Can You Spot Axial Spondyloarthritis? by Integritas Communications

Can You Spot Axial Spondyloarthritis?

Faculty

Lianne Gensler, MD Associate Professor Department of Medicine Division of Rheumatology Director, Ankylosing Spondylitis Clinic University of California, San Francisco San Francisco, California

Dr. Lianne Gensler is a rheumatologist at University of California, San Francisco (UCSF) Medical Center and director of the Ankylosing Spondylitis Clinic. She is also an associate professor of medicine at UCSF School of Medicine. Dr. Gensler earned her medical degree at the University of California, Irvine. She completed an internal medicine residency, chief residency, and rheumatology fellowship at UCSF and then joined the medical staff in Rheumatology. Her primary research interests are the disease progression, outcomes, and biomarkers of ankylosing spondylitis and axial spondyloarthritis, and the predictors of osteoporosis development in patients with systemic lupus erythematosus. Dr. Gensler is one of the authors of the American College of Rheumatology/ Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. She has been honored with the Ira M. Goldstein Teaching Award in Rheumatology, the Spondylitis Association Young Investigator Award, and the UCSF Research Mentoring Award.

Paul Nadler, MD Clinical Professor of Medicine Medical Director, Screening and Acute Care Clinic University of California, San Francisco San Francisco, California

Dr. Paul Nadler, medical director of the University of California, San Francisco (UCSF) Screening and Acute Care Clinic, has extensive experience in outpatient urgent care. His research focuses on new technologies to increase the quality of urgent care and to improve the management of orthopedic problems in primary care. Dr. Nadler is board certified in internal medicine and a clinical professor of medicine at UCSF. He earned his medical degree at the State University of New York at Buffalo, School of Medicine and Biomedical Sciences and completed a residency in internal medicine at UC Davis Medical Center.

Preamble

Target Audience The educational design of this activity addresses the needs of primary care providers (PCPs), including family medicine and internal medicine physicians, nurse practitioners (NPs), and physician assistants (PAs).

Educational Objectives After completing this activity, the participant should be better able to: • Identify patients with inflammatory back pain (IBP) and correlate clinical findings with axial spondyloarthritis (AxSpA) via historical features, manifestations, and comorbidities • Apply first-line diagnostic modalities for the provisional identification of AxSpA • Refer patients to rheumatologists for diagnostic confirmation and targeted treatment of AxSpA within a clinically advantageous time frame • Provide longitudinal support for patients with AxSpA

Statement of Need/Program Overview Axial spondyloarthritis (AxSpA) is a chronic, inflammatory arthritis of the sacroiliac joints and spine.1 The disease may also present with peripheral arthritis and/or extra-articular manifestations.1 Progressive joint damage, irreversible loss of spinal mobility, and impaired patient function are accompanied by significant psychosocial and quality-of-life burdens. All too often, the diagnosis of AxSpA is delayed—historically, by an average of 10–14 years from the time of symptom onset—profoundly exacerbating the disease sequelae.2,3 Given their frontline position in the assessment of back pain, PCPs are essential to accelerating the identification of AxSpA. This multimedia eHealth Source™ program has been designed to help PCPs efficiently screen patients with suspicious clinical presentations, correlate signs and symptoms with various AxSpA subtypes, and utilize available first-line diagnostic modalities. The overall goal is to expedite evidence-based management of AxSpA by enhancing disease awareness among PCPs, improving patient evaluations in primary care, and encouraging rheumatology referrals with an expectation of ongoing collaborative care.4,5

References 1. Sieper J, Poddubnyy D. Axial spondyloarthritis. Lancet. 2017;390(10089):73-84. 2. Martindale J, Goodacre L. The journey to diagnosis in AS/axial SpA: the impact of delay. Musculoskeletal Care. 2014;12(4): 221-231. 3. Ramonda R, Marchesoni A, Carletto A, et al. Patient-reported impact of spondyloarthritis on work disability and working life: the ATLANTIS survey. Arthritis Res Ther. 2016;18:78. 4. Ward MM, Deodhar A, Akl EA, et al. American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 2016;68(2): 282-298. 5. Rudwaleit M, Sieper J. Referral strategies for early diagnosis of axial spondyloarthritis. Nat Rev Rheumatol. 2012;8(5): 262-268.

Physician Accreditation Statement This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Global Education Group (Global) and Integritas Communications. Global is accredited by the ACCME to provide continuing medical education for physicians. This CME/CE activity complies with all requirements of the federal Physician Payment Sunshine Act. If a reportable event is associated with this activity, the accredited provider managing the program will provide the appropriate physician data to the Open Payments database.

Physician Credit Designation Global Education Group designates this enduring activity for a maximum of 1.0 AMA PRA Category 1 Creditâ&#x201E;˘. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Nursing Continuing Education Global Education Group is accredited with distinction as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. This educational activity for 1.0 contact hours is provided by Global Education Group. Nurses should claim only the credit commensurate with the extent of their participation in the activity.

Global Contact Information For information about the accreditation of this program, please contact Global at 303-395-1782 or cme@globaleducationgroup.com.

Instructions to Receive Credit In order to receive credit, learners must pass the post test with a score of at least 70% and complete the evaluation/application for credit at www.ExchangeCME.com/2017eHealthAxSpA.

Fee Information & Refund/Cancellation Policy There is no fee for this educational activity.

Disclosure of Conflicts of Interest Global Education Group (Global) requires instructors, planners, managers, and other individuals and their spouses/life partners who are in a position to control the content of this activity to disclose any real or apparent conflict of interest they may have as related to the content of this activity. All identified conflicts of interest are thoroughly vetted by Global for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations. The faculty reported the following financial relationships or relationships to products or devices they or their spouses/life partners have with commercial interests related to the content of this CME activity: Lianne Gensler, MD

Consultant/Independent Contractor: Janssen Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation

Paul Nadler, MD

Nothing to disclose

The planners and managers reported the following financial relationships or relationships to products or devices they or their spouses/life partners have with commercial interests related to the content of this CME activity: Andrea Funk

Nothing to disclose

Ashley Marostica, RN, MSN

Nothing to disclose

Jeanette Ruby, MD

Nothing to disclose

Jim Kappler, PhD

Nothing to disclose

Disclosure of Unlabeled Use This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the US Food and Drug Administration (FDA). Global Education Group (Global) and Integritas Communications do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of any organization associated with this activity. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

Disclaimer Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed in this activity should not be used by clinicians without evaluation of patient conditions and possible contraindications on dangers in use, review of any applicable manufacturerâ&#x20AC;&#x2122;s product information, and comparison with recommendations of other authorities.

