Published Clinical Papers 2011

This page includes a selection of some of the research findings in AS from 2011.

Two new susceptibility genes, EDIL3-HAPLN1 and ANO6, identified as being involved in bone formation and cartilage development

A research team at the Genome Institute of Singapore and Sun Yat-Sen University have carried out a large genome-wide association study involving people in China. They first looked for common genetic variants in 1,837 people with ankylosing spondylitis and a further 4,231 disease-free volunteers. They then validated 30 of the genes they identified in a further 2,100 patients and 3,496 healthy people.

This allowed them to discover two new susceptibility genes, EDIL3-HAPLN1 and ANO6, which are thought to be involved in bone formation and cartilage development. The study also confirmed the role of the previously identified gene HLA-B27 in ankylosing spondylitis.

Physical Fitness in Patients With Ankylosing Spondylitis

This study was published in the Physical Therapy Journal. Bearing in mind the increased risk of cardio-vascular disease for people with AS, the reesearchers wanted to compare physical fitness in people with AS versus those who did not have AS and then to explore associations between physical fitness and disease activity in the group with AS.

The study found lower cardiorespiratory fitness and reduced flexibility in the AS group indicating that physical therapy programs should include cardiorespiratory fitness exercises as a basic component to reduce the risk of cardiovascular disease.

The effect of whole body vibration training on patients with AS 

Rudi Chaplin is the sports rehabilitator that works with NASS Milton Keynes. His research, which was published in the Journal of Sports Therapy, looked at the use of whole body vibration training on patients with AS. His data showed a significant improvement in some outcome measures at 6 weeks and 12 weeks. He only had 10 subjects (all from NASS Milton Keynes). and is hoping to find funding to conduct further research.

Assessment of quality of life and depression in spouses of patients with ankylosing spondylitis

This fairly small scale Turkish study investigated the quality of life and the rates of depression in spouses/partners of patients with AS compared with spouses/partners of healthy controls. Twenty-five people with AS and their 25 spouses (21 women and 4 men) and 25 healthy controls were recruited. They concluded that being a spouse of a patient with AS significantly interferes with quality of life and increases depression frequency.

Postural control is altered in patients with ankylosing spondylitis

The researchers from this study note that impaired axial mobility due to vertebral ankylosis may result in changes in standing postural control. They point out that little research has addressed changes in standing postural control in the ankylosing spondylitis population, nor how these issues might affect clinical understanding and treatment.

They conclude that quiet standing postural control was altered particularly in the frontal plane in patients with ankylosing spondylitis, which may be associated with increased fall risk. The researchers believe that posturographic measures of postural control may serve as valuable clinical tools for the monitoring of disease progression and disease status in ankylosing spondylitis.

Smokers with early axial spondyloarthritis have earlier disease onset, more disease activity, inflammation and damage, and poorer function and health-related quality of life

The purpose of this study was to look into what association smoking has with various clinical, functional and imaging outcomes in people with early axial (area of spine and neck) spondyloarthritis (SpA). 647 patients with early inflammatory back pain fulfilling at least one of the internationally accepted SpA criteria and with available smoking data were included in the analyses. Clinical, demographic and imaging parameters were compared between smokers and non-smokers at a cross-sectional level.

Results showed that smoking was independently associated with earlier onset of inflammatory back pain, higher disease activity, increased axial inflammation on MRI, increased axial structural damage on MRI and x-ray, poorer functional status and poorer quality of life.

For more information on getting help with stopping smoking do look at the NHS Choices website.

Comparison of anti TNF recommendations across 23 countries

This clinical paper gives an overview of the recommendations for the use of anti TNF therapy across 23 different countries. The authors conclude that general consensus exists about the use of anti TNF therapy in AS across the world, although some countries require additional objective signs of inflammation and/or more pre-treatment, which limits access.

