Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy Treatment & Management

Updated: Sep 23, 2020
  • Author: Lawrence H Brent, MD; Chief Editor: Herbert S Diamond, MD  more...
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Treatment

Approach Considerations

No definite disease-modifying treatment exists for individuals with ankylosing spondylitis (AS). Early diagnosis is important. As with any chronic disease, patient education is vital to familiarize the patient with the symptoms, course, and treatment of the disease. Treatment measures include pharmacologic, surgical, and physical therapy.

No drugs have been proved to modify the course of the disease, although tumor necrosis factor alpha (TNF-α) antagonists appear to have potential as disease-modifying agents. [95] Symptoms are generally not affected by pregnancy or childbirth. Medical management of AS, including medications, must be adjusted during pregnancy in accordance with the specific pregnancy profiles of the medications.

Inpatient care is generally not necessary for patients with AS. The exceptions to this include patients with coexisting or extra-articular disease and those requiring surgery.

Extra-articular manifestations, which may necessitate specialist referral for appropriate care, include the following:

  • Acute anterior uveitis
  • Aortitis
  • Conduction defects
  • Pulmonary fibrosis
  • Amyloidosis
  • Neurologic deficits, including cauda equina

Disease progress and response to therapy can be monitored by following laboratory values, including the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level.

Surgical treatment is geared toward resolution of the complications related to AS; it is occasionally useful for correcting spinal deformities or repairing damaged peripheral joints. Patients with fusion of the spine secondary to AS who report a change in position of the spine should be cautiously treated and should be considered to have sustained a spinal fracture. Surgical intervention may be necessary to stabilize the fracture and prevent neurologic deficit. [96, 97]

Outpatient care should be aimed toward providing adequate pain control and maximizing motion and functional ability. Such care includes pain medication, exercise programs, recreational therapy, and vocational therapy. Regular exercise helps reduce the symptoms and may slow the progress of the disease. Generally, no dietary restrictions are implemented for patients with AS; however, patients with coexisting diseases, such as inflammatory bowel disease (IBD), have dietary restrictions.

Peripheral spondyloarthritis

Pharmacologic treatment for peripheral spondyloarthritis includes the following:

  • Nonsteroidal anti-inflammatory drugs
  • Corticosteroid injections
  • Sulfasalazine
  • TNF inhibitors (eg, infliximab, etanercept, adalimumab, certolizumab, golimumab)

In a study of adult patients with recent-onset peripheral spondyloarthritis (symptom duration < 12 weeks), early use of the TNF-α inhibitor golimumab resulted in sustained clinical remission in 49 of 60 patients (82%). Most patients (n=30) fulfilled criteria for sustained clinical remission by week 24. On follow-up at least 18 months after drug withdrawal, 26 of the 49 patients (53%) were still in drug-free remission. [98, 99]

Nonradiographic axial spondyloarthritis

In March 2019, the US Food and Drug Administration (FDA) approved certolizumab for treatment of nonradiographic axial spondyloarthritis (nr-axSpA) with objective inflammation. Certolizumab is the first therapy approved for nr-axSpA. Approval was based on data from the phase 3 C-AXSPAND study, which favored certolizumab over placebo at both week 12 and week 52. At week 52, major improvement in the Ankylosing Spondylitis Disease Activity Score (ASDAS) had occurred in 42% of patients receiving certolizumab, compared with 7% of those receiving placebo. [100]

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Pharmacologic Therapy

Nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) improve the symptoms of the disease by reducing pain and decreasing inflammation. Numerous choices are available, and they are separated into different families of agents. [101] If one NSAID is ineffective, another from a different family can often provide relief.

Efficacy and adverse effect profiles differ among agents and families. Indomethacin may be more effective than other NSAIDs, although this potential advantage has not been proved. Salicylates seldom give adequate relief. Cyclooxygenase-2 (COX-2) inhibitors appear to be as effective as nonselective NSAIDs. [102]

Sieper et al, in a randomized, double-blind, controlled study comparing two dosages of celecoxib (200 mg once daily and 200 mg twice daily) to diclofenac (75 mg twice daily), noted that both dosages of celecoxib were comparable to the diclofenac dosage with respect to global pain intensity. [103] However, with respect to changes in disease activity, functional and mobility capacities, and adverse events, once-daily celecoxib was not as effective in reducing certain inflammation-associated parameters as twice-daily celecoxib and diclofenac were.

