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Spondyloarthritides (SpAs), are a group of idiopathic inflammatory rheumatologic disorders first recognized in the 1970s with common defining phenotypic, genetic, and serologic features.1 They are characterized by inflammation of the spine, sacroiliac (SI) joints, peripheral joints, enthesitis, dactylitis, as well as extra-articular manifestations such as uveitis and skin rashes. Serologically, they are rheumatoid factor (RF) and antinuclear antibody (ANA) negative. Genetically, they are associated with human haplotype antigen, HLA-B27, which suggests a common pathologic mechanism. Early diagnosis is crucial to limit disease-related disability. Non-pharmacologic treatment is aimed at prevention of progression, compensation, and restoration of function. Pharmacologic therapies involve non-steroidal anti-inflammatory drugs (NSAIDs) and biologics agents such as tumor necrosis factor (TNF) antagonists.

Traditionally, there were four subtypes of spondyloarthritides: ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis (formerly Reiter Syndrome) (ReA), and spondyloarthropathy associated with inflammatory bowel disease (IBD). Recent developments have expanded the concept of SpA to include undifferentiated spondyloarthropathy (USpA) and axial SpA. Undifferentiated SpA includes patients who are diagnosed with SpA, but do not fall into any specific subtype.Axial SpA includes patients with both non-radiographic (AS without sacroiliitis) and with radiographic findings.30

Spondyloarthritis and spondyloarthropathy are often used interchangeably, but the term spondyloarthritis is more appropriate because it refers to joint inflammation whereas arthropathy is a more general term referring to any joint pathology.  Spondyloarthritides is the plural of spondyloarthritis.2,3 Spondyloarthritides are sometimes prefixed with the term seronegative in the literature; however, the prefix has been dropped because unlike rheumatoid arthritis (RA), SpAs are seronegative (rheumatoid factor (RF) and antinuclear antibody (ANA) negative).5,6,7


The exact cause of SpAs is unknown. HLA-B27 is the biggest risk factor for the development of SpA.The exact role that HLA-B27 plays in this group of diseases is not well understood. The pathogenesis appears to be a complicated interplay of genetic and environmental factors. In the ReA subtype, bacterial organisms precipitate the disease process.

Epidemiology including risk factors and primary prevention

As a group, the spondyloarthritides may be as common as RA with a prevalence of 0.5% to 1%.6,9,10 Worldwide, there are variations in the prevalence of SpA which correlate with the prevalence of HLA-B27.59 HLA-B27 is seen in 90% of patients with AS, 50-80% of patients with reactive arthritis, 25-78% of patients with IBD-associated AS, 50% of patients with acute anterior uveitis, and 10-25% of patients with psoriatic arthritis.31-35 The prevalence of HLA-B27 varies among the different forms of spondyloarthritides and ethnic groups.6,8-10 In the United States, HLA-B27 may be found in 7.5% of American whites and in less than 1% of African Americans.The SpA with the highest HLA-B27 association is AS with up to 95% of American whites and 50% of African Americans testing positive for the geneotype.6,10


The pathogenesis of SpA has not been fully elucidated. The strong association of HLA-B27 with this group of diseases suggests it is a key contributor to the pathogenesis of SpAs. In humans, HLA-B27 is an allele of the MHC Class I molecule, found on all nucleated cells, which presents intracellular antigens to CD8+ T lymphocytes (cytotoxic T cells). Presentation of viral peptides bound to Class I MHC molecules found on infected cells results in their lysis.11

One theory, regarding the pathogenesis of ReA, is that this disease is triggered after the presentation of “arthritogenic” peptides to CD4+ and CD8+ T-cells, thus stimulating the associated inflammatory reactions.12 Certain bacteria, such as Yersinia, Salmonella, Shigella, and Campylobacter, have been clearly associated with ReA.13 Interestingly, bacterial DNA has been found in synovial fluid and synovial cells in those with ReA, suggesting a possible link between enteric infection and joint inflammation.12

