Spondyloarthritis in over 16s: diagnosis and management

This guideline covers diagnosing and managing spondyloarthritis that is suspected or confirmed in adults who are 16 years or older. It aims to raise awareness of the features of spondyloarthritis and provide clear advice on what action to take when people with signs and symptoms first present in healthcare settings. It also provides advice on the range of treatments available.

# Recommendations
People have the right to be involved in discussions and make informed decisions about their care, as described in NICE's information on making decisions about your care.
Making decisions using NICE guidelines explains how we use words to show the strength (or certainty) of our recommendations, and has information about prescribing medicines (including off-label use), professional guidelines, standards and laws (including on consent and mental capacity), and safeguarding.
Spondyloarthritis is a group of inflammatory conditions that have a range of manifestations. Spondyloarthritis may be predominantly:
axial:
radiographic axial spondyloarthritis (ankylosing spondylitis)
non-radiographic axial spondyloarthritis or
peripheral:
psoriatic arthritis
reactive arthritis
enteropathic spondyloarthritis.
People with predominantly axial spondyloarthritis may have additional peripheral symptoms, and vice versa.
Axial presentations of spondyloarthritis are often misdiagnosed as mechanical low back pain, leading to delays in access to effective treatments. Peripheral presentations are often seen as unrelated joint or tendon problems, and can be misdiagnosed because problems can move around between joints.

# Recognition and referral in non-specialist care settings
Do not rule out the possibility that a person has spondyloarthritis solely on the presence or absence of any individual sign, symptom or test result.

## Suspecting spondyloarthritis
Recognise that spondyloarthritis can have diverse symptoms and be difficult to identify, which can lead to delayed or missed diagnoses. Signs and symptoms may be musculoskeletal (for example, inflammatory back pain, enthesitis and dactylitis) or extra-articular (for example, uveitis and psoriasis ). Risk factors include recent genitourinary infection and a family history of spondyloarthritis or psoriasis.
Be aware that axial and peripheral spondyloarthritis may be missed, even if the onset is associated with established comorbidities (for example, uveitis, psoriasis, inflammatory bowel disease , or a gastrointestinal or genitourinary infection).
Be aware that axial spondyloarthritis:
affects a similar number of women as men
can occur in people who are human leukocyte antigen B27 (HLAB27) negative
may be present despite no evidence of sacroiliitis on a plain film Xray.

## Referral for suspected axial spondyloarthritis
If a person has low back pain that started before the age of 45 years and has lasted for longer than 3 months, refer the person to a rheumatologist for a spondyloarthritis assessment if 4 or more of the following additional criteria are also present:
low back pain that started before the age of 35 years (this further increases the likelihood that back pain is due to spondyloarthritis compared with low back pain that started between 35 and 44 years)
waking during the second half of the night because of symptoms
buttock pain
improvement with movement
improvement within 48 hours of taking non-steroidal anti-inflammatory drugs (NSAIDs)
a first-degree relative with spondyloarthritis
current or past arthritis
current or past enthesitis
current or past psoriasis.If exactly 3 of the additional criteria are present, perform an HLAB27 test. If the test is positive, refer the person to a rheumatologist for a spondyloarthritis assessment.
If the person does not meet the criteria in recommendation 1.1.5 but clinical suspicion of axial spondyloarthritis remains, advise the person to seek repeat assessment if new signs, symptoms or risk factors listed in recommendation 1.1.5 develop. This may be especially appropriate if the person has current or past inflammatory bowel disease (Crohn's disease or ulcerative colitis), psoriasis or uveitis (see recommendation 1.1.12 for guidance on referral for immediate  ophthalmological assessment for people with acute anterior uveitis).

