Published Clinical Papers 2016

A selection of the latest research findings

Effects of anti-TNF treatment on lipid profile in rheumatic diseases

The aim of this research was to assess the influence of long-term treatment with anti TNF on total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and atherogenic index (AI) in RA, psoriatic arthritis , and AS patients. Researchers found anti TNF treatment was associated with a significant increase in TC and TG levels and the AI. Adding statins to the treatment was associated with a significant decrease in LDL levels.


Increasing smoking intensity is associated with increased disease activity in axial spondyloarthritis

The researchers note that while a history of ever-smoking appears to be associated with a more severe disease, evidence is sparse for the effect of increased smoking exposure on disease outcomes or whether smoking reduction or cessation improves outcomes. This cross-sectional study demonstrated that smoking is associated with increased axSpA severity markers in a dose-response manner. Particular effort should be made to restrict smoking exposure early before accruing a significant number of pack-years.


Prevalence and factors associated with disturbed sleep in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a systematic review

This review explores the prevalence and factors associated with disturbed sleep for patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis. The association of physical, demographic and psychological factors correlating with poor sleep was explored, and the effectiveness of interventions assessed. Poor sleep was reported in 35-90% of patients with axial spondyloarthritis and is more prevalent within this clinical population compared to healthy control subjects. Disturbed sleep is an important aspect of disease for patients and reflects the severity of disease activity, pain, fatigue and functional disability. However, the direction of this relationship is undetermined. Associations with age, gender, years spent in education, quality of life and depression have also been demonstrated. Anti-TNF medication is effective in reducing poor sleep, and exercise has also produced beneficial results. Future research into poor sleep should take account of its multifactorial nature. There is also a current lack of research investigating non-pharmacological interventions or combination therapies. A standardised, validated measurement of poor sleep, appropriate for regular patient screening, would be a useful first step for future research.


Burden of illness associated with non-radiographic axial spondyloarthritis: a multiperspective European cross-sectional observational study

It was clear that nr-axSpA was associated with a significant QoL and societal burden in this study of German, French, Spanish, Italian and UK patients. Treatment with biological agents was associated with improved QoL. Considerable variability in patients’ clinical characteristics were observed across the countries studied and further education, aimed at improving awareness of the condition, may be needed.


BSR and BHPR guideline for the treatment of axial spondyloarthritis (including ankylosing spondylitis) with biologics

This revision of the 2005 BSR guidelines provides evidence-based guidance for UK clinicians prescribing biologic drugs for adult patients across the spectrum of axial spondyloarthritis. We would like to thank NASS member Robin Brittain for his hard work in ensuring the patient view was taken into account.


Web-based physiotherapy for people with axial spondyloarthritis (WEBPASS) – a study protocol

Evidence suggests people with axial spondyloarthritis should exercise up to five times a week but lack of time, symptoms, cost and distance are barriers to regular exercise. Personalised exercise programmes delivered via the internet might support people  to reach these exercise targets. The aim of this Glasgow-based study is to investigate the effect of, and adherence to, a 12 month personalised web-based physiotherapy programme for people with axial spondyloarthritis.


A Difficult Diagnosis: A Qualitative Study of the Daily Lives of Young Men Diagnosed with Ankylosing Spondylitis

The study consisted of semi-structured interviews with five men diagnosed with AS. The men were recruited from a rheumatological hospital in Denmark. It had taken a long time for all the men to get the correct diagnosis, and the period before diagnosis was characterised by great uncertainty regarding the men’s prospects. In addition, physical limitations, depression and stress had an inhibitory impact on the men’s everyday lives. It was important for the men to stay in the work force and to be able to change their career direction, which was necessary for the men whose jobs involved hard physical work.


Secukinumab for rheumatology: development and its potential place in therapy

This article in Drug Design, Development and Therapy explores the role of secukinumab in AS and other rheumatic conditions.


Differences in the prevalence of ankylosing spondylitis in primary and secondary care: only one-third of patients are managed in rheumatology

This study from the SIRAS team at Aberdeen University aimed to determine the prevalence of SpA and the proportion managed in rheumatology and to examine differences in group characteristics. The results indicate only one-third of patients are managed in rheumatology. This has important ramifications for health care planning and indicates a large ‘silent’ proportion of patients who may have serious pathology and would benefit from additional assessment in a specialist clinic.


The effectiveness of a real life dose reduction strategy for TNF inhibitors in ankylosing spondylitis and psoriatic arthritis

This study aimed to determine the feasibility of TNF inhibitor (TNFi) dose reduction for severe AS and PsA patients. It concluded that, in a real-world setting, 60% of individuals with severe AS and PsA who achieve low disease activity can successfully reduce the dose of TNFi therapy by a third for a mean of 1 year.


Pregnancy and foetal outcomes following anti-tumor necrosis factor alpha therapy: A prospective multicentre study

This study evaluated the effects of anti TNF on pregnancy/foetal outcomes.The researchers followed 38 pregnancies, of which 24 were exposed to anti TNF at conception. The study results suggest that anti-TNFα drugs could be safe when administered during conception/I trimester and following paternal exposure.


