Maybe It’s NOT Mechanical Back Pain by Integritas Communications

FACULTY Marina Magrey, MD

Division Chief, Rheumatology University Hospitals (UH) Cleveland Medical Center Professor Case Western Reserve University (CWRU) School of Medicine Cleveland, Ohio Dr. Marina Magrey is Division Chief of Rheumatology at UH Cleveland Medical Center and a Professor at CWRU School of Medicine. After she received her medical degree from the University of Kashmir, India, Dr. Magrey completed an internal medicine residency and fellowship in rheumatology at the Cleveland Clinic. Dr. Magrey’s scholarship focuses on the management of AxSpA, psoriatic arthritis, and metabolic bone disease to improve outcomes in patients. Driven by her passion for providing high-quality, evidence-based care with cost containment, she developed a disease-speci ic clinic for spondyloarthritis in a prior role at The MetroHealth System in Cleveland, Ohio. Nationally, Dr. Magrey is considered a thought leader in spondyloarthritis. She serves on the Board of Spondyloarthritis Research and Treatment Network (SPARTAN). Dr. Magrey is an invited member of both the Assessment in Spondyloarthritis International Society (ASAS) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), which are study groups comprised of international experts in spondyloarthritis. Dr. Magrey is co-chair of the American College of Rheumatology (ACR) subcommittee for abstracts in AxSpA, also serving on the ACR guideline subcommittee to develop guidelines for the treatment of psoriatic arthritis and glucocorticoid-induced osteoporosis.

Dr. Magrey is involved in clinical and translational research for biomarkers in spondyloarthritis and participates in clinical trials for spondyloarthritis treatment. She has served as principal investigator of multiple National Institutes of Health grants and international collaborative projects and has 44 publications in various peer-reviewed journals. Dr. Magrey serves as a consultant in spondyloarthritis clinical research to the pharmaceutical industry. She is also a consultant for the rational design of randomized controlled spondyloarthritis treatment trials, analysis

of the results of such trials and the presentation of novel products for approval to the US Food and Drug Administration. Additionally, Dr. Magrey enjoys teaching. She served as the rheumatology fellowship training director at MetroHealth Medical Center. Presently, she serves on the education committee of SPARTAN and on the steering committee of the Medscape spondyloarthritis section. She is also a board member of the Cleveland Society of Rheumatology.

Dr. Magrey has earned several honors and is consistently rated as one of the best rheumatologists in the country. Along with being a respected clinician and researcher, Dr. Magrey strongly believes in giving back to her community. She started the Salam Free Clinic, the irst free clinic of its kind in the historically disadvantaged Hough neighborhood of Cleveland, Ohio. Beyond her work, Marina loves her family, especially her two sons. In her free time, she likes to go on walks, follow the news, and watch the latest shows on Net lix.

Shireesh Bhalerao, MCR, DC Chiropractic Physician & Owner Equilibrium, LLC Associate Professor and Chair Department of Chiropractic Sciences University of Western States (UWS) Founder, Tulip Seminars Portland, Oregon Adjunct Assistant Professor Department of Physical Therapy University of Pittsburgh Pittsburgh, Pennsylvania

Dr. Shireesh Bhalerao was born in Saskatoon, Saskatchewan, and graduated from Western States Chiropractic College (now UWS) in Portland, Oregon, in 2000. In 2013, Dr. Bhalerao was awarded a master’s in clinical research at Oregon Health & Science University (OHSU) in Portland. While opening and maintaining Equilibrium, LLC with his wife, Dr. Bhalerao became an Associate Professor and Chair of the Department of Chiropractic Sciences at UWS. His teaching expertise is in the realms of spinal and extraspinal diagnosis and management and evidence-based practice (EBP). He is an Adjunct Assistant Professor in the Department of Physical Therapy at the University of Pittsburgh in Pittsburgh, Pennsylvania. He is also currently co-authoring a new edition of the textbook Chiropractic Technique: Principles and Procedures with Dr. Stephen Perle. Dr. Bhalerao is passionate about further integrating the chiropractic ield with mainstream medicine and has created a research collaboration between several Portland chiropractic clinics and the OHSU Department of Rheumatology. Focused on improving patient outcomes, Dr. Bhalerao created Tulip Seminars, LLC to provide small-group, hands-on, evidence-based CE from experienced and EBPsavvy clinicians. Tulip Seminars raises the CE bar so that chiropractors and other manual therapists can immediately TUrn what they Learn Into Practice (TULIP).

In his spare time, Dr. Bhalerao enjoys spending time cooking, gardening, and birdwatching with his wife and playing golf with his son.

Charis Hill

Disability Advocate Rheumatology Professional Patient with AxSpA Sacramento, California

Charis Hill (they/them) is a disability advocate, rheumatology professional, and patient with spondylitis working to make spondyloarthritis a household name. They serve on committees for the Spondylitis Association of America, CreakyJoints/ Global Healthy Living Foundation, and the National Pain Advocacy Center. Charis has been instrumental in translating spondyloarthritis disease treatment guidelines into plain language; designing and conducting patient-centered rheumatological research; forming international criteria for disease treatment outcomes; and creating medical research guidelines. Charis’ work and story have been featured in dozens of publications and media outlets, including Arthritis Today magazine, Mother Jones, the Associated Press, and in the documentary ilm Becoming Incurable. They graduated from Meredith College in 2009 with a BA in Sociology.

Angelo Papachristos, BSc PT, MBA Advance Practice Physiotherapist Unity Health Toronto – St. Michael’s Hospital Clinical Lecturer University of Toronto Toronto, Ontario

Angelo Papachristos graduated from the University of Toronto in 1994 with a Bachelor of Science degree and went on to complete a physical therapy degree in 1998. In 2006, he completed the Advanced Clinician Practitioner in Arthritis Care Program (ACPAC). Finally, he completed his Master of Business Administration at Schulich School of Business in North York, Ontario, in 2007. Mr. Papachristos has been employed by Unity Health Toronto – St. Michael’s Hospital in outpatient orthopedics and rheumatology since 1998 and has worked as the advance practice physiotherapist since 2005. He has a special clinical interest in early in lammatory arthritis, ankylosing spondylitis, and osteoarthritis. He also has an interest in providing patient, student, and postgraduate clinician education.

Mr. Papachristos is a member of the Ontario Rheumatology Association Model of Care Committee, which is working to develop comprehensive strategies to improve access to care (including to allied health care providers) and delivery models for patients with in lammatory arthritis.

Ben Smith, DMSc, PA-C, DFAAPA Associate Director, Assistant Professor School of Physician Assistant Practice Florida State University College of Medicine Tallahassee, Florida Rheumatology PA McIntosh Clinic, P.C. Thomasville, Georgia

Dr. Ben Smith is the Associate Director and an Assistant Professor for the School of Physician Assistant Practice at Florida State University College of Medicine. In 1997, he received a Bachelor of Science in Biology (cum laude) from the University of Georgia in Athens, Georgia, and his PA degree (summa cum laude) in 1999 from the Medical College of Georgia in Augusta, Georgia.

Dr. Smith’s professional memberships include being a distinguished fellow and member of the American Academy of Physician Assistants (AAPA) and a member of the Association of Rheumatology Professionals (ARP), Georgia Association of Physician Assistants (GAPA), Florida Academy of Physician Assistants (FAPA), and the Georgia Society of Rheumatology (GSR).

PREAMBLE Target Audience The educational design of this activity addresses the needs of primary care providers (PCPs), including family and internal medicine physicians, nurse practitioners (NPs), and physician assistants (PAs), as well as physiatrists, physical therapists (PTs), chiropractors, orthopedists, and pain medicine specialists.

Statement of Need/Program Overview This multimedia program is intended to provide continuing medical education/ continuing education (CME/CE) to the diverse group of clinicians who are well positioned to identify and refer patients with axial spondyloarthritis (AxSpA). The proposed multifaceted initiative will provide critical education to improve awareness of AxSpA and knowledge of its presentation, natural history, and impact, with the aim of improving early identi ication and referral of all patients with diagnosed or suspected AxSpA for specialist evaluation and treatment.

Educational Objectives After completing this activity, the participant should be better able to: • Identify patients with in lammatory back pain and correlate clinical indings with AxSpA historical features, manifestations, and comorbidities • Select guideline-recommended imaging modalities for provisional diagnosis of AxSpA • Provide early referral of patients with diagnosed or clinically suspected AxSpA to rheumatologists for diagnostic con irmation and targeted treatment of AxSpA • Discuss the psychosocial and occupational impacts of AxSpA

• Participate in interprofessional communication and collaboration to optimize patient care

Joint Accreditation Statement In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine (PIM) and Integritas Communications. PIM is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Credit Designation Physician Continuing Medical Education PIM designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Continuing Nursing Education The maximum number of hours awarded for this Continuing Nursing Education activity is 1.25 contact hours. Designated for 0.5 contact hours of pharmacotherapy credit for Advance Practice Registered Nurses.

Interprofessional Continuing Education This activity was planned by and for the healthcare team, and learners will receive 1.25 Interprofessional Continuing Education (IPCE) credits for learning and change.

Continuing Physician Assistant Education

Postgraduate Institute for Medicine has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for 1.25 AAPA Category 1 CME credits. Approval is valid until December 15, 2022. PAs should only claim credit commensurate with the extent of their participation.

In order to receive credit for this activity, the participant must complete the preactivity questionnaire, score 75% or better on the posttest, and complete the program evaluation.

Disclosure of Con licts of Interest PIM adheres to the policies and guidelines, including the Standards for Integrity and Independence in Accredited CE, set forth to providers by the Accreditation Council for Continuing Medical Education (ACCME) and all other professional organizations, as applicable, stating those activities where continuing education credits are awarded must be balanced, independent, objective, and scienti ically rigorous. All persons in a position to control the content of an accredited continuing education program provided by PIM are required to disclose all inancial relationships with any ineligible company within the past 24 months to PIM. All inancial relationships reported are identi ied as relevant and mitigated by PIM in accordance with the Standards for Integrity and Independence in Accredited CE in advance of delivery of the activity to learners. The content of this activity was vetted by PIM to assure objectivity and that the activity is free of commercial bias. The faculty have the following relevant inancial relationships with ineligible companies: Marina Magrey, MD Consulting Fees: AbbVie, Bristol Myers Squibb, Eli Lilly and Company, Janssen Pharmaceuticals, Novartis International AG, P izer, Inc., UCB S.A. Contracted Research: AbbVie, UCB S.A. Shireesh Bhalerao, MCR, DC Nothing to disclose Charis Hill Consulting Fees: GlaxoSmithKline plc., Janssen Pharmaceuticals, Salix Pharmaceuticals, Inc. Angelo Papachristos, BSc PT, MBA Consulting Fees: AbbVie, F. Ho mann-La Roche Ltd

Ben Smith, DMSc, PA-C, DFAAPA Nothing to disclose

Instructions to Receive Credit

PIM and Integritas planners and managers have no relevant inancial relationships with ineligible companies.