## Referral for suspected psoriatic arthritis and other peripheral spondyloarthritides
For guidance on identifying spondyloarthritis in people with an existing diagnosis of psoriasis, see assessment and referral for psoriatic arthritis in the NICE guideline on psoriasis.
Urgently refer people with suspected newonset inflammatory arthritis to a rheumatologist for a spondyloarthritis assessment, unless rheumatoid arthritis, gout or acute calcium pyrophosphate (CPP) arthritis ('pseudogout') is suspected. If rheumatoid arthritis is suspected, see referral for specialist treatment in the NICE guideline on rheumatoid arthritis in adults.
Refer people with dactylitis to a rheumatologist for a spondyloarthritis assessment.
Refer people with enthesitis without apparent mechanical cause to a rheumatologist for a spondyloarthritis assessment if:
it is persistent or
it is in multiple sites or
any of the following are also present:
back pain without apparent mechanical cause
current or past uveitis (see recommendation 1.1.12 for guidance on immediate  ophthalmological assessment for people with acute anterior uveitis)
current or past psoriasis
gastrointestinal or genitourinary infection
inflammatory bowel disease (Crohn's disease or ulcerative colitis)
a first-degree relative with spondyloarthritis or psoriasis.

## Recognising psoriasis
If a person with suspected spondyloarthritis has signs or symptoms of undiagnosed psoriasis, follow the recommendations in the NICE guideline on psoriasis.

## Referral for suspected acute anterior uveitis
Refer people for an immediate (sameday) ophthalmological assessment if they have symptoms of acute anterior uveitis (for example, eye pain, eye redness, sensitivity to light or blurred vision).

## Case-finding in people with acute anterior uveitis
Ophthalmologists should ask people with acute anterior uveitis whether they have:
consulted their GP about joint pains or
experienced low back pain that started before the age of 45 years and has lasted for longer than 3 months.
If the person meets either of the criteria in recommendation 1.1.13, establish whether they have psoriasis or skin complaints that appear psoriatic on physical examination.
If they do, refer the person to a rheumatologist for a spondyloarthritis assessment.
If they do not, perform an HLAB27 test. If the test is positive, refer the person to a rheumatologist for a spondyloarthritis assessment.

# Diagnosing spondyloarthritis in specialist care settings

## Diagnostic criteria for suspected spondyloarthritis
In specialist care settings, consider using validated spondyloarthritis criteria to guide clinical judgement when diagnosing spondyloarthritis. Examples include:
general spondyloarthritis criteria:
Amor
European Spondyloarthropathy Study Group (ESSG)
axial spondyloarthritis criteria:
Assessment of Spondyloarthritis International Society (ASAS; axial)
Berlin
Rome
modified New York
peripheral spondyloarthritis criteria:
ASAS (peripheral)
Classification of Psoriatic Arthritis (CASPAR)
French Society of Rheumatology (reactive arthritis).
Do not rule out a diagnosis of spondyloarthritis solely on the basis of a negative HLAB27 result.
Do not rule out a diagnosis of spondyloarthritis if a person's Creactive protein (CRP) and erythrocyte sedimentation rate (ESR) are normal.

## Imaging for suspected axial spondyloarthritis
Offer plain film Xray of the sacroiliac joints for people with suspected axial spondyloarthritis, unless the person is likely to have an immature skeleton.
Diagnose radiographic axial spondyloarthritis (ankylosing spondylitis) if the plain film Xray shows sacroiliitis meeting the modified New York criteria (bilateral grade 24 or unilateral grade 34 sacroiliitis).
If the plain film Xray does not show sacroiliitis meeting modified New York criteria (bilateral grade 24 or unilateral grade 34 sacroiliitis), or an Xray is not appropriate because the person's skeleton is not fully mature, request unenhanced MRI using an inflammatory back pain protocol.
Radiologists receiving a request for an inflammatory back pain MRI should perform short T1 inversion recovery (STIR) and T1 weighted sequences of the whole spine (sagittal view), and sacroiliac joints (coronal oblique view).
Use the ASAS/Outcome Measures in Rheumatology (OMERACT) MRI criteria to interpret the MRI as follows:
If the MRI meets the ASAS/OMERACT MRI criteria:
diagnose non-radiographic axial spondyloarthritis.
If the MRI does not meet the ASAS/OMERACT MRI criteria:
do not exclude the possibility of axial spondyloarthritis
consider specialist musculoskeletal radiology review if there is disparity between the clinical suspicion and imaging findings, particularly in people with an immature skeleton
-ffer an HLAB27 test if it has not already been done. If positive, base the diagnosis of non-radiographic axial spondyloarthritis on clinical features, for example, using the clinical 'arm' of the ASAS axial classification criteria.
If a diagnosis of axial spondyloarthritis cannot be confirmed and clinical suspicion remains high, consider a followup MRI.
Do not offer scintigraphy for people with suspected axial spondyloarthritis.