Give NSAIDs in full anti-inflammatory doses. Continuous treatment with NSAIDs appears to reduce radiographic progression in AS. [102] Common toxicities involve the gastrointestinal (GI) tract (nausea, dyspepsia, ulceration, bleeding), the kidneys, and the central nervous system (CNS).

Sulfasalazine

Sulfasalazine is useful in AS patients who do not respond to or who have contraindications to NSAIDs, as well as in those with coexisting IBD. In particular, it is often given to treat peripheral joint involvement, for which it has demonstrated efficacy. Sulfasalazine reduces spinal stiffness, peripheral arthritis, and the erythrocyte sedimentation rate (ESR), but there is no evidence that it improves spinal mobility, enthesitis, or physical function. [104, 105, 106] In a randomized, double-blind study, treatment with sulfasalazine resulted in significantly lesser improvement when compared to treatment with the TNF inhibitor etanercept. [107] Sulfasalazine toxicities include rash, nausea, diarrhea, and agranulocytosis (rarely).

TNF-α antagonists

TNF is a cytokine with two identified forms, which have similar biologic properties. TNF-α (cachectin) is produced predominantly by macrophages, and TNF-β (lymphotoxin) is produced by lymphocytes. TNF is but one of many cytokines involved in the inflammatory cascade that may contribute to AS. [108, 101]

TNF-α antagonists have been shown to be very effective in the treatment of AS. [109] They have a fairly rapid onset of action (2 weeks), and have been shown to reduce the inflammatory activity of spinal disease as assessed with magnetic resonance imaging (MRI). [110]

The European League Against Rheumatism notes that extensive MRI inflammatory activity, particularly in the spine, might be used as a predictor of good clinical response to anti–TNF-α treatment in patients with AS. Thus, MRI might aid in the decision of initiating anti–TNF-α therapy, in addition to clinical examination and C-reactive protein (CRP) testing. [87]

TNF-α antagonists are indicated after NSAID therapy has failed. [95] The following TNF-α antagonists have been approved by the US Food and Drug Administration (FDA) as therapies for AS:

TNF-α antagonists are also approved for the treatment of rheumatoid arthritis and psoriatic arthritis (PsA). Other approved indications include the following:

  • Psoriasis (etanercept, infliximab, adalimumab, certolizumab pegol)
  • Juvenile idiopathic arthritis (etanercept, adalimumab)
  • Crohn disease (infliximab, adalimumab, certolizumab pegol)

Toxicities associated with TNF-α antagonists include injection-site and infusion reactions. Increased risks of bacterial infections, reactivation of latent tuberculosis, and certain fungal infections (eg, histoplasmosis, coccidioidomycosis) have been observed.

There is some concern regarding an increased risk of malignancy in patients receiving TNF-α antagonists. The most attention has been focused on lymphoma and nonmelanotic skin cancers in patients with rheumatoid arthritis, although this has been difficult to document in such patients and has not been described in patients with AS. In rare cases, cytopenias have been associated with TNF-α antagonist use.

Patients with rheumatoid arthritis who have recently started TNF-α antagonists may be at increased risk for new-onset congestive heart failure even in the absence of any obvious risk factors for the disease. These agents should not be initiated in patients with uncompensated congestive heart failure.

Patients should be screened for latent tuberculosis, hepatitis B, and HIV infection before beginning TNF-α antagonist therapy. [120] Although these agents should not be used in patients with active hepatitis B infection, they appear to be safe in patients with chronic hepatitis C infections. Rarely, autoimmune syndromes (eg, a lupuslike illness) have been noted in patients receiving TNF-α antagonists. More commonly, a positive antinuclear antibody (ANA) test result, in the absence of clinical disease, may occur during treatment.

Demyelinating syndromes have rarely been documented in patients receiving TNF-α antagonists, though no direct link has been proved. These agents should not be used in patients with multiple sclerosis or other demyelinating diseases. New-onset psoriatic skin lesions have been documented after initiation of TNF-α antagonists.

In a prospective study of 334 patients with AS, response to treatment with TNF-α inhibitors was associated with a 50% reduction in the risk of radiographic progression of AS. However, nearly 4 years of treatment were necessary for the benefit to become apparent. Moreover, in patients who first began TNF-inhibitor treatment 10 or more years after disease onset, AS progression was twice as likely as it was in patients who started treatment earlier. [121, 122]

Interleukin inhibitors

Interleukin 17A (IL-17A) is a naturally occurring cytokine that is involved in normal inflammatory and immune responses and also plays a key role in the pathogenesis of AS. Two human IgG monoclonal antibodies that target IL-17A are approved for use in AS and active non-radiographic axial spondyloarthritis: Secukinumab and ixekizumab.