What Is Axial Spondyloarthritis?

Introduction Axial spondyloarthritis (AxSpA) is a chronic, inflammatory arthritis of the sacroiliac joints (sacroiliitis) and spine (spondylitis). Clinically, AxSpA is manifested by pain, stiffness, and eventual limitation of mobility due to inflammation and spinal fusion (ankylosis); however, it is also variably associated with peripheral arthritis and other, extra-articular, manifestations.1 The progressive course of joint damage, irreversible loss of spinal mobility, and functional impairment associated with AxSpA is accompanied by significant psychosocial burdens and detriments to quality of life. The all too frequent delay in diagnosis—historically, an average of 10–14 years from the time of symptom onset—profoundly exacerbates all disease sequelae.2-4 Primary care providers (PCPs) carry a disproportionate responsibility for identifying patients whose clinical presentations are suspicious for AxSpA, given these clinicians’ frontline position in the evaluation of the common complaint of back pain. With enhanced disease awareness, strategies for first-line diagnostic evaluation, and collaborative referral pathways, the PCP will support the goal of effectively identifying patients with AxSpA and initiating treatment within a clinically advantageous time frame.5 AxSpA is a disease of younger individuals, typically extending well into and throughout the most productive years of many patients’ working lives.4 Although the disease process may begin as early as childhood or adolescence, onset of symptoms most commonly occurs in the third decade of life, with a male-to-female ratio of 2–3:1 for radiographically evident disease and of 1:1 for the nonradiographic form.6 The prevalence of AxSpA in the United States is estimated at 0.09%–1.4%, corresponding with approximately 5% of all patients with chronic back pain.7 As many as 2.7 million (95% confidence interval [CI] 1.9-3.7 million) adults in the United States have AxSpA, based on the National Health and Nutrition Examination Survey (NHANES) conducted by the Centers for Disease Control and Prevention (CDC) between 2009 and 2010.8

Axial Spondyloarthritis: Two Radiographic Forms, One Disease The term axial spondyloarthritis comprises ankylosing spondylitis (AS)—classic, radiographically evident disease—and nonradiographic axial spondyloarthritis (nr-AxSpA), the latter term first being included in classification criteria in 2009.9 These clinical forms are differentiated primarily on the basis of imaging findings and duration of symptoms (Figure 1.1). Approximately 10% of patients who initially present with nrAxSpA will develop radiographically evident disease (ie, AS) within 2 years, and as many as 80% or more of these patients will have radiographic evidence within 20 years.10,11 These radiographically defined variants, however, are equivalent in terms of disease activity, pain, peripheral and extra-articular manifestations, and quality-of-life impairment, as measured by disease-activity and health-related quality-of-life instruments.12,13 Therefore, it has been proposed that the terms AS and nr-AxSpA should be used for research-based classification of patients within AxSpA and not as separate diagnoses, unless there is a meaningful medical reason to differentiate nr-AxSpA from AS.9

Placing Axial Spondyloarthritis Within the Spectrum of Spondyloarthritis Phenotypes AxSpA exists within the broader spectrum of spondyloarthritis (SpA) phenotypes, inflammatory arthritis variants affecting the spine with or without peripheral-joint involvement. The current SpA classification distinguishes between axial spondyloarthritis (radiographic and nonradiographic) and peripheral spondyloarthritis phenotypes. SpA phenotypes, including psoriatic arthritis (PsA), reactive arthritis (ReA), enteropathic arthritis (EnA; associated with Crohn’s disease or ulcerative colitis), and undifferentiated spondyloarthritis (USpA), may fall under the axial (either radiographic or nonradiographic) or peripheral classification, depending on the jointdistribution pattern and/or predominance. Enthesitis-related arthritis (ERA), a subcategory of juvenile idiopathic arthritis, may include the presence of or history of sacroiliac joint tenderness and/or inflammatory lumbosacral pain (juvenile spondyloarthritis)[Table 1.1].14 7

Sharing genetic, immunologic, and clinical features, the spondyloarthritis phenotypes are differentiated beyond joint distribution by the patient’s clinical history, extra-articular manifestations, and comorbidities, in conjunction with the selective use of diagnostic modalities.15

AS Heritability and Pathogenesis Although the exact etiology of AxSpA has not been established, there have been advances in the understanding of genetic susceptibility for AS and VIDEO 1: Placing Axial spondyloarthritis within the environmentally mediated epigenetic spectrum of spondyloarthritis phenotypes  aberrations involved in triggering and Lianne Gensler, MD promoting disease progression.16 HLAB27 has been known to be the major contributing genetic-risk allele for AS for over 40 years, yet its presence is not sufficient to cause disease.17 AS is a polygenic disease with more than 100 genes known to contribute to its susceptibility; AS heritability is not clearly discernible. The probability that a parent with AS will have an HLA-B27–positive offspring of a parent with AS is only 12.5% to 20%, indicating that the likelihood of their developing the disease is less than that of not developing the disease. Genetics and heritability data come from the AS literature and cannot be generalized to nr-AxSpA.18 AxSpA is an immune-mediated inflammatory disorder, the disease burden of which reflects the degree of acute inflammation (pain and stiffness), new bone formation (reduced spinal mobility and functional impairment), and extra-articular systems involvement (gut, eyes, skin, heart, and lungs). Numerous studies have established the central position of the proinflammatory interleukin (IL)-23/IL-17 pathway in AxSpA pathogenesis. IL-17 has been shown to enhance T-cell priming and to stimulate various cell types to produce proinflammatory mediators; ie, IL-1, IL-6, tumor necrosis factor (TNF)-α, and chemokines.17 Targeting the IL-17 pathway is now established as a safe and effective strategy for treatment of patients with AxSpA.19 Additional environmental factors—microbiome, infections, and drug and toxin exposure—may also play significant roles in AxSpA pathogenesis.17 The relationship between intestinal dysbiosis (gut microbiota overgrowth and/or imbalance), chronic gut inflammation, and innate immune responses in patients with AxSpA is a growing focus of investigation.20

References 1.

Ward MM, Deodhar A, Akl EA, et al. American College of Rheumatology/Spondylitis Association of America/ Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol. 2016;68(2):282-298.

2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

13.

14. 15. 16. 17. 18. 19. 20.