Research has demonstrated tumor necrosis factor (TNF), IL-23 and IL-17, their polymorphisms, and immunologic pathways to be related to the pathogenesis of inflammatory arthritis.53 Cells expressing the IL-23 receptor have been shown to become pathogenic after exposure to IL-23. In tissues, IL-17A exacerbates the chronicity and severity of the disease process. Interaction of IL-23+ and IL-17+cells with different tissue specific cells leads to activation of cytokine-mediated pathways resulting in severe inflammation causing bone erosion and tissue modeling. Clinical trials specifically targeting TNF and IL-17 have demonstrated encouraging outcomes for axial SpA.53,55

On a macroscopic level, the pathologic inflammatory cascade disrupts the normal homeostasis of bone formation and bone resorption. The net result is pathologic endochondral bone formation known as osteoproliferation.15 Axial syndesmophytes and peripheral osteophytes form. The eventual fusion of syndesmophytes leads to ankylosis.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

SpAs are characterized by a waxing and waning course of active inflammation alternating with periods of little to no inflammation. Symptoms correlate with sites of inflammation around peri-articulator and tendon insertion sites. Inflammatory back pain is a common manifestation of SpAs. It is characterized by morning stiffness lasting more than 30 minutes. Peripheral entheses occur at sites that bear greater physical stress such as plantar fascia and Achilles tendon. There is also asymmetric peripheral arthritis of the lower limbs most notably at the hips and knees. Dactylitis may be seen in reactive arthritis, psoriatic arthritis, and undifferentiated SpA.6,10,11

The natural history of SpAs depends on the particular subtypes. Even within subtypes, disease severity may vary. AS is the best studied SpA. The natural history of more severe forms of AS, if left unchecked, is fusion of the spine beginning with the sacroiliac joints and progressing cranially. This leads to limited lumbar flexion, limited chest expansion, and hyperkyphosis.6,10

Specific secondary or associated conditions and complications

The most common extra-articular finding is anterior uveitis which occurs in 20-30% of AS patients but less than 1% of PsA patients.6,10 Skin involvement is in the form of psoriasis.3 There also appears to be a relationship between SpAs and inflammatory bowel disease (IBD). Asymptomatic inflammation of the terminal ileum and proximal colon may be found with serial colonoscopies in 60% of AS and USpA cases.10,11 About 10% of patients diagnosed with SpA develop IBD.16

Osteoporosis is commonly found in AS, and SpAs in general, and is responsible for loss of bone strength. Bone loss may be present early in the course of the disease and is predominantly found in the spine. It is associated with male gender, duration, severity of disease, and the presence of syndesmophytes in the spine. Low bone mineral density (BMD) increases the risk of vertebral fractures which contribute to kyphosis, vertebral deformity, and functional loss.16,17

Other associated conditions include diabetes, hyperlipidemia, obesity, hypertension, cardiovascular disease, urethritis, and, occasionally, increased mortality.12

Essentials of Assessment

Some studies indicate a 5 to 6-year delay between symptom onset and diagnosis.6,10 But untreated SpAs can lead to considerable disease burden and disability. This makes early diagnosis and treatment crucial. The first step is to recognize inflammatory low back pain. The second step is prompt referral to a Rheumatologist. In the “Supplemental Assessment Tools” below, there are some materials which will help guide you. Note the criteria used to determine inflammatory low back pain.


Individuals with SpAs commonly report morning stiffness and low back pain that improves with exercise and NSAIDs. Inflammatory low back is pain is the hallmark of SpAs and recognizing this is critical for early diagnosis. The morning stiffness usually lasts more than 30 minutes. Low back pain radiates into the buttocks and nocturnal back pain only occurs during the second half of the night.6,10,13 Chronic LBP lasting greater than 3 months with an age of onset before age 45 should raise suspicion of an autoimmune disorder.

