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Nonradiographic axial spondyloarthritis

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Abstract

Non-radiographic axial spondyloarthritis (nr-axSpA) is a complex disease process that is part of the spectrum of axial spondyloarthritis (axSpA). This article reviews the current state of the literature as the understanding of this disease spectrum expands. The conceptual history and terminology, genetics, and epidemiology are reviewed. The clinical manifestations, diagnostic approach, and measures of disease activity are examined. Finally the current treatment modalities and recommendations and the research agenda for nr-axSpA are reviewed. With the advent of new criteria, the disease spectrum can be studied in a systematic manner. These data have enriched our knowledge that reflects an earlier or milder form of disease on a spectrum same as that of ankylosing spondylitis (or radiographic axSpA). We learned how patients present in this stage and that despite an unacceptable delay in diagnosis (regardless of the stage), the burden of disease is high and unremitting. nr-axSpA clinical trials have been somewhat heterogeneous (with variable inclusion criteria) but have nevertheless shown considerable efficacy with tumor necrosis factor inhibitors and flare on withdrawal of therapy.

Section snippets

Conceptual history and terminology

Axial spondyloarthritis (axSpA) is a chronic inflammatory arthritis classically affecting the axial skeleton and entheses, with occasional involvement of the appendicular skeleton. The clinical phenotype was recognized as early as the 1600s, with case descriptions throughout the 18th and 19th centuries, however, without the current terminology [1]. The development of radiography in the early 20th century led to the discovery of sacroiliitis and its ubiquity in inflammatory axial disease and its

Genetics and pathogenesis

There are several hypotheses regarding the immunopathogenesis of SpA, where genetics has a central role, although the primary trigger remains unclear. Although this topic is beyond the scope of this specific review, there are currently no data to suggest that the pathogenesis of non-radiographic disease is different from that of radiographic disease.

The human leukocyte antigen B27 (HLA-B27) is a surface antigen in the major histocompatibility complex class I. Its association with AS has been

Epidemiology and demographics

According to National Health and Nutrition Examination Survey (NHANES) data in the United States, more than 2 million individuals between the ages of 20 and 69 years suffer from SpA [29]. According to this population study, more than 1% of adults are affected by SpA, which is similar to or greater than the prevalence of rheumatoid arthritis. Most cohorts suggest a 1:1 proportion of patients with AS to patients with nr-axSpA [37], although no population level data exist for nr-axSpA specifically.

Clinical manifestations

The classic clinical symptom of axSpA is inflammatory back pain (IBP). There are several criteria sets including the Calin criteria [51] and Berlin criteria [52] but most recently defined by an expert ASAS panel [53]. Application of the IBP criteria aids in the early diagnosis of axSpA, especially as a referral screening tool in the primary care setting [30], [32], [54], [55]. The classic parameters for IBP include age of onset <40 years, insidious symptom onset, stiffness improved with

Diagnosis

The diagnosis of axSpA is a complex process that requires clinical, laboratory, and MRI data. It also requires the explicit consideration of the differential diagnoses and pretest probability for a given population. The purpose of the classification criteria is for the inclusion of patients in a research study after a clinical diagnosis has already been made. Classification criteria should not be used as diagnostic criteria. The distinction between radiographic and nonradiographic axSpA can be

Measures of disease activity

Several tools have been developed to measure disease activity and outcomes in axSpA. The most important measure of disease activity is through self-reported disease activity and composite scoring, adding objective biomarkers of inflammation like the C-reactive protein (CRP). The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is an assessment tool used to measure disease activity through patient-reported measures of fatigue, joint pain, localized tenderness, and morning stiffness

Treatment

AxSpA is a complex disease process that requires a multidisciplinary approach led by a rheumatologist and centered on the patient. The primary goal of treatment is to maximize quality of life, to reduce the symptom burden and functional impairment, to prevent progression of structural damage, and to minimize disease complications and comorbidities. Several international organizations have published guidelines for the treatment of axSpA, including nr-axSpA [16], [17]. The most recent

Summary

In summary, nr-axSpA is a complex disease process that is part of the spectrum of axSpA and affects more than 1% of the United States population, although this has not been well studied at population levels globally. The major rheumatologic societies recognize nr-axSpA as part of a spectrum of a single disease process. The most recent classification criteria put forth by ASAS recognize the nonradiographic spectrum of axSpA and enable the study of these patients in clinical trials and

Funding statement

Professor Gensler received research funding from Amgen, AbbVie, Novartis, and UCB and honoraria for consulting from Galapagos, Janssen, Lilly, and Pfizer. She also received funding from the Spondylitis Association of America and from the Russel/Engleman Rheumatology Research Center at UCSF.

Dr. Lockwood has no disclosures to disclose.

Conflicts of interest statement

Professor Gensler has no further conflicts of interest. Dr. Lockwood has no funding to disclose.

Practice points

  • Non-radiographic axial Spondyloarthritis (nr-axSpA) is a chronic inflammatory condition on a spectrum same as that of ankylosing spondylitis (AS) or radiographic axial spondyloarthritis.

  • Females have more commonly nr-axSpA than males (who more commonly have radiographic sacroiliitis [AS]).

  • Similar to AS, nr-axSpA warrants treatment with standard therapies (NSAIDs and biologics [with TNFi

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