Mortality in AS

Excess mortality (death rates) has been reported in patients with AS. The researchers for this French study reviewed recent studies of patients with AS who were treated and monitored according to the improved methods developed in the past few years, without radiation therapy. Their results do not support excess mortality in these patients. Long-term follow-up data from patients enrolled in biologics registries will provide additional information.

Cardiovascular disease is the leading cause of death in patients with AS, as in the general population. However, the cardiovascular mortality rate may be slightly increased in patients with AS, probably as a result of dyslipidemia and early endothelial dysfunction. Similarly, there is excess mortality related to the spinal disease itself and to renal and gastrointestinal disease. Alcohol abuse and injury or suicide also cause excess mortality compared to the general population.

The effects of combined spa therapy and rehabilitation on patients with ankylosing spondylitis being treated with TNF inhibitors

This is not a UK based study, as you might expect, as I'm sure that few, if any UK AS patients have ever been offered spa therapy by the NHS.

The objective of the study was to evaluate the effects of combined spa therapy and rehabilitation in a group of AS patients being treated with ant TNF therapy. Thirty AS patients attending the rheumatology unit of the University of Padova in Italy who had been treated with anti TNF therapy for at least 3 months were randomised and assessed by an investigator independent from the spa staff: 15 were prescribed 10 sessions of spa therapy (mud packs and thermal baths) and rehabilitation (exercises in a thermal pool) and the other 15 were considered controls.

Evaluations were performed in all patients at the start of the study, at the end of the spa treatment, and after 3 and 6 months. Most of the evaluation indices were significantly improved at the end of the spa treatment, as well as at the 3 and 6 months follow-up assessments. No significant alterations in the evaluation indices were found in the control group.

It was thus concluded that combined spa therapy and rehabilitation lead to a clear, long-term clinical improvement in AS patients being treated with anti TNF therapy. Thermal treatment was found to be well tolerated and none of the patients had disease relapse.

Update on the management of inflammatory bowel disease: specific role of adalimumab

This study appeared in the Clinical and Experimental Gastroenterology journal. It discusses the role of adalimumab in the treatment of Crohn's Disease and its potential future role in ulcerative colitis. The full article is available.

Effect of pregnancy on AS

This study aimed to determine the severity of back pain and stiffness in women with AS before, during, and after pregnancy. The study included 19 women with AS (35 pregnancies) and 33 women without AS who were used as the controls (77 pregnancies).

Improvement in pain was reported in 51% of AS patients, predominantly in the first trimester, with significant improvement in pain rather than stiffness. In both groups, pain worsened in later stages. Following childbirth, pain scores in AS returned to the same level as prior to pregnancy..

Researchers concluded from this that pregnancy does not substantially aggravate disease activity or severity in AS.

Lumbar osteotomy for AS

A new clinical paper has appeared in the European Spine Journal which compares 3 types of lumbar osteomtomy for AS and makes some interesting conclusions.

Some people with AS can develop curving of the spine (kyphosis) which is so severe that they can no longer look straight forward comfortably or look people in the eye. In addition to practical difficulties such as eating and drinking this can lead to social isolation, neck pain and unsteadiness. Lumbar osteomy is a technique carried out by spinal surgeons to help correct the curvature.

If you have severe curving of the spine we recommend that you discuss the possibility of spinal surgery with your consultant. If your consultant does feel surgery might benefit you, then you should be referred on to a team specialising in spinal surgery. Surgery will be considered if :

  • Your spine is unstable, meaning that it has fractured
  • Your spine is very deformed making it difficult to carry out activities of daily living such as eating or drinking
  • The deformity in your spine is leading to nerve damage

Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility

A study involving over 5,000 people with AS has identified a series of genetic variants associated with increased susceptibility to the condition as well as providing new clues to how the condition may be treated in the future.

The study, a collaboration between the Australo-Anglo-American Spondyloarthritis Consortium and the Wellcome Trust Case Control Consortium, also provides one of the first confirmed examples of gene-gene interaction seen in humans.