The oral microbiome of patients with axial spondyloarthritis compared to healthy individuals

The purpose of these studies was to investigate microbial communities that colonise the oral cavity of patients with axial spondyloarthritis (AxSpA) and to compare these with microbial profiles of a matched healthy population. Analysis of operational taxonomic units (OTUs) and higher levels of taxonomic assignment did not provide strong evidence of any single taxa associated with AxSpA in the subgingival plaque. However, researchers believe there remains the potential for the microbiota to exert functional and metabolic influences in the oral cavity which could be involved in the pathogenesis of AxSpA.


Targeting the interleukin-23/17 axis in axial spondyloarthritis

This article highlights and emphasizes how new knowledge of mechanisms linked to the interleukin-23 (IL-23)/IL-17 pathway is relevant to the pathophysiology of axial spondyloarthritis (axSpA) and demonstrates how molecules in IL-23/IL-17 pathway provide novel therapeutic targets for axSpA patients.

Recent studies highlight central position of the IL-23/IL-17 pathway in the pathogenesis of axSpA. Recent findings include:

  • The contribution of IL-23/IL-17 signaling pathways may differs in male and female AS patients.
  • IL-17 and IL-22 secreting-type 3 innate lymphoid cells are increased in AS patients which point to their potential role in the pathogenesis of axSpA.
  • Reports of dysbiosis in the gut microbiome of AS patients support previous work indicating a possible causal relationship between altered gut flora, ileocolonic inflammation and axSpA.
  • Results from clinical trials support the efficacy and safety of agents that block IL-12/23 (ustekinumab) and IL-17 (secukinumab and ixekizumab) in AS patients.

Targeting the IL-23/IL-17 pathway appears to be a safe and effective strategy for treatment of axSpA patients.


The interaction between host genetics and the microbiome in the pathogenesis of spondyloarthropathies.

The intestinal microbiome is increasingly implicated in the pathogenesis of AS and other diseases collectively known as the spondyloarthropathies (SpAs).

In common with other complex inflammatory diseases, SpAs have both a strong genetic and environmental component. Recent genetic studies have highlighted host pathways that may intersect the host-microbiota interaction:

  • Genetic association studies have identified genes such as RUNX3, PTPEN2, and IL-33 as susceptibility loci for SpAs.
  • Functional studies in humans have extended knowledge of established genetic risk factors for AS that include ERAP1, ERAP2, and interleukin-23R.
  • Recent basic research has identified new mechanisms that regulate host immune responses to the microbiota that may be dysregulated in SpA.


Cancer risk in patients with spondyloarthritis treated with TNF inhibitors: a collaborative study from the ARTIS and DANBIO registers

The objective of this research was to assess risks for cancer overall and for common subtypes in patients with spondyloarthritis (SpA) treated with anti TNF therapy compared with SpA patients who have never taken anti TNF and to the general population.

The researchers used the the Swedish (ARTIS) and Danish (DANBIO) biologics registers, to examine 8703 patients with SpA who started anti TNF therapy between 2001 and 2011. From the Swedish National Patient and Population Registers they assembled an anti TNF naïve SpA cohort (2,864) and a Swedish age-matched and sex-matched general population comparator cohort (131,687).

Cancers were identified by linking with the nationwide Swedish and Danish Cancer Registers 2001-2011, and calculated age-standardised and sex-standardised incidence ratios as measures of relative risk.

The researchers have concluded that, in patients with SpA, treatment with anti TNF was not associated with increased risks of cancer, neither overall nor for the six most common cancer types.


Factors associated with a bad functional prognosis in early inflammatory back pain: results from the DESIR cohort

Spondyloarthritis is an unpredictable condition. This research looked into what factors might predict a bad functional outcome.

Data from patients included in the French multicentre devenir des spondylarthropathies indifférenciées récentes (DESIR) cohort, were used. A bad functional outcome at 24 months was defined as an increase in BASFI, or BASFI at 2 years higher than the 75th centile in the cohort. Demographic, clinical, biological and radiological data collected at inclusion were compared in patients with bad functional outcome versus others.

Researchers discovered older age and a high disease activity at diagnosis were assoiated with worse prognosis. They also found smokers and women were independently associated with a poor outcome.


Preliminary definitions of `flare` in axial spondyloarthritis, based on pain, BASDAI and ASDAS-CRP: an ASAS initiative

The objective of this research was to develop a definition for ‘flare’ (or worsening) in AS, to be used in the context of clinical trial design.

Researchers carried out a review of the available literature and obtained 12 preliminary draft definitions of ‘flare’. These preliminary definitions will need validation in real patient data.


Do extra-articular manifestations influence outcome in ankylosing spondylitis? 12-year results from OASIS

The objective of this research was to assess whether extra-articular manifestations (EAMs) in AS are associated with worse functioning, worse quality of life (QoL), and more radiographic damage over time. Researchers used 12 year follow-up data from the Outcome in Ankylosing Spondylitis International Study, along with data on EAMs extracted from medical charts. It was discovered that the presence of EAMs was not associated with functional disability, QoL or radiographic damage over time.


Nonsteroidal Antiinflammatory Drugs for Axial Spondyloarthritis: A Cochrane Review

The objective of this research was to To determine the benefits and harms of nonsteroidal antiinflammatory drugs (NSAID) in AS by carrying out a systematic review using Cochrane Collaboration methodology. High-quality evidence indicated that both traditional and COX-2 NSAID are efficacious for treating axSpA, and harms are not different from placebo in the short term. Various NSAID are equally effective.