## Imaging for suspected psoriatic arthritis and other peripheral spondyloarthritides
Offer plain film Xray of symptomatic hands and feet for people with suspected peripheral spondyloarthritis in these areas.
If a diagnosis cannot be made from the plain film Xray, consider ultrasound of:
the hands and feet to assess for joint involvement
suspected enthesitis sites.
Consider plain film Xrays, ultrasound and/or MRI of other peripheral and axial symptomatic sites.
Interpret a positive HLAB27 result as increasing the likelihood of peripheral spondyloarthritis.
If a diagnosis of peripheral spondyloarthritis is confirmed, offer plain film Xray of the sacroiliac joints to assess for axial involvement, even if the person does not have any symptoms.

## Antibody testing for suspected reactive arthritis
Do not routinely test for infective antibody status to diagnose reactive arthritis in people with a history of gastrointestinal infection.

# Information and support

## Information about spondyloarthritis
Provide people with spondyloarthritis, and their family members or carers (as appropriate), with information that is:
available on an ongoing basis
relevant to the stage of the person's condition
tailored to the person's needs.For more guidance on providing information to people and discussing their preferences with them, see the NICE guideline on patient experience in adult NHS services.
Provide explanations and information about spondyloarthritis, for example:
what spondyloarthritis is
diagnosis and prognosis
treatment options (pharmacological and non-pharmacological), including possible side effects
likely symptoms and how they can be managed
flare episodes and extra-articular symptoms
self-help options
-pportunities for people with spondyloarthritis to be involved in research
which healthcare professionals will be involved with the person's care and how to get in touch with them
information about employment rights and ability to work
local support groups, online forums and national charities, and how to get in touch with them.

## Information about disease flares
Advise people with spondyloarthritis about the possibility of experiencing flare episodes and extra-articular symptoms.
Consider developing a flare management plan that is tailored to the person's individual needs, preferences and circumstances.
When discussing any flare management plan, provide information on:
access to care during flares (including details of a named person to contact )
self-care (for example, exercises, stretching and joint protection)
pain and fatigue management
potential changes to medicines
managing the impact on daily life and ability to work.