Adshead R, Tahir H, Donnelly S. A UK best practice model for diagnosis and treatment of axial spondyloarthritis. EMJ Rheumatol. 2015;2(1):103-110. Martindale J, Goodacre L. The journey to diagnosis in AS/axial SpA: the impact of delay. Musculoskeletal Care. 2014;12(4): 221-231. Ramonda R, Marchesoni A, Carletto A, et al. Patient-reported impact of spondyloarthritis on work disability and working life: the ATLANTIS survey. Arthritis Res Ther. 2016;18:78. Rudwaleit M, Sieper J. Referral strategies for early diagnosis of axial spondyloarthritis. Nat Rev Rheumatol. 2012;8(5): 262-268. Sieper J, Poddubnyy D. Axial spondyloarthritis. Lancet. 2017; 390(10089):73-84. Taurog JD, et al. Ankylosing spondylitis and axial spondyloarthritis. N Engl J Med. 2016;374(26):2563-2574. Reveille JD, Witter JP, Weisman MH. Prevalence of axial spondylarthritis in the United States: estimates from a crosssectional survey. Arthritis Care Res. 2012;64(6):905-910. Deodhar A, Strand V, Kay J, Braun J. The term 'non-radiographic axial spondyloarthritis' is much more important to classify than to diagnose patients with axial spondyloarthritis. Ann Rheum Dis. 2016;75(5):791-794. Keat A, Bennett AN, Gaffney K, Marzo-Ortega H, Sengupta R, Everiss T. Should axial spondyloarthritis without radiographic changes be treated with anti-TNF agents? Rheumatology Int. 2016; 37(3):327-336. Malaviya AN, Rawat R, Agrawal N, Patil NS. The nonradiographic axial spondyloarthritis, the radiographic axial spondyloarthritis, and ankylosing spondylitis: the tangled skein of rheumatology. Int J Rheumatol. 2017;2017:1824794. Sieper J, Holbrook T, Black CM, Wood R, Hu X, Kachroo S. Burden of illness associated with non-radiographic axial spondyloarthritis: a multiperspective European cross-sectional observational study. Clin Exp Rheumatol. 2016;34(6): 975-983. de Winter JJ, van Mens LJ, van der Heijde D, LandewĂŠ R, Baeten DL. Prevalence of peripheral and extra-articular disease in ankylosing spondylitis versus non-radiographic axial spondyloarthritis: a meta-analysis. Arthritis Res Ther. 2016;18(1): 196. Colbert RA. Classification of juvenile spondyloarthritis: enthesitis-related arthritis and beyond. Nat Rev Rheumatol. 2010;6(8):477-485. Reveille JD for the American College of Rheumatology. Spondyloarthritis. 2013; http://www.rheumatology.org/I-Am-A/ Patient-Caregiver/Diseases-Conditions/Spondyloarthritis. Accessed January 26, 2017. Ciccia F, Ferrante A, Triolo G. Intestinal dysbiosis and innate immune responses in axial spondyloarthritis. Curr Opin Rheumatol. 2016;28(4):352-358. Jethwa H, Bowness P. The interleukin (IL)-23/IL-17 axis in ankylosing spondylitis: new advances and potentials for treatment. Clin Exp Immunol. 2016;183(1):30-36. Reveille JD. Recent studies on the genetic basis of ankylosing spondylitis. Curr Rheumatol Rep. 2009;11(5):340-348. Paine A, Ritchlin CT. Targeting the interleukin-23/17 axis in axial spondyloarthritis. Curr Opin Rheumatol. 2016;28(4): 359-367. Kabeerdoss J, Sandhya P, Danda D. Gut inflammation and microbiome in spondyloarthritis. Rheumatol Int. 2016;36(4): 457-468.

The Clinical Presentation of AxSpA

The Clinical Presentation: Look for Red Flags With Heightened Suspicion Primary care providers (PCPs) are not alone in their failure to identify axial spondyloarthritis (AxSpA) in both its radiographic and nonradiographic forms in a timely manner, yet a disproportionate share (an estimated 60%) of initial assessment of the high-frequency symptom of back pain falls to these clinicians.1 Differentiating between inflammatory and mechanical back pain is the often challenging first step in evaluating the patient who presents with back pain.2 In the absence of a heightened clinical suspicion of a nonmechanical etiology, the presence of AxSpA is often missed by first-line clinicians, notably PCPs. As is true of diagnosing many medical conditions, the clinician must think of the condition to look for it. Here, the diagnostic challenge is that of recognizing nonmechanical processes. This underscores the critical importance of the overall presentational context of the patientâ&#x20AC;&#x2122;s back-pain symptoms and the clinicianâ&#x20AC;&#x2122;s resulting interrogation for historical red flags and corroborative physical findings. The 2009 ASAS Clinical Criteria for Inflammatory Back Pain in Patients With Chronic Back Pain (Table 2.1) provides the PCP with easyto-elicit historical features. Suspicion of inflammatory back pain (IBP) is raised if at least 4 of 5 of the features are present (sensitivity 77.0%, 10

specificity 91.7%): age at onset <40 years (odds ratio [OR], 9.9); insidious onset (OR, 12.7); improvement with exercise (OR, 23.1); pain at night (OR, 20.4); or, no improvement with rest (OR, 7.7).3 This is a first step only toward developing a differential diagnosis; ie, the presence of IBP does not constitute a diagnosis. Other nonmechanical etiologies (eg, infectious, neoplastic) may warrant consideration; and, the medical workup should reflect these diagnostic considerations, if indicated by a careful history and physical exam. The suspected presence of IBP, augmented by further investigation of the patientâ&#x20AC;&#x2122;s clinical presentation, including any extra-articular manifestations and comorbidities (eg, peripheral arthritis, enthesitis, dactylitis, uveitis, psoriasis, and/or inflammatory bowel disease) will lay the groundwork for diagnostic workup of AxSpA.