In addition, other common symptoms to look for are those that include enthesitis (e.g. of the heel or ischial tuberosity), unilateral or symmetrical arthritic-type pain, along with the common extra-articular manifestations of SpA such as uveitis, iritis, skin rash, constitutional symptoms, dactylitis, and aortitis. ReA usually presents 2-4 weeks after a urogenital (including sexually transmitted diseases) or gastrointestinal infection.13

Physical examination

Findings on physical examination in patients with SpA include restricted spinal range of motion, tenderness of the sacroiliac and peripheral joints to palpation, swelling, warmth and erythema (synovitis) in the peripheral joints, enthesitis (edema, warmth, tenderness, erythema at tendon insertion points), dactylitis, and pertinent skin rashes (such as psoriasis). Patients with moderate to severe AS typically have a positive Schober’s test (very limited lumbar intersegmental flexion range of motion – see below).

Functional assessment

Functional difficulties due to spine pain and peripheral joint arthritis should be assessed in patients suspected of SpA. Functional assessment should be tailored to the individual’s disease. All patients with AS should have their cervical spine range of motion assessed. This group of patients is at risk of developing a progressive spinal flexion deformity which can be measured with the occiput to wall test. Involvement of a patient’s thoracic spine can be measured by the degree of chest expansion. Lumbar spine range of motion is measured in the sagittal and coronal planes. Lumbar flexion is assessed using the modified Schober test.18,19 Functional assessment tool such as the Bath Ankylosing Spondylitis Functional Index (BASFI) should be used.20

Laboratory studies

There are no specific lab tests to confirm a suspected diagnosis of SpA. Rather, a diagnosis is made through the combination of clinical, radiological, and laboratory findings. Most patients with SpAs have a positive HLA-B27, elevated C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), and negative RF and antinuclear antibody (ANA) tests. Ninety to 95% of AS patients and 81% of ReA patients are HLA-B27 positive. CRP or ESR is elevated in 72%-90% of AS and ReA patients.21


Each of the SpAs has some degree of sacroiliac and spinal inflammation. Although plain radiographs are the imaging modality of choice, they detect bony changes approximately 6 months from the onset of clinical symptoms, leading to a delay in diagnosis. MRI is the most sensitive imaging modality for detecting active inflammation of the SI joints using fat-saturated T2-weighted turbo spin-echo sequence or short tau inversion recovery (STIR) sequences with high resolution settings.22 Ultrasonography (US) is also better than plain radiographs in detecting inflammatory changes early, and it is better than MRI in detecting and treating enthesitis. Computerized axial tomography (CT) scans may be useful in assessing the spine for occult fractures as well as structural/bony changes indicative of sacroiliitis (such as syndesmophytes). These may not be as clear on MRI which is better suited for localizing signs of active inflammation which would suggest an expected response to TNF-blockers. 2,6,10,22,23,44

Interestingly, recent studies suggest the utilization of so-called “opportunistic” abdominal CT scans (which have already been performed for other purposes) as a screening tool in at-risk patients. Given the impressive sensitivities and specificities for identifying sacroiliitis this would be a reasonable approach when MRI is not available or feasible.45, 46 Moreover, abdominal CT scans include the thoracic spine (where the majority of syndesmophytes are found in AS). These scans were performed in at-risk patients with comorbidities, suspected neoplasms or latent/recurrent infections precluding the use of TNF-blockers. 47,48,49

Radiographs are also helpful in differentiating the SpA sub-types while ruling out similar diseases. Sacroiliitis in AS is bilateral and symmetrical, whereas in ReA and PsA it is often unilateral or asymmetrical. SpA- related sacroiliitis must be distinguished from other causes such as infection and osteitis condensans ilii. The absence of sacroiliitis is typical of diffuse idiopathic skeletal hyperostosis (DISH) syndrome which can be confused with AS.23 DISH syndrome usually occurs in older patients and its spinal manifestations progress craniocaudally with paravertebral and paradiscal ossification and osteophytes with ligamentous calcification particularly of the anterior longitudinal ligament.23 In contrast, AS begins in the SI joints and progresses up the spine.2,5,6,7