The study, carried out in the UK, Australia and North America, compares the genomes of 3,023 cases against those of 8,779 healthy controls. The findings have confirmed in an independent cohort of 2,111 cases and 4,483 controls. The results are published in the journal Nature Genetics.

Professor Peter Donnelly from the University of Oxford, Chair of the Wellcome Trust Case Control Consortium says: "Thanks to over 5,000 people with ankylosing spondylitis who have provided DNA samples, we were able to undertake the largest study of the genetics of this painful and often disabling disease.  It revealed important, and in some cases surprising, new insights into the disease."

The study identified three regions of the genome - RUNX3, LTBR and TNFRSF1A - in which genetic variants were strongly associated with AS. In addition, they found a further four which are likely candidates: PTGER4, TBKBP1, ANTXR2 and CARD9.

As well as furthering our understanding of the genetics underlying the condition, the findings also strengthen evidence that a particular process by which signals are transmitted within cells - known as the IL-23R pathway - is involved in the disorder and could be a target for drugs.

The study also provided clues as to why a particular genetic variant known as HLA-B27 is associated with the disease. Scientists have known for almost forty years that this variant significantly increases the risk of developing the disease. Nine out of ten people with ankylosing spondylitis carry the variant. Whilst not everyone with the variant develops the condition, those who carry the variant are up to eighty times more likely to develop it than non-carriers. Yet despite this knowledge, the mechanism by which the variant causes the disease is still unknown.

The researchers found that variants of the gene ERAP1 interact with HLA-B27 to affect disease susceptibility - one of the first confirmed examples of gene-gene interaction seen in humans. For individuals who carry HLA-B27, their risk of developing ankylosing spondylitis decreases by a factor of four if they also carry two copies of the protective variants of ERAP1.

ERAP1 plays a role in breaking down proteins within the body into smaller molecules known as peptides. The gene interacts with HLA-B27 to affect how these peptides are presented to the immune system. This is an essential process for mounting an immune response to invading pathogens, but when it goes awry it can result in the immune system causing inflammation and damaging tissue. The researchers found that some variants of ERAP1 protect against the development of ankylosing spondylitis by reducing the amount of peptide available to HLA-B27 within cells. The researchers believe that inhibiting ERAP1 may help treat the condition.

The researchers also analysed the genetic make-up of individuals with ankylosing spondylitis who did not carry the HLA-B27 variant and found associations with several genetic regions, the first time that associations have been found in HLA-B27 negative individuals. These findings indicate considerable similarity between the way HLA-B27 positive and negative ankylosing spondylitis develop.

Impact of home-based exercise therapy in patients with AS

It's simple and cheap to do your AS exercises at home. The aim of this study was to investigate the effects of home-based exercise therapy on pain, mobility, function, disease activity, quality of life, and respiratory function in patients with AS.

80 AS patients were included in the study. A home-based exercise program including range of motion, stretching, strengthening, posture, and respiratory exercises was practically demonstrated by a physiotherapist and a training and exercise booklet was given to all patients. The researchers then compared patients following the home-based exercise program five times a week for at least 30 minutes per session per session (exercise group) for 3 months with those exercising less than five times a week (control group).

The exercise group showed significant improvements in pain, mobility, respiration and quality of life over the control group after 3 months.

The researchers recommended that regular home-based exercise therapy should be a part of main therapy in patients with AS with patients exercising at least five times a week for at least 30 minutes per session.

Baseline predictors of response and discontinuation of anti TNF therapy

Identifying AS patients who are likely to benefit from anti TNF therapy is important, in terms of both the cost and potential side effects. The aim of this present study was to identify baseline predictors of response and discontinuation of anti TNF therapy in AS patients in daily clinical practice.

The study, published in Arthritis Research and Therapy, found that younger age, male gender, higher inflammatory markers and high ASDAS score were identified as independent baseline predictors of response and/or continuation of TNF-alpha blocking therapy. In contrast, higher baseline BASDAI score was independently associated with treatment discontinuation.