Disclosure of Unlabeled Use This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity 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 the planners. Please refer to the o icial 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 or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/ or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

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

CME Questions – PIM Contact Information For information about the accreditation of this program, please contact PIM via email at inquiries@pimed.com or at http://www.pimed.com/.

Integritas Contact Information

For all other questions regarding this monograph, please contact Integritas via email at info@exchangecme.com.

CHAPTER 1

FOUNDATIONS IN AXIAL SPONDYLOARTHRITIS Introduction

ack pain is an extremely common clinical problem. Its association with occupational and recreational activities is well known, as are its increased frequency related to the degenerative changes of normal aging and acute occurrence without attributable cause in the course of day-to-day life. With an average point prevalence of 30%, low back pain presentations are extremely commonplace.1 Frontline providers — especially primary care clinicians and chiropractors — often serve as “back pain gatekeepers” through their use of a habitual approach that may overlook or discount “outlier” presentations. This can result in failure to initiate further, warranted, diagnostic procedures or clinical interventions. The diagnostic pitfalls and opportunities inherent to all health care disciplines calls for elevated degrees of “educated suspicion” for higherrisk constellations of signs and symptoms. In the context of back pain, such clinical vigilance is needed to di erentiate mechanical and in lammatory back pain.2 Recognition of in lammatory back pain is the irst step in getting on the fast track to identifying axial spondyloarthritis (AxSpA), an in lammatory rheumatic disease primarily a ecting the sacroiliac joints (sacroiliitis) and spine (spondylitis). Historically, delays in diagnosis of AxSpA of 14 years or more have occurred, allowing progressive joint damage and disease sequelae to ensue.3

Di erentiating Mechanical and In lammatory Back Pain

Mechanical back pain (MBP), arising from the intrinsic structures of the spine and its surrounding supportive tissues, presents with variable rapidity of onset, duration, intensity, and tendency toward recurrence. MBP may or may not have a speci ic cause identi ied by the patient. Radicular nerve pain and/or paresthesia may be present. A hallmark of MBP is worsening with activity and improvement with rest and — for many but not all individuals — resolution without intervention. Nonpharmacologic, pharmacologic, and surgical therapies have roles in the

treatment of MBP, but evidence for the overall e icacy of any particular intervention may be limited.4 In lammatory back pain (IBP) is more speci ically de ined (Table 1): age at onset is typically younger than 45 years, onset is insidious, and symptoms are present for more than 3 months. In contrast to MBP, IBP-related symptoms improve with exercise and do not improve with rest or inactivity. IBP is commonly worse at night and often followed by morning sti ness of >30 minutes. Radicular nerve pain and paresthesia are not present.2

From IBP to Recognition of Axial Spondyloarthritis

Di erentiating IBP features from high-prevalence MBP presentations is the irst step in the identi ication of AxSpA. As of 2021, the estimated US population prevalence of AxSpA was 0.85%–1.4% (non-Medicare proprietary database; 2.12%–3.60%, Medicare database) with an overall 1.6:1 male-to-female ratio.5,6 Clinically, AxSpA manifests as progressive pain and sti ness and, in more severe cases, eventual limitation of mobility due to in lammation and spinal fusion (ankylosis). Additionally, AxSpA is variably associated with peripheral arthritis and other, extra-articular, manifestations. The progressive course of joint damage, irreversible loss of spinal mobility, and functional impairment associated with AxSpA is frequently accompanied by signi icant psychosocial burdens and detriments to quality of life. These deleterious outcomes are often exacerbated by delayed diagnosis.7

In addition to AxSpA, there are several other spondyloarthritis phenotypes, including those with both axial and peripheral joint involvement (Figure 1.1). Sharing genetic, immunologic, and clinical features, the spondyloarthritis phenotypes are di erentiated beyond joint distribution by the patient’s clinical history, extra-articular manifestations, and comorbidities, in conjunction with the selective use of diagnostic modalities.8

Clinicians’ recognition of AxSpA will be enhanced by their attunement to common nonarticular AxSpA manifestations, as shown in Figure 1.2. Symptom patterns may be critical keys to AxSpA diagnosis; for example, the presence of IBP plus in lammatory eye complaints or the co-occurrence of IBP and symptoms consistent with in lammatory bowel disease. Specialists’ evaluation of nonarticular manifestations may uncover previously unrecognized AxSpA.

AxSpA presentations may be further complicated by the presence of medical comorbidities, some of the most common of which are cardiovascular disease, chronic pulmonary disorders, and depression. Overall comorbidity burden is associated with higher levels of AxSpA disease activity and functional impairment, as well as increased mortality.9,10

The Natural History of AxSpA Underlying AxSpA’s overt continuum of clinical manifestations is the broader natural history of the disease state, as conceptualized in Figure 1.3. Subclinical processes not only precede clinical manifestations of IBP, but clinical onset may be followed by periods of quiescence, emphasizing the critical importance of recognizing overt disease features as early as possible.11 Disease occurrence and progression in the absence of radiographic or other imaging indings — nonradiographic (nr-) AxSpA — is not uncommon and its clinical signi icance is equivalent to that of radiographic AxSpA, as will be discussed in Chapter 2.

It should be noted that the nomenclature surrounding AxSpA has evolved over time. Currently, the term AxSpA encompasses both nonradiographic and radiographic disease, with the latter also referred to as ankylosing spondylitis (AS).

An Overview of AxSpA Genetics and Heritability The spondyloarthritis variants are both clinically and genetically heterogeneous. Genome-wide association studies have brought to light hundreds of genes associated with these conditions. Genetic studies of human leukocyte antigen B27 (HLA-B27) — the presence of which has historically been considered a major risk factor for AxSpA — have now provided a more nuanced understanding of the risk this allele carries for spondyloarthritis phenotypes and their common comorbidities. For example, HLA-B27 is an even greater risk factor for acute anterior uveitis than it is for AxSpA.12 Clinically, a positive family history for AxSpA or acute anterior uveitis (as correlates of HLA-B27–associated relative risk) may help identify AxSpA in the patient whose presentation is consistent with IBP, while a family history of in lammatory bowel disease or psoriasis is less supportive of an AxSpA diagnosis.13

Practice Tips13 • Only one-third of patients suspected of having AxSpA have a positive family history. • A positive family history for AxSpA is not associated with an AxSpA diagnosis independently of HLA-B27 positivity.

Understanding AxSpA Pathogenesis and Pathophysiology

Our understanding of the pathogenesis of AxSpA remains incomplete. It appears to be multifactorial, re lecting genetic susceptibilities, innate and acquired immune

Two critical pathways are thought to be responsible for initiating (activation or enhancement) and maintaining the in lammatory processes: the tumor necrosis factor and interleukin-17 in lammatory pathways. Biologic agents that target these pathways successfully suppress clinical signs and symptoms of AxSpA, as will be discussed in Chapter 4.14

Choose Your Path

VIDEO 2: The ChiropractorModeled IBP/AxSpA-Focused Patient Interview

VIDEO 1: The PCP-Modeled IBP/AxSpA-Focused Patient Interview

responses, and exogenous factors, all contributing to ongoing damage and repair processes. A primary immunologically driven pathologic process includes subchondral bone in lammation in the areas where tendons and ligaments bind to ibrocartilage and bone (entheses). Subchondral pannus formation (vascular/ in lammatory granulation tissue) is the most signi icant manifestation of early sacroiliitis; its invasion is central to the pathologic degeneration of the cartilage. Subsequent pathophysiologic stages ultimately e ect subchondral bone disruption, osteoclast activation, and pathologic new bone formation at these sites. Triggers are known to include biomechanical stresses a ecting the entheses. Infectious signals originating from bacteria within the gut microbiome may also play a role.14-16

To request copies of the tool, email: info@exchangecme.com For a video demonstration of the tool, go to: ExchangeCME.com/AxSpAEesources

References 1. Andersson GBJ. Epidemiological features of chronic low-back pain. Lancet. 1999;354(9178):581-585. 2. Magrey MN, et al. Recognizing axial spondyloarthri s: a guide for primary care. Mayo Clin Proc. 2020;95(11):2499-2508. 3. Danve A, Deodhar A. Axial spondyloarthri s in the USA: diagnos c challenges and missed opportuni es. Clin Rheumatol. 2019;38(3):625-634. 4. Will JS, et al. Mechanical low back pain. Am Fam Physician. 2018;98(7):421-428. 5. Cur s JR, et al. The annual diagnos c prevalence of ankylosing spondyli s and axial spondyloarthri s in the United States using Medicare and Marketscan databases. ACR Open Rheumatology. h ps://onlinelibrary.wiley.com/doi/abs/ 10.1002/acr2.11316. Accessed October 30, 2021. 6. Mease PJ, et al. Comparison of men and women with axial spondyloarthri s in the US-based Corrona Psoria c Arthri s/Spondyloarthri s Registry. J Rheumatol. 2021;48(10):1528-1536. 7. Mar ndale J, Goodacre L. The journey to diagnosis in AS/AxSpA: the impact of delay. Musculoskeletal Care. 2014;12(4):221-231. 8. Pro F, Poddubnyy D. Ankylosing spondyli s and axial spondyloarthri s: recent insights and impact of new classi ca on criteria. Ther Adv Musculoskelet Dis. 2018;10(5-6):129-139. 9. Redeker I, et al. The prevalence and impact of comorbidi es on pa ents with axial spondyloarthri s: results from a na onwide popula on-based study. Arthri s Res Ther. 2020;22(1):210. 10. Zhao SS, et al. Prevalence and impact of comorbidi es in axial spondyloarthri s: systema c review and metaanalysis. Rheumatology (Oxford). 2020;59(suppl 4):iv47-iv57. 11. Deodhar A. Rheumatologists make progress de ning spectrum of axial spondyloarthri s. The Rheumatologist. h ps://www.the-rheumatologist.org/ar cle/rheumatologists-make-progress-de ning-spectrum-of-axialspondyloarthri s/3/. Accessed October 30, 2021. 12. Brown MA, et al. Gene cs and the axial spondyloarthri s spectrum. Rheumatology (Oxford). 2020;59(suppl 4):iv58iv66. 13. van Lunteren M, et al. Is a posi ve family history of spondyloarthri s relevant for diagnosing axial spondyloarthri s once HLA-B27 status is known? Rheumatology. 2019;58(9):1649-1654.

14. Furst DE, Louie JS. Targe ng in ammatory pathways in axial spondyloarthri s. Arthri s Res Ther. 2019;21(1):135.

15. So J, Tam LS. Gut microbiome and its interac on with immune system in spondyloarthri s. Microorganisms. 2020;8(11):1727.