Secukinumab

Secukinumab (Cosentyx), a human IgG1 monoclonal antibody that selectively binds to and neutralizes IL-17A, was approved by the FDA for adults with active AS in January 2016. In June 2020, approval was expanded to include nonradiographic axial spondyloarthritis (nr-axSpA).

Approval of secukinumab for AS was based on 2 phase III trials (MEASURE 1 and 2). In MEASURE 1 (n=371), the Assessment of Spondyloarthritis International Society (ASAS20) response rates at week 16 were 61%, 60%, and 29% for secukinumab doses of 150 mg and 75 mg subcutaneously and for placebo, respectively (P < 0.001 for both comparisons with placebo). In MEASURE 2 (n=219), the rates were 61%, 41%, and 28% for secukinumab doses of 150 mg and 75 mg and for placebo, respectively (P < 0.001 for the 150-mg dose and P=0.10 for the 75-mg dose). The significant improvements were sustained through 52 weeks. [123]

The approval of secukinumab for nr-axSpA was based outcomes from the PREVENT phase III study (n = 555) in adults with active nr-axSpA who were biologic-treatment naïve or had an inadequate response or  intolerance to an anti–TNF-α therapy. Of the 481 patients who completed 52 weeks of treatment, ASAS40 in TNFi-naïve patients was significantly higher with a loading dose (41.5%) at week 16 and without a loading dose (39.8%) at week 52 compared with placebo (29.2% at week 16 and 19.9% at week 52; both P < 0.05). [124]

Ixekizumab 

Ixekizumab (Taltz), a humanized monoclonal IgG4 antibody, also targets IL-17A. In August 2019, ixekizumab was approved by the FDA for adults with active AS. In June 2020, approval was expanded to include nr-axSpA. Approval was based on two phase III trials (COAST-V and COAST-W) that included 657 adults with active AS. In COAST-V, which included patients who had not been treated with biological DMARDs, at week 16, significantly more patients achieved improvement with ixekizumab than with placebo or adalimumab. [125]  In the COAST-W trial, patients with active AS with a previous inadequate response or intolerance to TNF inhibitors showed a statistical improvement at 16 weeks with ixekizumab, compared with placebo (30.6% versus 12.5%; P=0.003%). [126]

Approval of ixekizumab for active nr-axSpA with objective signs of inflammation was based on the COAST-X phase III trial. The primary endpoint,  the proportion of patients achieving ASAS40 at 52 weeks, was achieved in 30% of patients treated with ixekizumab versus 13% for placebo (P = 0.0045). [127]

Corticosteroids

Oral corticosteroids are occasionally helpful in controlling AS symptoms. However they should be used only for short-term management; long-term management carries a high risk of adverse effects. No evidence has shown that corticosteroids alter the outcome of the disease, and these agents are known to increase the tendency toward spinal osteoporosis.

Local corticosteroid injections are useful for symptomatic sacroiliitis, peripheral enthesitis, and arthritis, although the response is not typically as rapid as in patients with rheumatoid arthritis.

Other agents

Anecdotal reports suggest that other medications may be helpful in the treatment of AS, including methotrexate, azathioprine, cyclophosphamide, and cyclosporine. Methotrexate is of questionable benefit in AS; various studies have shown conflicting results. [128] At present, it is reserved for patients with symptoms that are not adequately controlled with NSAIDs or sulfasalazine.

Leflunomide was evaluated in a randomized, double-blind, placebo-controlled study in active AS but was not found to be effective. [129] Bisphosphonates may modestly affect clinical disease activity in AS. Anakinra, a recombinant human IL-1 receptor antagonist, may be effective in treatment-resistant AS.