Premature ejaculation in patients with ankylosing spondylitis

Researchers into Turkey looked into whether men with AS were more likely to suffer with premature ejaculation than the general population. They compared 50 men with AS against 50 men from the general population and found there was no difference between the two groups with regard to rates of premature ejaculation.

Update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis

This first update of the ASAS/EULAR recommendations on the management of ankylosing spondylitis (AS) is based on the original paper, a systematic review of existing recommendations and the literature since 2005 and the discussion and agreement among 21 international experts, 2 patients and 2 physiotherapists in a meeting in February 2010. Each original bullet point was discussed in detail and reworded if necessary. Decisions on new recommendations were made - if necessary after voting. The strength of the recommendations (SOR) was scored on an 11-point numerical rating scale after the meeting by email.

These recommendations apply to patients of all ages that fulfill the modified NY criteria for AS, independent of extra-articular manifestations, and they take into account all drug and non-drug interventions related to AS.

Four overarching principles were introduced and there are now 11 bullet points including 2 new ones, one related to extra-articular manifestations and one to changes in the disease course.

Update of the international ASAS recommendations for the use of anti TNF agents in patients with axial spondyloarthritis

This paper presents the second update of the Assessment in SpondyloArthritis international Society (ASAS) consensus statement on the use of anti TNFs in patients with axial spondyloarthritis (SpA). A major change from the previous recommendations is that patients fulfilling the ASAS axial SpA criteria, which also include patients fulfilling the modified New York criteria for ankylosing spondylitis, can be treated with anti TNF agents. This makes an earlier start in the disease process possible.

A second major change is the pre-treatment before anti-TNF agents can be started. According to ASAS, all patients should have tried a minimum of 2 non-steroidal anti-inflammatory drugs for a minimum of 4 weeks in total. This is significantly shorter than the previous requirement of 3 months. As previously, patients with axial symptoms require no further pre-treatment. Patients with symptomatic peripheral symptoms should normally have had an adequate therapeutic trial of a disease-modifying anti rheumatic drug, preferably sulfasalazine. Sulfasalazine is no longer mandatory in this group of patients. Finally, efficacy should be evaluated after at least 12 weeks. The remaining recommendations stayed largely unchanged.

Please bear in mind that these are international guidelines and rheumatologists in the UK have to follow NICE guidance.

Sick leave in patients with ankylosing spondylitis before and after anti-TNF therapy: a population-based cohort study

Using the population-based South Swedish Arthritis Treatment Group register, 139 AS patients were investigated (aged 18-58 years, 78% men), who between January 2002 and December 2008 started their first treatment with adalimumab, etanercept or infliximab. The proportion of sick leave in 30-day intervals from 12 months before treatment start until 12 months after was calculated for each patient.

The researchers found that in the 1-3 months before treatment, an average of 24% of AS patients were on sick leave. During the first 6 months after treatment started, this proportion dropped to 15%, and further declined to 12% at 12 months.

Smoking increases levels of disease activity in patients with severe AS

The largest study to date on the effects of smoking in patients with ankylosing spondylitis (AS) has shown that smoking increases disease severity.

The study was carried out on a large population of AS patients, from 10 rheumatology departments across the UK.

Results from the study found that associations with increased disease activity, decreased function and poor quality of life in smokers were independent of age, sex and disease duration.

Dr Mattey, author of the study said:

"This is the first study to show a dose-dependent relationship between smoking and disease outcome in AS. This suggests that cessation of smoking is likely to be beneficial in terms of functional outcome and long term quality of life in patients with AS".

Effect of pilates training on people with AS

The objective of this study was to investigate the effects of pilates on pain, functional status, and quality of life in people with AS.

55 people with AS took part in the study and they were divided into 2 groups. One group took part in 3 pilates classes a week for 24 weeks while the second group continued with their standard exercise routine.

