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Published Clinical Papers 2018

A selection of the latest research findings

Progress in our understanding of the pathogenesis of ankylosing spondylitis

The pathogenesis of axial SpA (AS) is likely to be multi-factorial and has not been fully elucidated to date. A major genetic role has been demonstrated. The strongest genetic association is with HLA B27. Numerous other associated genetic polymorphisms have been identified, including those affecting the type 17 immune pathway, although the precise link between genetics and pathogenesis remains unexplained. Several immunological alterations, together with recent therapeutic advances, support a central role for IL-23- and IL-17-producing immune cells in disease pathogenesis. Recently, perturbations of gut microbiota of AS patients have further catalysed research and offer potential for future therapeutic intervention. In this review the authors outline the genetic basis of axial SpA (AS) and describe the current hypotheses for disease pathogenesis.

Optimizing outcomes for ankylosing spondylitis and axial spondyloarthritis patients: a holistic approach to care

Axial SpA (AS) can affect diverse elements of an individual’s life. The areas affected can be much more wide-ranging than the historical medical model. A more holistic view of the individual means many other areas of life can be adversely affected, from the ability to work effectively and function socially, to effects on quality of life and the onset of worsening fatigue or mood disturbance. A good understanding of these areas outside the medical model allows for an improved understanding of the overall life impact of axial SpA (AS). This highlights the importance of understanding how to measure these elements of life using patient-reported outcome measures that can truly reflect an individual’s experience.

Axial spondyloarthritis including ankylosing spondylitis

This interesting article discusses the concept of axial spondyloarthritis.

Recent advances in ankylosing spondylitis: understanding the disease and management

This review analyses the latest therapies for spondyloarthritis and the most relevant discoveries over the last three years, together with their implications for different aspects of the disease.

Ankylosing spondylitis: A novel risk factor for atrial fibrillation – A nationwide population-based study

The researchers in this study investigated whether AS increases the risk of atrial fibrillation (AF) in a nationwide population-based study. They conclude AS is an independent risk factor for AF, especially in those under 40 years of age and those taking anti TNF therapy. The researchers conclude it would be reasonable to screen for AF and stroke prevention in these high-risk patients.

Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor

The TORTUGA trial investigated the efficacy and safety of filgotinib, an oral selective Janus kinase 1 (JAK1) inhibitor, for the treatment of patients with active ankylosing spondylitis. This was a randomised, double-blind, placebo-controlled, phase 2 trial, enrolling adult patients from 30 sites in seven countries (Belgium, Bulgaria, Czech Republic, Estonia, Poland, Spain, and Ukraine). Eligible patients had active ankylosing spondylitis and an inadequate response or intolerance to two or more NSAIDs. Patients were randomly assigned to receive filgotinib or placebo  for 12 weeks. Between March 7, 2017, and July 2, 2018, 263 patients were screened and 116 randomly assigned to filgotinib.

Initial results were positive and the study concludes further investigation is warranted.

Biologics and cardiovascular events in inflammatory arthritis

The aim of this study was to evaluate whether the risk of cardiovascular events in patients with inflammatory arthritis is associated with treatment with biologic therapy. The study looked at over 4,000 patients and concluded current biologic use was associated with a reduction in major cardio vascular events.

A five-year prospective study of spinal radiographic progression and its predictors

Knowledge about predictors of new spinal bone formation in AS is limited. Researchers are aware that AS-related spinal alterations are more common in men; however, knowledge of whether predictors differ between sexes is lacking. The objectives of this research were to study spinal radiographic progression in AS and investigate predictors of progression. The researchers found predictors may partly differ between the sexes. New predictors identified were obesity in both sexes and exposure to bisphosphonates in women. Among previously known predictors, baseline AS-related spinal radiographic alterations predicted radiographic progression in both sexes, high CRP was a predictor in men (with a trend in women) and smoking was a predictor only in men.

The prevalence of depression in axial spondyloarthritis and its association with disease activity

The authors establish through a systematic review of papers that depression is common among axSpA patients and is associated with more severe disease activity and functional impairment. They conclude identifying and managing depression should form part of  holistic care. They note further longitudinal studies are needed to explore the impact of depression on treatment outcomes and axSpA treatment on symptoms of depression.

2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis

Regular physical activity is increasingly promoted for people with rheumatic and musculoskeletal diseases as well as the general population. EULAR evaluated if the public health recommendations for physical activity  are applicable for people with inflammatory arthritis, including AS.  Evidence and expert opinion inform these recommendations to provide guidance in the development, conduct and evaluation of physical activity interventions and promotion. It is advised that these recommendations should be implemented considering individual needs and national health systems.

Ankylosing spondylitis and axial spondyloarthritis: recent insights and impact of new classification criteria

Development of the Assessment in Spondyloarthritis International Society (ASAS) classification criteria for axial spondyloarthritis (axial SpA) was one of the major breakthroughs in the field over the past decade. Despite some concerns related to the specificity of the criteria, they stimulated research into the early stage of the disease. This resulted in major advances in the understanding of the course of the disease, revealing predictors of progression, improvement in early diagnosis and treatment in axial SpA. This summarises the recent developments resulting from the introduction of the ASAS classification criteria for axial SpA and the implications for research and clinical practice.

Abrupt and unexpected stressful life events are followed with increased disease activity in spondyloarthritis

272 axial SpA patients were followed for two years. Every second month patients reported whether they had been exposed to stressful life events, vaccinations or other environmental factors. Patients were asked to rate the distress resulting from exposure to life events on a numerical rating scale.

Researchers discovered stressful life events, abrupt and unexpected events were associated with transient worsening of disease activity in SpA, which reached a clinically meaningful increase for the highest rating of distress. Association between vaccines and disease flare was not confirmed.