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Guideline-directed Therapy

Guidelines on treatment for ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis have been issued by the American College of Rheumatology. [130]

In adults with active AS:

  • Strongly recommend treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) over no treatment with NSAIDs
  • Conditionally recommend continuous treatment with NSAIDs over on-demand treatment with NSAIDs
  • No recommendation for any particular NSAID as the preferred choice
  • Strongly recommend against treatment with systemic glucocorticoids

In adults with active AS despite treatment with NSAIDs:

  • Conditionally recommend treatment with sulfasalazine, methotrexate, or tofacitinib over no treatment with those medications; sulfasalazine or methotrexate should be considered only in patients with prominent peripheral arthritis or when a tumor necrosis factor inhibitor (TNFi) is not available. 
  • Conditionally recommend treatment with a TNFi over treatment with tofacitinib
  • Strongly recommend treatment with a TNFi over no treatment with TNFi
  • No recommendation for any particular TNFi as the preferred choice
  • Strongly recommend treatment with secukinumab or ixekizumab over no treatment with those agents;
  • Conditionally recommend treatment with a TNFi over treatment with secukinumab or ixekizumab 
  • Conditionally recommend treatment with secukinumab or ixekizumab over treatment with tofacitinib
  • In patients who have contraindications to TNFis, conditionally recommend treatment with secukinumab or ixekizumab over treatment with sulfasalazine, methotrexate, or tofacitinib 
  • In patients with primary nonresponse to TNFi therapy, conditionally recommend treatment with secukinumab or ixekizumab over treatment with a different TNFi
  • In patients with secondary nonresponse to TNFi therapy, conditionally recommend treatment with a different TNFi over treatment with a non-TNFi biologic
  • In patients whose AS does not respond to treatment with the first TNFi used, strongly recommend against switching to treatment with a biosimilar of the first TNFi
  •  In patients whose AS does not respond to treatment with the first TNFi used, conditionally recommend against the addition of sulfasalazine or methotrexate in favor of treatment with a new biologic
  • In adults with AS and isolated active sacroiliitis despite treatment with NSAIDs, conditionally recommend treatment with locally administered parenteral glucocorticoids over no treatment with local glucocorticoids
  • In adults with AS with stable axial disease and active enthesitis despite treatment with NSAIDs, conditionally recommend using treatment with locally administered parenteral glucocorticoids over no treatment with local glucocorticoids; however, peri-tendon injections of Achilles, patellar, and quadriceps tendons should be avoided
  • In adults with AS with stable axial disease and active peripheral arthritis despite treatment with NSAIDs, conditionally recommend using treatment with locally administered parenteral glucocorticoids over no treatment with local glucocorticoids
  • Strongly recommend treatment with physical therapy over no treatment with physical therapy
  • Conditionally recommend active physical therapy interventions (supervised exercise) over passive physical therapy interventions (massage, ultrasound, heat)
  • Conditionally recommend land-based physical therapy interventions over aquatic therapy interventions

In adults with stable AS:

  • Conditionally recommend on-demand treatment with NSAIDs over continuous treatment with NSAIDs
  • In patients receiving treatment with TNFi and NSAIDs, conditionally recommend continuing treatment with TNFi alone versus continuing both treatments
  • In patients receiving treatment with TNFi and a conventional synthetic antirheumatic drug, conditionally recommend continuing treatment with TNFi alone over continuing both treatments
  • In patients receiving treatment with a biologic, conditionally recommend against discontinuing it
  • In patients receiving treatment with a biologic, conditionally recommend against tapering of the biologic dose as a standard approach
  • In patients receiving treatment with an originator TNFi, strongly recommend continuing treatment with the originator TNFi over mandated switching to its biosimilar
  • Strongly recommend treatment with physical therapy over no treatment with physical therapy

In adults with active or stable AS:

  • Conditionally recommend against co-treatment with a TNFi and low-dose methotrexate
  • Conditionally recommend advising unsupervised back exercises
  • Conditionally recommend evaluation and counseling regarding falls
  • Conditionally recommend participation in formal group or individual self-management education
  • In patients with spinal fusion or advanced spinal osteoporosis,strongly recommend against treatment with spinal manipulation
  • In patients with advanced hip arthritis, strongly recommend treatment with total hip arthroplasty over no surgery
  • In patients with severe kyphosis, conditionally recommend against elective spinal osteotomy

In adults with AS-related comorbidities:

  •  In patients with acute iritis, strongly recommend treatment by an ophthalmologist to decrease the severity, duration, or complications of episodes
  • In patients with recurrent iritis, conditionally recommend prescription of topical glucocorticoids over no prescription for prompt at-home use in the event of eye symptoms, to decrease the severity or duration of iritis episodes
  • In patients with recurrent iritis,conditionally recommend treatment with TNFi monoclonal antibodies over treatment with other biologics
  • In patients with inflammatory bowel disease, do not recommend any particular NSAID as the preferred choice to decrease the risk of worsening of inflammatory bowel disease symptoms
  • In patients with inflammatory bowel disease, conditionally recommend treatment with TNFi monoclonal antibodies over treatment with other biologics

