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Spondyloarthritis

Axial, peripheral, radiographic and non-radiographic

Medizinische Fachkräfte

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Spondyloarthritis is a term given to a range of inflammatory arthritis which can predominantly affect the spine (known as axial spondyloarthritis) or the peripheral joints (known as peripheral spondyloarthritis). The most common symptoms are inflammatory Rückenschmerzen, stiffness, swelling and tenderness of joints.

Spondyloarthritis can be associated with other inflammatory conditions such as psoriasis, Uveitis, and inflammatory bowel disease (Crohn’s disease oder Colitis ulcerosa).

Spondyloarthritis may be classified as:1

People with predominantly axial spondyloarthritis may have additional peripheral spondyloarthritis symptoms, and vice versa.2

Progression of patients with non-radiographic axial spondyloarthritis to radiographic axial spondyloarthritis is slow, with estimates of 5.1% in 5 years and 19% in 10 years.3

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Epidemiologie1

A UK cross-sectional cohort study found a prevalence of axial spondyloarthritis of 0.66% (using modified New York criteria) in an adult primary care population with low back pain, and 0.15% in the general adult primary care population.4

Axial spondyloarthritis is associated with the HLA-B27 antigen, but can occur in people without HLA-B27. Over 90% of patients with axial spondyloarthritis are HLA-B27 positive.

The initial presentation may be musculoskeletal - eg, back pain, enthesitis (inflammation of the sites where ligaments or tendons attach to bone) or dactylitis (swelling of a finger or toe), or extra-articular - eg, Uveitis or psoriasis.

Half of the patients classified as having axial spondyloarthritis also have peripheral disease manifestations such as arthritis, enthesitis and/or dactylitis. These peripheral disease manifestations contribute significantly to overall disease activity.5

Spondyloarthritis can have diverse symptoms and be difficult to identify, which can lead to delayed or missed diagnoses. A delay of several years between symptom onset and diagnosis is common.6

Several factors are independently associated with a long diagnostic delay, including female sex, HLA-B27 negativity, presence of psoriasis and young age of symptom onset.7

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Spondyloarthritis4 cannot be reliably diagnosed or ruled out by a single test.

  • Blood tests for ESR, and/or CRP. The diagnosis of spondyloarthritis should not be ruled out if CRP and ESR are normal.

  • X-rays:

    • Radiographic axial spondyloarthritis is suggested by X-ray changes of the sacroiliac joints and spine, including sacroiliitis, sclerosis (thickening of bone), erosions, and partial or total ankylosis (fusion of joints).

    • Axial spondyloarthritis may be present despite no evidence of sacroiliitis on a plain film X-ray.

  • MRI:

    • Inflammation of the sacroiliac joints can be detected on MRI despite an absence of changes on X-ray.

    • The use of MRI has enabled an increase in detection of sacroiliitis and inflammatory back pain, and the diagnosis of non-radiographic axial spondyloarthritis.

    • Refer for MRI if the plain film X-ray does not show sacroiliitis or an X-ray is not appropriate because the person's skeleton is not fully mature.

  • HLA-B27: only perform an HLA-B27 test in primary care if a person has exactly three referral criteria, to help determine whether referral to a rheumatologist is necessary (see below).

Axial spondyloarthritis presentations of spondyloarthritis are often misdiagnosed as mechanical low back pain, leading to delays in access to effective treatments.

Peripheral spondyloarthritis presentations are often seen as unrelated joint or tendon problems, and can be misdiagnosed because problems can move around between joints.

The differential diagnoses of axial spondyloarthritis include:1

  • Degenerative or mechanical problems - eg, degenerative disc disease, spondylosis, congenital vertebral anomalies, degenerative changes in the intevertebral (facet) joints, osteoarthritis of sacroiliac joints.

  • Frakturen.

  • Infektiöse Sakroiliitis.

  • Bone metastasis.

  • Primary bone tumours.

  • Spinalkanalstenose.

  • Hypermobility.