In more severe and advanced cases, the spinal inflammation of AS leads to attrition and squaring of vertebrae followed by osteoproliferation and the formation of syndesmophytes. Fusion of these bony outgrowths is known as ankylosis and gives the appearance of a “bamboo spine” on plain radiography.23 Of note, CT scans may detect changes in AS earlier than radiographs, specifically with respect to syndesmophytes. Importantly, limitations in spinal mobility are commonly attributed to these syndesmophytes as well as bridging, and are therefore regarded as applicable imaging markers for monitoring the progression of AS.44,50

The classic “pencil-in-cup” radiographic finding which occurs in arthritis mutilans, the most severe form of PsA, is a manifestation of the severe destruction and proliferation of bone resulting in shortening of the phalanges.6,10

Dual energy x-ray absorptiometry (DEXA) scans should be considered as osteoporosis is commonly found in AS and SpAs in general. Low BMD will increase the risk of vertebral fractures which contribute to kyphosis, vertebral deformity, and functional loss.17 Measurements of the spine may be normal or even high because the bridging syndesmophytes found in AS may mask osteoporosis. Measurements of the femoral neck may be more accurate.23

Supplemental assessment tools

The Assessment of SpondyloArthritis International Society (ASAS) Criteria for Inflammatory Back Pain18 (need at least 4 out of 5)

  • Greater than 3 months of LBP
  • Age of onset before 40 years
  • Insidious onset
  • Improvement with exercise
  • Pain at night (with improvement upon getting up)

Bath Ankylosing Spondylitis Functional Index (BASFI)20

The BASFI is the mean of 10 item scores completed on a numerical rating scale. Items to be scored by the patient

  • Putting on your socks or tights without help or aids (e.g., sock aid).
  • Bending forward from the waist to pick up a pen from the floor without an aid.
  • Reaching up to a high shelf without help or aids (e.g., helping hand).
  • Getting up out of an armless dining room chair without using your hands or any other help.
  • Getting up off the floor without help from lying on your back.
  • Standing unsupported for 10 min without discomfort.
  • Climbing 12 to 15 steps without using a handrail or walking aid. One foot at each step.
  • Looking over your shoulder without turning your body.
  • Doing physically demanding activities (e.g., physiotherapy, exercises, gardening or sports).
  • Doing a full day’s activities, whether it be at home or at work.

Modified Schober test17 (patient must be standing erect)

  • Mark an imaginary line connecting both posterior superior iliac spines (close to the dimples of Venus) (A).
  • The next mark is placed 10 cm above (B).
  • The patient bends forward maximally: measure the difference (C).
  • Report the increase (in cm to the nearest 0.1 cm).
  • The better of two tries is recorded.

Assessment of SpondyloArthritis International Society (ASAS) Classification Criteria for axial spondyloarthritis and spondyloarthritis in general:24

Currently, there are no diagnostic criteria for the spondyloarthritides. Rather, there are classification criteria developed by ASAS with the goal of early identification and treatment. ASAS divides SpAs into predominantly axial (axSpA) or predominantly peripheral (pSpA). A patient may be classified as axSpA either through a pathway beginning with the presence of HLA-B27 or radiographic evidence of sacroiliitis.

In order to identify patients with SpAs, symptoms of LBP lasting ≥ 3months should be present, and occur before age 45 years. In addition, the following criteria should be met: Sacroiliitis on imaging plus one or more of the SpA features listed below. Or, alternatively, HLA-B27 positivity plus two or more of the following SpA features listed below:

  • Inflammatory back pain
  • Arthritis
  • Enthesitis (e.g., heel)
  • Uveitis
  • Dactylitis
  • Psoriasis
  • Crohn’s/colitis
  • Good response to NSAIDs
  • Family history of SpA
  • HLA-B27
  • Elevated c-reactive protein (CRP)

In patients with only peripheral symptoms, arthritis, enthesitis or dactylitis must be present plus one or more SpA feature listed below:

  • Uveitis
  • Psoriasis
  • Crohn’s/ ulcerative colitis
  • Preceding infection
  • HLA-B27
  • Sacroiliitis on imaging


Two or more other SpA features:

  • Arthritis
  • Enthesitis
  • Dactylitis
  • Inflammatory back pain history
  • Family history of SpA

Early predictions of outcomes

Poor prognostic indicators include a younger age of onset, greater peripheral than axial joint involvement, uveitis, and elevated erythrocyte sedimentation rate (ESR), and poor response to non-steroidal anti-inflammatory drugs (NSAIDs).12


As with rheumatoid arthritis, changes in barometric pressure can affect spine or joint pain associated with SpAs. Repetitive work environments can provoke pain and may increase risk of disability. Functional barriers at home or work should be addressed.

