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n PRESCRIBING IN PRACTICE

Axial spondyloarthritis:

diagnosis and management

Hannah Ruth Mathieson BSc, MRCP and Helena Marzo-Ortega PhD, LMS, MRCP

Primary care plays a vital role in the identification and early referral of axial spondyloarthritis. Here, the authors discuss how to recognise the signs and rec- ommend a multidisciplinary approach to management.

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spondyloarthropathies primary axial SpA primary peripheral SpA • reactive arthritis • non-radiographic axial SpA
spondyloarthropathies
primary axial SpA
primary peripheral SpA
• reactive arthritis
• non-radiographic axial SpA
• psoriatric arthritis
• radiographic axial SpA
(ankylosing spondylitis)
• arthritis with inflammatory
bowel disease
• undifferentiated SpA
Figure 1. Axial and peripheral spondyloarthropathies

A xial spondyloarthritis (AxSpA) is a chronic inflammatory disorder of

which ankylosing spondylitis (AS) is the most recognisable phenotype. AxSpA typically affects young individuals and may remain undiagnosed for decades due to the paucity of specific signs and symptoms associated with the disease. The cardinal symptom of AxSpA and AS is inflammatory back pain (IBP), that can sometimes be indistinguishable from chronic back pain of other cause.

Background

AS is a common inflammatory condition of the axial skeleton with an estimated prevalence of 0.86 per cent among whites. 1 The name AS is derived from the Greek word ankylosis meaning bent or crooked; and spondylos meaning vertebrae. Indeed this came from the observation of extreme back deformities stemming from the structural involve- ment characteristic of late disease. The current diagnostic criteria, the modi- fied New York criteria, are heavily hinged on the presence of unequivocal radi- ographic changes of bone damage in the sacroiliac joints. 2

These bone changes, namely sclero- sis, erosions, new bone formation and/or ankylosis, may not be readily visible in the early disease stages, hence making it impossible for the diagnosis of AS to be made based on conventional radiography appearances. Typically, these radio- graphic changes only show after 10–15 years of disease activity and in some cases may never appear yet the patient may suffer grately. 3 The advent of MRI as

a sensitive imaging tool, has allowed for

a greater insight into the pathogenesis of

AxSpA, helping to identify inflammatory spinal disease up to a decade earlier than conventional radiography. This stage of disease is known as non-radiographic (nr-AxSpA) because of the lack of radi- ographically identifiable features. In an attempt to address this large group of patients, new nomenclature was recently introduced by the Assessment in Spondyloarthritis Society (ASAS). 4 AxSpA is one of the clinical entities included in the clinical family of spondy- loarthritis, that also includes psoriatic arthritis, reactive arthritis and arthritis associated to inflammatory bowel dis- ease. Some of these entities may affect

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n PRESCRIBING IN PRACTICE l Axial spondyloarthritis

primarily the peripheral rather than the axial skeleton although they share many common articular and extra-articular features (see Figure 1). This article will focus on AxSpA of which two large subgroups are recognised: non-radiographic (nr-AxSpA) and radiographic (AS) (see Figure 1), with the latter being one possible clinical ‘out- come’ of any of the clinical entities known as spondyloarthropathies.

Aetiology and epidemiology

Most of the published epidemiological data stem from AS cohorts showing a higher male prevalence of this subgroup (male to female ratio of 2:1) with patients typically presenting within the third decade of life with less than 5 per cent presenting above age 45. 5 The cause of AS is unknown, although there is a strong genetic component with approximately 90 per cent of AS patients carrying the HLA-B27 gene. 6 It is also likely that many other genes around the MHC and complex environmental factors play a role. Understanding of how nr-AxSpA interrelates with AS is still unclear. In the absence of longitudinal inception cohorts, data derived from cross- sectional interventional trials show that these patients differ from the AS group with a predominant female popu- lation and less spinal inflammation. This is consistent with previous findings that male AS patients have worse radiological outcomes. 7 It remains unclear what proportion of nr-AxSpA patients will evolve into AS however, both groups appear to have a similar burden of disease that impacts significantly in the quality of life of indi- viduals with most of the loss of function occurring within the first 10 years of disease in AS. 3,8

Presenting features and co-morbidities

Identifying patients with AxSpA early can be difficult because of the lack of patho- gnomonic signs and symptoms. Indeed, one of the cardinal features of AxSpA is IBP, that can be difficult to differentiate from chronic pain of non-inflammatory ori- gin. There are many clinical criteria to identify IBP (see Figure 2), 9 the latest of