Assessment of disease activity, imaging, and screening:

  • Conditionally recommend the monitoring of a validated AS disease activity measure at regular intervals
  • Conditionally recommend regular-interval monitoring of C-reactive protein (CRP) concentrations or erythrocyte sedimentation rate (ESR) over usual care without regular CRP or ESR monitoring
  • In adults with active AS, conditionally recommend against using a treat-to-target strategy using a target Ankylosing Spondylitis Disease Activity Score (ASDAS) of < 1.3 (or 2.1) over a treatment strategy based on physician assessment
  • Conditionally recommend screening for osteopenia/osteoporosis with dual-energy x-ray absorptiometry (DXA) scan over no screening
  • In adults with syndesmophytes or spinal fusion, conditionally recommend screening for osteoporosis/osteopenia with DXA scan of the spine as well as the hips, compared with DXA scan solely of the hip or other non-spine sites
  • Strongly recommend against screening for cardiac conduction defects with electrocardiograms
  • Strongly recommend against screening for valvular heart disease with echocardiograms
  • In adults with AS of unclear activity while on a biologic, conditionally recommend obtaining a spinal or pelvis MRI to assess activity
  • In adults with stable AS, conditionally recommend against obtaining a spinal or pelvis MRI to confirm inactivity
  • In adults with active or stable AS on any treatment, conditionally recommend against obtaining repeat spine radiographs at a scheduled interval (eg, every 2 years) as a standard approach

In adults with active nonradiographic axial spondyloarthritis (SpA):

  • Strongly recommend treatment with NSAIDs over no treatment with NSAIDs
  • Conditionally recommend continuous treatment with NSAIDs over on-demand treatment with NSAIDs
  • Do not recommend any particular NSAID as the preferred choice

In adults with active nonradiographic axial SpA despite treatment with NSAIDs​:

  • Conditionally recommend treatment with sulfasalazine, methotrexate, or tofacitinib over no treatment with these medications
  • Strongly recommend treatment with TNFi over no treatment with TNFi
  • Do not recommend any particular TNFi as the preferred choice
  • Conditionally recommend treatment with TNFi over treatment with tofacitinib
  • Conditionally recommend treatment with secukinumab or ixekizumab over no treatment with secukinumab or ixekizumab
  • Conditionally recommend treatment with TNFi over treatment with secukinumab or ixekizumab
  • Conditionally recommend treatment with secukinumab or ixekizumab over treatment with tofacitinib
  • In patients who have contraindications to TNFi, conditionally recommend treatment with secukinumab or ixekizumab over treatment with sulfasalazine, methotrexate, or tofacitinib
  • In adults with active nonradiographic axial SpA and primary nonresponse to the first TNFi used, we conditionally recommend switching to secukinumab or ixekizumab over switching to a different TNFi. Very low 42 64. In adults with active nonradiographic axial SpA and secondary nonresponse to the first TNFi used, we conditionally recommend switching to a different TNFi over switching to a non-TNFi biologic. Very low 42 65. In adults with active nonradiographic axial SpA despite treatment with the first TNFi used, we strongly recommend against switching to the biosimilar of the first TNFi. Very low 75 66. In adults with active nonradiographic axial SpA despite treatment with the first TNFi used, we conditionally recommend against the addition of sulfasalazine or methotrexate in favor of treatment with a different biologic. Very low 41 67.

Other recommendations for adults with nonradiographic axial SpA:

  • Strongly recommend against treatment with systemic glucocorticoids
  • In patients with isolated active sacroiliitis despite treatment with NSAIDs, conditionally recommend treatment with local glucocorticoids over no treatment with local glucocorticoids
  • In patients with active enthesitis despite treatment with NSAIDs, conditionally recommend using treatment with locally administered parenteral glucocorticoids over no treatment with local glucocorticoid; however, peri-tendon injections of Achilles, patellar, and quadriceps tendons should be avoided
  • In patients with active peripheral arthritis despite treatment with NSAIDs, conditionally recommend using treatment with locally administered parenteral glucocorticoids over no treatment with local glucocorticoids
  • Strongly recommend treatment with physical therapy over no treatment with physical therapy
  • Conditionally recommend active physical therapy interventions (supervised exercise) over passive physical therapy interventions (massage, ultrasound, heat)
  • Conditionally recommend land-based physical therapy interventions over aquatic therapy interventions

