Treatment of Spondyloarthropathy

Original Editor - Jess Bell Top Contributors - Jess Bell, Tarina van der Stockt, Kim Jackson and Lucinda hampton

Introduction

Spondyloarthropathy is an umbrella term for a group of seronegative inflammatory conditions. Included in this family of diseases are:

The primary aim of spondyloarthropathy treatment is to reduce inflammation. In addition, issues such as pain, stiffness, fatigue, sleep disturbance, depression, reduced physical activity levels, and increased cardiovascular disease risk need to be addressed.[1] This page will explore both the pharmacological and nonpharmacological treatment options for spondyloarthropathy.

Pharmacological Treatment

Non-Steroidal Anti-Inflammatory Drugs

Initial treatment of spondyloarthropathy is focused on non-steroidal anti-inflammatory drugs (NSAIDs) and exercise management.[1]

NSAIDs are commonly used to manage pain and inflammation, and as an antipyretic (i.e. to treat fever / reduce temperature).[1] NSAIDs work by blocking the enzyme cyclooxygenase (COX). There are two COX isoforms: COX-1 and COX-2. COX-1 has a homeostatic role while COX-2 generates the prostaglandins seen in fever, inflammation, and carcinogenesis.[2]

[3]

NSAIDs are available in tablets, capsules, suppositories, creams, gels and potentially as injections. Some NSAIDs can be bought over-the-counter while others require a prescription.[1] Commonly used NSAIDs are:[1]

  • Diclofenac
  • Ibuprofen
  • Neproxin
  • Arcoxia
  • Etoricoxib

For many years, NSAIDs have been used as the first-line treatment for spondyloarthropathy.[2][4] Around 70 to 80 percent of patients with axial spondyloarthritis take NSAIDs although the efficacy of these medications varies between patients.[5] A positive response to NSAIDs has been included as a criterion for the diagnosis of inflammatory back pain and spondyloarthropathy in the ASAS criteria.[5][6]

Patients can respond quite differently to NSAIDs, so it may be necessary to try different forms of NSAIDs to determine the best option. A poor response to NSAIDs is considered to be a poor prognostic sign in axial spondyloarthritis.[5]

Due to the chronic nature of these conditions, patients may need to take NSAIDs continuously or for long periods of time. This can cause various side effects:[2]

  • Gastrointestinal Effects
    • Gastrointestinal complications may be relatively minor (i.e. dyspepsia, nausea, and heartburn) or severe (life-threatening gastrointestinal bleed). The risk of adverse effects increases with age and for patients also taking other medications (such as aspirin and corticosteroids)[2]
  • Renal Adverse Effects
    • Around one to five percent of patients who require NSAIDs regularly go on to develop adverse renal effects, including:[2]
      • A reduction in glomerular filtration rate
      • Acute renal failure
      • Renal papillary necrosis
      • Nephrotic syndrome
      • Acute interstitial nephritis
      • Chronic renal failure
      • Fluid and electrolyte retention
  • Cardiovascular adverse effects
[7]

Disease Modifying Anti-Rheumatic Drugs

Disease modifying anti-rheumatic drugs (DMARD) are immunosuppressive and immunomodulatory agents. They are classified as either conventional DMARDs or biological DMARDs.[8]

1. Conventional DMARDs

Conventional DMARDs have been considered a second-line treatment for patients who do not tolerate or respond to NSAIDs.[9]  DMARDs can either be used on their own (monotherapy) or in combination with other medications.[1] However, there is not enough evidence to support their efficacy.[9] It is believed that they can be effective in managing peripheral spondyloarthropathy, but not for axial symptoms.[2][9][10] They are considered effective and used widely to manage psoriatic arthritis.[9]

Examples of DMARDs are:[1][9]

  • Sulphasalazine - this DMARD has often been used to treat patients with ankylosing spondylitis, but few studies have explored its efficacy. One study found some improvement in peripheral joint disease, but no improvement in axial symptoms. Another study found that it was no better than a placebo in managing overall inflammatory low back pain[9]
  • Methotrexate - the evidence for this DMARD is limited in spondyloarthropathy, but it is considered to be the first-choice DMARD for psoriatic arthritis[9]
  • Leflunomide - while there is a lack of strong evidence, leflunomide is often used to treat psoriatic arthritis in clinical practice[9]