16. Wang DM, et al. Pannus in amma on in sacroilii s following immune pathological injury and radiological structural damage: a study of 193 pa ents with spondyloarthri s. Arthri s Res Ther. 2018;20(1):120.

CHAPTER 2

ZEROING IN ON AxSpA Introduction: From Clinical Suspicion to Prompt Action

istorical trends clearly demonstrate that axial spondyloarthritis (AxSpA) is an elusive disease process. With average delays in diagnosis of 5–10 years cited in 2020 — down from previous reports of more than 14 years’ delay — the natural course of the disease may progress to an alarming degree before AxSpA is de initively identi ied and treated.1-4 Delays may occur at any point in the clinical continuum: di erentiation of in lammatory back pain (IBP) from mechanical back pain (MBP), suspicion of AxSpA, diagnostic con irmation of AxSpA, rheumatology referral, or treatment initiation. Primary care clinicians are aware of delays in AxSpA recognition and initiation of intervention, often attributing them to diverse, multifactorial causes, as shown in Table 2.1. Valid reasons in the mind and experience of these clinicians, such delays can and should be placed in the past.3 The well-known, often devastating, impact of delayed “action” on the patient will be discussed in Chapter 5: Understanding the Patient’s Perspective and Experience of AxSpA.

Your history-taking skills, as modeled in the Chapter 1 videos, may bring you to a point of strong clinical suspicion for the presence of AxSpA. Coupled with your physical exam skills and a targeted diagnostic work-up, your informed clinical impression will now set the stage for prompt referral of your patient to a rheumatology care provider.

It should be noted that there are no diagnostic criteria for AxSpA. Although classi ication criteria exist that de ine spondyloarthritis subtypes (eg, 2009 Assessment of SpondyloArthritis International Society classi ication criteria for AxSpA), these are intended for research purposes only. Further understanding of AxSpA through emerging imaging strategies and genetic biomarkers may eventually provide practice-friendly diagnostic criteria.5

The Physical Examination The physical exam may or may not contribute signi icantly to early recognition of AxSpA. In fact, the absence of speci ic physical indings — especially in early disease — is cited as a factor in delayed diagnosis.4 Nonetheless, the informed clinician will pursue both articular and nonarticular physical indings suggestive of or consistent with a diagnosis of AxSpA.

Reduced mobility of the spine, if present, is a key inding. The extraspinal articular and nonarticular exam may provide critical corroborative indings in its absence (Table 2.2).

VIDEO 3: The IBP/AxSpA-Focused Physical Examination

The history and physical exam may elicit “red lags” that point to IBP etiologies other than in lammatory arthritis variants. It is critical to heed these indings, which may lead to other diagnoses — notably infectious and malignant processes — and clinically correlate them with the results of your diagnostic workup.11 Discussion of these other IBP etiologies is not covered in this activity.

Recommendations for the Initial Diagnostic Workup of Suspected AxSpA Serum Biomarkers of AxSpA Laboratory assessment of suspected AxSpA can be quite simple. Typically, this consists of testing for the presence of human leukocyte antigen B27 (HLA-B27) and measuring the C-reactive protein (CRP) level (normal <0.3–0.8 mg/dL; mild elevations of 0.8–1.0 mg/dL are seen with conditions ranging from colds to chronic disease [eg, diabetes mellitus]). Values between 1.0 and 10.0 mg/dL are consistent with systemic in lammatory conditions, including AxSpA.12 CRP may not be elevated in early AxSpA. In one study (N=310; SpondyloArthritis Caught Early [SPACE] cohort) CRP levels did not distinguish patients with early-stage AxSpA and control (ie, healthy) patients with back pain. The same held true for erythrocyte sedimentation rate (ESR) in this clinical setting. None of the other potential serum biomarkers of early AxSpA studied proved useful.13 Clinical interpretation of HLA-B27 results, as discussed in Chapter 1, may not be straightforward. Whereas its presence is signi icant within the composite impression of AxSpA, its absence does not exclude AxSpA. Further, the prevalence of HLA-B27 positivity varies between racial/ethnic groups, as seen in a study of 925 patients with AxSpA, with Black participants having a signi icantly lower rate (62.5%) than White and Latino participants (85.3% and 86.7%, respectively; P<0.0001). Among this study cohort, Black participants were nonetheless shown to have higher in lammatory marker levels (ESR and CRP), higher disease activity, and greater functional impairment.14 HLA-B27–positive vs –negative patients may manifest di erent disease courses. In one study (N=1080), symptomatic AxSpA onset at >40 years of age was signi icantly higher in HLA-B27–negative patients. Further, the average delay in diagnosis for HLA-B27–negative patients was signi icantly longer than for HLA-B27–positive patients.15

Imaging

Recommendations for diagnostic imaging are informed by acute and chronic AxSpA pathophysiology plus the various imaging modalities’ di erent capabilities for visualizing the e ects of such pathophysiology (Table 2.3). Acute or active AxSpA disease processes are in lammatory in nature; whereas the consequences of chronic disease progression are characterized by osseous structural changes.16,17

As the historical “gold standard” for AxSpA diagnosis, plain X-rays of the sacroiliac joints (SIJs) readily demonstrate structural changes — when present. The result of in lammation-driven osteodestructive or osteoproliferative processes, such radiographic changes of the SIJs include erosions, pseudo-widening, sclerosis, bony bridging, and/or SIJ fusion (ankylosis). Similarly, X-rays of the spine may reveal a variety of changes, including erosions, sclerosis, spondylophytes, syndesmophytes, bony intervertebral bridging, and ankylosis. A single anterior-posterior (AP) view of the SIJs is usually performed with the patient in the supine position. Supplementary oblique views do not add diagnostic value compared with the AP view. Plain X-rays of the spine are not included in recommendations for irst-line diagnostic imaging of suspected AxSpA.16,18

In contrast to radiography, magnetic resonance imaging (MRI) of the SIJs without contrast can show lesions associated with early-stage active in lammation. Importantly, these changes include subchondral and periarticular bone-marrow edema, a key corroborative inding, or biomarker, of early AxSpA. MRI is used when plain X-rays are noncon irmatory (normal or equivocal) in the face of clinical suspicion of AxSpA. Although MRI can provide evidence of earlyVIDEO 4: Faculty Demonstration of stage in lammatory disease — that may or may not advance to Key Imaging Findings in AxSpA

structural changes seen on X-ray — it is neither highly sensitive nor highly speci ic.19 Combining radiography and MRI has been shown to add no value with regard to the radiologist’s reading of indings or inter-rater reliability compared with MRI alone.18 Low-dose computerized tomography (CT) is a third option for imaging of suspected AxSpA. CT is a highly speci ic alternative when MRI is inconclusive or unavailable. CT potentially may become the new gold standard for detecting structural lesions, even though it may be inferior in assessing bone marrow changes and active in lammation of the SIJs. CT produces higher spatial resolution and better visualization of cortical bone than does MRI.18

Practice Tips A single plain X-ray AP view of the pelvis remains the gold standard. • If radiographic indings are normal or inconclusive, MRI of the SIJs without contrast should be used to visualize early nonstructural changes. • Low-dose CT may provide superior spatial resolution and visualization of structural lesions.

Nonradiographic AxSpA Clinical correlation of imaging indings — their presence or absence — is central to the integration of all sources of diagnostic information: history, physical exam, imaging, and serum biomarkers. Nonradiographic AxSpA (nr-AxSpA) is AxSpA! The working diagnosis of AxSpA does not di erentiate nr-AxSpA. It is the same disease, with the same clinical considerations and the same interventions. Although CRP levels are lower and less structural damage may be present, clinical manifestations are similar to those associated with radiographic AxSpA.20

There is a larger percentage of women represented in nr-AxSpA cohorts (a 1:1 male-to-female ratio vs a 1:6 overall male-to-female ratio in AxSpA, inclusive of nr-AxSpA). Historically, the misguided belief that AxSpA is uncommon in women has contributed to failure to identify women with AxSpA at earlier disease stages. Other AxSpA clinical characteristics that distinguish presentations among women from those of men are shown in Table 2.4.21,22

Recognition of the nr-AxSpA variant has not only allowed for earlier diagnosis, it has prompted greater diversity of individuals enrolled — and greater inclusion of women — in clinical trials and spurred an expanding understanding of the natural history of AxSpA and its targeted biologic treatment.20

To request copies of the tool, email: info@exchangecme.com For a video demonstration of the tool, go to: ExchangeCME.com/AxSpAEesources

References 1. Danve A, Deodhar A. Axial spondyloarthri s in the USA: diagnos c challenges and missed opportuni es. Clin Rheumatol. 2019;38(3):625-634.

2. Fallahi S, Jamshidi AR. Diagnos c delay in ankylosing spondyli s: related factors and prognos c outcomes. Arch Rheumatol. 2016;31(1):24-30.

3. Lapane KL, et al. Primary care physician perspec ves on barriers to diagnosing axial spondyloarthri s: a qualita ve study. BMC Fam Pract. 2020;21(1):204. 4. Magrey MN, et al. Recognizing axial spondyloarthri s: a guide for primary care. Mayo Clin Proc. 2020;95(11):2499-2508. 5. Robinson PC, et al. Axial spondyloarthri s: concept, construct, classi ca on and implica ons for therapy. Nat Rev Rheumatol. 2021;17(2):109-118. 6. Slobodin G, et al. Sacroilii s—early diagnosis is key. J In amm Res. 2018;11:339-344. 7. Kataria RK, Brent LH. Spondyloarthropathies. Am Fam Physician. 2004;69(12):2853-2860. 8. Resnick D. Pa erns of peripheral joint disease in ankylosing spondyli s. Radiology. 1974;110(3):523-532. 9. Dermatology. Psoriasis: Signs and Symptoms. h ps://www.aad.org/public/diseases/psoriasis/what/symptoms. Accessed October 30, 2021. 10. Veauthier B, Hornecker JR. Crohn’s disease: diagnosis and management. Am Fam Physician. 2018;98(11):661-669. 11. Will JS, et al. Mechanical low back pain. Am Fam Physician. 2018;98(7):421-428. 12. Nehring S, et al. C reac ve protein. In: STAT Pearls [Internet]. Treasure Island, FL: StatPearls Publishing; h ps:// www.ncbi.nlm.nih.gov/books/NBK441843/. Accessed October 30, 2021. 13. Turina MC, et al. Serum in ammatory biomarkers fail to iden fy early axial spondyloarthri s: results from the Spondyloarthri s Caught Early (SPACE) cohort. RMD Open. 2017;3(1):e000319. 14. Jamalyaria F, et al. Ethnicity and disease severity in ankylosing spondyli s a cross-sec onal analysis of three ethnic groups. Clin Rheumatol. 2017;36(10):2359-2364. 15. Feldtkeller E, et al. Age at disease onset and diagnosis delay in HLA-B27 nega ve vs posi ve pa ents with ankylosing spondyli s. Rheumatol Int. 2003;23(2):61-66. 16. Khmelinskii N, et al. The role of imaging in diagnosing axial spondyloarthri s. Front Med (Lausanne). 2018;5:106. 17. Ward MM, et al. 2019 update of the American College of Rheumatology/Spondyli s Associa on of America/ Spondyloarthri s Research and Treatment Network recommenda ons for the treatment of ankylosing spondyli s and nonradiographic axial spondyloarthri s. Arthri s Care Res. 2019;71(10):1285-1299. 18. Diekho T, et al. Choose wisely: imaging for diagnosis of axial spondyloarthri s. Ann Rheum Dis. 2021. doi:10.1136/ annrheumdis-2021-220136. 19. Lukas C, et al. MRI for diagnosis of axial spondyloarthri s: major advance with cri cal limita ons ‘not everything that glisters is gold (standard)’. RMD Open. 2018;4(1):e000586. 20. Ritchlin C, Adamopoulos IE. Axial spondyloarthri s: new advances in diagnosis and management. BMJ. 2021;372:m4447. 21. Mease PJ, et al. Comparison of men and women with axial spondyloarthri s in the US-based Corrona Psoria c Arthri s/Spondyloarthri s Registry. J Rheumatol. 2021;48(10):1528-1536.