Initial Workup of the Patient With Suspected Axial Spondyloarthritis Diagnostic Imaging Appropriate use of imaging can provide objective signs of sacroiliac joint (SIJ) pathology, upon which timely referral for further rheumatologic evaluation and treatment can be initiated. First-line imaging for identifying sacroiliitis is conventional radiography of the pelvis (anteroposterior [AP] view). Magnetic resonance imaging (MRI) of the sacrum, SI joints, or pelvis (no contrast needed) may be considered as an alternative first imaging method in certain cases, including for children (Table 2.2). In general, MRI of the SI joints is recommended if the diagnosis of axial SpA cannot be established based on clinical features and conventional radiography and AxSpA is still clinically suspected. The definition of a positive MRI for axial SpA primarily depends on the imaging features of active sacroiliitis (inflammation), the defining indicator of which is the presence of bone-marrow edema in subchondral bone; with structural-damage lesions as contributory, but not required, indicators.4 Studies have shown that imaging modalities are underutilized and/or inappropriately ordered by PCPs and other nonrheumatologist health care providers.5 A few considerations will help guide imaging selection6: â&#x20AC;˘ For the diagnosis of AxSpA, the only place that the clinician should be looking is the SIJs. It is very rare that an individual will have spinal involvement (thoracic or lumbar) without sacroiliitis. Moreover, many individuals may have changes suggestive of spinal involvement that are not significant for AxSpA in the absence of SIJ involvement

• If the differential diagnosis includes spinal etiologies, consider AP and lateral X-rays of the lumbosacral spine for that specific purpose, that is, not to help with the diagnosis of AxSpA. If findings suggestive of AxSpA are present on spinal views, they will also be demonstrable on AP pelvis • If there is concern that the MRI may not be ordered correctly, performed correctly, or interpreted correctly, then it is reasonable to defer MRI ordering to the rheumatologist, particularly if that’s the rheumatologist’s preference • If there is clinical suspicion of sacroiliitis, degenerative changes on an AP-pelvic X-ray will not negate the need for additional imaging. AxSpA can coexist with degenerative changes, although this is less likely in younger patients

Serologic biomarkers Only a limited panel of serologic tests is indicated when AxSpA is suspected (Table 2.2): HLA-B27, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) can be helpful. HLA-B27 is considered the best genetic biomarker suggesting the diagnosis of AxSpA; C-reactive protein (CRP) is the best marker for assessing disease activity. Therefore, theoretically very few steps are necessary to diagnose AxSpA after determining the presence of IBP; but, several factors reflecting the disease, the patient, and/or the clinician may stymie, or even preclude, the diagnostic process. With more than 30% of adults reporting low-back pain within the preceding 3 months—with symptoms typically nonspecific and self-limiting—the low-frequency presentation of AxSpA features is often not recognized by PCPs.6 Stigmatization of chronic low-back pain is often cited as a factor detracting from identification of patients with AxSpA. Such discrimination, often perpetuated by both clinicians and nonclinicians, historically stems from the doubting of low-back-pain sufferers’ symptomatic legitimacy and credibility, often coupled with clinicians’ perception of patients as seeking a secondary gain (eg, related to disability, litigation, or drug misuse). Counter to the patient’s interests, stigmatization may be further compounded by the clinician’s diagnostic uncertainty and need for pathology-driven diagnostic validation.7,8 Several patient characteristics may also erroneously diminish the clinician’s level of concern: young age at presentation and/or symptom onset; symptoms being mild to moderate at presentation and/or slowly progressing per history: symptomatic fluctuation; employmentrelated factors; and, gender-specific presentations. For example, widespread pain, which is more

VIDEO 2: The Role of the PCP in Diagnosing Axial Spondyloarthritis  Lianne Gensler, MD 12

common in women, almost doubles the delay in diagnosis, even if no gender-attributable differences in disease activity or physical function over time are found.9-13 PCPs can hit the reset button for this historically short-changed condition and get a new start on referring more well-screened patients to rheumatology specialists within a clinically advantageous time frame. This entails having an unbiased approach to back-pain symptoms, a high degree of suspicion of nonmechanical back pain and AxSpA, and ordering targeted diagnostic evaluations as guided by the differential diagnosis.14

References 1. 2. 3.

4. 5. 6. 7. 8. 9. 10.

11. 12. 13. 14.

Deodhar A, Mease PJ, Reveille JD, et al. Frequency of axial spondyloarthritis diagnosis among patients seen by US rheumatologists for evaluation of chronic back pain. Arthritis Rheumatol. 2016;68(7):1669-1676. Walker BF, Williamson OD. Mechanical or inflammatory low back pain. What are the potential signs and symptoms? Man Ther. 2009;14(3):314-320. Sieper J, van der Heijde D, Landewe R, et al. New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS). Ann Rheum Dis. 2009;68(6):784-788. Lambert RG, Bakker PA, van der Heijde D, et al. Defining active sacroiliitis on MRI for classification of axial spondyloarthritis: update by the ASAS MRI working group. Ann Rheum Dis. 2016;75(11):1958-1963. Deodhar A, Mittal M, Reilly P, et al. Ankylosing spondylitis diagnosis in US patients with back pain: identifying providers involved and factors associated with rheumatology referral delay. Clin Rheumatol. 2016;35(7):1769-1776. Keat A, Bennett AN, Gaffney K, Marzo-Ortega H, Sengupta R, Everiss T. Should axial spondyloarthritis without radiographic changes be treated with anti-TNF agents? Rheumatology Int. 2017;37(3):327-336. Holloway I, Sofaer-Bennett B, Walker J. The stigmatisation of people with chronic back pain. Disabil Rehabil. 2007;29(18): 1456-1464. Slade SC, Molloy E, Keating JL. Stigma experienced by people with nonspecific chronic low back pain: a qualitative study. Pain Med. 2009;10(1):143-154. Boonen A, Sieper J, van der Heijde D, et al. The burden of non-radiographic axial spondyloarthritis. Semin Arthritis Rheum. 2015;44(5):556-562. Bandinelli F, Salvadorini G, Delle Sedie A, Riente L, Bombardieri S, Matucci-Cerinic M. Impact of gender, work, and clinical presentation on diagnostic delay in Italian patients with primary ankylosing spondylitis. Clin Rheumatol. 2016;35(2): 473-478. Slobodin G, Reyhan I, Avshovich N, et al. Recently diagnosed axial spondyloarthritis: gender differences and factors related to delay in diagnosis. Clin Rheumatol. 2011;30(8):1075-1080. Ramiro S, Landewe R, van Tubergen A, et al. Lifestyle factors may modify the effect of disease activity on radiographic progression in patients with ankylosing spondylitis: a longitudinal analysis. RMD Open. 2015;1(1):e000153. Webers C, Essers I, Ramiro S, et al. Gender-attributable differences in outcome of ankylosing spondylitis: long-term results from the Outcome in Ankylosing Spondylitis International Study. Rheumatology (Oxford). 2016;55(3):419-428. Taurog JD, et al. Ankylosing spondylitis and axial spondyloarthritis. N Engl J Med. 2016;374:2563-2574.