2. Biologic DMARDs

Biologic DMARDs can be beneficial for patients who do not tolerate or respond well to NSAIDs.[9] They are usually injected or given as intravenous infusions although some newer products are available in tablet form.[1] They act to modulate the immune system by inhibiting specific pathways or molecules in order to reduce inflammation.[1][8] ASAS/EULAR recommend that two classes of biologic DMARDs be used to treat spondyloarthropathy:[2]

  • Tumour necrosis factor inhibitors (TNF inhibitors)  - these are recommended for patients who do not respond or are intolerant to NSAIDs[9]
  • Interleukin inhibitors (interleukin therapies)

However, it is not yet known if patients will benefit from long-term treatment from these medications, if radiological progression and ankylosis can be stopped or if long-term use is safe.[5] These medications are known to have significant side effects in some patients, including serious infection.[2][8]

Because of these side effects, patients must fulfil several criteria before being prescribed this medication:[2]

  • Radiographic evidence of sacroiliitis
  • Increased CRP or evidence of active sacroiliitis on MRI
  • High disease activity measured using the Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) despite taking the maximal dose of at least two different NSAIDs for at least four weeks
  • Patients with peripheral manifestations will usually have tried a local steroid injection without success or a therapeutic trial of sulphasalazine

A positive response to TNF inhibitors is linked to the HLA-B27 gene.[2] Other factors that predict a better response to these medications include:[2]

  • Young age
  • Male sex
  • Low base-line Bath Ankylosing Spondylitis Functional Index, high base-line BASDAI and CRP in patients with ankylosing spondylitis
[11]

Non-Pharmacological Treatment

Physiotherapy and occupational therapy play a significant role in the management of spondyloarthropathy. Promoting physical activity and engaging patients in exercise is an important part of physiotherapy management. Physiotherapists must try to support patients to enhance their function, and to learn to manage symptoms of pain, fatigue, disease activity, loss of range of motion and reduced physical fitness.[1]

EULAR Recommendations

The European League Against Rheumatism (EULAR) put out guidelines in 2018 to support the use of exercise therapy to help manage a range of spondyloarthropathies. These guidelines support the notion that exercise is not only safe, but an integral, and life-long, part of the care that needs to be promoted by all healthcare professionals.[12]

EULAR recommends that exercise programmes should include four key areas:[12]

While further research is required about the dosage and the long-term effects of exercise therapy, patients should, on the whole, be encouraged to exercise at levels recommended in local and national physical activity guidelines.[1] Exercise programmes should be targeted in order to optimise outcomes, ensure that all domains of exercise are included, and to prevent under-dosing.[1]

The following video provides some information about the first three domains of exercise.

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Types of Exercise

Various exercise programmes have been investigated in spondyloarthropathy research. However, there is a lack of specific information about exercise planning in clinical practice.[14] While there is insufficient evidence to support the use of one type of exercise over another,[12][14] some key features of exercise planning are discussed below. These are based largely on the Exercise for Ankylosing Spondylitis Consensus Statement by Millner and colleagues and the EULAR Recommendations from 2018.

Assessment

Before making any changes to physical activity or prescribing exercise programmes, physiotherapists must conduct a thorough individualised assessment, including:[12][14]

  • Musculoskeletal features
  • Psychosocial factors
  • Spondyloarthropathy specific measures, including objective axial mobility and chest expansion 

Please click here, for information on the assessment of spondyloarthropathy.

Monitoring

Monitoring and feedback should be provided in order to enhance a patient’s confidence and ability. This will also ensure that exercise programmes are updated as needed. It is recommended these reviews be completed at least annually, but more often if symptoms, function and mobility change.[14] All interventions should be designed based on the patient's identified goals, which also need to be regularly reviewed.[12]

Safety

Safety is a key consideration for all patients, but especially for those who have more severe, late-stage disease. Specific physical changes to be aware of are:[14]

  • The amount of bony change / ankylosis
  • Balance and / or mobility changes
  • Osteoporosis
  • Cardiorespiratory risk factors

Key safety concerns in regards to exercise include:[14]

  • High impact exercise or activity (such as contact sports, martial arts, four-wheel driving, boating in rough seas, and rides at fairs)
  • High velocity or strong resistance exercise (especially trunk flexion and rotation)
  • Excessive gains in spinal or peripheral mobility where there is adjacent ankylosis
  • Excessive gains in end range mobility following total hip joint replacement

Specific co-morbidities associated with spondyloarthropathy and their management are discussed in more detail here.