22. Rusman T, et al. Sex and gender di erences in axial spondyloarthri s: myths and truths. Rheumatology. 2020;59(suppl 4):iv38-iv46.

CHAPTER 3

GETTING TO GOAL — EARLY RHEUMATOLOGY REFERRAL Introduction: From Initial Symptom Management Rheumatology Referral

our clinical impression may not be corroborated by tangible diagnostic evidence for the presence of axial spondyloarthritis (AxSpA). Initial imaging could be noncon irmatory and the patient may be human leukocyte antigen B27 (HLA-B27)–negative. This doesn’t mean your impression is unfounded, nor does it mean your job is done. All patients whom you suspect as having AxSpA should receive early rheumatologic referral — even in the absence of diagnostic con irmation.1-3 Referral may follow or occur contemporaneously with your initiation of irst-line symptom management measures. These include nonsteroidal antiin lammatory drugs (NSAIDs; eg, ibuprofen, naproxen) at full dosage on a regular basis and exercise as prescribed by a physical therapist with knowledge of preferred modes. These initial measures are discussed in Chapter 4.

VIDEO 5: Optimizing the Rheumatology Referral

The Rheumatology Provider’s Evaluation of the Patient With Suspected AxSpA

The purpose of early rheumatologic referral is manifold. First, it allows for more indepth evaluation of suspected AxSpA, as brought to light through your clinical acumen. This evaluation could include additional second-line imaging, as well as further laboratory tests to rule out other in lammatory, infectious, autoimmune, or

neoplastic processes, if prompted by the individual patient’s clinical presentation. This evaluation will also assess the patient’s response to any symptom management measures you have prescribed.4 These next steps on the part of the rheumatology care provider will lay the groundwork for consideration of treatment options, as discussed in Chapter 4.

Addressing Referral Barriers Day-to-day clinical practice does not always proceed according to plan. You may face barriers to getting your patient specialty evaluation and care. These barriers can be related to access: It is not uncommon in rural/semirural areas to have a signi icant underrepresentation of specialists. This may result in patients having to travel long distances to see a rheumatology provider. Even if care is available in a larger medical community at a distance from the patient’s home, they may need to wait several months — or longer — for an appointment. Many major centers, as well as Project ECHO–modeled programs, provide virtual specialty support for nonrheumatologists.5,6 And, as revealed during the COVID-19 pandemic, a much broader scope of health care can be e ectively provided via telemedicine than previously believed. It behooves primary care providers (PCPs) and other frontline providers to explore the accessibility and availability of timely rheumatologic consultation services within an expanded geographic radius from their practice. Not all barriers to rheumatology referral are systemic/structural issues. PCPs/ frontline providers, themselves, may play a role because of misinformed assumptions. With regard to AxSpA, examples of common inaccurate assumptions that may delay referral include the following: • The patient is too young to have AxSpA • AxSpA is rare in women • AxSpA is rare in people of color • The patient doesn’t have a family history of AxSpA • Symptoms have been inconsistent or intermittent • Generalized pain means ibromyalgia • The patient has had multiple sports-related or on-the-job injuries

Assumptions or misattribution often contribute to diagnostic uncertainty: at best de ined as self-awareness of one’s inability to formulate an accurate explanation for the given concern or presentation; at worst, experienced as a sense of unease and being “stuck.” While diagnostic uncertainty drives excess health care utilization, it may also drive the opposite: inaction or clinical hesitancy. Uncertainty causes

anxiety for many, if not most, providers and, for some, negative feelings about one’s own capabilities.7,8 But absolute certainty is not needed to initiate referral. Framing a concern in broader terms, for example — This looks like in lammatory back pain — may reduce uncertainty and unease to a tolerable level, allowing for initiation of a de initive plan of action. Rather than masking one’s uncertainty, communicating it to the patient and/or consultant may facilitate a more open and productive 3-way collaboration.7,8

Specialty Referral Considerations Referrals and consultations are central to patient care. Ideally, this is a collaboration based on open communication of both needs and expectations.9 In the setting of AxSpA, the expectation should be established that this is a referral for management of the patient’s care, as the prescribing and monitoring of targeted therapies for AxSpA is nearly always performed by rheumatology care providers.4 Unfortunately, communication between the referring clinician and the specialist can be poorly managed — often to the detriment of collaboration and the patient’s continuity of care.10 Therefore, it is very reasonable for the referring clinician to clearly present the expectation that they will be “kept in the loop” regarding the patient’s specialty evaluation, additional test results, new therapies, response to medication, future interventions, and any secondary referrals. Not all clinicians have the luxury of sharing electronic medical records. Therefore, the referring provider can and should establish not only the mode of communication they would like to receive (written, verbal, both), but also the extent of information that they want to receive in a timely and continuous manner. Importantly, the referring clinician should, as desired, clearly establish that they want to play an active co-management role — sharing patient monitoring and optimizing the patient’s speci ic healthmaintenance needs (Chapter 4).

Referral Models in the Care of the Patient With Diagnosed or Suspected AxSpA

Referral models for at-risk patients (de ined as the presence of low back pain of >3 months’ duration and age of onset ≤45 years) are informed by the primary features of the AxSpA constellation: symptoms consistent with in lammatory back pain; HLA-B27 positivity; and sacroiliitis on imaging. The operationalization of these clinical features — or parameters — within the various referral models di ers in terms of complexity (ie, number of parameters included), resulting in di ering

levels of sensitivity and speci icity.11,12 Clinical studies involving the use of these referral models point to “less is more.” That is, models with fewer parameters performed better in terms of the percentage of de initive diagnoses of AxSpA among referral cohorts.12 Figure 3.1 illustrates this simpli ied strategy, under which at-risk patients with ≥1 AxSpA parameter receive a rheumatology referral.13 Per Assessment of SpondyloArthritis International Society recommendations for PCPs and other nonspecialists, additional features may be used as the ≥1 parameter. These include peripheral manifestations (arthritis, enthesitis, and/or dactylitis), extra-articular manifestations (psoriasis, in lammatory bowel disease, and/or uveitis), positive family history for spondyloarthritis, good response to NSAIDs, and elevated acute phase reactants (eg, C-reactive protein). Using 2 of these parameters rather than 1 increases the probability of AxSpA being present.2,14

Setting the Stage for the PCP’s Co-Management of the Patient With AxSpA

The timely referral of a patient with suspected or diagnosed AxSpA may go a long way toward establishing a good working relationship with the rheumatology provider. Con irmatory feedback from the specialist reinforces the nonspecialist’s clinical acumen, having a positive carryover e ect on early AxSpA recognition and referral of other patients. Your patient, as well, will be grateful for your moving their care forward to a de initive diagnosis and/or initiation of treatment. This is an

important irst step in ensuring the ongoing co-management role for the PCP in the care of patients with AxSpA, as will be discussed in Chapter 4.

To request copies of the tool, email: info@exchangecme.com For a video demonstration of the tool, go to: ExchangeCME.com/AxSpAEesources

References 1. Danve A, Deodhar A. Axial spondyloarthri s in the USA: diagnos c challenges and missed opportuni es. Clin Rheumatol. 2019;38(3):625-634. 2. Poddubnyy D, et al. Development of an ASAS-endorsed recommenda on for the early referral of pa ents with a suspicion of axial spondyloarthri s. Ann Rheum Dis. 2015;74(8):1483-1487. 3. Barne R, et al. Axial spondyloarthri s 10 years on: s ll looking for the lost tribe. Rheumatology (Oxford). 2020;59(suppl 4):iv25-iv37. 4. Gelman L. How doctors diagnose ankylosing spondyli s: What to expect at the rheumatologist. Creeky Joints. h ps://creakyjoints.org/about-arthri s/axial-spondyloarthri s/axspa-overview/how-ankylosing-spondyli s-isdiagnosed/. Accessed October 30, 2021. 5. ECHO. Rheumatology. h ps://hsc.unm.edu/echo/partner-portal/programs/rheumatology/. Accessed October 30, 2021. 6. Helio. The virtual doctor is in: advancing care through tele-rheumatology. h ps://www.healio.com/news/ rheumatology/20180914/the-virtual-doctor-is-in-advancing-care-through-telerheumatology. Accessed Ocotober 30, 2021. 7. Bhise V, et al. De ning and measuring diagnos c uncertainty in medicine: a systema c review. J Gen Intern Med. 2018;33(1):103-115. 8. Simpkin AL, Schwartzstein RM. Tolera ng uncertainty — the next medical revolu on? N Engl J Med. 2016;375(18):1713-1715. 9. Reichman M. Op mizing referrals & consults with a standardized process. Fam Pract Manag. 2007;14(10):38-42. 10. Mehrotra A, et al. Dropping the baton: specialty referrals in the United States. Milbank Q. 2011;89(1):39-68. 11. Solmaz D, et al. Performance of di erent criteria sets for in ammatory back pain in pa ents with axial spondyloarthri s with and without radiographic sacroilii s. Clin Rheumatol. 2014;33(10):1475-1479.

ca on of pa ents with axial spondyloarthri s

12. Poddubnyy D, et al. Evalua on of 2 screening strategies for early iden in primary care. J Rheumatol. 2011;38(11):2452-2460.

13. Rudwaleit M, Sieper J. Referral strategies for early diagnosis of axial spondyloarthri s. Nat Rev Rheumatol. 2012;8(5):262-268. 14. van Hoeven L, et al. Evalua ng the ASAS recommenda ons for early referral of axial spondyloarthri s in pa ents with chronic low back pain; Is one parameter present su cient for primary care prac ce? Ann Rheum Dis. 2015;74(12):e68-e68.