Treatment of AxSpA: What Does the PCP Need to Know?

Understanding the AxSpA Treatment Continuum The composite goal of treating the patient with AxSpA is to optimize control of symptoms and inflammation, prevent progressive structural damage, preserve function, and normalize psychosocial well-being and quality of life.1 PCPs will likely not be involved in prescribing therapies beyond initial treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). However, it is beneficial for frontline providers to understand the AxSpA treatment continuum, as they may play a significant role in longitudinal patient support and/or serve in a secondary capacity for clinical-course monitoring. NSAIDs—indicated as initial treatment of AxSpA—provide a high degree of initial symptom reduction, but typically only marginal benefit as the disease progresses. Consequently, TNF inhibitors, the first approved class of biologic therapies, became the “cornerstone” of therapy for AxSpA over the last decade, having demonstrated efficacy in decreasing disease activity and improving functional outcomes in patients receiving inadequate benefit from NSAIDs. TNF inhibitors commonly prescribed for AS include etanercept, infliximab, adalimumab, golimumab, and certolizumab. Response to TNF inhibitors is similar between nrAxSpA and AS patients, although TNF inhibitors have not been approved for nr-AxSpA patients.2 New insights into pathophysiologic mechanisms linked to the IL-17 cytokine pathways are relevant to AxSpA and have provided novel therapeutic targets. Like TNF inhibitors, anti–IL-17 agents may impact both inflammation and new bone formation/remodeling; however, further studies are needed.3,4 Secukinumab, an IL-17A inhibitor, is the first non–anti-TNF biologic approved (January 2016) for the treatment of AS and psoriatic arthritis.4-8 Secukinumab remains under investigation for treatment of nonradiographic AxSpA.9 Rituximab, a non–TNF-inhibitor biologic targeting B cells, and tofacitinib, a synthetic small-molecule Janus kinase inhibitor, have also been under investigation for their potential in treatment of AxSpA.10,11 Going forward, with as many as 30% to 40% of AxSpA patients having inadequate/poor response or intolerance

to TNF inhibitors, IL-17 inhibitors and other emerging biologics and small molecules may play an expanding role in the management of AxSpA.4 The benefits of early targeted intervention are further promoted by treat-to-target disease-management strategies. These strategies define composite measures of disease activity, employ longitudinal monitoring of such measures, and provide recommendations for adjusting therapy accordingly, thereby improving clinical outcomes.12

The PCP’s Roles in Treating AxSpA Prompt and accurate diagnosis and referral for targeted therapy is associated with improved functional outcomes and quality of life.13 Additionally, data support a window of opportunity for early biologic treatment. This is associated with less radiographic progression over time.14 First-line treatment with NSAIDs can and should be provided by PCPs. Patients respond very well to full-dose NSAIDs in the setting of active disease. An NSAID that can be used variable times per day at prescription strength should be initiated for patients with newly diagnosed active AxSpA. The patient should be reevaluated at 2–4 weeks. When patients do not respond to 2 NSAIDs as first-line therapy or are intolerant, they often need escalation of treatment to biologic agents—the only other approved therapies for AS— and this should typically be performed by a rheumatologist.2 However,

VIDEO 3: The Role of the PCP in Treating Axial Spondyloarthritis  Lianne Gensler, MD

rheumatology referral is indicated even for patients who obtain adequate symptom control with NSAIDs. That is, beyond timely initiation of a biologic agent, all AxSpA patients should have the full benefit of a rheumatologist’s expertise in disease counseling and prognostication and assessment of extra-articular manifestations and comorbidities.13 Nonetheless, the PCP remains very important in the ongoing comanagement of the patient with AxSpA. This is especially true when patients on biologic therapy present to the frontline PCP with a complication associated with the agent. As immunomodulatory drugs, TNF inhibitors and the IL-17 inhibitor secukinumab suppress the immune system, increasing risk of infection. TNF inhibitors are associated with upper respiratory infections, pneumonia, tuberculosis, and bacterial skin infections. They also place the patient at increased risk of fungal infections, including coccidiomycosis and histoplasmosis.15 IL-17 inhibition is associated with bacterial and candidal infections.16 The PCP is tasked with recognizing the association of the presenting symptoms with the biologic therapy and treating or referring the patient, as needed. Further, the PCP may be responsible for vigilantly maintaining the immunocompromised patient’s routine vaccination schedule.17 This underscores the need for PCPs to be familiar with the biologic therapies for AxSpA, even though they are not in the prescribing role.

References 1. 2.

3. 4. 5. 6. 7. 8. 9. 10. 11.

12.

13.

14.

van der Heijde D, Ramiro S, Landewe R, et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017;76(6):1113-1136. Ward MM, Deodhar A, Akl EA, et al. American College of Rheumatology/Spondylitis Association of America/ Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol. 2016;68(2):282-298. Raychaudhuri SP, Raychaudhuri SK. Mechanistic rationales for targeting interleukin-17A in spondyloarthritis. Arthritis Res Ther. 2017;19(1):51. Sieper J. New treatment targets for axial spondyloarthritis. Rheumatology (Oxford). 2016;55(suppl 2):ii38-ii42. Paine A, Ritchlin CT. Targeting the interleukin-23/17 axis in axial spondyloarthritis. Curr Opin Rheumatol. 2016;28(4): 359-367. Chen C, Zhang X, Xiao L, Zhang X, Ma X. Comparative effectiveness of biologic therapy regimens for ankylosing spondylitis: a systematic review and a network meta-analysis. Medicine (Baltimore). 2016;95(11):e3060. Lubrano E, Perrotta FM. Secukinumab for ankylosing spondylitis and psoriatic arthritis. Ther Clin Risk Manag. 2016;12:1587-1592. Maldonado-Ficco H, Perez-Alamino R, Maldonado-Cocco JA. Secukinumab: a promising therapeutic option in spondyloarthritis. Clin Rheumatol. 2016;35(9):2151-2161. clinicaltrials.gov. Study of Efficacy and Safety of Secukinumab in Patients With Non-radiographic Axial Spondyloarthritis. https://clinicaltrials.gov/ct2/show/NCT02696031. Peng J, Gong Y, Zhang Y, Wang D, Xiao Z. Immunohistological analysis of active sacroiliitis in patients with axial spondyloarthritis. Medicine (Baltimore). 2017;96(16):e6605. Sepriano A, Regel A, van der Heijde D, et al. Efficacy and safety of biological and targeted-synthetic DMARDs: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis. RMD Open. 2017;3(1):e000396. Smolen JS, Schöls M, Braun J, et al. Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force. Ann Rheum Dis. [Epub ahead of print July 6, 2017]. Garrido-Cumbrera M, Hillmann O, Mahapatra R, et al. Improving the management of psoriatic arthritis and axial spondyloarthritis: roundtable discussions with healthcare professionals and patients. Rheumatol Ther. [Epub ahead of print June 9, 2017]. Haroon N, Inman RD, Learch TJ, et al. The impact of tumor necrosis factor alpha inhibitors on radiographic progression in ankylosing spondylitis. Arthritis Rheum. 2013;65(10):2645-2654.