Gender Differences in Axial Spondyloarthritis: Women Are Not So Lucky

Ankylosing spondylitis (AS) was historically seen as a predominantly male disease. However, more recent data shows it affects both men and women. The purpose of this review was to aggregate the existing data on gender differences in axial spondyloarthritis in order to increase the awareness that female patients are still under-recognised.

The authors point to several studies revealing that female axSpA patients have different disease manifestations due to different immunological, hormonal, and genetic responses. Thiese differences include:

  • Allelic frequencies of the AHNK-gene and tissue non-specific alkaline phosphatase (TNAP) haplotypes differ between men and women with ankylosing spondylitis (AS)
  • Different levels of tumor necrosis factor (TNF), interleukins IL-6, IL-17, and IL-18, have been found between men and women.
  • Women have a higher diagnostic delay compared to men
  • Several studies indicate a higher frequency of extra-articular manifestations (EAM) in female axSpA patients, such as enthesitis, psoriasis, and inflammatory bowel disease (IBD), whereas acute anterior uveitis is more prevalent in male patients
  • Male AS patients more frequently show a higher Bath Ankylosing Spondylitis Radiology Index (BASRI) scores and modified Stoke Ankylosing Spondylitis Spine Scores (mSASSS) than females, which indicates that males have higher radiological damage and radiographic progression.
  • Disease activity (BASDAI) and quality of life (AsQol) scores are significantly higher in women
  • Women have significantly lower response rates to treatment with TNF inhibitors (anti TNF) and a significantly lower drug adherence
Overall, despite the fact that men with axial SpA have a worse radiologic prognosis, women have a high disease burden, in part because they have a longer delay in diagnosis, higher disease activity, and significantly less responsiveness to treatment with anti TNF.

Determinants of psychological well-being in axial spondyloarthritis: an analysis based on linked claims and patient-reported survey data

The aim of this study was to assess the psychological well-being of people with AS  and analyse factors associated with depressive symptoms. Researchers found a high prevalence of depression  among people with AS.  Higher BASDAI and BASFI, stress, lack of exercise, lower income level and younger age are factors associated with moderate-to-severe depressive symptoms. These findings highlight the need for the careful evaluation of depressive symptoms as a part of the management strategy for AS, helping to improve outcomes.

Comparative Analysis and predictors of 10-year anti TNF survival in patients with spondyloarthritis

This research aimed to evaluate the 10-year drug survival of the first anti TNF tried and to identify predictors of drug retention.

The longterm retention of the first TNFi administered to patients with SpA is high, especially for males with axial disease. The strongest predictor of longterm TNFi survival is a major response within the first year of treatment.

Prevalence of axial spondyloarthritis in patients with acute anterior uveitis: a cross-sectional study utilising MRI

Acute anterior uveitis (AAU) is the most common extra-articular manifestation of axial spondyloarthritis (axSpA). In this study, patients presennt.ting with AAU were evaluated clinically and with MRI in order to estimate the prevalence of axSpA.

Of 366 patients with AAU, 57 had a pre-existing diagnosis of axSpA; 77 others fulfilled the study eligibility criteria and 73 (95%) completed the study. Seventeen patients (23%) were diagnosed with axSpA by an experienced rheumatologist; of these, eight were human leucocyte antigen-B27 negative. Including those with a previous diagnosis, this equates to a minimum axSpA prevalence of 20.2%; one-quarter of patients were previously undiagnosed.

This is the first study to actively search for the presence of axSpA in unselected patients presenting with AAU utilising MRI as an essential part of the assessment. There is a significant burden of undiagnosed axSpA in patients with AAU, but there does not appear to be a simple mechanism for screening. The researchers recommend that ophthalmologists refer all patients with AAU with CBP, onset <45 years, to rheumatology for further evaluation.

Services for spondyloarthitis: a survey of patients and rheumatologists

NASS surveyed 2000 people with axSpA, while, separately, a web-based questionnaire about axSpA services was sent to rheumatologists at all 172 acute hospital trusts in the UK.

Although overall patient satisfaction with rheumatology care was high, the results indicate significant unmet patient needs and discrepancies in service provision. This information will inform the development of quality standards for axSpA in order to improve quality and deliver equitable care for all patients.

New advances in the understanding and treatment of axial spondyloarthritis: from chance to choice

This interesting article covers the possibility of diagnosing axSpA early, along with new therapeutic options. The authors highlight that defining the most effective sequence of therapy with biologics, the search for biomarkers of treatment response and the careful study of longitudinal axSpA cohorts, remain key domains to research for the coming decade.

Using Self-Reported Patient Experiences to Understand Patient Burden: Learnings from Digital Patient Communities in Ankylosing Spondylitis

This study described patient experiences reported online to better understand the day-to-day disease burden of ankylosing spondylitis (AS). A total of 34,780 narratives from 3449 patients with AS were included. Physical aspects of AS (e.g., pain and mobility) were most commonly reported by patients (87%), followed by emotional (33%), cognitive (24%), role activity (9%) and social (5%).

The Sex Influence on Response to Tumor Necrosis Factor-α Inhibitors and Remission in Axial Spondyloarthritis

In this retrospective multicenter study, patients with axSpA, according to the Assessment of Spondyloarthritis international Society (ASAS) criteria for axSpA, and treated with anti TNF were studied. We compared clinical characteristics, patient-reported outcomes, disease activity, function, and response to treatment in male and female patients with this disease.

Three hundred forty patients with axSpA (270 with ankylosing spondylitis, 19 with psoriatic arthritis with axial involvement, and 51 with nonradiographic axSpA) were studied. The data suggested the female sex was associated with a lower rate of response to treatment and of disease remission in patients with axSpA treated with anti TNF.