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15. Magrey MN, et al. Recognizing axial spondyloarthri s: a guide for primary care. Mayo Clin Proc. 2020;95(11):2499-2508.

CHAPTER 4

THE NON-RHEUMATOLOGIST’S CONTINUED ROLE IN AxSpA Introduction: From Action to Sustained Engagement in Your Patient’s Care

our participation in the patient’s care may be ongoing after rheumatology consultation and establishment of a de initive axial spondyloarthritis (AxSpA) diagnosis. Whether you are a primary care provider (PCP), chiropractor, physical therapist, or other involved clinician, you can make signi icant contributions to your patient’s health and well-being. As with any chronic disease state, general health maintenance should proceed in line with both sex/age guidelines and recommendations speci ic to the given disease state.1,2

Initial Symptom Management Nonsteroidal Anti-In lammatory Drugs Nonsteroidal anti-in lammatory drugs (NSAIDs) are the cornerstone of irst-line medical management of pain and other in lammatory symptoms in patients with AxSpA.2,3 The frontline clinician is encouraged to initiate early symptomatic management. In individuals with no contraindication to their use, the full therapeutic dosage of the selected NSAID (eg, naproxen, celecoxib) at regular, prescribed dosing intervals is recommended. Clinical studies suggest direct antiin lammatory e ects of NSAIDs in AxSpA, as seen in one study showing reductions in magnetic resonance imaging (MRI)-visualized sacroiliac joint (SIJ) bone marrow edema.4 It appears that NSAIDs do not retard radiographic disease progression, having been studied at high vs standard dosages and as continuous vs on-demand schedules.5-7 Symptomatic response to full-dosage NSAIDs is equivalent in radiographic AxSpA (also known as ankylosing spondylitis, or AS) and nonradiographic AxSpA (nr-AxSpA).8

There are generally no signi icant di erences in e icacy among the commonly prescribed NSAID agents. Caution must be used with sustained high-dose NSAIDs. Patients should be monitored for medication intolerance, yet many drop out of their

own accord due to adverse events, of which gastrointestinal side e ects are the most common.4,9 Long-term cardiovascular (CV) safety of NSAIDs is also a concern, as AxSpA is associated with high increased background risk of CV-related death.10 On the whole, however, there has been no consistent evidence that NSAIDs increase CV risk in AxSpA, and they may even have an anti-in lammatory CV-protective e ect. CV risk should be evaluated on a case-by-case basis.3

Physical Therapist–Prescribed Exercise The bene icial role of exercise in AxSpA management is well established. Regular exercise (including high-intensity activity and active physical therapy) is e ective in symptom management and functional improvement.11-13 Recent research has brought to light the potential role of biomechanical stress and microdamage in the pathogenesis of AxSpA. It is hypothesized that physical activity that produces entheseal stress may promote in lammation and new bone formation at entheseal and articular sites via activation of the innate immune system and the release of cytokines. Figure 4.1 conceptualizes these concerns.12

Exercise, nonetheless, remains a foundational component of AxSpA disease management, with bene its including but not limited to decreases in systemic in lammation, disease activity, and osteoporosis, along with increases in bone mass and improvement in overall function, CV health, and quality of life.12,14 Individualized exercise plans for patients with AxSpA may need to take into consideration a wide range of factors: level of itness (both systemic and local), degree of sedentary lifestyle (in luencing strength and joint stability), occupational demands, and smoking status. Overarching considerations include sex di erences in disease progression and both gender and socioeconomic factors that in luence types of occupational physical activity.12

An array of exercise programs and modalities is currently recommended. These range from preventive to rehabilitative, from individual to group-based, from lowintensity to high-intensity aerobic activities. In general, active interventions are recommended over passive interventions (massage, ultrasound, heat).2 This applies to both physical therapy and chiropractic treatment modalities. Exercise programs may improve AxSpA disease activity, pain, function, and spinal mobility, yet the e ect varies by type of exercise and by disease feature. Endurance training plus strength training (compared with no exercise) has been shown to provide the largest e ect on disease activity. Aquatic exercises, as compared with land-based exercises, o er the best improvements in pain.16 Nonwalking activities, such as cycling, bodybuilding, and dancing, provide a number of endurance, strength, and CV bene its.16,17 An ideal exercise program for patients with AxSpA incorporates components that address range of motion, stretching, CV itness, strengthening, and balance.18

Vigorous-intensity aerobic physical activity appears to have more health bene its than other forms of exercise. While not speci ically de ined for this population in terms of energy expenditure, vigorous-intensity physical activity goals are set in terms of minutes per week. US Centers for Disease Control and Prevention (CDC)promoted guidelines call for 75 minutes per week, in combination with strengthening exercises for all major muscle groups 2 days per week.19 Vigorousintensity aerobic physical activity may improve fatigue, sleep, and mood in patients with AxSpA.14 Not only is aerobic exercise considered to be safe for individuals with

AxSpA, it’s the most e ective in improving clinical cardiorespiratory parameters, which is especially important, as AxSpA is associated with decreased cardiorespiratory itness and increased CV risks.20-22 Vigorous-intensity aerobic physical activity may be pursued by patients who do not have undue risk of CV events during exercise. Patients should be o ered suggestions for a variety of recreational activities, such as cycling and swimming. Vigorous-intensity goals are frequently unmet, but moderate- and combinedintensity physical activity may have greater uptake if carried out in conjunction with physical therapy.21 Ideally, high-intensity programs are monitored by physical therapists specialized in rheumatology and trained in the exercise protocol.14 Supervised group-based exercise has bene its beyond unsupervised, individual exercise programs. Clinical studies have shown greater improvement in multiple parameters: spinal mobility, global condition, depression, and quality of life.23 Programs may include both land-based exercise and/or aquatic exercise; with either setting having varying degrees of aerobic activity monitored by appropriately trained physical therapists.14,24 Programs that incorporate a biopsychosocial model (eg, McKenzie Method®) demonstrate additional bene its in all AxSpA parameters.23,25 Preventive intervention, by de inition, involves both acknowledgement of disease progression risk and the motivation to proactively mitigate it. A willingness to increase physical activity and make other lifestyle changes (eg, smoking cessation, weight reduction) has been shown to be high among patients with AxSpA. One Dutch study (2020; N=185, n=52 at risk for AxSpA), however, revealed that rheumatologists were more likely to initiate preventive drug therapy than to promote lifestyle modi ications because of a lack of evidence for the e ects of lifestyle change on disease risk.26 Activity trackers (smartwatches or bracelets, eg, Fitbit®) provide a means to longitudinally assess physical activity in patients with rheumatoid disease, especially in patients whose level is insu icient. CDC guidelines calling for 150 minutes/week of moderate activity have been converted to number of steps/day (average 7000 to 11,000).19 A French study (2018; N=157, n=74 with AxSpA) demonstrated both acceptability of and good adherence to use of activity trackers on the part of patients with AxSpA.17

Overall, the bene icial e ects of physical activity in patients with AxSpA have been demonstrated; however, more evidence is needed on the e ects of exercise across the full spectrum of AxSpA disease activity, including nr-AxSpA.23 Additionally,

speci ic guidance on the amount of exercise required to produce a bene icial e ect is lacking.27 No one size its all: both expanded programs and tailored programs are needed to meet the range of individuals’ needs.

Chiropractic Care Many people identify chiropractors as their PCP for concerns beyond musculoskeletal complaints. As such, chiropractors may see an excess number of patients with a primary complaint of low back pain, among whom, statistically, there will be individuals with in lammatory back pain (IBP) who are at risk of AxSpA. Referral of patients with chronic low back pain to rheumatologists, however, appears to be disproportionately low — despite there being insu icient data on the incidence of IBP in chiropractic care. AxSpA may go unrecognized by chiropractors even in the presence of positive radiographic indings, including degenerative SIJ changes.28,29 Chiropractic students were shown in one study to have generally high acumen for detecting conditions that could worsen with spinal adjustments (81%–97% accuracy). However, these conditions were not identi ied among patients subsequently found to have AxSpA, for which spinal manipulation is strongly contraindicated in the presence of ankylosis.30 Nonetheless, several studies report the positive bene its of chiropractic care in a variety of AxSpA-related outcomes, including improvements in symptoms, function, and disease activity in individuals with evidence of advanced disease.31-33

The American College of Rheumatology, Spondylitis Association of America, and Spondyloarthritis Research and Treatment Network treatment guidelines for AxSpA stand in strong opposition to the use of spinal manipulation in patients with any degree of fusion of the spine and/or spinal osteoporosis because of the risks of vertebral fracture and neurologic damage.2 However, chiropractors can still play a signi icant role in the early diagnosis of the disease process by di erentiating IBP from mechanical back pain, identifying peripheral joint involvement and extraarticular AxSpA manifestations, and assessing response to NSAIDs. The development of validated screening tools could ultimately ensure that patients receive timely and appropriate referral from chiropractors and other frontline providers.28

Co-Management Roles for the Frontline Provider: PCP, Chiropractor, Physical Therapist There are several clinical activities — and responsibilities — in common for all frontline providers caring for patients with AxSpA. These include promotion of general health maintenance, provision of psychosocial support and referral, and recognition of adverse e ects of medical treatment and interventions. Providers in each of these 3 disciplines — primary care, chiropractic care, and physical therapy — are known for their e ective relationship building with patients. And, while practice scope or authority may vary, patient-centeredness remains a constant.

General Health Maintenance No health care discipline is conducted in a vacuum, as individual patients have diverse characteristics, concerns, and needs that call for providers — to the extent of their training — to take a holistic perspective. Nowhere is this more true than in the setting of chronic systemic disease, as exempli ied by AxSpA. In some cases, general health maintenance may take the form of, How are you doing with your plan to quit smoking? In others, especially for primary care medical providers, this consists of a larger set of activities, including routine screening per prevailing sex/ age–based recommendations (eg, hypertension, breast cancer, hepatitis C).1 But for all providers caring for patients with AxSpA, a general health maintenance stance requires fundamental knowledge of the breadth of the disease state, even if one is playing only a supporting role.

Psychosocial Inquiry, Support, and Referral

The psychosocial impact of AxSpA can be far-reaching, especially for those patients who have incurred inordinate diagnostic delays, during which the disease state progressed. AxSpA-related debilitation may impact any/all aspects of day-today life: occupational responsibilities, social activity, marital/family roles and relationships, and the intrapersonal spheres of well-being, self-e icacy, and mood regulation.34 The time- and resource-constricted realities of contemporary health care may not allow for in-depth psychosocial inquiry, but a simple, global question can su ice to initiate action on behalf of the patient. How is AxSpA impacting your life at this point? What follows may be further real-time inquiries, rescheduling for further discussion, suggestions for participation in support groups or organizations, or formal referral for counseling, psychiatric assessment, or social services.