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Ali T, Kaitha S, Mahmood S, Ftesi A, Stone J, Bronze MS. Clinical use of anti-TNF therapy and increased risk of infections. Drug Healthc Patient Saf. 2013;5:79-99. Miossec P. Update on interleukin-17: a role in the pathogenesis of inflammatory arthritis and implication for clinical practice. RMD Open. 2017;3(1):e000284. Centers for Disease Control and Prevention. Altered Immunocompetence. https://www.cdc.gov/vaccines/hcp/acip-recs/ general-recs/immunocompetence.html. Accessed October 23, 2017.

The Patient’s Experience: Beyond Back Pain

The Biopsychosocial Burden of AxSpA The patient’s prediagnosis experience of AxSpA commonly goes beyond back pain, stiffness, and functional impairment. Having a disease of relatively early onset and, too commonly a delayed diagnosis, these patients may experience years of progressive symptomatology, inappropriate diagnostic procedures and/or treatments, psychological distress, and diminished quality of life. AxSpA is associated with a complex and compounding biopsychosocial burden comparable to that of rheumatoid arthritis, whether AxSpA is radiographically corroborated or not. Therefore, early diagnosis is critical.1 Through use of interpersonal methodologies that dig deeper into an individual’s perceptions, attitudes, and beliefs, qualitative research can provide insights into a patient’s disease experience.2,3 One such qualitative AxSpA study offers a critical cautionary perspective on the consequences of a delayed diagnosis.1 Participants described the common theme of having an “invisible” condition; their overall anger and frustration with health care professionals’ inability to recognize and diagnose their protracted physical complaints was central for many. Participants further described their own lack of knowledge and control as “distressing and disheartening.” Having to “fight for a diagnosis,” “feeling dismissed” and “stigmatized,” many patients experienced the psychological consequences of depression and anxiety, poor self-esteem, and diminished quality of life—findings that correlated with standardized quantitative measures.1,4,5 Many young adults who are impacted by AxSpA in their most productive years are challenged to meet physical demands and remain employed.6 As in many other chronic disease states, a cascade of limited career prospects, financial stressors, lifestyle diminishment, and marital/relationship strain is not uncommon in the clinical context of AxSpA. Many individuals report a feeling of “relief” upon eventual diagnosis of AxSpA, despite the new knowledge that they are facing a long-term, progressive disease course. For some, 18

understanding what they have been dealing with for years allows for improved functioning.1,7 These themes illuminate the importance of PCPs being prepared to actively seek out and address the health-related concerns and needs of people in the early stages of the AxSpA disease trajectory.1 PCPs are well known for their expertise in and commitment to the comprehensive biopsychosocial-care model. They are positioned on the frontline of backpain evaluation and—with increased awareness of AxSpA and its farreaching impact—can shorten the time frame between symptom onset and specialty referral.

How Can PCPs Prevent or Offset the Cumulative Adverse Impact on the Patient With AxSpA? Of foremost importance is the timely establishment of an accurate diagnosis through individualized, comprehensive assessment of the patient presenting with back pain of ≥3 months’ duration. The PCP’s use of “red flags” for the identification of inflammatory back pain should become routine, as should recognition of patterns consistent with SpA phenotypes.8,9 This sets the stage for the timely use of diagnostic imaging appropriate to the patient’s presentation and subsequent rheumatology referral. But, the PCP’s role does not end there: Several proactive steps on the part of the PCP can promote the patient’s general health, physical function and conditioning, and well-being. These include age/gender-appropriate health-maintenance activities; physical/occupational therapy referral 19

for evaluation, treatment, and education; serial inquiries regarding the disease’s psychosocial impact and consequences, with referral for further mental-health evaluation and services, as needed; referral for vocational evaluation, as needed; and maintenance of open communication with both the patient and the treating rheumatologist.10

Presenting a Forward-Looking Perspective to the Patient Who Has Had a Delayed Diagnosis of AxSpA Although these same proactive steps to promote general health, conditioning, and well-being apply to the patient who has incurred a significant delay in diagnosis of AxSpA, other communication skills and strategies may take precedence. The patient who is frustrated, possibly angry, and experiencing physical and/ or psychological distress may need acknowledgment of the fact that AxSpA is a disease that often is not recognized in young patients, thereby leading to delayed diagnosis. Or, a patient may need acknowledgment that the natural course of the disease has caused cumulative damage and psychosocial distress. Advising the rheumatologist of the patient’s delayed diagnosis—whether delayed by you and/or other serial providers—and communicating the patient’s VIDEO 4: Caring for the Patient Whose Diagnosis of heightened concerns may allow for a AxSpA Has Been Delayed  smoother transition to specialty care. Paul Nadler, MD

References 1. 2. 3. 4. 5.

7. 8.

Martindale J, Goodacre L. The journey to diagnosis in AS/axial SpA: the impact of delay. Musculoskeletal Care. 2014;12(4): 221-231. Englander M. The interview: data collection in descriptive phenomenological human scientific research. J Phenonomenol Psychol. 2012;43(1):13-35. Ritchie J, Lewis J, McNaughton Nicholls C, Ormston R. eds. Qualitative Research: A Guide for Social Science Students and Researchers. 2nd ed. Los Angeles, CA: SAGE Publications Inc.; 2013. Kilic G, Kilic E, Ozgocmen S. Relationship between psychiatric status, self-reported outcome measures, and clinical parameters in axial spondyloarthritis. Medicine (Baltimore). 2014;93(29):e337. Sieper J, Hu X, Black CM, Grootscholten K, van den Broek RW, Kachroo S. Systematic review of clinical, humanistic, and economic outcome comparisons between radiographic and non-radiographic axial spondyloarthritis. Semin Arthritis Rheum. 2017;46(6):746-753. van Hoeven L, Boonen AERCH, Hazes JMW, Weel AEAM. Work outcome in yet undiagnosed patients with non-radiographic axial spondyloarthritis and ankylosing spondylitis; results of a cross-sectional study among patients with chronic low back pain. Arthritis Res Ther. 2017;19(1):143. Ramonda R, Marchesoni A, Carletto A, et al. Patient-reported impact of spondyloarthritis on work disability and working life: the ATLANTIS survey. Arthritis Res Ther. 2016;18:78. Bratton RL. Assessment and management of acute low back pain. Am Family Physician. 1999;60:2299-2308.