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ASAS criteria for inflammatory back pain (IBP) Must have back pain for >3 months Patients
ASAS criteria for inflammatory
back pain (IBP)
Must have back pain for >3 months
Patients must answer yes to 4 out of
the 5 following criteria
1. improvement with exercise
2. pain at night (with improvement on
getting up)
3. insidious onset
4. age at onset of less than 40 years
5. no improvement with rest
Figure 2. ASAS criteria for IBP (sensitivity
of 79.6 per cent and specificity of 72.4 per
cent in the validation cohort) 9

which has been incorporated into the new classification criteria for AxSpA. 4 Aside from IBP, inflammation within the sacroiliac joints can cause alternating buttock pain whereas inflammation within sterno-costal joints can cause ante- rior chest wall pain. Inflammation may also occur at any site of ligament, tendon, joint capsule or fascia insertion into bone; known as entheses. These enthesitis are most commonly seen at the Achilles ten- don or plantar fascia. 10 Other peripheral musculoskeletal features include periph- eral arthritis and dactylitis (sausage dig- its) where inflammation arises within the flexor tendon, sheath and adjacent soft tissue causing the entire digit to swell. Non-musculoskeletal associations seen in AxSpA include psoriasis, inflam- matory bowel disease, aortitis, pulmonary fibrosis and uveitis, that can represent an ophthalmology emergency in some cases as permanent visual damage may occur. Young patients with AS are at higher risk of cardiovascular disease and stroke in comparison to healthy controls and it is likely that this is partly due to chronic inflammation and chronic usage of anti- inflammatory drugs. 11,12 Patients should benefit from early cardiovascular risk assessments and monitoring. Smokers should be encouraged to quit as this is an independent risk factor for severe dis- ease, poor function and health. 13 Finally, long-term inflammation can cause osteopenia and osteoporosis in up to 40 per cent of AS patients aged over 50 years and patients should be advised to have a diet rich in calcium and vitamin D. 14

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Diagnosis and classification

In a patient with suspected AxSpA, a refer- ral to rheumatology should be initiated as early as possible. Aside from a compre- hensive clinical history, patients may require a plain AP pelvic film to visualise the sacroiliac joints and to allow for assessment of hip joints, that can be affected early in poor prognosis cases. If no diagnostic abnormalities are elucidated in these films, MRI of the sacroiliiac joints and spine may be useful to identify inflammatory lesions sugges- tive of an active disease state. These imaging tests should only be requested and interpreted by experts trained in the recognition of AxSpA. Blood tests include HLA-B27 and CRP. In a patient with clinical history sug- gestive of AxSpA, the diagnosis may be aided by the ASAS criteria (see Figure 3). 4 If patients fulfil these criteria but do not yet have X-ray changes of sacroiliitis they are labelled as nr-AxSpA. If they do have X-ray changes, and fulfill the modified New York criteria, they may be diagnosed as established AS 2 (see Figure 4).

Management

Management of AxSpA should be under- taken as part of a multidisciplinary approach inclusive of education, exercise, medication and psycho-social support. Patients should be advised to keep active and ideally should receive an initial phys- iotherapy assessment with the opportu- nity to participate in individual or group therapy sessions ±hydrotherapy. Video demonstrations of exercises aimed at patients with AS are available through the National Ankylosing Spondylitis Society (NASS). Furthermore, NASS provides a wealth of information and a support net- work on their website (www.nass.co.uk).

First line medications Current NICE guidelines 15 state patients should be initially trialled on non-steroidal anti-inflammatory (NSAID) therapy or COX- 2 inhibitors as 70–80 per cent of patients will show good response. 1618 The European League Against Rheumatism (EULAR) 19 recommends continuous use of anti-inflammatories in patients with persistent, active disease although their use in inactive disease is also supported

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Axial spondyloarthritis l PRESCRIBING IN PRACTICE n

ASAS criteria for axial spondyloarthritis in patients with ≥3 months back pain and age of
ASAS criteria for axial spondyloarthritis
in patients with ≥3 months back pain and age of onset <45 years
sacroiliitis on imaging plus ≥1
SpA feature
OR
HLA-B27 plus ≥2 other SpA
features
SpA features
• inflammatory back pain (IBP)
• Crohn’s/colitis
arthritis
• enthesitis (heel)
• uveitis
• good response to NSAIDs
• family history for SpA
• HLA-B27
dactylitis
• elevated CRP
• psoriasis
Figure 3. ASAS criteria for axial spondyloarthritis

by preliminary data showing slower radiological progression in the spine. 20 This however needs to be balanced against the potential risk for side-effects in particular gastrointestinal and cardio- vascular, the latter already increased in this group when compared to a healthy population. Corticosteroids given intra-articularly into peripheral joints or sacroiliac joints can be very effective, however benefits tend to be short term. IV or IM cortico- steroids are sometimes used although there is a lack of evidence to support their efficacy.