In adults with stable nonradiographic axial spondyloarthritis (SpA):

  • Conditionally recommend on-demand treatment with NSAIDs over continuous treatment with NSAIDs
  • In adults receiving treatment with TNFi and NSAIDs, conditionally recommend continuing treatment with TNFi alone over continuing both medications
  • In patients receiving treatment with TNFi and a conventional synthetic antirheumatic drug, conditionally recommend continuing treatment with the TNFi alone over continuing treatment with both medications
  • In patients receiving treatment with a biologic, conditionally recommend against discontinuing it
  • In patients receiving treatment with a biologic, conditionally recommend against tapering of the biologic dose as a standard approach
  • In patients receiving treatment with an originator TNFi, strongly recommend continuation of treatment with the originator TNFi over mandated switching to its biosimilar

In adults with active or stable nonradiographic axial SpA:

  • Conditionally recommend against co-treatment with a TNFi and low-dose methotrexate

Assessment of disease activity and imaging:

  • Conditionally recommend monitoring of a validated AS disease activity measure at regular intervals
  • Conditionally recommend regular monitoring of the CRP concentrations or ESR over usual care without regular CRP or ESR monitoring
  • In adults with active nonradiographic axial SpA, conditionally recommend against using a treat-to-target strategy using a target of ASDAS < 1.3 (or 2.1) over a treatment strategy based on physician assessment
  • In adults with nonradiographic axial SpA of unclear activity while on a biologic, conditionally recommend obtaining a pelvis MRI to assess activity
  • In adults with stable nonradiographic axial SpA, conditionally recommend against obtaining a spinal or pelvis MRI to confirm inactivity
  • In adults with active or stable nonradiographic axial SpA on any treatment, conditionally recommend against obtaining repeat spine radiographs at a scheduled interval (eg, every 2 years) as a standard approach

Guidelines issued by an international task force on treating axial and peripheral spondyloarthritis to target include the following recommendations [131] :

  • The treatment target should be clinical remission/inactive disease of musculoskeletal (arthritis, dactylitis, enthesitis, axial disease) and extra-articular manifestations.
  • The treatment target should be individualized on the basis of current clinical manifestations, and the treatment modality should be considered when defining the time required to reach the target.
  • Clinical remission/inactive disease is defined as the absence of clinical and laboratory evidence of significant disease activity; low or minimal disease activity may be an alternative treatment target .
  • Disease activity should be measured on the basis of clinical signs and symptoms, and acute phase reactants.
  • Validated measures of musculoskeletal disease activity and assessment of cutaneous and/or other relevant extra-articular manifestations should be used in clinical practice to define the target and to guide treatment decisions; the frequency of the measurements depends on the level of disease activity.
  • In axial spondyloarthritis, the Ankylosing Spondylitis Disease Activity Score (ASDAS) is a preferred measure.
  • The choice of the target and of the disease activity measure should take comorbidities, patient factors, and drug-related risks into account.
  • In addition to clinical and laboratory measures, imaging results may be considered in clinical management.
  • Once the target is achieved, it should ideally be maintained throughout the course of the disease. 
  • The patient should be appropriately informed and involved in the discussions about the treatment target and the risks and benefits of the strategy planned to reach this target.

Joint guidelines on axial SpA (axSpA) issued by the Assessment of SpondyloArthritis international Society (ASAS) and the European League Against Rheumatism (EULAR) update and aggregate previous ASAS-EULAR guidelines on AS and ASAS guidelines on management of axSpA with TNFi into a single set of recommendations. [95]

The ASAS-EULAR guidelines begin with the following five overarching principles:

  1. AxSpA is a potentially severe disease with diverse manifestations, usually requiring multidisciplinary management coordinated by the rheumatologist.
  2. The primary goal of treating the patient with axSpA is to maximize long-term health-related quality of life through control of symptoms and inflammation, prevention of progressive structural damage, and preservation/normalization of function and social participation.
  3. The optimal management of patients with axSpA requires a combination of non-pharmacological and pharmacological treatment modalities.
  4. Treatment of axSpA should aim at the best care and must be based on a shared decision between the patient and the rheumatologist.
  5. AxSpA incurs high individual, medical, and societal costs, all of which should be considered in its management by the treating rheumatologist.