10.

Sieper J, van der Heijde D, Landewe R, et al. New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis International Society (ASAS). Ann Rheum Dis. 2009;68(6):784-788. Garrido-Cumbrera M, Hillmann O, Mahapatra R, et al. Improving the management of psoriatic arthritis and axial spondyloarthritis: roundtable discussions with healthcare professionals and patients. Rheumatol Ther. [Epub ahead of print June 9, 2017].

Optimizing Referral Pathways and Relationships

Consultation Needs May Begin Before Formal Referral to the Rheumatologist PCPs carry a disproportionate responsibility for identifying IBP and arriving at the provisional diagnosis of AxSpA, given their frontline position in the evaluation of back-pain complaints. Not surprisingly, a majority of surveyed rheumatologists have reported that PCPs were the main referral source of patients with chronic back pain (≥3 months) that manifested before 45 years of age.1 This referral pattern nonetheless coexists with the well-documented underdiagnosis of this chronic, progressive disease for years following symptom onset. Optimizing referral pathways and the PCP-rheumatologist consultative/comanagement relationship will help achieve the goal of effectively treating patients with AxSpA within a clinically advantageous time frame.2 Although PCPs are tasked with referring patients to rheumatologists for diagnostic confirmation and targeted treatment of AxSpA, there may be need for bidirectional consultative pathways prior to formal referral. For example, the PCP may wish to consult the rheumatologist regarding selection of imaging modality and/or views for a specific patient’s presentation. On occasion, the PCP may want specialty confirmation that imaging was performed appropriately and that the findings were reported correctly. Moreover, the nonspecialist clinician may seek specialist validation of a provisional diagnosis of AxSpA. This may benefit the current patient and has the potential to increase the clinician’s self-confidence in diagnosing subsequent patients with suspected AxSpA. In some locales and health care systems, eConsult services (ie, remote, multimedia-enabled consultation) may fulfill these consultative needs. This is especially true when the rheumatologist is geographically remote from the PCP’s practice area; a preliminary eConsult may facilitate getting the patient “into the system.”3

Enhanced Disease Awareness and Easy-to-Use Referral Parameters Go Hand in Hand American College of Rheumatology and other specialty society recommendations for when a patient should be referred to a rheumatologist for suspected AxSpA can be helpful to the busy PCP. The most straightforward of these recommendations addresses the patient with chronic back pain who is young, or whose symptoms started before the age of 45 years, AND has 1 additional feature: inflammatory back pain, positive HLA-B27, or sacroiliitis on imaging (X-ray or MRI). Any of these features is sufficient to say that the patient should be evaluated further.3 However, the Assessment of SpondyloArthritis International Society recommendations (2015) provide additional parameters, any of which, if present, may constitute the 1 additional clinical feature: peripheral manifestations (arthritis, enthesitis, dactylitis); extra-articular manifestations (psoriasis, inflammatory bowel disease, uveitis); family history of spondyloarthritis; good response to NSAIDs; or, elevated acute phase reactant.4 The aim of the ASAS referral recommendations is to have all patients with AxSpA referred (high sensitivity); that is, to not miss any patients with disease. Although this referral strategy applies at the level of the PCP or other nonrheumatology clinician, rheumatologists can collaborate with referring clinicians to decide which referral parameters are of greatest relevance for both practices.5,6 However, ongoing research on referral parameters and practices points to targeted education of PCPs—covering epidemiology, history-taking, and physical examination—as being most critical to improving recognition and referral of patients suspected of having AxSpA.1,5-7 This may be more important than the selection and use of any particular referral model. A 2017 review

VIDEO 5: Reasons for Delayed Diagnosis and/or Referral from the PCP Perspective  Lianne Gensler, MD, and Paul Nadler, MD 23

of 13 referral models evaluated the strategies’ performance in terms of sensitivity, specificity, and positive likelihood ratio using diagnosis by a rheumatologist as an external standard. The potential of these 13 referral strategies was clearly shown, yet no referral strategy combined high sensitivity with high specificity.8 Ultimately, increasing awareness of AxSpA along with easy-to-apply referral parameters will increase the number of AxSpA referrals; conversely, an increasing percentage of AxSpA diagnoses among referred patients will reflect both raised disease recognition and appropriate use of referral parameters.2,8

The PCP Has an Essential Role in the AxSpA Patient’s Longitudinal Care PCP-rheumatologist collaboration and comanagement are essential across the longitudinal AxSpA treatment course. From general health maintenance and psychosocial and occupational support to management of comorbidities and recognition of treatment complications, the PCP has a critical role in the comprehensive care of the patient. A solid understanding of the natural disease course and comorbidities, recognition of the disease’s real and/or potential impact on quality of life and well-being, and appreciation for current and emerging biologics for the treatment of AxSpA— including potential adverse events—will provide the PCP with a proactive, frontline readiness to support their patients with AxSpA.9,10

References 1. 2. 3. 4. 5.

6. 7.

8. 9.

10.

