Treatment of Spondyloarthropathy

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

• Axial spondyloarthritis
• Psoriatic arthritis
• Enteropathic arthritis
• Reactive arthritis
• Undifferentiated spondyloarthritis

A primary aim of 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.

Many different health care professionals are involved in the management of spondyloarthropathy, from diagnosis to treatment. 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.

NSAIDs are commonly used to manage pain and inflammation, and as an antipyretic (i.e. to treat fever / reduce temperature). 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.

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. Commonly used NSAIDs are:

• Diclofenac
• Ibuprofen
• Neproxin
• Arcoxia
• Etoricoxib

For many years, NSAIDs have been used as the first-line treatment for spondyloarthropathy. Around 70 to 80 percent of patients with axial spondyloarthritis take NSAIDs with varying degrees of efficacy. A positive response to NSAIDs has been included as a criterion for the diagnosis of inflammatory back pain and spondyloarthropathy in the ASAS criteria.

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.

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:

• 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).
• Renal Adverse Effects
  • Around one to five percent of patients who require NSAIDs regularly go on to develop adverse renal effects, including:
    • 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
  • NSAIDs can worsen hypertension and have been linked to a heightened risk for myocardial infarction.

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.

Conventional DMARDs

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

Examples of DMARDs are:

• 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
• Methotrexate - the evidence for this DMARD is even more limited in spondyloarthropathy although it is used extensively in rheumatoid arthritis and is considered to be the first-choice DMARD for psoriatic arthritis
• Leflunomide - while there is a lack of strong evidence, leflunomide is often used to treat psoriatic arthritis in clinical practice

Biologic DMARDs

Over the last 20 years, there have been a number of developments in the treatment of spondyloarthropathy, including the use of biologic drugs. Biologic DMARDs can be beneficial for patients who do not tolerate or respond well to NSAIDs.

They are usually injected or given as  intravenous infusions although some newer products are available in tablet form. They act to try to modulate the immune system by inhibiting specific pathways or molecules in order to reduce inflammation. ASAS/EULAR recommend two classes of biological DMARDs be used to treat spondyloarthropathy:

• Tumor necrosis factor inhibitors (TNF inhibitors)  - these are recommended for patients who do not respond to or are intolerant to NSAIDs
• 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 and if long-term use is safe. These medications are known to have series side effects in some patients, including serious infection.

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

• Radiographic evidence of sacroiliitis
• Increased CRP or evidence of active sacroiliitis on MRI
• High disease activity as measured by Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) despite using at least two different NSAIDs at their maximum dose for at least four weeks
• Patients with peripheral manifestations must usually have a failure of a local steroid infection or first tried a therapeutic trial of sulphasalazine

NB: the response to TNF-alpha blockers is linked to HLA-B27. Other factors that predict a better response to these medications include:

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

Non Pharmacological Treatment

Physiotherapy and occupational therapy play a significant role in the management of spondyloarthropathy.  Management tends to focus on addressing a patient’s specific symptoms (i.e. reduced physical activity, fatigue, poor sleep and more).

Promoting Physical Activity and Exercise

Promoting physical activity and engaging patients in exercise is fundamental for the management of spondyloarthropathy. 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.

EULAR Recommendations

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

EULAR recommends that exercise programmes should include four key areas:

• Aerobic exercise (i.e. cardiovascular)
• Strength
• Flexibility
• Neuromuscular (i.e. balance challenging exercises)

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

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. While there is insufficient evidence to support the use of one type of exercise over another, 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.

Assessment

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

• 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. All interventions should be designed based on the patient's identified goals, which also need to be regularly reviewed.