# Pharmacological management of spondyloarthritis

## Axial spondyloarthritis
Offer NSAIDs at the lowest effective dose to people with pain associated with axial spondyloarthritis, and think about appropriate clinical assessment, ongoing monitoring of risk factors, and the use of gastroprotective treatment.
If an NSAID taken at the maximum tolerated dose for 24 weeks does not provide adequate pain relief, consider switching to another NSAID.
Adalimumab, certolizumab pegol, etanercept, golimumab and infliximab are recommended, within their marketing authorisations, as options for treating severe active ankylosing spondylitis in adults whose disease has responded inadequately to, or who cannot tolerate, NSAIDs. Infliximab is recommended only if treatment is started with the least expensive infliximab product. People currently receiving infliximab should be able to continue treatment with the same infliximab product until they and their NHS clinician consider it appropriate to stop. 
Adalimumab, certolizumab pegol and etanercept are recommended, within their marketing authorisations, as options for treating severe non-radiographic axial spondyloarthritis in adults whose disease has responded inadequately to, or who cannot tolerate, NSAIDs. 
The choice of treatment should be made after discussion between the clinician and the patient about the advantages and disadvantages of the treatments available. This may include considering associated conditions such as extra-articular manifestations. If more than 1 treatment is suitable, the least expensive (taking into account administration costs and patient access schemes) should be chosen. 
The response to adalimumab, certolizumab pegol, etanercept, golimumab or infliximab treatment should be assessed 12 weeks after the start of treatment. Treatment should only be continued if there is clear evidence of response, defined as:
a reduction in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score to 50% of the pre-treatment value or by 2 or more units and
a reduction in the spinal pain visual analogue scale (VAS) by 2 cm or more. 
Treatment with another tumour necrosis factor (TNF)alpha inhibitor is recommended for people who cannot tolerate, or whose disease has not responded to, treatment with the first TNFalpha inhibitor, or whose disease has stopped responding after an initial response. 
When using BASDAI and spinal pain VAS scores, healthcare professionals should take into account any physical, sensory or learning disabilities, or communication difficulties that could affect the responses to the questionnaires, and make any adjustments they consider appropriate. 
Secukinumab is recommended, within its marketing authorisation, as an option for treating active ankylosing spondylitis in adults whose disease has responded inadequately to conventional therapy (NSAIDs or TNFalpha inhibitors). The drug is recommended only if the company provides it with the discount agreed in the patient access scheme. 
Assess the response to secukinumab after 16 weeks of treatment and only continue if there is clear evidence of response, defined as:
a reduction in the BASDAI score to 50% of the pre-treatment value or by 2 or more units and
a reduction in the spinal pain VAS by 2 cm or more. 
When using BASDAI and spinal pain VAS scores, healthcare professionals should take into account any physical, sensory or learning disabilities, or communication difficulties that could affect the responses to the questionnaires, and make any adjustments they consider appropriate.