Basic Knowledge of the AxSpA Biologic Therapies While the prescribing, management, and monitoring of biologic and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs; tsDMARDs) are provided by rheumatologists, PCPs and other frontline providers caring for patients with AxSpA may encounter potential side e ects, adverse events, or other concerns associated with these drugs. Their recognition of pertinent signs and symptoms — and alerting the patient and rheumatologist — are important components of the PCP’s co-management role. These considerations are further discussed in the following section on AxSpA biologics and small-molecule drugs.

AxSpA Biologics and Small-Molecule Drugs 101: An Overview for the Nonrheumatologist As discussed in Chapter 1, the triggers and pathogenesis of AxSpA remain unclear, but the therapeutic agents targeting tumor necrosis factor (TNF) and interleukin-17 (IL-17) in lammatory pathways suppress clinical signs and symptoms of AxSpA, giving support for correct identi ication of involved pathways.35 Advances in the management of AxSpA now provide the potential for e ective targeting of TNF and IL-17A and inhibition of components of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway.36,37 These drug classes have in common increased risk of infection, including tuberculosis and fungal infections.38 Biological products (biologic drugs, biologics) comprise diverse categories of large complex molecules that are produced through biotechnology in a living system. Monoclonal antibodies and vaccines are well-known examples.39 In the management of AxSpA, biologic therapies — TNF inhibitors and IL-17 inhibitors — are currently indicated for patients with active disease who are intolerant of NSAIDs or have had inadequate response to therapeutics dosages of 2 di erent NSAIDs, each of 2 weeks’ duration.40

Most recently introduced, JAK inhibitors (eg, tofacitinib), are synthetic smallmolecule agents (vs biologics) that have downstream impact on the IL-23/IL-17 pathway, which is thought to be central to AxSpA pathogenesis and partly controlled by JAK.36 JAK inhibitors, as a class, have the signi icant advantage of oral administration.41 Other drug classes, notably glucocorticoids and traditional (or conventional) DMARDs (antirheumatic/antimetabolic/immunosuppressive drugs, eg, methotrexate, sulfasalazine) have had a role in the treatment of AxSpA but are no longer irst-line drugs. They are now used only in peripheral arthritis.2

Multiple factors will inform the rheumatologist’s selection of biologic therapy for AxSpA. Prevailing guidelines cite factors that include active disease, radiographic progression, extra-articular manifestations, and comorbidities, among other considerations.3 There are many persistent questions related to the optimized treatment-sequencing strategies.2,6

AxSpA Biologics and Small-Molecule Agents: Approved or Emerging Therapies Table 4.1 presents current AxSpA biologics and small-molecule agents that have been approved or are currently in later-stage clinical trials. Classes are listed by order of development and alphabetically within classes.

Basic familiarity with these drug classes and agents will allow for enhanced communication with both the rheumatologist and your patient.

Choose Your Path

VIDEO 6: The PCP’s Role in Preparing the Patient for Rheumatology Care

VIDEO 7: A Role for Chiropractic Care: What’s OK — What’s Not OK?

VIDEO 8: PT Modalities for the Patient With AxSpA: What’s In, What’s Out?

To request copies of the tool, email: info@exchangecme.com For a video demonstration of the tool, go to: ExchangeCME.com/AxSpAEesources

References 1. USPSTF. A & B recommenda ons. h ps://www.uspreven veservicestaskforce.org/usps /recommenda on-topics/ usps -and-b-recommenda ons. Accessed October 30, 2021. 2. Ward MM, et al. 2019 update of the American College of Rheumatology/Spondyli s Associa on of America/ Spondyloarthri s Research and Treatment Network recommenda ons for the treatment of ankylosing spondyli s and nonradiographic axial spondyloarthri s. Arthri s Care Res. 2019;71(10):1285-1299. 3. Fragoulis GE, Siebert S. Treatment strategies in axial spondyloarthri s: What, when and how? Rheumatology (Oxford). 2020;59(suppl 4):iv79-iv89. 4. Varkas G, et al. Brief report: Six-week treatment of axial spondyloarthri s pa ents with an op mal dose of nonsteroidal an in ammatory drugs: early response to treatment in signal intensity on magne c resonance imaging of the sacroiliac joints. Arthri s Rheumatol. 2016;68(3):672-678. 5. Karmacharya P, et al. E ect of therapy on radiographic progression in axial spondyloarthri s: a systema c review and meta-analysis. Arthri s Rheumatol. 2020;72(5):733-749. 6. Poddubnyy D, Sieper J. Treatment of axial spondyloarthri s: What does the future hold? Curr Rheumatol Rep. 2020;22(9):47. 7. Zhang JR, et al. Non-steroidal an -in ammatory drugs are unlikely to inhibit radiographic progression of ankylosing spondyli s: a systema c review. Front Med (Lausanne). 2019;6:214. 8. Baraliakos X, et al. E ciency of treatment with non-steroidal an -in ammatory drugs according to current recommenda ons in pa ents with radiographic and non-radiographic axial spondyloarthri s. Rheumatology (Oxford). 2017;56(1):95-102. 9. Arroyo M, Lanas A. NSAIDs-induced gastrointes nal damage. Review. Minerva Gastroenterol Dietol. 2006;52(3):249-259. 10. Bakland G, et al. Increased mortality in ankylosing spondyli s is related to disease ac vity. Ann Rheum Dis. 2011;70(11):1921-1925. 11. Dag nrud H, et al. Physiotherapy interven ons for ankylosing spondyli s. Cochrane Database Syst Rev. 2008(1):CD002822.

ffi

12. Perro a FM, et al. To move or not to move: the paradoxical e ect of physical exercise in axial spondyloarthri s. RMD Open. 2021;7(1):e001480.

13. Poddubnyy D. Axial spondyloarthri s: Is there a treatment of choice? Ther Adv Musculoskelet Dis. 2013;5(1):45-54. 14. Sveaas SH, et al. High-intensity exercise improves fa gue, sleep, and mood in pa ents with axial spondyloarthri s: secondary analysis of a randomized controlled trial. Physical Therapy. 2020;100(8):1323-1332. 15. Sche G, et al. Enthesi s: from pathophysiology to treatment. Nat Rev Rheumatol. 2017;13(12):731-741. 16. Regel A, et al. E cacy and safety of non-pharmacological and non-biological pharmacological treatment: a systema c literature review informing the 2016 update of the ASAS-EULAR recommenda ons for the management of axial spondyloarthri s. RMD Open. 2017;3(1):e000397. 17. Jacquemin C, et al. Physical ac vity assessment using an ac vity tracker in pa ents with rheumatoid arthri s and axial spondyloarthri s: prospec ve observa onal study. JMIR Mhealth Uhealth. 2018;6(1):e1. 18. SAA. Exercise. h ps://spondyli s.org/about-spondyli s/treatment-informa on/exercise/. Accessed October 30, 2021. 19. CDC. How much physical ac vity do adults need? h ps://www.cdc.gov/physicalac vity/basics/adults/ index.htm#:~:text=Vigorous%2Dintensity%20aerobic%20ac vity%20means,of%20your%20aerobic%20physical%20a c vity. Accessed October 30, 2021. 20. Hannan AL, et al. High-intensity interval training versus moderate-intensity con nuous training within cardiac rehabilita on: a systema c review and meta-analysis. Open Access J Sports Med. 2018;9:1-17. 21. Hilberdink B, et al. Adequately dosed aerobic physical ac vity in people with axial spondyloarthri s: associa ons with physical therapy. Rheumatol Int. 2020;40(9):1519-1528. 22. Zhao SS, et al. Prevalence and impact of comorbidi es in axial spondyloarthri s: systema c review and metaanalysis. Rheumatology (Oxford). 2020;59(suppl 4):iv47-iv57. 23. Perro a FM, et al. New insights in physical therapy and rehabilita on in axial spondyloarthri s: a review. Rheumatol Ther. 2019;6(4):479-486. 24. Project Nigh ngale. December AxSpA research highlights – focus on physical ac vity. h ps:// www.projectnigh ngale.org/blogs/december-axspa-research-highlights-focus-on-physical-ac vity/. Accessed October 30, 2021. 25. Rosu O, Ancuta C. McKenzie training in pa ents with early stages of ankylosing spondyli s: results of a 24-week controlled study. Eur J Phys Rehabil Med. 2015;51(3):261-268. 26. van Boheemen L, et al. Pa ents’ and rheumatologists’ percep ons on preven ve interven on in rheumatoid arthri s and axial spondyloarthri s. Arthri s Res Ther. 2020;22(1):217. 27. Martey C, Sengupta R. Physical therapy in axial spondyloarthri s: guidelines, evidence and clinical prac ce. Curr Opin Rheumatol. 2020;32(4):365-370. 28. Deodhar A, et al. Axial spondyloarthri s in the chiroprac c care se ng: a systema c literature review. J Clin Rheumatol. 2021. doi:10.1097/RHU.0000000000001776. 29. O’Shea FD, et al. In ammatory and degenera ve sacroiliac joint disease in a primary back pain cohort. Arthri s Care Res. 2010;62(4):447-454. 30. Goncalves G, et al. Chiroprac c conserva sm and the ability to determine contra-indica ons, non-indica ons, and indica ons to chiroprac c care: a cross-sec onal survey of chiroprac c students. Chiropr Man Therap. 2019;27(1):3. 31. Cornelson SM, et al. Chiroprac c care in the management of inac ve ankylosing spondyli s: a case series. J Chiropr Med. 2017;16(4):300-307. 32. Rose KA, Kim WS. The e ect of chiroprac c care for a 30-year-old male with advanced ankylosing spondyli s: a me series case report. J Manipula ve Physiol Ther. 2003;26(8):E9. 33. Rutherford SM, et al. Symptoma c improvement in func on and disease ac vity in a pa ent with ankylosing spondyli s u lizing a course of chiroprac c therapy: a prospec ve case study. J Can Chiropr Assoc. 2005;49(2):81-91. 34. Mar ndale J, Goodacre L. The journey to diagnosis in AS/AxSpA: the impact of delay. Musculoskelet Care. 2014;12(4):221-231.

tti

ffi

35. Furst DE, Louie JS. Targe ng in ammatory pathways in axial spondyloarthri s. Arthri s Res Ther. 2019;21(1):135.

36. Hammitzsch A, et al. Impact of Janus kinase inhibi on on the treatment of axial spondyloarthropathies. Front Immunol. 2020;11:591176. 37. Harrison DA. The JAK/STAT pathway. Cold Spring Harb Perspect Biol. 2012;4(3). 38. FDA. Drugs@FDA: FDA-approved drugs. h ps://www.accessdata.fda.gov/scripts/cder/daf/index.cfm? event=BasicSearch.process. Accessed October 30, 2021. 39. FDA. Biological product de ni ons. h ps://www.fda.gov/ les/drugs/published/Biological-Product-De ni ons.pdf. Accessed October 30, 2021. 40. van der Heijde D, et al. 2016 update of the ASAS-EULAR management recommenda ons for axial spondyloarthri s. Ann Rheum Dis. 2017;76(6):978-991. 41. Agrawal P, Machado PM. Recent advances in managing axial spondyloarthri s. F1000Res. 2020;9.