Comparison of the two groups showed significantly superior results for the group taking part in pilates classes.

The authors suggest pilates is an effective and safe way to improve physical capacity in people with AS patients.

A second study into pilates and AS also found it had a good impact on mobility, as well as patients' perception about their condition

Spondyloarthropathies: an independent cardiovascular risk factor?

An increase in cardiovascular mortality and morbidity has been convincingly documented in RA but data on AS and the other spondyloarthropathies (SpA) are more limited.

The authors of this paper look at published studies indicating that patients with SpA are at increased risk for cardiovascular disease. They conclude that increased risk is probably multifactorial, being related both to chronic systemic inflammation and to a high prevalence of conventional cardiovascular risk factors.

They note that cardiovascular risk management in patients with SpA requires optimal control of disease activity combined with interventions targeting conventional cardiovascular risk factors.

Services for people with ankylosing spondylitis in the UK - a survey of rheumatologists and patients

NASS were involved in the research and writing of this research paper with more than 800 members filling in a survey about their experiences surrounding diagnosis, treatment and access to therapies.  A separate questionnaire was completed by 117 rheumatology departments.

Key findings were delays in the diagnosis of AS, access to anti TNF therapy and the large proportion of people with AS who are not being managed in secondary care.

This clinical research paper was published in Rheumatology and is covered in AS News and you can contact Sally Dickinson for a full copy of the paper.

Improving the treatment of ankylosing spondylitis in the UK

This is an editorial article which appears in the same issue of Rheumatology. It's written by the authors of our Looking Ahead publication which discusses best practice in the management of AS. It represents another big step forward in improving the understanding of AS and ensuring that all rheumatology units in the UK work towards the same high standards of care.

Again you can contact Sally Dickinson if you'd like a full copy of the paper.

Impaired gait in ankylosing spondylitis

New research has been conducted into the way people with AS walk. This research shows that conducting an expert analysis of gait gives physiotherapists much better information, allowing them to intervene more specifically. This can lead to less stiffness, improved balanced and reduced muscle fatigue.

Reduced vital capacity leads to exercise intolerance in patients with AS

This research, which was published in the European journal of physical and rehabilitation medicine, found that people with AS have lower chest expansion, vital capacity and exercise tolerance than the general population. The authors conclud that exercise intolerance is mainly explained by lung function impairment in AS patients rather than musculoskeletal changes.

They argue that this means that it's important for people with AS to not only work towards improving spinal mobility but also towards increasing cardiopulmonary fitness.

Assessment of subclinical vascular disease associated with ankylosing spondylitis

The authors of this clinical paper note that current studies indicate that AS, as well as rheumatoid arthritis, may be associated with accelerated atherosclerosis and vascular disease.

Audiovestibular manifestations in patients with ankylosing spondylitis

The authors of this study note that currently little is known about audiovestibular impairment in patients with AS. Thus research was conducted among 50 people with AS who were compared against 40 people who did not have AS.

29 of the people with AS (58%) showed abnormal hearing loss in the audiogram compared to only 8 (18%) of the people who did not have AS.

The authors conclude that people with AS are more likely to have changes in their inner ear than the general population.

Diet, disease activity, and gastrointestinal symptoms in patients with ankylosing spondylitis

This paper was published in Clinical Rheumatology in December 2010. The aims of the study were to investigate, first, the relationship between diet and disease activity and, secondly, the presence of gastrointestinal symptoms and their relationship to diet among patients with ankylosing spondylitis (AS). The research took place in Sweden.

In the 165 AS patients who took part,  no correlation between diet and disease activity could be detected. There were, however, correlations between diet and gastrointestinal pain. Gastrointestinal problems were also found to be prevalent in AS, independent of NSAID usage.

Predictors of response to anti TNF therapy in ankylosing spondylitis: results from the British Society for Rheumatology Biologics Register

Currently there isn't much data on the routine use of anti TNF drugs for AS in the UK. The British Society for Rheumatology Biologics Register (BSRBR) recruited patients starting anti TNF therapy for AS between 2002 and 2006. The patients included in the study were young (median age 43 years) and 82% were males.