## Psoriatic arthritis and other peripheral spondyloarthritides
Consider local corticosteroid injections as monotherapy for non-progressive monoarthritis.
Offer standard disease-modifying anti-rheumatic drugs (DMARDs) to people with:
peripheral polyarthritis
-ligoarthritis
persistent or progressive monoarthritis associated with peripheral spondyloarthritis.
When deciding which standard DMARD to offer, take into account:
the person's needs, preferences and circumstances (such as pregnancy planning and alcohol consumption)
comorbidities such as uveitis, psoriasis and inflammatory bowel disease
disease characteristics
potential side effects.
If a standard DMARD taken at the maximum tolerated dose for at least 3 months does not provide adequate relief from symptoms, consider switching to or adding another standard DMARD.
Consider NSAIDs as an adjunct to standard DMARDs or biological DMARDs to manage symptoms. Use oral NSAIDs at the lowest effective dose for the shortest possible period of time, and think about appropriate clinical assessment, ongoing monitoring of risk factors, and the use of gastroprotective treatment.
If NSAIDs do not provide adequate relief from symptoms, consider steroid injections (local or intramuscular) or short-term oral steroid therapy as an adjunct to standard DMARDs or biological DMARDs to manage symptoms.
If extra-articular disease is adequately controlled by an existing standard DMARD but peripheral spondyloarthritis is not, consider adding another standard DMARD.
For guidance on treating psoriatic arthritis with apremilast, see NICE's technology appraisal guidance on apremilast for treating active psoriatic arthritis.
Etanercept, infliximab and adalimumab are recommended for the treatment of adults with active and progressive psoriatic arthritis when the following criteria are met.
The person has peripheral arthritis with 3 or more tender joints and 3 or more swollen joints, and
The psoriatic arthritis has not responded to adequate trials of at least 2 standard DMARDs, administered either individually or in combination. 
Treatment as described in 1.4.20 should normally be started with the least expensive drug (taking into account drug administration costs, required dose and product price per dose). This may need to be varied for individual patients because of differences in the method of administration and treatment schedules. 
Etanercept, adalimumab or infliximab treatment should be discontinued in people whose psoriatic arthritis has not shown an adequate response using the Psoriatic Arthritis Response Criteria (PsARC) at 12 weeks. An adequate response is defined as an improvement in at least 2 of the 4 PsARC criteria (1 of which has to be joint tenderness or swelling score) with no worsening in any of the 4 criteria. People whose disease has a Psoriasis Area and Severity Index (PASI) 75 response at 12 weeks but whose PsARC response does not justify continuation of treatment should be assessed by a dermatologist to determine whether continuing treatment is appropriate on the basis of skin response (see NICE's technology appraisal guidance on etanercept and efalizumab for the treatment of adults with psoriasis , infliximab for the treatment of adults with psoriasis  and adalimumab for the treatment of adults with psoriasis  for guidance on the use of TNF inhibitors in psoriasis). 
When using the PsARC healthcare professionals should take into account any physical, sensory or learning disabilities, or communication difficulties that could affect a person's responses to components of the PsARC and make any adjustments they consider appropriate. 
Golimumab is recommended as an option for the treatment of active and progressive psoriatic arthritis in adults only if:
it is used as described for other TNFinhibitor treatments in NICE technology appraisal guidance etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis  (see recommendations 1.4.201.4.23 in this guideline) and
the manufacturer provides the 100 mg dose of golimumab at the same cost as the 50 mg dose. 
When using the PsARC (as set out in NICE technology appraisal guidance on etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis  (see recommendations 1.4.201.4.23 in this guideline), healthcare professionals should take into account any physical, sensory or learning disabilities, or communication difficulties that could affect a person's responses to components of the PsARC and make any adjustments they consider appropriate. 
Ustekinumab is recommended as an option, alone or in combination with methotrexate, for treating active psoriatic arthritis in adults only when:
treatment with TNFalpha inhibitors is contraindicated but would otherwise be considered (as described in NICE technology appraisal guidance on etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis  , and golimumab for the treatment of psoriatic arthritis  ) or
the person has had treatment with 1 or more TNFalpha inhibitors.Ustekinumab is recommended only if the company provides the 90 mg dose of ustekinumab for people who weigh more than 100 kg at the same cost as the 45 mg dose, as agreed in the patient access scheme. 
Ustekinumab treatment should be stopped if the person's psoriatic arthritis has not shown an adequate response using the PsARC at 24 weeks. An adequate response is defined as an improvement in at least 2 of the 4 criteria (1 of which must be joint tenderness or swelling score), with no worsening in any of the 4 criteria. As recommended in NICE technology appraisal guidance on etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis (see recommendations 1.4.201.4.23 in this guideline), people whose disease has a PASI 75 response but whose PsARC response does not justify continuing treatment should be assessed by a dermatologist to determine whether continuing treatment is appropriate on the basis of skin response (see NICE technology appraisal guidance on ustekinumab for the treatment of adults with moderate to severe psoriasis). 
When using the PsARC healthcare professionals should take into account any physical, sensory or learning disabilities, or communication difficulties that could affect a person's responses to components of the PsARC and make any adjustments they consider appropriate. 
People whose treatment with ustekinumab is not recommended in this NICE guidance, but was started within the NHS before this guidance was published, should be able to continue ustekinumab until they and their NHS clinician consider it appropriate to stop. 

## Reactive arthritis
After treating the initial infection, do not offer long-term (4 weeks or longer) treatment with antibiotics solely to manage reactive arthritis caused by a gastrointestinal or genitourinary infection.

# Non-pharmacological management of spondyloarthritis
Refer people with axial spondyloarthritis to a specialist physiotherapist to start an individualised, structured exercise programme, which should include:
stretching, strengthening and postural exercises
deep breathing
spinal extension
range of motion exercises for the lumbar, thoracic and cervical sections of the spine
aerobic exercise.
Consider hydrotherapy as an adjunctive therapy to manage pain and maintain or improve function for people with axial spondyloarthritis.
Consider a referral to a specialist therapist (such as a physiotherapist, occupational therapist, hand therapist, orthotist or podiatrist) for people with spondyloarthritis who have difficulties with any of their everyday activities. The specialist therapist should:
assess people's needs
provide advice about physical aids
arrange periodic reviews to assess people's changing needs.