van der Heijde D, Sieper J, Elewaut D, Deodhar A, Pangan AL, Dorr AP. Referral patterns, diagnosis, and disease management of patients with axial spondyloarthritis: results of an international survey. J Clin Rheum. 2014;20(8):411-417. Rudwaleit M, Sieper J. Referral strategies for early diagnosis of axial spondyloarthritis. Nat Rev Rheumatol. 2012;8(5): 262-268. Keely EJ, Archibald D, Tuot DS, Lochnan H, Liddy C. Unique educational opportunities for PCPs and specialists arising from electronic consultation services. Acad Med. 2017;92(1):45-51. Poddubnyy D, van Tubergen A, Landewe R, Sieper J, van der Heijde D. Development of an ASAS-endorsed recommendation for the early referral of patients with a suspicion of axial spondyloarthritis. Ann Rheum Dis. 2015;74(8):1483-1487. Poddubnyy D, van Tubergen A, Landewe R, Sieper J, van der Heijde D. Defining an optimal referral strategy for patients with a suspicion of axial spondyloarthritis: what is really important? Response to: 'Evaluating the ASAS recommendations for early referral of axial spondyloarthritis in patients with chronic low back pain; is one parameter present sufficient for primary care practice?' by van Hoeven et al. Ann Rheum Dis. 2015;74(12):e69. van Hoeven L, Vergouwe Y, de Buck PD, Luime JJ, Hazes JMW, Weel AE. External validation of a referral rule for axial spondyloarthritis in primary care patients with chronic low back pain. PLoS One. 2015;10(7):e0131963. van Onna M, Gorter S, Maiburg B, Waagenaar G, van Tubergen A. Education improves referral of patients suspected of having spondyloarthritis by general practitioners: a study with unannounced standardised patients in daily practice. RMD Open. 2015;1(1):e000152. Abawi O, van den Berg R, van der Heijde D, van Gaalen FA. Evaluation of multiple referral strategies for axial spondyloarthritis in the SPondyloArthritis Caught Early (SPACE) cohort. RMD Open. 2017;3(1):e000389. Garrido-Cumbrera M, Hillmann O, Mahapatra R, et al. Improving the management of psoriatic arthritis and axial spondyloarthritis: roundtable discussions with healthcare professionals and patients. Rheumatol Ther.   [Epub ahead of print June 9, 2017]. Lee K, Wright, SM, Wolfe L. The clinically excellent primary care physician: examples from the published literature. BMC Fam Pract. 2016;17(1):169.

Axial Spondyloarthritis Clinical Resource Centerâ&#x201E;¢

Clinical Recommendations and Tools 2016 Update of the ASAS-EULAR Management Recommendations for Axial Spondyloarthritis. van der Heijde D, et al. Ann Rheum Dis. 2017;76(6):978-991.

http://ard.bmj.com/content/76/6/978

American College of Rheumatology/Spondylitis Association of America/ Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Ward MM, et al. Arthritis Rheumatol. 2016;68(2):282-298.

https://www.rheumatology.org/Portals/0/Files/ Recommendations%20for%20the%20Treatment%20of%20Ankylosing%20Spondylitis.pdf

The SIMPLE (Screening for InflaMmatory Back Pain in the LowEr) Back Questionnaire. Canadian Research and Education (CaRE), 2012.

https://www.carearthritis.com/tools/tools_html.launch?toolid=1&refid=/patient.php%23tab1

Ankylosing Spondylitis Disease Activity Score (ASDAS; online calculator). Assessment of Spondyloarthritis International Society (ASAS).

http://www.asas-group.org/clinical-instruments/asdas_calculator/asdas.html

Patient-Education Resources Spondylitis Association of America, 2017. The Spondylitis Association of America (SAA) is a nonprofit organization founded in 1983 to address the needs of people living with spondylitis. This site includes an inflammatory back pain quiz, disease education, and links to numerous patient-support resources. https://www.spondylitis.org

American College of Rheumatology, 2013. This patient-oriented site addresses frequently asked questions regarding spondyloarthritis. https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Spondyloarthritis

Arthritis Foundation. This site provides a succinct overview of spondyloarthritis causes, symptoms, diagnosis, â&#x20AC;¨ treatment, and self-care. http://www.arthritis.org/about-arthritis/types/spondyloarthritis/

Suggested Reading Ankylosing spondylitis diagnosis in US patients with back pain: Identifying providers involved and factors associated with rheumatology referral delay. Deodhar A, et al. Clin Rheumatol. 2016;35(7):1769-1776.

https://link.springer.com/content/pdf/10.1007%2Fs10067-016-3231-z.pdf

Evaluation of multiple referral strategies for axial spondyloarthritis in the SPondyloArthritis Caught Early (SPACE) cohort. Abawi O, et al. RMD Open. 2017;3(1):e000389.

http://rmdopen.bmj.com/content/rmdopen/3/1/e000389.full.pdf

Gender-attributable differences in outcome of ankylosing spondylitis: Long-term results from the Outcome in Ankylosing Spondylitis International Study. Webers C, et al. Rheumatology (Oxford). 2016;55(3):419-428.

https://academic.oup.com/rheumatology/article-lookup/doi/10.1093/rheumatology/kev340

Improving the management of psoriatic arthritis and axial spondyloarthritis: roundtable discussions with healthcare professionals and patients. Garrido-Cumbrera M, et al. Rheumatol Ther. [Epub ahead of print June 9, 2017].

https://link.springer.com/content/pdf/10.1007%2Fs40744-017-0066-2.pdf

Is the current ASAS expert definition of a positive family history useful in identifying axial spondyloarthritis? Results from the SPACE and DESIR cohorts. Ez-Zaitouni Z, et al. Arthritis Res Ther. 2017;19(1):118.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452625/pdf/13075_2017_Article_1335.pdf

MRI evidence of structural changes in the sacroiliac joints of patients with nonradiographic axial spondyloarthritis even in the absence of MRI inflammation. Maksymowych WP, et al. Arthritis Res Ther. 2017;19(1):126.

https://arthritis-research.biomedcentral.com/track/pdf/10.1186/s13075-017-1342-9?site=arthritisresearch.biomedcentral.com

Patient-reported impact of spondyloarthritis on work disability and working life: the ATLANTIS survey. Ramonda R, et al. Arthritis Res Ther. 2016;18:78.

https://arthritis-research.biomedcentral.com/track/pdf/10.1186/s13075-016-0977-2?site=arthritisresearch.biomedcentral.com

The journey to diagnosis in AS/Axial SpA: the impact of delay. Martindale J, Goodacre L. Musculoskeletal Care. 2014;12(4):221-231.

http://onlinelibrary.wiley.com/doi/10.1002/msc.1080/epdf?r3_referer=wol

The prevalence and clinical characteristics of nonradiographic axial spondyloarthritis among patients with inflammatory back pain in rheumatology practices: A multinational, multicenter study. Burgos-Varga R, et al. Arthritis Res Ther. 2016;18:132.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896040/pdf/13075_2016_Article_1027.pdf

Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force. Smolen JS, et al. Ann Rheum Dis. [Epub ahead of print July 6, 2017].

http://ard.bmj.com/content/annrheumdis/early/2017/07/06/annrheumdis-2017-211734.full.pdf

CME Posttest To receive CME credit, participants should direct their Web browsers to http://www.ExchangeCME.com/ 2017eHealthAxSpA. Participants will have two attempts to obtain a passing grade of 70% on the posttest and be eligible to obtain CME credit .