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For a person presenting with low back pain that started before the age of 45 years and which has lasted for longer than three months, the National Institute for Health and Care Excellence (NICE) recommends referral to a rheumatologist for a spondyloarthritis assessment if four 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).

  • Aufwachen in der zweiten Nachthälfte aufgrund von Symptomen.

  • Gesäßschmerzen.

  • Verbesserung durch Bewegung.

  • Verbesserung innerhalb von 48 Stunden nach Einnahme von nichtsteroidalen Antirheumatika (NSAR).

  • A first-degree relative with spondyloarthritis.

  • Current or past arthritis.

  • Current or past enthesitis.

  • Aktuelle oder frühere Psoriasis.

Wenn genau drei der zusätzlichen Kriterien vorliegen, führen Sie einen HLA-B27-Test durch. Wenn der Test positiv ist, überweisen Sie die Person an einen Rheumatologen zur Beurteilung einer Spondyloarthritis.

Wenn die Person diese Kriterien nicht erfüllt, aber der klinische Verdacht auf axiale Spondyloarthritis besteht, raten Sie der Person, eine erneute Beurteilung zu suchen, wenn neue Anzeichen, Symptome oder Risikofaktoren auftreten. Dies kann besonders angebracht sein, wenn die Person derzeit oder in der Vergangenheit an einer entzündlichen Darmerkrankung (Morbus Crohn oder Colitis ulcerosa), Psoriasis oder Uveitis leidet oder gelitten hat.

Urgently refer people with suspected new-onset inflammatory arthritis to a rheumatologist for a spondyloarthritis assessment, unless rheumatoid arthritis, gout or acute calcium pyrophosphate (CPP) arthritis ('pseudogout') is suspected.

Überweisen Sie Personen mit Daktylitis an einen Rheumatologen zur Beurteilung einer Spondyloarthritis.

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 if any of the following are also present:

  • Rückenschmerzen ohne offensichtliche mechanische Ursache.

  • Aktuelle oder frühere Uveitis. Überweisen Sie Personen für eine sofortige (am selben Tag) augenärztliche Untersuchung, wenn sie Symptome einer akuten anterioren Uveitis haben (zum Beispiel Augenschmerzen, Augenrötung, Lichtempfindlichkeit oder verschwommenes Sehen).

  • Aktuelle oder frühere Psoriasis.

  • Gastrointestinale oder urogenitale Infektion.

  • Inflammatory bowel disease (Crohn's disease or ulcerative colitis).

  • A first-degree relative with spondyloarthritis or psoriasis.

Early treatment is very important to prevent long-term complications and joint damage.

Self-care advice

  • Regular physical activity is very important and helps to reduce stiffness and increase range of movements.

  • Maintaining good posture can help ease pain and stiffness.

  • Stretching exercises also help to relieve pain and stiffness.

Discuss risk factors for cardiovascular disease with all people with spondyloarthritis, in view of the increased risk of cardiovascular disease.

Physical therapies

  • Specialist physiotherapist: 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, and aerobic exercise.

  • 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.

Medikation

Non-steroidal anti-inflammatory drugs

  • Both traditional and COX-2 NSAIDs are effective for treating axial spondyloarthritis. Various NSAIDs are equally effective.8

  • 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 2-4 weeks does not provide adequate pain relief, consider switching to another NSAID.

Biological disease modifying antirheumatic drugs

  • Adalimumab, certolizumab pegol, etanercept, golimumab and infliximab:9

    • Are recommended as options for treating severe active radiographic axial spondyloarthritis or non-radiographic axial spondyloarthritis in adults whose disease has responded inadequately to, or who cannot tolerate, NSAIDs.

    • Die Reaktion auf die Behandlung mit Adalimumab, Certolizumab Pegol, Etanercept, Golimumab oder Infliximab sollte 12 Wochen nach Beginn der Behandlung bewertet werden. Die Behandlung sollte nur fortgesetzt werden, wenn es klare Anzeichen einer Reaktion gibt.

    • 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 TNF-alpha inhibitor, or whose disease has stopped responding after an initial response.