# Surgery for spondyloarthritis
Do not refer people with axial spondyloarthritis to a complex spinal surgery service to be assessed for spinal deformity correction unless the spinal deformity is:
significantly affecting their quality of life and
severe or progressing despite optimal non-surgical management (including physiotherapy).
If a person with axial spondyloarthritis presents with a suspected spinal fracture, refer them to a specialist to confirm the spinal fracture and carry out a stability assessment. After the stability assessment, the specialist should refer people with a potentially unstable spinal fracture to a spinal surgeon.

# Managing flares
Manage flares in either specialist care or primary care depending on the person's needs.
When managing flares in primary care, seek advice from specialist care as needed, particularly for people who:
have recurrent or persistent flares
are taking biological DMARDs
have comorbidities that may affect treatment or management of flares.
Be aware that uveitis can occur during flare episodes. See recommendation 1.1.12 for guidance on immediate (sameday) ophthalmological assessment for people with acute anterior uveitis.

# Long-term complications
For guidance on monitoring long-term pharmacological treatments, see the NICE guideline on medicines optimisation.
Take into account the adverse effects associated with NSAIDs, standard DMARDs and biological DMARDs when monitoring spondyloarthritis in primary care.
Advise people that there may be a greater risk of skin cancer in people treated with TNFalpha inhibitors.
Discuss risk factors for cardiovascular comorbidities with all people with spondyloarthritis.
Consider regular osteoporosis assessments (every 2 years) for people with axial spondyloarthritis. Be aware that bone mineral density measures may be elevated on spinal dualenergy Xray absorptiometry (DEXA) due to the presence of syndesmophytes and ligamentous calcification, whereas hip measurements may be more reliable.
Advise people with axial spondyloarthritis that they may be prone to fractures, and should consult a healthcare professional following falls or physical trauma, particularly in the event of increased musculoskeletal pain.

# Organisation of care

## Coordinating care across settings
Commissioners should ensure that local arrangements are in place to coordinate care for people across primary and secondary (specialist) care. These should cover:
prescribing NSAIDs and standard DMARDs
monitoring NSAIDs, standard DMARDs and biological DMARDs
managing flares
ensuring prompt access to specialist rheumatology care when needed
ensuring prompt access to other specialist services to manage comorbidities and extra-articular symptoms.
Ensure that people with spondyloarthritis have access to specialist care in primary or secondary care settings throughout the disease course to ensure optimal long-term spondyloarthritis management (see section 1.7 for arrangements for managing flares).
Ensure that there is effective communication and coordination between all healthcare professionals involved in the person's care, particularly if the person has comorbidities or extra-articular symptoms.
Ensure that there is communication and coordination between rheumatology and other relevant specialities (such as dermatology, gastroenterology and ophthalmology). This is particularly important for people who:
are already receiving standard DMARDs or biological DMARDs for another condition
need to start taking standard DMARDs or biological DMARDs for another condition.
For guidance on managing the transition of young people with juvenile idiopathic arthritis to adult services, see the NICE guideline on transition from children's to adults' services for young people using health or social care services.# Context
Spondyloarthritis encompasses a group of inflammatory conditions with some shared features, including extra-articular manifestations. Both peripheral and axial joints can be affected. The spondyloarthritides are distinct from rheumatoid arthritis but are as important to recognise and manage early in their presentation to improve health outcomes.
Most people with these conditions have either psoriatic arthritis or axial spondyloarthritis, which includes ankylosing spondylitis. Ankylosing spondylitis and non-radiographic axial spondyloarthritis primarily affect the spine, in particular the sacroiliac joint. Both conditions present in similar ways; the primary classification difference is whether sacroiliitis is detectable on Xray.
Psoriatic arthritis may manifest in a number of different patterns. These include predominant involvement of small joints in the hands and feet, predominant large joint involvement, particularly in the knees, or combinations of these. Psoriatic arthritis may also involve the axial joints, and inflammation of the entheses and/or finger and toe joints. Skin and nail involvement may not be present at diagnosis and in its absence, a family history of psoriasis is required to meet the diagnostic criteria.
Less common subgroups are enteropathic spondyloarthritis, which is associated with inflammatory bowel disease (Crohn's disease and ulcerative colitis), and reactive arthritis, which can occur in people after gastrointestinal or genitourinary infections.
The final subgroup is people who have undifferentiated spondyloarthritis. These people generally have an asymmetrical oligoarticular (fewer than 5 involved joints) arthritis, often involving the knees. They do not meet the diagnostic criteria of the other subgroups at presentation but their disease may evolve to do so at a later stage.
This guideline also includes people who are 16 years or older with axial or peripheral symptoms who have previously been diagnosed with juvenile idiopathic arthritis.
Healthcare professionals in non-specialist settings do not always recognise the signs and symptoms of spondyloarthritis, particularly spinal symptoms, which may be mistakenly attributed to other causes of low back pain. This can lead to substantial delays in diagnosis and treatment with consequent disease progression and disability. This guideline seeks to raise awareness of the features of spondyloarthritis and provide clear advice on what action to take when people with signs and symptoms first present in healthcare settings.
This guideline also provides advice on the interventions available to people with spondyloarthritis. These include pharmacological and non-pharmacological treatments, and surgery. The guidance also provides advice on how care for people with spondyloarthritis should be organised across healthcare settings, and what information and support should be provided.# Recommendations for research
The guideline committee has made the following recommendations for research. The committee's full set of research recommendations is detailed in the full guideline.