The ASAS recommendations are as follows:

  • The treatment of patients with axSpA should be individualized according to the current signs and symptoms of the disease (axial, peripheral, extra-articular manifestations) and the patient characteristics, including comorbidities and psychosocial factors.
  • Disease monitoring of patients with axSpA should include patient-reported outcomes, clinical findings, laboratory tests and imaging, all with the appropriate instruments and relevant to the clinical presentation. The frequency of monitoring should be decided on an individual basis, depending on symptoms, severity and treatment.
  • Treatment should be guided according to a predefined treatment target.
  • Patients should be educated about axSpA and encouraged to exercise on a regular basis and stop smoking; physical therapy should be considered.
  • Patients suffering from pain and stiffness should use an NSAID as first-line drug treatment up to the maximum dose, taking risks and benefits into account. For patients who respond well to NSAIDs and whose symptoms recur after stopping the NSAID or reducing the dose, continuous use is advised.
  • Analgesics, such as acetaminophen and opioid-(like) drugs, might be considered for residual pain after previously recommended treatments have failed, are contraindicated, and/or are poorly tolerated.
  • Glucocorticoid injections directed to the local site of musculoskeletal inflammation may be considered. Patients with axial disease should not receive long-term treatment with systemic glucocorticoids.
  • Patients with purely axial disease should normally not be treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs); sulfasalazine may be considered in patients with peripheral arthritis.
  • Biologic DMARDs (bDMARDs) should be considered in patients with persistently high disease activity despite conventional treatments; current practice is to start with TNFi therapy.
  • If TNFi therapy fails, switching to another TNFi or an anti–interleukin-17 (IL-17) therapy should be considered.
  • If a patient is in sustained remission, tapering of a bDMARD can be considered.
  • Total hip arthroplasty should be considered in patients with refractory pain or disability and radiographic evidence of structural damage, independent of age; spinal corrective osteotomy in specialized centers may be considered in patients with severe disabling deformity.
  • If a significant change in the course of the disease occurs, causes other than inflammation (eg, a spinal fracture) should be considered and appropriate evaluation, including imaging, should be performed.
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Treatment of Uveitis

Acute anterior uveitis presents as a painful red eye that is associated with photophobia and often recurs. Untreated uveitis may lead to vision loss. Evaluation and treatment of uveitis should be performed under the guidance of an ophthalmologist.

Generally, patients respond well to topical corticosteroids, mydriatics, and artificial tears, with resolution of the attack over 2-3 months. Treatment occasionally requires topical NSAIDs, retrobulbar corticosteroid injections, or immunosuppressive drugs. TNF-α antagonists may be helpful in selected cases. A study by van Denderen and colleagues reported a significant reduction in the recurrence rate of anterior uveitis in patients with AS who were treated with adalimumab. [132]

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Evaluation of Disease Activity and Treatment Response

Laboratory values, including the ESR and the C-reactive protein (CRP) level, are commonly employed to monitor the progression of the disease and the effectiveness of treatment. Guidelines from the European League Against Rheumatism (EULAR) recommend that conventional radiography of the sacroiliac (SI) joints, spine, or both may be used for long-term monitoring of structural damage, particularly new bone formation. If performed, it should not be repeated more frequently than every second year. [87]

MRI may provide additional information. MRI of the SI joints and/or the spine may be used to assess and monitor disease activity in axial spondyloarthropathy. In general, short tau inversion recovery (STIR) sequences are sufficient to detect inflammation, and the use of contrast medium is not needed. [87]

In addition, numerous tools have been developed to measure AS disease activity, especially in the setting of clinical trials. [133, 134, 135] These tools include the following:

  • Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) - A questionnaire that assesses fatigue, pain (in the neck, back, and hip), peripheral joint pain and swelling, discomfort, and severity and duration of morning stiffness

  • Bath Ankylosing Spondylitis Functional Index (BASFI) - A questionnaire of physical function that evaluates dressing, bending, mobility, standing, stairs, and full-day activities

  • Bath Ankylosing Spondylitis Metrology Index (BASMI) - A physical evaluation of range of motion (ROM) of the cervical and lumbar spine