Social role and social support system

As SpAs progress, disability can occur, affecting a patient’s role at home or work and potentially adversely affecting their relationships. Formal support groups, both in person and online do exist. There are numerous ones and should be screened by practitioners before their patient joins. One place to find a list of support groups in through the Spondylitis Association of America. https://spondylitis.org/resources-support/support-resources/support-groups/

Rehabilitation Management and Treatments

Available or current treatment guidelines

Treatment is directed at preventing progression of disease, preservation of joint architecture and function, and individual symptom management. The approach to treatment is multimodal involving education, referral to specialists, lifestyle and workplace modifications, prevention, occupational and physical therapy, regular exercise, and medication.

The American College of Rheumatology, Spondylitis Association of America, and Spondylitis Research and Treatment Network collaborated to develop treatment guidelines in 2015.25 These guidelines encompass the spectrum of both pharmacologic and non-pharmacologic treatments. Separately, in 2015, members of an AS special interest group in Australia developed the first comprehensive exercise recommendations for AS patients.26 These recommendations are extrapolated for all SpAs and are incorporated below.

There are no functional measures specific for SpAs. However, the Bath Ankylosing Spondylitis Metrology Index (BASMI), is categorical for AS.18 It is an axial mobility measure and is associated with quality of life, physical function and psychological status. Hip involvement may be assessed with tape-based hip internal rotation. Strength, balance, and cardiopulmonary status should be evaluated. The Ankylosing Spondylitis Quality of Life Scale (ASQoL) is a tool for assessing the impact of interventions on the quality of life for AS and is commonly used for evaluating treatment effects.36

Lifestyle modifications are directed at minimizing repetitive mechanical stress. For those who smoke, cessation should be a priority to prevent worse outcomes and spinal damage. Dietary consults may be appropriate, and obesity should be addressed as it places more stress on the spine and contributes to low back pain. Adaptations and modifications to home and workspace may be necessary. A firm but not hard mattress may be preferred. Similarly, preference should be given to office chairs which promote good posture. 23

Exercise should be a part of the non-pharmacologic treatment approach.23,25,27 Exercise programs have been shown to improve function, reduce pain, and reduce global patient assessment of disease activity when compared to no intervention.37 Exergames which are games based on a virtual avatar’s body movement and ultrasound therapy have been shown to increase physical activity and decrease pain scores in patients with AS.38,39 SpA patients should strive for a life-long exercise program. In general, exercises prescriptions best focus on low impact exercises. Pilates, Tai Chi and certain forms of yoga may be beneficial and may be done in a group setting. Patients wishing to engage in more aggressive types of activities should be assessed on a case by case basis. Careful consideration needs to be given before permitting high impact exercise or physical activity such as martial arts or theme park rides. High velocity or strongly resistance exercises place a lot of pressure on joints. Exercises which place excessive challenges to balance, postural stability or cardiopulmonary function may need to be modified. Excessive spinal or peripheral joint mobility where there are ankyloses are to be avoided.26 Bony change, balance, mobility, osteoporosis, and cardiopulmonary status should be taken into consideration while writing an exercise prescription.