# Referral criteria for people with suspected axial spondyloarthritis
What are the optimal referral criteria for people with suspected axial spondyloarthritis?

## Why this is important
The Dutch CaFaSpA study (van Hoeven et al. 2014, 2015) should be repeated in a UK population. This would involve examining GP databases to identify a cohort of people who have a diagnosis of non-specific back pain who first consulted their GP for back symptoms under the age of 45. These people would be invited for a full rheumatological assessment (including identifying signs and symptoms relevant to axial spondyloarthritis, Xray, MRI and HLAB27 test). All participants would be given a reference-standard diagnosis of axial spondyloarthritis or not (ideally using expert clinician opinion, or if this is not possible, using the ASAS  classification criteria). The cohort would be split into a development and validation set, to derive and validate optimal rules for case-finding from the available data, with each candidate strategy judged according to expected cost per quality-adjusted life year (QALY) gained (the NICE economic model developed for this guideline could easily be used to estimate these).
As a result of the large number of permutations of possible referral strategies, it is impractical to run separate validation studies for all referral criteria that are developed. Therefore, a single large, representative cohort study would, provided it measured the predictor variables for all reasonable referral strategies, provide the ability to develop and validate any number of possible referral strategies. The study would need to be large enough that sufficient data are available to derive new referral rules and to validate those rules in a separate, independent subset of the data. A UKspecific dataset would provide more relevant data to do this than is currently available from the Dutch CaFaSpA study. For example, that study found an HLAB27 prevalence of 20% in people with axial spondyloarthritis and 2% in people without; much lower than the estimates found elsewhere (75% and 20% respectively). This lowers the validity of extrapolating any results found to the UK, and reinforces the need for UKspecific data to address this question.

# Long-term complications of spondyloarthritis
What is the incidence of long-term complications, in particular osteoporosis, cardiovascular disease (CVD) and metabolic syndrome, in people with spondyloarthritis, and how does this compare with the general population? Are any specific spondyloarthritis features or risk factors associated with the incidence and outcomes of these complications?