Mobility Exercises

Exercises that emphasise spinal mobility and peripheral joint range of motion are necessary inclusions in an exercise plan. There is no evidence to support one type of mobility exercise over another. Exercises should be chosen based on specific functional or movement deficits.[14] In the early stages of the disease, mobility exercises may focus on restoring full spinal range and normal posture. In the later stages of disease, the emphasis may be on maintaining existing range.[14]

The following videos provide examples of mobility exercises that may be beneficial for patients with spondyloarthropathy.

[15]

Other Exercises

There is some evidence that (modified) pilates, tai chi, incentive spirometry and global postural re-education are effective modalities. Hydrotherapy and swimming may also be beneficial.[1][14] Strengthening, cardiovascular and functional exercises should also be incorporated into an exercise programme.[14]

It is likely that patients with early-stage spondyloarthropathy may benefit more from a greater range of exercise than those in the later stages of the disease. For patients with advanced axial spondyloarthritis, safety factors must be considered and national guidelines for older populations may be a useful guide.[14]

High-Intensity Exercise Programmes

Sveaas and colleagues explored the effect of a high-intensity exercise programme on cardiovascular risk in patients with active axial spondyloarthritis. The programme was based on the American College of Sports Medicine (ACSM) recommendations for maintenance and improvement of cardiorespiratory and muscular fitness.[16]

Not only did this programme reduce cardiovascular risk factors for patients with active axial spondyloarthritis, but it also improved disease activity. BASDAI improved significantly, improvements in physical function were also noted based on BASFI scores and there was a trend towards a reduction in interleukin (IL) 17a and IL-23.[16] Based on the improvements reported by patients, as well as stable inflammatory markers, it appears that high-intensity exercise can be used in this patient group.[16]

The programme was as follows:[16]

  • Patients were encouraged to exercise 40–60 minutes, three times a week
  • Sessions consisted of endurance and strength training
    • Endurance training was high-intensity interval training that lasted for 40 minutes
    • Strength training lasted 20 minutes and focused on external load for the major muscle groups (six exercises, eight to ten repetitions maximum, two to three sets)

The following video demonstrates a High-Intensity Interval Training exercise session for patients with axial spondyloarthritis.

[17]
Resistance Training

Muscle wasting is common in a number of chronic diseases, including spondyloarthropathy and can significantly increase morbidity and mortality.[18] In particular, cachexia (defined as: “an accelerated loss of skeletal muscle in the context of a chronic inflammatory response”[19]) has been recognised as a systemic complication of axial spondyloarthritis. This is particularly common in patients with long-standing disease and radiological changes. Thus, it is believed that progressive resistance training may be beneficial for patients with spondyloarthropathy.[19]

General Physical Activity

It is important to encourage regular physical activity in order to promote general health, well-being and functional outcomes. No type of activity has been found to be superior to another. Activity may occur at work when commuting and / or during leisure activities. Breaking up sedentary activities with movement should also be encouraged.[14]

Dosage

Exercise frequency, intensity, duration and type should be adapted based on a patient’s assessment findings, goals and lifestyle.[14] Some important points to consider include:[14]

  • Mobility, stretching and postural exercises need to be practised regularly
  • While national physical activity guidelines are useful guides, they may require modification based on disease stage, activity and progression (e.g. pain / fatigue / secondary consequences such as cardiovascular disease, osteoporosis, balance impairment, ankylosis)

Adherence

Group activities and supervised exercises have been shown to enhance adherence to exercise. Patient preference for certain exercises is also an important consideration to help ensure adherence.[14]

Summary

  • NSAIDs are the first-line treatment of spondyloarthropathy. This can be escalated further to include conventional or biologic DMARDs
  • Exercise and physical activity are essential to the management of spondyloarthropathy. Exercise programmes need to be carefully structured to suit the patient, and then regularly evaluated based on changes in disease activity or function
  • Patients with spondyloarthropathy should be prescribed exercises from all four domains identified by EULAR (aerobic, strengthening, flexibility and neuromuscular)