The research concluded that the majority of patients receiving anti TNF therapy for AS showed improvements in disease activity. Raised inflammatory markers at the start of therapy predicted a greater improvement, identifying a group of patients who may be more responsive to anti TNF therapies, although the results were not confined to this group.

Clinical efficacy and safety of etanercept versus sulfasalazine in ankylosing spondylitis patients

The Rheumatology Medical Center in Bochum, Germany compared the effectiveness and safety of etanercept versus sulfasalazine after 16 weeks in patients with axial (spine) and peripheral manifestations (outside of the spine e.g. hips, knees) of AS.

The average age of the patients involved in the trial was 41 years, 74% were male, and average disease duration was 7.6 years. The authors concluded that, in this population of patients with AS, etanercept was significantly more effective than sulfasalazine in improving signs and symptoms of the axial skeleton and of the peripheral joints. Serious adverse events rarely occurred and did not differ between groups.

Delayed presentation and diagnosis of cervical spine injuries in long-standing ankylosing spondylitis

The Queen Elizabeth National Spinal Injuries Unit in Glasgow published a very interesting paper in the European Spine journal in December 2010. It highlights that patients with ankylosing spondylitis (AS) are vulnerable to cervical spine fractures and that long-standing pain may mask the symptoms of the fracture. Radiological imaging of the cervical spine may fail to identify the fracture due to distorted anatomy and ossified ligaments.

Retrospective case series study of all patients with AS and cervical spine fracture admitted over a 12-year period at Queen Elizabeth National Spinal Injuries Unit show that total of 32 patients were reviewed with AS and cervical spine fractures. In 19 patients (59.4%), a fracture was not identified on plain radiographs. Only five patients (15.6%) presented immediately after the injury. Of the 15 patients (46.9%) who were initially neurologically intact, three patients had neurological deterioration before admission.

The research concludes that cervical spine fractures in patients with long-standing AS are common and usually under evaluated. Early diagnosis with appropriate radiological investigations may prevent possible long-term neurological cord damage.

After reading this information a NASS member who had delayed presentation and diagnosis of a cervical spine injury and was treated at the Queen Elizabeth National Spinal Injuries Centre sent in his experience.

Association of Variants at 1q32 and STAT3 with Ankylosing Spondylitis Suggests Genetic Overlap with Crohn's Disease

One of our trustees, Dr Paul Wordsworth, is one of the authors of a new paper on the genetics of AS which genetically links AS and Crohn's disease. It was published in December 2010 in a specialist genetics journal.

Ankylosing spondylitis and inflammatory bowel disease (Crohn's disease and ulcerative colitis) frequently occur together in the same families and individuals, suggesting that they share common risk factors. The researchers tested whether genes associated with Crohn's disease are also associated with ankylosing spondylitis and confirmed that the two diseases share associations at chromosome 1q32 near KIF21B, STAT3, IL12B, CDKAL1, LRRK2/MUC19, and chromosome 13q14. These associations were present even in ankylosing spondylitis cases with no clinical inflammatory bowel disease. These findings greatly expand our understanding of why these conditions occur together.

Developing and validating an index for measuring health in patients with ankylosing spondylitis

Thank you again to all those who took part in research on behalf of ASAS this year. A preliminary research paper was published in Rheumatology in December 2010. Dr Uta Kiltz who asked NASS members to take part in the UK research is one of the main authors of the paper. We will keep you informed on further developments.

The objective of the new research is to outline the development and validation of a health index for patients with AS based on the ICF as a use case. In the paper, the researchers conclude that the goal of developing a health index for patients with AS based on the ICF is very much in line with the broader goal of the WHO to define health indices to ensure the comparability of them within the framework of the ICF.

Last reviewed: November 2011