  • Assessment in Ankylosing Spondylitis (ASAS) - The ASAS core set of domains (parameters) measures disease activity and includes patient global assessment of disease activity, patient assessment of back pain, BASFI, morning stiffness, synovitis and enthesitis score, ESR, CRP level, and fatigue

The ASAS response criteria are used to assess improvement in AS in clinical trials. Each of four domains is scored by the patient on a visual analog scale ranging from 0 to 10. The four domains are as follows:

  • Patient global assessment of disease activity for the past week

  • Patient assessment of back over the past week

  • Function (BASFI)

  • Inflammation (severity and duration of morning stiffness)

An ASAS20 response is defined as an improvement of at least 20% and an absolute improvement of at least 1 unit (on a 0-10 scale) in at least three of four domains, with no worsening of the remaining domain. An ASAS40 response is similar but requires a 40% improvement. An ASAS partial remission is defined as values of less than 2 for all four ASAS20 domains.

ASAS5/6 includes the four domains included in the ASAS20 plus spinal mobility (BASMI) and acute-phase reactants (CRP). An ASAS5/6 response is defined as improvement of at least 20% and an improvement of at least 1 unit in at least five of six domains, with no worsening of the remaining domain.

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Surgical Correction and Stabilization

Surgical interventions for AS include the following:

  • Vertebral osteotomy
  • Fracture stabilization
  • Joint replacement

Vertebral osteotomy

Patients with fusion of the cervical or upper thoracic spine may have significant impairment in line of sight, eating, and psychosocial well-being. These patients may benefit from extension osteotomy of the cervical spine. [12] This procedure is difficult and hazardous and should be performed only by surgeons specializing in spine surgery who have experience with the operation. The risk of major neurologic morbidity is significant; however, if the procedure is successful, it allows the patient to return to a more functional life.

Fracture stabilization

Many patients with advanced disease have fusion of the spine. If these patients report any change in position or movement of the spine, they should be assumed to have a spinal fracture because such an injury is the only way for a fused spine to move. Patients should be treated cautiously until fracture has been ruled out. If spinal fracture is present, surgical stabilization may be necessary.

Joint replacement

Patients with significant involvement of the hips may benefit from total hip arthroplasty [13] ; occasionally, total shoulder replacement may be indicated. These procedures may be very useful for reducing pain and improving function when the hip and shoulder joints become severely damaged. However, patients with AS at increased risk for complications after total hip arthroplasty, as the alteration in biomechanics resulting from spinal rigidity and kyphosis place higher demands on hip joints. [136]

Heterotopic bone formation may occur after total joint replacement, especially around the hip. Heterotopic bone formation can be reduced by giving NSAIDs (eg, indomethacin) or employing radiation therapy postoperatively. In general, outcomes of total joint replacement in patients have been satisfactory.

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Physical Therapy and Exercise

Physical therapy is important for maintaining function. [137, 138] A proper exercise program is a crucial component of such therapy. Patients obtain a significant reduction in symptoms after exercising. Referral to physical therapy or to a rehabilitation specialist is useful in assisting patients to develop an appropriate exercise program.  

Water therapy and swimming are excellent activities for maintaining mobility and fitness. In addition, a meta-analysis concluded that aquatic physical therapy can statistically significantly reduce pain and disease activity in patients with AS. [139]

Postural training is also useful. Spinal extension and deep-breathing exercises help maintain spinal mobility, encourage erect posture, and promote chest expansion. Maintaining an erect posture during daily activities and sleeping on a firm mattress with a thin pillow also tend to reduce the tendency toward thoracic kyphosis.

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Consultations

Consultations with the following specialists may be appropriate:

  • Rheumatologist - This consultation is indicated for evaluation and management of ongoing medical treatment of patients with AS; additional coexisting spondyloarthropathies can be assessed

  • Ophthalmologist - This consultation is indicated for patients with symptoms of acute anterior uveitis

  • Gastroenterologist - This consultation is indicated for patients with symptoms suggesting coexisting IBD

  • Cardiologist - This consultation is indicated for patients with cardiac involvement, including aortitis or heart block

  • Physical therapist or physical medicine and rehabilitation specialist - This consultation is indicated for all patients

  • Surgeon (orthopedic, neurologic, or both)

  • Geneticist - Patients may be referred for genetic counseling to assess questions regarding the probabilities of relatives developing the disease

  • Support groups - Many patients benefit from various support groups, which can provide further education on the disease process and available treatment options

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