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 Martey C. Treatment in Spondyloarthropathy Course. Physioplus 2020.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 Wong RSY. Disease-Modifying Effects of Long-Term and Continuous Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in Spondyloarthritis. Adv Pharmacol Sci. 2019; 2019: 5324170.
  3. Dr Matt & Dr Mike. Non-steroidal anti-inflammatory drugs | NSAIDs. Available from: https://www.youtube.com/watch?v=2CDdMmv6nh0 [last accessed 28/11/2020]
  4. Toussirot E. Pharmacological management of axial spondyloarthritis in adults. Expert Opin Pharmacother. 2019; 20(12): 1483-91.
  5. 5.0 5.1 5.2 5.3 Braun J, Sieper J. Therapy of ankylosing spondylitis and other spondyloarthritides: established medical treatment, anti-TNF-alpha therapy and other novel approaches. Arthritis Res. 2002; 4(5): 307-21.
  6. Slobodin G, Eshed I. Non-Radiographic Axial Spondyloarthritis. Isr Med Assoc J. 2015; 17(12): 770-6.
  7. Alliance for Aging Research. Taking NSAIDs Safely. Available from: https://www.youtube.com/watch?v=PqLTGRJO_LM [last accessed 28/11/2020]
  8. 8.0 8.1 8.2 Benjamin O, Bansal P, Goyal A, et al. Disease Modifying Anti-Rheumatic Drugs (DMARD) [Updated 2020 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507863/
  9. 9.0 9.1 9.2 9.3 9.4 9.5 9.6 9.7 9.8 9.9 Simone D, Nowik M, Gremese E, Ferraccioli GF. Disease-modifying Antirheumatic Drugs (DMARD) and Combination Therapy of Conventional DMARD in Patients with Spondyloarthritis and Psoriatic Arthritis with Axial Involvement. J Rheumatol Suppl. 2015; 93: 65-9.
  10. Lee, R.Z., Veale, D.J. Management of Spondyloarthropathy. Drugs. 2002; 62: 2349–59.
  11. AJMCtv. Treating Axial Spondyloarthritis. Available from https://www.youtube.com/watch?v=QatYl8RsqVE [last accessed 28/11/2020]
  12. 12.0 12.1 12.2 12.3 12.4 Rausch Osthoff AK, Niedermann K, Braun J, Adams J, Brodin N, Dagfinrud H et al. 2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis. Ann Rheum Dis. 2018; 77(9): 1251-60.
  13. BJC Health. Exercise and Ankylosing Spondilytis. Available from: https://www.youtube.com/watch?v=8Ta3LGKhw1k [last accessed 28/11/2020]
  14. 14.00 14.01 14.02 14.03 14.04 14.05 14.06 14.07 14.08 14.09 14.10 14.11 14.12 14.13 14.14 Millner JR, Barron JS, Beinke KM, Butterworth RH, Chasle BE, Dutton LJ et al. Exercise for ankylosing spondylitis: An evidence-based consensus statement. Semin Arthritis Rheum. 2016; 45(4): 411-27.
  15. National Axial Spondyloarthritis Society. Axial spondyloarthritis (axial SpA)/ankylosing spondylitis (AS) stretches with physio Emily Clarke. Available from: https://www.youtube.com/watch?v=vXNv1mX6NqU [last accessed 28/11/2020]
  16. 16.0 16.1 16.2 16.3 Sveaas SH, Berg IJ, Provan SA, Semb AG, Hagen KB, Vollestad N et al. Efficacy of high intensity exercise on disease activity and cardiovascular risk in active axial spondyloarthritis: a randomized controlled pilot study. PLoS One. 2014; 9(9): e108688.
  17. National Axial Spondyloarthritis Society. HIIT session for people with axial spondyloarthritis (axial SpA), inc. ankylosing spondylitis (AS). Available from: https://www.youtube.com/watch?v=fRPX5v1EAQI [last accessed 28/11/2020]
  18. Valido A, Crespo CL, Pimentel-Santos FM. Muscle Evaluation in Axial Spondyloarthritis-The Evidence for Sarcopenia. Front Med (Lausanne). 2019; 6: 219.
  19. 19.0 19.1 Marcora S, Casanova F, Williams E, Jones J, Elamanchi R, Lemmey A. Preliminary evidence for cachexia in patients with well-established ankylosing spondylitis. Rheumatology (Oxford). 2006; 45(11):1385-8.