  • Secukinumab:10

    • Is recommended as an option for treating active non-radiographic axial spondyloarthritis with objective signs of inflammation (shown by elevated C-reactive protein or MRI) that is not controlled well enough with non-steroidal anti-inflammatory drugs in adults.

    • It is recommended only if TNF-alpha inhibitors are not suitable or do not control the condition well enough.

    • Response to secukinumab should be assessed after 16 weeks of treatment, and treatment continued only if there is clear evidence of response.

  • Ixekizumab:11

    • Is recommended as an option for treating active radiographic axial spondylitis that is not controlled well enough with conventional therapy, or active non-radiographic axial spondyloarthritis with objective signs of inflammation (shown by elevated C-reactive protein or MRI) that is not controlled well enough NSAIDs, in adults.

    • It is recommended only if TNF-alpha inhibitors are not suitable or do not control the condition well enough.

    • Response to ixekizumab should be assessed after 16-20 weeks of treatment, and treatment continued only if there is clear evidence of response.

Hinweis des Herausgebers

Dr. Krishna Vakharia, 22nd February 2023

Upadacitinib for treating active non-radiographic axial spondyloarthritis12

NICE has recommended upadacitinib as an option for treating active non-radiographic axial spondyloarthritis with objective signs of inflammation that is not controlled well enough with NSAIDs in adults. Objective signs include an elevated CRP or inflammation seen on MRI. It is only recommended in those who are not suitable to have TNF-alpha inhibitors or that the TNF-alpha inhibitors do not control their disease well enough. Evidence has shown that this medication improves the quality of life and works just as well as secukinumab and ixekizumab.

Hinweis des Herausgebers

Dr. Krishna Vakharia, 18th October 2023

Bimekizumab for treating axial spondyloarthritis13

NICE has recommended bimekizumab as an option in adults for treating active ankylosing spondylitis (AS) when conventional therapy has not worked well enough or is not tolerated. It is also recommended in active non‑radiographic axial spondyloarthritis (nr‑axSpA) with signs of inflammation - an elevated C‑reactive protein or MRI - when non-steroidal anti‑inflammatory drugs (NSAIDs), have not worked well enough or are not tolerated.

It can be used only if TNF-alpha inhibitors are not suitable or do not control the condition well enough.

When prescribing, response to bimekizumab should be assessed after 16 weeks of treatment and only continued if there is a response using the criteria below:

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.

Surgery for spondyloarthritis

Most people with axial spondyloarthritis will not need surgery. However:

  • Joint replacement may be needed for people with severe pain or joint damage.

  • Corrective surgery may also be required for severe scoliosis or kyphosis.

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

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 disease-modifying antirheumatic drugs (DMARDs), and have comorbidities that may affect treatment or management of flares.

Uveitis can occur during flare episodes.

  • Osteoporose: consider regular osteoporosis assessments (every two years). Bone mineral density measures may be elevated on spinal dual-energy X-ray absorptiometry (DXA) due to the presence of syndesmophytes and ligamentous calcification, whereas hip measurements may be more reliable.

  • Increased risk of fractures.

  • Kyphosis and scoliosis.

  • Increased risk of cardiovascular disease. It is therefore particularly important to identify and manage modifiable kardiovaskuläre Risikofaktoren.

  • Aortic and non-aortic valvular heart disease.

  • Kongestive Herzinsuffizienz.

  • Cardiac arrhythmias - eg, ventricular and supraventricular extrasystoles.

  • Lung involvement such as restrictive pulmonary disease and apical fibrosis. Dyspnoea may also occur as a result of costovertebral involvement decreasing vital capacity.

  • Neurological involvement: vertebral fracture, dislocation, or Cauda-equina-Syndrom.

  • Adverse effects from drugs used for treatment, including NSAIDs (eg, gastritis, peptic ulcers, adverse renal effects), biological DMARDs (eg, infection, immunosuppression, malignancy).