## Why this is important
Spondyloarthritides are a group of systemic inflammatory conditions, and as such it is thought that people with these conditions may have an elevated risk of CVD, particularly if their disease is not adequately controlled. This may have direct vascular effects as well as precluding maintenance of a good level of cardiovascular fitness.
There is also clinical uncertainty around the long-term use of non-steroidal anti-inflammatory drugs (NSAIDs): whether the long-term CVD risks associated with this class of drugs are observed in this population, or whether the suppression of inflammation with these drugs mitigates some of the CVD risks associated with these conditions. In addition, risks of osteoporosis and fracture are known to be higher in people with axial spondyloarthritis than the general population, and the prevalence of axial manifestations in people diagnosed with peripheral disease implies the risks may also be high in peripheral spondyloarthritis.
The longer-term complication rates in the spondyloarthritides need to be established, as well as whether standard biological disease-modifying anti-rheumatic drug (DMARD) therapies and biological DMARDs influence these outcomes. Research that evaluates incidence of osteoporosis, CVD and metabolic syndrome in people with either axial or peripheral spondyloarthritis compared with the general population would therefore be of value. This research should take into account disease stage, personal activity levels and medicine use, and look to address how frequently it is appropriate to monitor people with spondyloarthritis for long-term complications.

# Educational intervention to improve healthcare professionals' awareness of spondyloarthritis
What is the effectiveness and cost effectiveness of educational interventions for healthcare professionals in order to increase the number of prompt diagnoses of spondyloarthritis?

## Why this is important
One of the major reasons for the delays in diagnosing spondyloarthritis is a lack of awareness of the condition by healthcare professionals. This can take many forms, such as a lack of awareness of different spondyloarthritis subtypes, lack of knowledge about associated clinical features (for example, the differences between inflammatory and mechanical back pain) or characteristics of the patient populations (for example, that spondyloarthritis affects similar numbers of men and women, or that a substantial proportion of people with spondyloarthritis are HLAB27 negative). Educational interventions to improve the level of awareness may therefore lead to reductions in diagnosis delays, but there is a lack of evidence as to the efficacy of these interventions. Randomised controlled trials of structured educational interventions are therefore needed to assess both whether they reduce the length of time it takes for people to be correctly diagnosed, and whether they represent a cost-effective use of NHS resources.

# Pharmacological management of peripheral spondyloarthritis
What is the comparative effectiveness and cost effectiveness of standard DMARDs for managing peripheral spondyloarthritis, and is this effectiveness affected by differences in dose escalation protocols?

## Why this is important
The committee noted that, although there are a number of randomised controlled trials comparing standard DMARDs with placebo for managing peripheral spondyloarthritis, there is a lack of evidence comparing individual standard DMARDs to other standard DMARDs. This lack of evidence makes it difficult to optimise initial therapy, either by specifying specific drugs within the class or optimising dose, administration and monitoring protocols. There is therefore the need for randomised controlled trials looking at alternative drug, dosing and administration route alternatives for the administration of standard DMARDs for managing peripheral spondyloarthritis. These trials should ensure NSAIDs and steroids are available to participants as needed, and should include (as outcome measures) both health-related quality of life (measured using the EQ5D) and health service resource use, to enable the results to be used to assess the cost effectiveness of the interventions.

# Biological therapies for peripheral spondyloarthritis
What is the effectiveness and cost effectiveness of biological DMARDs in people with persistent peripheral spondyloarthritis (excluding psoriatic arthritis) or undifferentiated spondyloarthritis?

## Why this is important
Although there have been trials conducted of biological therapies for psoriatic arthritis, which have led to positive recommendations in NICE technology appraisals, no such good-quality evidence exists in enteropathic arthritis, reactive arthritis or undifferentiated spondyloarthritis. The substantial side effects possible with biological therapies, and their significant cost, means it is difficult to justify offering them to these groups without good evidence of efficacy. There is therefore the need for randomised controlled trials, with a sufficient sample size to identify possible benefits, in these 3 populations. If trials were to recruit participants from multiple spondyloarthritis subpopulations, results should be clearly stratified by diagnosis to enable any differences in benefits or harms between the groups to be identified. These trials should include (as outcome measures) both health-related quality of life (measured using the EQ5D) and health service resource use, to enable the results to be used to assess the cost effectiveness of the interventions.