwan. Clinicians and patients should be aware of this association.
Relationship between dementia and ankylosing spondylitis: A nationwide, population-based, retrospective longitudinal cohort study.
Jang Hae-Dong,Park Jin-Sung,Kim Dae Woong,Han Kyungdo,Shin Byung-Joon,Lee Jae Chul,Choi Sung-Woo,Suh Seung-Woo,Yang Jae-Hyuk,Park Si-Young,Cho Whi Je,Hong Jae-Young
Among a variety of comorbidities of ankylosing spondylitis (AS), the association between dementia and AS by using an extensive dataset from the Korean National Health Insurance System was evaluated in this study. We extracted 15,547 newly diagnosed AS subjects among the entire Korean population and excluded wash-out patients (n = 162) and patients that were inappropriate for cohort match (n = 1192). Finally, 14,193 subjects were chosen as the AS group, and through 1:5 age- and sex-stratified matching, 70,965 subjects were chosen as the control group. We evaluated patient demographics, household incomes, and comorbidities, including hypertension, diabetes, and dyslipidemia. The prevalence of overall dementia (1.37%) and Alzheimer's dementia (AD) (0.99%) in the AS group was significantly higher than in the control group (0.87% and 0.63%), respectively. The adjusted hazard ratio of the AS group for overall dementia (1.758) and AD (1.782) showed statistical significance also. On the other hand, the prevalence of vascular dementia did not differ significantly between the two groups. Subgroup analyses revealed the following risk factors for dementia in the AS group: male gender, greater than 65 years in age, fair income (household income greater than 20% of the median), urban residency, no diabetes, and no hypertension. From the nationwide, population-based, retrospective, longitudinal cohort study, AS patients showed a significantly higher prevalence of overall dementia and Alzheimer's dementia. Comprehensive patient assessment using our subgroup analysis could help to prevent dementia in patients suffering from AS.
Risk of Psychiatric Disorders following Ankylosing Spondylitis: A Nationwide Population-based Retrospective Cohort Study.
Shen Cheng-Che,Hu Li-Yu,Yang Albert C,Kuo Benjamin Ing-Tiau,Chiang Yung-Yen,Tsai Shih-Jen
The Journal of rheumatology
OBJECTIVE:Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease. A higher prevalence of psychiatric comorbidities, including depressive disorder, has been proven in patients with AS. However, a clear temporal causal relationship between AS and psychiatric disorders has not been well established. We performed a nationwide population-based retrospective cohort study to analyze the relationship between AS and the subsequent development of psychiatric disorders, including schizophrenia, bipolar disorder, depressive disorders, anxiety disorders, and sleep disorders. METHODS:We identified subjects who were newly diagnosed with AS between January 1, 2000, and December 31, 2008, in the Taiwan National Health Insurance (NHI) Research Database. A comparison cohort was constructed of patients without AS who were matched according to age and sex. All patients with AS and control patients were observed until diagnosed with psychiatric disorders, or until death or withdrawal from the NHI system, or until December 31, 2009. RESULTS:The AS cohort consisted of 2331 patients and the comparison cohort consisted of 9324 matched control patients without AS. The adjusted HR for depressive disorders, anxiety disorders, and sleep disorders in subjects with AS were higher than those of the controls during followup (HR 1.718, 95% CI 1.303-2.265; HR 1.848, 95% CI 1.369-2.494; and HR 1.494, 95% CI 1.031-2.162, respectively). CONCLUSION:AS might increase the risk of a subsequent newly diagnosed depressive disorder, anxiety disorder, or sleep disorder, but not schizophrenia or bipolar disorder. These observations highlight the need for psychiatric evaluation and intervention for patients with AS.
Survival benefit of statin use in ankylosing spondylitis: a general population-based cohort study.