  • Verringerte Lebensqualität und Arbeitsproduktivität aufgrund von Schmerzen, Steifheit, Müdigkeit, eingeschränkter Wirbelsäulenbeweglichkeit und körperlicher Funktion sowie Schlafproblemen.

Please see the NICE CKS reference guidance as well.4

Axial spondyloarthritis is often characterised by persistent or fluctuating axial inflammation (on MRI) and structural progression (on X-ray). Both the inflammation and new bone formation (if inflammation is ongoing) affect quality of life due to pain, reduction in mobility and function.4

Weiterführende Lektüre und Referenzen

  • van der Heijde D, Ramiro S, Landewe R, et al; 2016 Aktualisierung der ASAS-EULAR Managementempfehlungen für axiale Spondyloarthritis. Ann Rheum Dis. 2017 Jun;76(6):978-991. doi: 10.1136/annrheumdis-2016-210770. Epub 2017 Jan 13.
  • Ward MM, Deodhar A, Gensler LS, et al; 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Care Res (Hoboken). 2019 Oct;71(10):1285-1299. doi: 10.1002/acr.24025. Epub 2019 Aug 21.
  • Carron P, De Craemer AS, Van den Bosch F; Peripheral spondyloarthritis: a neglected entity-state of the art. RMD Open. 2020 May;6(1). pii: rmdopen-2019-001136. doi: 10.1136/rmdopen-2019-001136.
  1. Spondyloarthritis bei über 16-Jährigen: Diagnose und Behandlung; NICE-Leitlinien (Februar 2017)
  2. Lopez-Medina C, Molto A, Sieper J, et al; Prevalence and distribution of peripheral musculoskeletal manifestations in spondyloarthritis including psoriatic arthritis: results of the worldwide, cross-sectional ASAS-PerSpA study. RMD Open. 2021 Jan;7(1). pii: rmdopen-2020-001450. doi: 10.1136/rmdopen-2020-001450.
  3. Wang R, Ward MM; Epidemiology of axial spondyloarthritis: an update. Curr Opin Rheumatol. 2018 Mar;30(2):137-143. doi: 10.1097/BOR.0000000000000475.
  4. Morbus Bechterew; NICE CKS, May 2019 (UK access only)
  5. de Winter JJ, Paramarta JE, de Jong HM, et al; Peripheral disease contributes significantly to the level of disease activity in axial spondyloarthritis. RMD Open. 2019 Jan 11;5(1):e000802. doi: 10.1136/rmdopen-2018-000802. eCollection 2019.
  6. Magrey MN, Danve AS, Ermann J, et al; Recognizing Axial Spondyloarthritis: A Guide for Primary Care. Mayo Clin Proc. 2020 Nov;95(11):2499-2508. doi: 10.1016/j.mayocp.2020.02.007. Epub 2020 Jul 29.
  7. Barnett R, Ingram T, Sengupta R; Axial spondyloarthritis 10 years on: still looking for the lost tribe. Rheumatology (Oxford). 2020 Oct 1;59(Suppl4):iv25-iv37. doi: 10.1093/rheumatology/keaa472.
  8. Kroon FP, van der Burg LR, Ramiro S, et al; Non-steroidal anti-inflammatory drugs (NSAIDs) for axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis). Cochrane Database Syst Rev. 2015 Jul 17;(7):CD010952. doi: 10.1002/14651858.CD010952.pub2.
  9. TNF-alpha-Inhibitoren für ankylosierende Spondylitis und nicht-radiographische axiale Spondyloarthritis; NICE-Technologiebewertungsleitlinie, Februar 2016
  10. Secukinumab for treating non-radiographic axial spondyloarthritis; NICE Technologie-Bewertungsleitlinie, Juli 2021
  11. Ixekizumab zur Behandlung der axialen Spondyloarthritis; NICE Technologie-Bewertungsleitlinie, Juli 2021
  12. Upadacitinib for treating active non-radiographic axial spondyloarthritis; NICE Technology appraisal guidance, February 2023
  13. Bimekizumab for treating axial spondyloarthritis; Technologie-Bewertungsrichtlinien, Oktober 2023

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