42. NIH. Clinicaltrials. h ps://clinicaltrials.gov/. Accessed October 30, 2021.

CHAPTER 5

UNDERSTANDING THE IMPACT OF LIVING WITH AxSpA Introduction

our ongoing care for a person with newly diagnosed axial spondyloarthritis (AxSpA) may encompass past, current, and future considerations. To go forward feeling seen and heard as a whole person, the patient — especially an individual who has incurred a diagnostic delay — will need acknowledgement and validation of their disease experience, along with assurance of well-attuned communication and collaboration. You may need to engage in active listening, allowing the patient to recount the cumulative impact of their disease experience. Many themes are common to the histories of people with delayed diagnosis of AxSpA, as shown in Table 5.

Impact of AxSpA on Psychosocial and Occupational Functioning

Despite the commonality of themes among people with AxSpA, the disease’s impact on psychosocial and occupational life parameters varies among individuals and may re lect disease duration and severity; degree of impaired mobility and physical limitations; presence of extra-articular manifestations; sex/gender di erences in both disease characteristics and “gendered” roles and responsibilities for daily activities and family needs; occupational demands; educational

attainment; and, perhaps, tolerance for uncertainty. Additional factors, including severe/chronic fatigue, pain level, disrupted sleep, and depression, may diminish the individual’s e orts and abilities to manage AxSpA’s toll.1-5

Fatigue

VIDEO 9: While potentially di icult to assess Part 1: The Patient Advocate: and measure, severe and/or chronic fatigue is highly prevalent Delayed Diagnosis and Lost Years among people living with AxSpA. Part 2: Clinician to Clinician Studies have revealed severe fatigue in approximately 32% (Western cohorts) to 55% (Asian cohorts), with the prevalence of fatigue of nonspeci ied severity being as high as 66% in Western cohorts.6,7 Fatigue is well known to reduce occupational productivity and participation in leisure activities. In the work environment, impaired performance may re lect diminished cognitive skills (“brain fog”), with resulting prolongation of the workday adversely impacting all other areas of life.8 Fatigue itself may lead individuals to opt out of socializing. Others may choose to reserve their energy for work. This is an example of a self-taught fatiguemanagement strategy. Occupational therapists may be a resource for enhancing these skills. This and other interventions may be needed to o set the toll fatigue and its lifestyle consequences can have on partnership, family, and social relationships.8 As discussed in Chapter 4, many forms of exercise can contribute to improvement of fatigue, sleep disruption, pain, and depression.9

Importantly, disease activity is a major driver of fatigue in AxSpA — with pain, sleep disruption, and depression as additional contributory factors. Biologic and targeted synthetic therapies have been shown to variably reduce fatigue levels.10,11 This supports multiple factors being responsible for signi icant fatigue and underscores a multimodality approach (eg, exercise, antidepressant medication) as key to its mitigation.6

Pain Pain is a complex AxSpA disease characteristic. Dominant axial pain is seen in men and women. However, pain in the lumbar, thoracic, and cervicothoracic spine has been shown to be signi icantly more prevalent in women, as has widespread peripheral articular pain. Central neural plasticity is thought to augment pain distribution and intensity in AxSpA, especially in women.12 Also of signi icance especially for women, ibromyalgia (FM) may coexist with AxSpA and confound pain attribution. Characterized by widespread pain and tenderness, FM prevalence among patients with AxSpA is 25%–38%, and among those with recent-onset AxSpA, it is reported to be as high as 56%. FM in women with AxSpA is associated with peripheral enthesitis.13 Despite a signi icant proportion of patients with AxSpA taking anti-in lammatory drugs, pain is not well controlled for many, suggesting that other pain mechanisms, such as neuropathic pain (NP), including radiculitis, may be a contributory cause. Patients with AxSpA who have active in lammatory back pain (IBP) and/or NP may experience more severe pain intensity, higher disease activity, and greater functional limitation than patients with AxSpA who do not have active IBP or NP. Further, AxSpA-related pain may interfere with multiple life domains.14

Sleep Disruption The description of IBP as tiring/exhausting illustrates the potential impact of IBP on patients’ mood.14 When such pain is coupled with disrupted sleep and poor sleep quality — known to be related to depressed mood and increased stress — patients with AxSpA may experience a compounding adverse impact on quality of life.15 More than 50% of patients with AxSpA experience sleep disturbances, including multiple awakenings accompanied by the need to get up and move to relieve symptoms of pain and sti ness. This often contributes to daytime fatigue and low motivation for physical activity. This may have critical impact, as physical activity has broadscale bene its in terms of function, mobility, and disease activity.15

Depression Depression is very common among patients with AxSpA, with estimated prevalence ranging from 11% to 64% depending on criteria used. Moderate to severe

depression is seen in approximately 15% of patients.16,17 Frequently, depression is associated with more severe disease activity, functional impairment, and psychosocial dysfunction. While current biologic and emerging targeted synthetic

disease-modifying therapies may decrease disease burden and potentially increase health-related quality of life in patients with high disease activity, identi ication and management of comorbid depression is critical to treatment response and outcomes. This may be particularly important for patients with signi icant disease activity and for younger patients (among whom the prevalence of depression is inversely related to age).17,18 Primary care providers (PCPs) can play an important role in depression screening, diagnosis, management, and referral.19 Several brief point-of-care depression screening tools are widely available (eg, Patient Health Questionnaire [PHQ]). The 2-question PHQ-2 is very useful as a routine survey, whereas the 9-question PHQ-9 can be used to con irm the diagnosis, assess severity, and monitor response to therapy.20,21

Identity and Social Determinants of Health Multiple factors may impact marginalized patients’ understanding and management of life with AxSpA. Identity (eg, race, ethnicity, gender, gender identity and expression, sexual orientation) are key intrinsic factors. Social determinants of health — access to quality health care and education, the socioenvironmental context, and the individual’s socioeconomic status (inclusive of their living situation) — must also be taken into consideration.22 An appreciation of both is critical to your support of the person living with AxSpA. A multifaceted, collaborative approach extending beyond clinical treatment may bene it those people living with AxSpA who are known to face greater barriers to care (health care disparities). This is especially true for individuals facing higher disease activity and greater functional impairment.23 Yet, others will bene it from an expanded approach — including but not limited to people of color, gender and ethnic minorities, LGBTQ+ patients, and, especially, patients facing multiple intersecting disparities.24

Occupational Assessment25

AxSpA typically a ects people of working age. Therefore, work-related outcomes are one of the key indicators of the impact of AxSpA on the patient’s functional status. Identi ied predictors of adverse work outcomes in AxSpA include laborintense job requirements, high disease activity, impaired spinal mobility, and overall poor functional status. Loss of employment and absenteeism rates are signi icant among workers with AxSpA.25 Likewise, work disability rates are substantial, with a reported 13% of patients with AxSpA being disabled vs 6% of the general population (2008).26 The socioeconomic toll of noncompensated inability to work, substantial absenteeism, and/or exhausted sick leave should be proactively addressed as part of the occupational assessment.27

Several instruments for assessing the individual’s physical functional abilities relevant to work requirements are available. These include assessments that take a broad-based perspective, eg, looking at the individual relative to the designated activity (Figure 5.1) and evaluating the extent of occupational impact (Figure 5.2). These conceptual models may be helpful when you review the occupational specialist’s individualized recommendations for adaptation of the patient’s work environment and/or job responsibilities.28

A 2020 meta-analysis of observational studies and trials demonstrated that treatment with biologics was associated with signi icant improvements in work productivity and activity impairment (N=1109).25 This underscores the importance of timely diagnosis and referral to a rheumatology care provider for individualized AxSpA therapy and management.

A Conceptual Framework for Understanding the Patient’s Perspective and Preferences

The individual patient brings their own lived experience to the patient-provider dialogue. This may encompass an array of “inputs,” as schematically depicted in

Figure 5.3. Through patientcentered education and support, the attuned provider can encourage and facilitate informed shared decision-making based on patient experience and preferences.29-32 Several approaches, including motivational interviewing (MI) and pain neuroscience education (PNE), also known as therapeutic VIDEO 10: A First-Person neuroscience education (TNE) may Perspective: What I’d Like You to augment this patient-provider Know dynamic. MI and PNE promote patient empowerment through education and individualized support.33,34 PCPs, chiropractors, physical therapists, and other frontline providers can o er valuable support for the patient’s treatment initiation and longitudinal management, as led by the rheumatology care provider.

Resources and Referrals

Your support of the general health and well-being of the patient with AxSpA calls for an e ective patient-provider partnership. This can be augmented by your

knowledge of patient resources that o er patient/caregiver education, individual and group support, peer-to-peer networking, and facilitated access to services, research, and providers. Many, if not all, of these patient-directed resources are readily available online. Through shared awareness of and familiarity with available local, regional, and national services, you will be able to e ectively refer patients according to their individual needs.

Spondylitis Association of America (SAA) SAA is a nationwide nonpro it organization that educates, empowers, and advocates for people living with AxSpA and related diseases. Through its partnership with patients and the medical community, SAA o ers extensive educational and support resources for patients, caregivers, and health care providers and champions research to ind a cure. https://spondylitis.org/

CreakyJoints Global Healthy Living Foundation CreakyJoints provides a digital worldwide community for patients with arthritis and their caregivers. Free-of-charge programming and services include education, support, advocacy, and patient-centered research. https://creakyjoints.org/

To request copies of the tool, email: info@exchangecme.com For a video demonstration of the tool, go to: ExchangeCME.com/AxSpAEesources

References

1. Mar ndale J, Goodacre L. The journey to diagnosis in AS/AxSpA: the impact of delay. Musculoskelet Care. 2014;12(4):221-231.