Oza Amar,Lu Na,Schoenfeld Sara R,Fisher Mark C,Dubreuil Maureen,Rai Sharan K,Zhang Yuqing,Choi Hyon K
Annals of the rheumatic diseases
OBJECTIVES:Recent studies have shown an increase in both cardiovascular and all-cause mortality in ankylosing spondylitis (AS). We examined the potential survival benefit of statin use in AS within a general population context. METHODS:We performed an incident user cohort study with time-stratified propensity score matching using a UK general population database between 1 January 2000 and 31 December 2014. To account for potential confounders, we compared propensity score-matched cohorts of statin initiators and non-initiators using 1-year cohort accrual blocks. The variables used to create the propensity score model included disease duration, body mass index, lifestyle factors, comorbidities and medication use. RESULTS:Using unmatched AS cohorts, statin initiators (n=1430) showed a 43% higher risk of mortality than non-initiators (n=1430) (HR=1.43; 95% CI 1.12 to 1.84). After propensity score matching, patients with AS who initiated statins (n=1108) had 96 deaths, and matched non-initiators (n=1108) had 134 deaths over a mean follow-up of 5.3 and 5.1 years, respectively. This corresponded to mortality rates of 16.5 and 23.8 per 1000 person-years (PY), respectively, resulting in an HR of 0.63 (95% CI 0.46 to 0.85) and an absolute mortality rate difference of 7.3 deaths per 1000 PY (95% CI 2.1 to 12.5). CONCLUSION:This general population-based cohort study suggests that statin initiation is associated with a substantially lower risk of mortality among patients with AS. The magnitude of the inverse association appears to be larger than that observed in randomised trials of the general population and in population-based cohort studies of patients with rheumatoid arthritis.
Are ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis associated with an increased risk of cardiovascular events? A prospective nationwide population-based cohort study.
Bengtsson Karin,Forsblad-d'Elia Helena,Lie Elisabeth,Klingberg Eva,Dehlin Mats,Exarchou Sofia,Lindström Ulf,Askling Johan,Jacobsson Lennart T H
Arthritis research & therapy
BACKGROUND:To investigate the risk of first-time acute coronary syndrome (ACS), stroke and venous thromboembolism (VTE) in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA) and undifferentiated spondyloarthritis (uSpA), compared to each other and to the general population (GP). METHODS:This is a prospective nationwide cohort study. Cohorts with AS (n = 6448), PsA (n = 16,063) and uSpA (n = 5190) patients and a GP (n = 266,435) cohort, were identified 2001-2009 in the Swedish National Patient and Population registers. The follow-up began 1 January 2006, or 6 months after the first registered spondyloarthritis (SpA) diagnosis thereafter, and ended at ACS/stroke/VTE event, death, emigration or 31 December 2012. Crude and age- and sex-standardized incidence rates (SIRs) and hazard ratios (HRs) were calculated for incident ACS, stroke or VTE, respectively. RESULTS:Standardized to the GP cohort, SIRs for ACS were 4.3, 5.4 and 4.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort, respectively, compared to 3.2 in the GP cohort. SIRs for stroke were 5.4, 5.9 and 5.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort compared to 4.7 in the GP cohort. Corresponding SIRs for VTE were 3.6, 3.2 and 3.5 events per 1000 person-years at risk compared to 2.2 in the GP cohort. Age-and sex-adjusted HRs (95% CI) for ACS events were significantly increased in AS (1.54 (1.31-1.82)), PsA (1.76 (1.59-1.95)) and uSpA (1.36 (1.05-1.76)) compared to GP. Age-adjusted HRs for ACS was significantly decreased in female AS patients (0.59 (0.37-0.97)) compared to female PsA patients. Age-and sex-adjusted HRs for stroke events were significantly increased in AS (1.25 (1.06-1.48)) and PsA (1.34 (1.22-1.48)), and nonsignificantly increased in uSpA (1.16 (0.91-1.47)) compared to GP. For VTE the age-and sex-adjusted HRs for AS, PsA and uSpA were equally and significantly increased with about 50% compared to GP. CONCLUSIONS:Patients with AS, PsA and uSpA are at increased risk for ACS and stroke events, which emphasizes the importance of identification of and intervention against cardiovascular risk factors in SpA patients. Increased alertness for VTE is warranted in patients with SpA.
The association between infection and ankylosing spondylitis: a population-based matched cohort study.
Wei James Cheng-Chung,Chou Mei-Chia,Huang Jing-Yang,Chang Renin,Hung Yao-Min
Current medical research and opinion
AIMS:To explore whether newly diagnosed infection increases the risk of developing ankylosing spondylitis (AS). METHODS AND MATERIALS:We investigated 61,550 patients with newly diagnosed infection between 1997 and 2013 from the Taiwan National Health Insurance Research Datasets to conduct a population-based matched-cohort study. Controls were 61,550 subjects without infection and propensity score matched with the exposure cohort. The follow-up period was defined as month from the initial diagnosis of infection (or nested index date for controls) to the date of AS, or 31 December 2013. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the occurrence of AS. RESULTS:The incidence rates of AS in the group and comparison group were respectively 4.58 and 3.88 per 100,000 person-months. The adjusted HR (95% CI) of AS for the group was 1.19 (0.99-1.44) compared to the control group after adjustment for age, gender and all covariates (95% CI = 1.77-2.27). However, an adjusted hazard ratio (aHR) of 1.77-fold (95% CI = 1.26-2.53) significant increase in the risk of developing AS was observed after 6 years of follow-up, when exposure to was at baseline. The effect of infection was significantly time varying ( value for interaction between follow-up period and infection is .018). CONCLUSIONS:A risk of AS was found after infection, and a year of follow-up acts as an effect modifier between the infection and risk of AS. Key messages ? Links between spondyloarthritis and fungal infections have been found in animal studies before. ? Our study demonstrated that infection is an independent risk factor for developing ankylosing spondylitis in terms of gender, age and relevant variables and comorbidities. A risk of ankylosing spondylitis was found after infection, and year of follow-up acts as an effect modifier between the infection and risk of AS. Clinicians should be aware of possible infection in managing patients with ankylosing spondylitis. : Clinicians must pay greater attention to patients with newly diagnosed infection. Specifically, they should conduct tests for ankylosing spondylitis. Further research is needed to examine if and how treatment of infection alleviates symptoms of AS.