Second line medications Unlike other inflammatory arthritides, there are no trials supporting the use of

traditional disease-modifying anti- rheumatic drugs (DMARD) in axial dis- ease. The only therapeutic agents proven

to be efficacious in all stages of AxSpA

are the biologics, in particular the

inhibitors of the pro-inflammatory cytokine TNF-alpha inhibitor (TNFi). Currently in the UK, NICE guidance sup- ports the use of anti-TNF medications; adalimumab, etanercept and golimumab

in AS. 15 In the ATLAS study, 58.2 per cent

of patients receiving adalimumab achieved at least a 20 per cent improve-

ment (ASAS 20) 21 at week 12, with similar numbers seen in other trials for etaner- cept 22 and golimumab. 23 Other promising drugs include the anti-IL-17 inhibitor secukinumab currently undergoing phase

III trials.

Modified New York criteria (1984) ≥1 clinical criteria AND ≥1 radiological criteria • low back
Modified New York criteria (1984)
≥1 clinical criteria
AND
≥1 radiological criteria
• low back pain and stiffness
for >3 months, improves with
exercise but not with rest
• radiographic sacroiliitis grade
≥2 bilaterally
• limitation of lumbar spine in
saggital and frontal planes
• limitation of chest expansion
relative to normal values
• radiographic sacroiliitis grade
≥3 unilaterally
Figure 4. Modified New York criteria (1984)

Prescriber December 2014 z 35

n PRESCRIBING IN PRACTICE l Axial spondyloarthritis

The role of primary care in AxSpA is of utmost importance to: • identify patients
The role of primary care in AxSpA is
of utmost importance to:
• identify patients with IBP and refer
to rheumatology early
• provide life long support including
psycho-social and physical therapy.
Patients should maintain postre
and participate in exercise
• provide early cardiovascular risk
assessment and advise smoking
cessation
• encourage adequate calcium and
vitamin D intake or replacement if
bone loss is already present.

NICE recommendation on biologic use in these patients is currently under review. It is expected that the updated version would support the use of TNFi across the clinical AxSpA spectrum as current guidelines only refer to AS. Indeed, the need for use of these drugs in the non-radiographic stage (nr-AxSpA) is currently unmet despite increasing evi- dence of enhanced response in the ear- lier disease stages. 24 This is now reflected in the updated EULAR and BSR guidelines (in progress) which support the use of biologics in nr-AxSpA. Furthermore, some patients with nr- AxSpA have gone into prolonged drug- free remission following TNFi therapy 24 highlighting the importance of early diag- nosis and consideration of biologic treat- ment. In addition there are mounting data suggesting that progression may be slowed down with continued use of these drugs. Two technologies (adalimumab and certolizumab) are currently approved for use in nr-AxSpA with new data from other agents expected imminently. For the most advanced cases, TNF is also show impressive short-term improvement 25 even in the presence of spinal fusion.

However in some cases, hip arthroplasty and spinal surgery may be required. Not all patients, however will have a

sustained clinical response to these

drugs, with some needing to discontinue

the treatments either through loss of

effect, or the development of adverse events. In these circumstances, a ‘switch’ of TNFi may be warranted. Real life expe-

rience shows that nearly one-third of AS

patients in clinical practice switch biolog- ical treatment with half of these achieving

treatment response. 26 Treatment options are otherwise sparse in the case of contraindication for use of biologic drugs: ie, history of cancer, recurrent infections, etc. Sulphasalazine has been shown to be of some benefit particularly in the subset of axial SpA patients who have peripheral arthritis. 27 There is also some preliminary data sug- gesting a positive of effect of bisphospho- nates (pamidronate 28 and zolendronic acid) 29 in the treatment of symptoms and inflammatory markers in active AS, although the mechanisms behind this response are not clearly elucidated.

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Declaration of interests

Dr Marzo-Ortega has received speaker fees, honoraria and/or grants from AbbVie, Celgene, Janssen, MSD, Pfizer, UCB. Dr Mathieson has none to declare.

Dr Mathieson is an NIHR Academic Clinical Fellow in rheumatology and Dr Marzo-Ortega is a consultant rheumatologist and Honorary Clinical Associate Professor in the Department of Rheumatology at Chapel Allerton Hospital, Leeds.

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