The prescription should cater to maintaining posture, flexibility and strengthening the core and cardiopulmonary system.27 After a complete musculoskeletal assessment, an exercise prescription may address specific muscle groups to correct posture. For example, in patients with excessive cervical kyphosis the cervical flexors are stretched while the cervical extensors are strengthened.27

Occupational and physical therapy play an important role in the multi-modal approach to care. Occupational therapists may survey home dwellings and workplaces to make recommendations for adaptive equipment and ergonomic modifications. Both occupational and physical therapy are useful in treating enthesitis with modalities and custom-made orthotics. For Achilles tendonitis and plantar fasciitis, custom-made insoles may be ordered. Nighttime resting splints may be used for tendonitis and tenosynovitis of the hands, wrists, ankles and feet to help prevent joint contractures. Physical and occupational therapists may help with active and passive range of motion of the joints and more importantly educate patients on doing this at home.

Pharmacologic options for SpAs are non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoid injections, and tumor necrosis factor (TNF) inhibitors. NSAIDs are the first line pharmacologic agents in treating SpAs and may have disease modifying activity and reduce radiographic spinal progression of the disease. They should be prescribed scheduled.25,28, A good response to NSAIDs strongly supports the diagnosis of a spondyloarthritides and is actually a part of the classification criteria for SpA.28 Long term use of glucocorticoids is not recommended; however, short-term glucocorticoids with rapidly tapering doses may be considered in severe arthritic flares. Glucocorticoid injections are beneficial for entheses and inflamed joints, but peri-tendon injections to the Achilles, patellar, or quadriceps should be avoided. Topical glucocorticoids may be prescribed for prompt home use in the event of acute iritis.23,25 There is currently insufficient evidence to support any benefit of methotrexate in the treatment of PA or AS. While low dose methotrexate has been shown to improve symptoms of psoriatic arthritis in patients with active psoriatic arthritis at 6 months, it does not have any significant benefit on objective measures of synovitis including ESR, CRP, and number of tender or swollen joints40. Similarly, multiple studies have demonstrated conflicting results regarding the efficacy of methotrexate on patients with active AS.41,42,43 Tumor necrosis factor (TNF) α blockers, in contrast, have shown significant benefit in the treatment of AS and SpAs. All manifestations of disease including synovitis, joint inflammation, enthesitis, dactylitis, axial disease, and skin and nail changes respond to TNF- α blockers. They are recommended for patients with insufficient response to NSAIDs.22,25

Coordination of care

Rheumatologists are usually directors of care for SpA patients. The approach to care is multimodal and may require other specialties. Dermatologists should be consulted in those with psoriatic manifestations or PsA. Gastroenterologist referral may be helpful as gastrointestinal involvement is often found in SpAs. Any patient with uveitis should be evaluated by an ophthalmologist.

Physiatrists play a critical role in the care of SpA patients and may even have more exposure to them than other specialties. Pain is a common presenting symptom, and SpA patients would greatly benefit from a PM&R pharmacologic and non-pharmacologic approach to pain. Furthermore, Physiatrists can assess the musculoskeletal system and write individualized therapy prescriptions.

Patient & family education

Education may be in the setting of a formal support group or individual self-management program.23,25 While there are numerous websites for learning, the practitioner should guide the patient to use reputable evidence-based ones.

Patients should be educated regarding the genetic implications of SpAs. For instance, if an individual under 40 years old has a family member with AS that is HLA-B27 positive, that individual has a 20% chance of developing AS.12

Emerging/unique interventions

Treatment result outcomes can be measured using blood work (CRP > ESR),12 imaging (x-ray and MRI of joints), physical examination (including Schober test), and functional performance examinations (observed activities of daily living) and surveys (Oswestry Disability Index, Short Form-36, Visual Analog Pain Scale). An outcome measure specifically designed for AS is the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).18

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Early diagnosis and treatment is a critical concept in SpAs. In order to achieve that, physiatrists must recognize signs and symptoms of SpAs and then promptly refer to rheumatologists. Sieper and Rudwaleit published an algorithm to assist with this. The steps are outlined below.54

If the patient has ≥ 3 months of LBP occurring before age 45 years, proceed to step 1.