2. Fallahi S, Jamshidi AR. Diagnos c delay in ankylosing spondyli s: related factors and prognos c outcomes. Arch Rheumatol. 2016;31(1):24-30. 3. Mease PJ, et al. Comparison of men and women with axial spondyloarthri s in the US-based Corrona Psoria c Arthri s/Spondyloarthri s Registry. J Rheumatol. 2021;48(10):1528-1536. 4. Simpkin AL, Schwartzstein RM. Tolera ng uncertainty — the next medical revolu on? N Engl J Med. 2016;375(18):1713-1715. 5. Wright GC, et al. Understanding di erences between men and women with axial spondyloarthri s. Semin Arthri s Rheum. 2020;50(4):687-694. 6. Lim WZ, et al. Exploring the prevalence and factors associated with fa gue in axial spondyloarthri s in an Asian cohort in Singapore. Front Med (Lausanne). 2021;8:603941. 7. Pearson NA, et al. Assessing fa gue in adults with axial spondyloarthri s: a systema c review of the quality and acceptability of pa ent-reported outcome measures. Rheumatol Adv Pract. 2018;2(2):rky017. 8. Connolly D, et al. Disease ac vity, occupa onal par cipa on, and quality of life for individuals with and without severe fa gue in ankylosing spondyli s. Occup Ther Int. 2019;2019:3027280. 9. Perro a FM, et al. New insights in physical therapy and rehabilita on in axial spondyloarthri s: a review. Rheumatol Ther. 2019;6(4):479-486. 10. Braun J, et al. Secukinumab in axial spondyloarthri s: a narra ve review of clinical evidence. Ther Adv Musculoskelet Dis. 2021;13:1759720x211041854. 11. Shim J, et al. Quan fying and predic ng the e ect of an -TNF therapy on AxSpA related fa gue: results from the BSRBR-AS registry and meta-analysis. Rheumatology. 2020;59(11):3408-3414. 12. Swinnen TW, et al. Widespread pain in axial spondyloarthri s: clinical importance and gender di erences. Arthri s Res Ther. 2018;20(1):156. 13. López-Medina C, Moltó A. Comorbid pain in axial spondyloarthri s, including bromyalgia. Ther Adv Musculoskelet Dis. 2020;12:1759720x20966123. 14. Ji Y, et al. In ammatory or neuropathic pain: characteris cs and their rela onships with disease ac vity and func onal status in axial spondyloarthri s pa ents. Pain Med. 2018;20(5):882-888. 15. Deodhar A, et al. Assessing physical ac vity and sleep in axial spondyloarthri s: measuring the gap. Rheumatol Ther. 2019;6(4):487-501. 16. Parkinson JT, et al. Depression in pa ents with spondyloarthri s: prevalence, incidence, risk factors, mechanisms and management. Ther Adv Musculoskelet Dis. 2020;12:1759720x20970028. 17. Zhao S, et al. The prevalence of depression in axial spondyloarthri s and its associa on with disease ac vity: a systema c review and meta-analysis. Arthri s Res Ther. 2018;20. 18. Strand V, Singh JA. Pa ent burden of axial spondyloarthri s. J Clin Rheumatol. 2017;23(7):383-391. 19. Ferenchick EK, et al. Depression in primary care: Part 1—screening and diagnosis. BMJ. 2019;365:l794. 20. Ebell MH. Screening instruments for depression. Am Fam Physician. 2008;78(2):244-246. 21. APA. Depression Assessment Instruments. h ps://www.apa.org/depression-guideline/assessment. Accessed October 30, 2021. 22. CDC. About Social Determinants of Health (SDOH). h ps://www.cdc.gov/socialdeterminants/about.html. Accessed October 30, 2021. 23. Jamalyaria F, et al. Ethnicity and disease severity in ankylosing spondyli s a cross-sec onal analysis of three ethnic groups. Clin Rheumatol. 2017;36(10):2359-2364. 24. Baah FO, et al. Marginaliza on: conceptualizing pa ent vulnerabili es in the framework of social determinants of health-an integra ve review. Nurs Inq. 2019;26(1):e12268. 25. Nikiphorou E, Ramiro S. Work disability in axial spondyloarthri s. Curr Rheumatol Rep. 2020;22(9):55.

26. Ward MM, et al. Impact of ankylosing spondyli s on work and family life: comparisons with the US popula on. Arthri s Rheum. 2008;59(4):497-503.

27. Boonen A, et al. Impact of ankylosing spondyli s on sick leave, presenteeism and unpaid produc vity, and es ma on of the societal cost. Ann Rheum Dis. 2010;69(6):1123-1128. 28. Gibson L, Strong J. A conceptual framework of func onal capacity evalua on for occupa onal therapy in work rehabilita on. Aust Occup Ther J. 2003;50:64-71. 29. Evon DM, et al. What’s important to the pa ent? Informa onal needs of pa ents making decisions about hepa treatment. Pa ent. 2017;10(3):335-344.

s C

30. Heath S. Pa ent engagement strategies for improving pa ent ac va on. Pa ent Engagement HIT. 2019. h ps:// pa entengagementhit.com/features/pa ent-engagement-strategies-for-improving-pa ent-ac va on. Accessed October 30, 2021. 31. Sherman KE, et al. Health values of pa ents with chronic hepa 2004;164(21):2377-2382.

s C infec on. Arch Intern Med.

32. Welzel TM, et al. Assessing pa ent preferences for treatment decisions for new direct ac ng an viral (DAA) therapies for chronic hepa s C virus infec ons. Adv Ther. 2019;36(9):2475-2486. 33. MINT. Understanding mo va onal interviewing. h ps://mo va onalinterviewing.org/understanding-mo va onalinterviewing. Accessed October 30, 2021.

34. Physiopedia. Pain Neuroscience Educa on (PNE). h ps://www.physio-pedia.com/ Pain_Neuroscience_Educa on_(PNE). Accessed October 30, 2021.

You can request 5 copies of this patient/provider education and discussion tool by completing the CME/CE evaluation form or by emailing info@exchangecme.com. Please include your name, mailing address, and phone number.

CLINICAL RESOURCE CENTER™ Clinical Practice Guidelines 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Ward MM, et al. Arthritis Rheumatol. 2019;71(10):1599-1613. https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.41042

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. https://ard.bmj.com/content/annrheumdis/76/6/978.full.pdf

Clinical Resources Spondylitis Resources and Information for Medical Professionals Spondylitis Association of America https://spondylitis.org/resources-support/educational-materials-resources/for-medicalprofessionals/

Education and Training Opportunities Advanced Clinician Practitioner in Arthritis Care (ACPAC) University of Toronto https://acpacprogram.ca/

Educational Activities American College of Rheumatology

https://www.rheumatology.org/Learning-Center/Educational-Activities

Primary Spine Practitioner Certi ication Program University of Pittsburgh https://www.psp.pitt.edu/

Patient Resources Serving the Spondyloarthritis Community Spondylitis Association of America (SAA) SAA is a nationwide nonpro it organization that educates, empowers, and advocates for people living with spondylitis and its related diseases. Through its partnership with patients and the medical community, SAA provides extensive resources and champions research to ind a cure. https://spondylitis.org/

Project Nightingale The Nightingale study is designed to empower people with AxSpA to take control of their symptoms and improve their quality of life. Real-time data gathered via the uMotif app tracks exercise, sleep, and other factors, allowing a level of disease selfmanagement. https://www.projectnightingale.org

Suggested Reading Axial spondyloarthritis in the USA: diagnostic challenges and missed opportunities. Danve A, Deodhar A. Clin Rheumatol. 2019;38(3):625-634.

https://link.springer.com/content/pdf/10.1007/s10067-018-4397-3.pdf

Axial spondyloarthritis in the chiropractic care setting: a systematic literature review. Deodhar A, et al. J Clin Rheumatol. 2021. doi:10.1097/RHU.0000000000001776. https://journals.lww.com/jclinrheum/Abstract/9000/ Axial_Spondyloarthritis_in_the_Chiropractic_Care.98330.aspx

Choose wisely: imaging for diagnosis of axial spondyloarthritis. Diekho T, et al. Ann Rheum Dis. 2021. doi:10.1136/annrheumdis-2021-220136. https://ard.bmj.com/content/annrheumdis/early/2021/05/28/ annrheumdis-2021-220136.full.pdf

Primary care physician perspectives on barriers to diagnosing axial spondyloarthritis: a qualitative study. Lapane KL, et al. PLoS One. 2021;16(5):e0252018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143395/pdf/pone.0252018.pdf

Recognizing axial spondyloarthritis: a guide for primary care. Magrey MN, et al. Mayo Clin Proc. 2020;95(11):2499-2508. https://www.mayoclinicproceedings.org/action/showPdf?pii=S0025-6196%2820%2930153-1

The American College of Rheumatology ibromyalgia criteria are useful in the evaluation of ibromyalgia symptoms in patients with ankylosing spondylitis: a cross-sectional study. Magrey MN, et al. J Clin Rheumatol. 2021;27(8):e399-e403. https://pubmed.ncbi.nlm.nih.gov/32701537/

Physical therapy in axial spondyloarthritis: guidelines, evidence and clinical practice. Martey C, Sengupta R. Curr Opin Rheumatol. 2020;32(4):365-370. https://journals.lww.com/co-rheumatology/Abstract/2020/07000/ Physical_therapy_in_axial_spondyloarthritis_.7.aspx

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

https://onlinelibrary.wiley.com/doi/10.1002/msc.1080

Comparison of men and women with axial spondyloarthritis in the USbased Corrona Psoriatic Arthritis/Spondyloarthritis Registry. Mease PJ, et al. J Rheumatol. 2021;48(10):1528-1536. https://www.jrheum.org/content/jrheum/48/10/1528.full.pdf

Treatment of axial spondyloarthritis: What does the future hold? Poddubnyy D, Sieper J. Curr Rheumatol Rep. 2020;22(9):47. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371669/pdf/11926_2020_Article_924.pdf

The prevalence and impact of comorbidities on patients with axial spondyloarthritis: results from a nationwide population-based study. Redeker I, et al. Arthritis Res Ther. 2020;22(1):210. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488243/pdf/13075_2020_Article_2301.pdf

Axial spondyloarthritis: new advances in diagnosis and management. Ritchlin C, Adamopoulos IE. BMJ. 2021;372:m4447. https://www.bmj.com/content/bmj/372/bmj.m4447.full.pdf

Non-radiographic axial spondyloarthritis (nr-axSpA): advances in classi ication, imaging, and therapy. Robinson PC, et al. Rheumatol Ther. 2019;6(2):165-177. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514020/pdf/40744_2019_Article_146.pdf

High-intensity exercise improves fatigue, sleep, and mood in patients with axial spondyloarthritis: secondary analysis of a randomized controlled trial. Sveaas SH, et al. Phys Ther. 2020;100(8):1323-1332. https://academic.oup.com/ptj/article/100/8/1323/5828393

Mechanical low back pain. Will JS, et al. Am Fam Physician. 2018;98(7):421-428.

https://www.aafp.org/afp/2018/1001/afp20181001p421.pdf

CME POSTTEST

In order to receive credit for this activity, the participant must direct their web browser to www.ExchangeCME.com/AxSpAeHealth to complete the preactivity questionnaire, score 75% or better on the posttest, and complete the program evaluation.