The risk of deliberate self-harm following a diagnosis of rheumatoid arthritis or ankylosing spondylitis: A population-based cohort study.
Kuriya Bindee,Vigod Simone,Luo Jin,Widdifield Jessica,Haroon Nigil
OBJECTIVE:Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are associated with mental illness. The risk of serious mental illness, including deliberate self-harm (DSH), in these conditions is not well known. We aimed to determine if RA or AS independently increases the risk for DSH. METHODS:We conducted retrospective, population-based cohort studies using administrative health data for the province of Ontario, Canada between April 1, 2002 and March 31, 2014. Individuals with incident RA (N = 53,240) or AS (N = 13,964) were separately matched 1:4 by age, sex, and year with comparators without RA or AS. The outcome was a first DSH attempt identified using emergency department data. We estimated hazard ratios (HR) and 95% confidence intervals (95% CI) for risk of DSH in RA and AS versus comparators, adjusting for demographic, clinical and health service utilization variables. RESULTS:Subjects with AS were significantly more likely to self-harm (crude incidence rate [IR] of 0.68/1,000 person years [PY] versus 0.32/1,000 PY in comparators), with an adjusted HR of 1.59 (95% CI 1.15 to 2.21). DSH was increased for RA subjects (IR 0.35/1,000 PY) versus comparators (IR 0.24/1,000 PY) only before (HR 1.43, 95% CI 1.16 to 1.74), but not after covariate adjustment (HR 1.07, 95% CI 0.86 to 1.33). CONCLUSIONS:AS carries an increased risk for DSH but no such risk was observed in RA. Further evaluation of at-risk AS subjects is needed, including the longitudinal effects of disease and arthritis therapies on self-harm behaviour. This will inform whether specific risk-reduction strategies for DSH in inflammatory arthritis are needed.
Validation of the Ankylosing Spondylitis Quality of Life assessment tool in patients with non-radiographic axial spondyloarthritis.
Hoepken Bengt,Serrano Daniel,Harris Kristina,Hwang Mark C,Reveille John
Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation
PURPOSE:To evaluate the psychometric performance of the Ankylosing Spondylitis Quality of Life (ASQoL) scale in patients with non-radiographic axial spondyloarthritis (nr-axSpA) to assess its appropriateness as an outcome measure in future clinical studies. METHODS:Patients with active axSpA from a Phase III, randomized, double-blind, placebo-controlled trial (RAPID-axSpA, NCT01087762) were included (N = 325). Modified New York (mNY) classification criteria were used to classify patients as having ankylosing spondylitis or nr-axSpA; those with nr-axSpA were further categorized based on objective signs of inflammation. Psychometric properties of the ASQoL were assessed/documented using a mixture of modern psychometric methods and classical test theory methods. These included exploratory factor analysis and item response theory models to assess the domain structure, test the utility of a single domain relative to subdomains, assess bias, and generate statistics to guide an empirical scoring algorithm. The reliability and validity of scores were evaluated via internal consistency, test-retest reliability, concurrent validity, and known-groups validity. Score responsiveness was assessed via anchor-based clinically meaningful change, supplemented with empirical cumulative distribution function visualizations. RESULTS:The ASQoL data were defined by four domains. However, a four-domain solution was found to be inferior to a bifactor solution in which the four domains were included within a total domain. Scoring statistics supported a unit-weighted total score. Within the nr-axSpA population with objective signs of inflammation, the ASQoL mean score had adequate reliability, validity, and ability to detect clinically meaningful change. CONCLUSIONS:Our findings suggest that the ASQoL is an appropriate outcome measure in interventional clinical trials in patients with nr-axSpA.