  1. Do not order any new imaging, but rather review imaging (MRI/X-ray) which is already present. If there is evidence of sacroiliitis then refer to rheumatologist. Otherwise proceed to step 2.
  1. Do the patient’s symptoms suggest inflammatory LBP? These symptoms are
    • morning stiffness lasting greater than 30mins
    • LBP occurs mostly late night/early morning
    • Pain improves with exercises
    • If patient’s symptoms do not suggest inflammatory LBP, proceed to step 3
  2. Check HLA-B27, if positive, refer to rheumatologist.

Other clinical pearls to note:

SpAs are usually very responsive to NSAIDs and unless there are any contraindications, NSAIDs should be scheduled.  Refrain from using oral glucocorticoids. Physiatrists can play a crucial role in the care of SpA patients. Physiatrists may well see these patients on a chronic basis more often than other specialties. As a result, we should be aware of the complications of this group of diseases and make referrals and coordinate with rheumatologists.

Cutting Edge/Emerging and Unique Concepts and Practice

As mentioned above, this is an exciting time in the research field for SpAs. In September 2016, the International Congress on Spondyloarthritides (SPA) studied the effectiveness of IL-17, IL-17A inhibitors (IL-17i, IL-17Ai, respectively). In 2017, a randomized-controlled, double-blind, trial demonstrated secukinumab, an IL-17A monoclonal antibody, to have significant improvement up to one year in multiple outcomes including pain, function, and disease activity in patients with moderate to severe AS.55 Despite evidence of the effectiveness of IL-17 and IL-17A inhibitors in AS, recent guidelines per the 2019 American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network now recommend use of tumor necrosis factor inhibitor (TNFi) as the first line biologic for patients with active AS and non-radiographic axial spondyloarthropathies (nr-axSPA) who have failed NSAIDs. IL-17 and IL-17A inhibitors (secukinumab and ixekizumab, respectively) are recommended as second line biologics with patients who have a primary nonresponse to the first TNFi.56,58 Jak1 inhibitors, specifically tofacitinib, are recommended as the third line biologic.56,58 However, recent studies were halted due to increased risk of cardiovascular events.57  Despite their roles in the inflammatory pathway, IL-12 and IL-23 inhibitors have not shown clinical efficacy in axial SpAs.57  

There are also interesting potential opportunities to investigate low-dose CT scans and modifications which can be made to conventional CT scan techniques (oblique vs axial scanning) that may maximize the scanning range while minimizing radiation exposure. Other technical improvements (such as iterative reconstruction) can also be utilized to reduce the noise associated with low-dose CT scans.48,51,52

Gaps in the Evidence-Based Knowledge

As discussed above, the role of HLA-B27 in this group of disease needs a deeper understanding. Further investigation is needed regarding the pathophysiologic processes of the subtypes of SpAs to determine if they are different phenotypes of the same pathological process or if there are different processes involved. In terms of imaging, while MRI does not involve radiation exposure, it is better suited for detecting early inflammatory changes rather than structural damage (syndesmophytes) given the absence of signal from cortical bone. For this reason more extensive studies are needed to compare the sensitivity and specificity of low-dose CT to conventional/full-dose CT scans for detecting structural lesions that are characteristic of sacroiliitis in an attempt to minimize radiation exposure.

Disease-modifying antirheumatic drugs (DMARDs), specifically biologics, continue to be investigated for their ability to suppress inflammation in axial SpA. Future comparative effectiveness trials between IL-17i/IL-17Ai and TNFi would prove to be beneficial to determine clinically meaningful differences between current treatment modalities.


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Original Version of the Topic 

David S Fitch, DO, MS, PT. Seronegative Spondyloarthropathy. 2/5/2013.

Previous Revision(s) of the Topic 

Pritesh Patel, MD. Seronegative Spondyloarthropathy. 4/4/2017.

Bryan Murtaugh, MD, Hannie Batal, MD, Steven Jow, MD. Seronegative Spondyloarthropathy. 5/4/2021.

Author Disclosures

Enrique Galang, MD
Nothing to Disclose

Nam Vo, DO
Nothing to Disclose

Emily Deschler
Nothing to Disclose

Janus Patel, MD
Nothing to Disclose