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      Increasing proportion of female patients with ankylosing spondylitis: a population-based study of trends in the incidence and prevalence of AS

      research-article
      1 , 2 , 3 , 4 , 2 , 5 , 6 , 7
      BMJ Open
      BMJ Publishing Group
      RHEUMATOLOGY

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          Abstract

          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.

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          Most cited references31

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          The impact of tumor necrosis factor α inhibitors on radiographic progression in ankylosing spondylitis.

          To study the effect of tumor necrosis factor α (TNFα) inhibitors on progressive spinal damage in patients with ankylosing spondylitis (AS). All AS patients meeting the modified New York criteria who had been monitored prospectively and had at least 2 sets of spinal radiographs a minimum of 1.5 years apart were included in the study (n=334). The patients received standard therapy, which included nonsteroidal antiinflammatory drugs and TNFα inhibitors. Radiographic severity was assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Patients with a rate of AS progression that was ≥1 mSASSS unit/year were considered progressors. Univariable and multivariable regression analyses were done. Propensity score matching and sensitivity analysis were performed. A zero-inflated negative binomial (ZINB) model was used to analyze the effect of TNFα inhibitors on the change in the mSASSS with varying followup periods. Potential confounders, such as disease activity (as assessed by the Bath Ankylosing Spondylitis Disease Activity Index), the erythrocyte sedimentation rate, C-reactive protein level, HLA-B27 positivity, sex, age at onset, smoking burden (number of pack-years), and baseline damage, were included in the model. TNFα inhibitor treatment was associated with a 50% reduction in the odds of progression, with an odds ratio (OR) of 0.52 (95% confidence interval [95% CI] 0.30-0.88, P=0.02). Patients with a delay of >10 years in starting therapy were more likely to experience progression as compared to those who started earlier (OR 2.4 [95% CI 1.09-5.3], P=0.03). In the ZINB model, the use of TNFα inhibitors significantly reduced disease progression when the gap between radiographs was >3.9 years. The protective effect of TNFα inhibitors was stronger after propensity score matching. Treatment with TNFα inhibitors appears to reduce radiographic progression in AS patients, especially with early initiation and with longer duration of followup. Copyright © 2013 by the American College of Rheumatology.
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            Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors.

            To determine the overall prevalence of spondylarthropathy (SpA) among whites. To screen for SpA symptoms, such as inflammatory back pain (IBP), joint swelling, psoriasis, and uveitis, or a specific family history, questionnaires were mailed to 348 blood donors (174 HLA-B27 positive and 174 HLA-B27 negative). From the responding 273 persons (78%; 140 B27 positive, 133 B27 negative), 126 were selected for further evaluation based on the symptoms reported. Of this group, 90 persons agreed to undergo physical examination (71.4%; 46 B27 positive, 44 B27 negative). There was no difference between the B27-positive and -negative groups in terms of age (mean +/- SD 38.4 +/- 10 versus 39.5 +/- 11 years) and sex ratio (67% versus 68% were men). In addition, 58 donors (32 B27 positive, 26 B27 negative) agreed to undergo magnetic resonance imaging (MRI) of the sacroiliac joints. A diagnosis of SpA and ankylosing spondylitis (AS) was made according to the European Spondylarthropathy Study Group criteria and the New York criteria. SpA was diagnosed in 20 persons: 19 of 140 B27-positive (13.6%) and 1 of 133 B27-negative (0.7%) subjects (15 male and 5 female). AS was diagnosed in 9 persons (7 male and 2 female; 45%), undifferentiated SpA (USpA) in 7 (5 male and 2 female; 35%), psoriatic arthritis (PsA) in 3 (2 male and 1 female; 15%), and chronic reactive arthritis (ReA; Reiter's syndrome) in 1 (male; 5%). On the basis of a B27 frequency of 9.3% among the population of Berlin (3.47 million persons), the estimated prevalence of SpA was 1.9%, AS was 0.86%, USpA was 0.67%, and PsA was 0.29%. The relative risk of developing SpA in B27-positive subjects was calculated as 20.7 (95% confidence interval 4.6-94.2; P = 0.001). Of 58 persons with IBP, sacroiliitis was detected by MRI in 15 of 32 B27-positive (46.9%) and 1 of 26 B27-negative (3.9%) subjects (P = 0.002). Four of these 16 donors did not fulfill diagnostic criteria for SpA. With a calculated prevalence of 1.9%, spondylarthropathies are among the most frequent rheumatic diseases in the white population. HLA-B27 positive persons carry a 20-fold increased risk of developing SpA. AS and USpA are the most frequent SpA subtypes. Persons with IBP who are B27 positive have a 50% likelihood of having sacroiliitis.
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              Efficacy of adalimumab in the treatment of axial spondylarthritis without radiographically defined sacroiliitis: results of a twelve-week randomized, double-blind, placebo-controlled trial followed by an open-label extension up to week fifty-two.

              To evaluate the efficacy and safety of the tumor necrosis factor (TNF) antagonist adalimumab in patients with axial spondylarthritis (SpA) without radiographically defined sacroiliitis refractory to conventional treatment. Patients with active axial SpA (n = 46) were randomized to receive placebo or adalimumab at a dosage of 40 mg subcutaneously every other week for 12 weeks, followed by an open-label extension that continued up to week 52. The diagnosis of axial SpA required the presence of 3 of 6 diagnostic criteria, including 2 of the following 3 criteria: inflammatory back pain, HLA-B27 positivity, or acute inflammation of the spine or sacroiliac joints on magnetic resonance imaging, in the absence of radiographic evidence of sacroiliitis. The primary end point was a 40% response according to the improvement criteria of the Assessment of SpondyloArthritis international Society (ASAS40). All 46 patients (22 receiving adalimumab and 24 receiving placebo) completed the 12-week trial; 38 patients completed the extension period to week 52. At week 12, an ASAS40 response was achieved by 54.5% of the adalimumab-treated patients, as compared with 12.5% of the placebo-treated patients (P = 0.004). After switching to adalimumab, a similar degree of efficacy was also achieved by the patients who were initially treated with placebo. Efficacy was maintained in all patients until week 52. Young age at study entry and an elevated C-reactive protein concentration were the best predictors of achieving an ASAS40 response. Serious adverse events occurred in 5 patients, none of which was related to the study drug. Adalimumab is the first TNF antagonist to demonstrate good clinical efficacy and safety in patients with axial SpA without radiographically defined sacroiliitis.
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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2014
                13 December 2014
                : 4
                : 12
                : e006634
                Affiliations
                [1 ]Division of Endocrinology, Department of Medicine, University of Toronto , Toronto, Ontario, Canada
                [2 ]Institute for Clinical Evaluative Sciences , Toronto, Ontario, Canada
                [3 ]Institute of Health Policy, Management and Evaluation, University of Toronto , Toronto, Ontario, Canada
                [4 ]Department of Family Medicine, McMaster University , Hamilton, Canada
                [5 ]University Health Network , Toronto, Ontario, Canada
                [6 ]Toronto Western Research Institute , Toronto, Ontario, Canada
                [7 ]Division of Rheumatology, Department of Medicine, University of Toronto , Toronto, Ontario, Canada
                Author notes
                [Correspondence to ] Dr Nigil Haroon; Nigil.Haroon@ 123456uhn.ca
                Author information
                http://orcid.org/0000-0003-3210-4771
                Article
                bmjopen-2014-006634
                10.1136/bmjopen-2014-006634
                4267076
                25510888
                bc942473-1859-4211-b7d4-66e424b72045
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                : 15 September 2014
                : 10 November 2014
                : 26 November 2014
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