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Arthritis Care & Research Oct 2019To update evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). (Review)
Review
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.
OBJECTIVE
To update evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA).
METHODS
We conducted updated systematic literature reviews for 20 clinical questions on pharmacologic treatment addressed in the 2015 guidelines, and for 26 new questions on pharmacologic treatment, treat-to-target strategy, and use of imaging. New questions addressed the use of secukinumab, ixekizumab, tofacitinib, tumor necrosis factor inhibitor (TNFi) biosimilars, and biologic tapering/discontinuation, among others. We used the Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations and required at least 70% agreement among the voting panel.
RESULTS
Recommendations for AS and nonradiographic axial SpA are similar. TNFi are recommended over secukinumab or ixekizumab as the first biologic to be used. Secukinumab or ixekizumab is recommended over the use of a second TNFi in patients with primary nonresponse to the first TNFi. TNFi, secukinumab, and ixekizumab are favored over tofacitinib. Co-administration of low-dose methotrexate with TNFi is not recommended, nor is a strict treat-to-target strategy or discontinuation or tapering of biologics in patients with stable disease. Sulfasalazine is recommended only for persistent peripheral arthritis when TNFi are contraindicated. For patients with unclear disease activity, spine or pelvis magnetic resonance imaging could aid assessment. Routine monitoring of radiographic changes with serial spine radiographs is not recommended.
CONCLUSION
These recommendations provide updated guidance regarding use of new medications and imaging of the axial skeleton in the management of AS and nonradiographic axial SpA.
Topics: Antirheumatic Agents; Biomedical Research; Clinical Trials as Topic; Humans; Rheumatology; Spondylarthritis; Spondylitis, Ankylosing; Treatment Outcome; United States
PubMed: 31436026
DOI: 10.1002/acr.24025 -
Biomolecules Oct 2020Spondyloarthritis comprises a group of inflammatory diseases of the joints and spine, with various clinical manifestations. The group includes ankylosing spondylitis,... (Review)
Review
Spondyloarthritis comprises a group of inflammatory diseases of the joints and spine, with various clinical manifestations. The group includes ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthritis. The exact etiology and pathogenesis of spondyloarthritis are still unknown, but five hypotheses explaining the pathogenesis exist. These hypotheses suggest that spondyloarthritis is caused by arthritogenic peptides, an unfolded protein response, HLA-B*27 homodimer formation, malfunctioning endoplasmic reticulum aminopeptidases, and, last but not least, gut inflammation and dysbiosis. Here we discuss the five hypotheses and the evidence supporting each. In all of these hypotheses, HLA-B*27 plays a central role. It is likely that a combination of these hypotheses, with HLA-B*27 taking center stage, will eventually explain the development of spondyloarthritis in predisposed individuals.
Topics: Arthritis, Psoriatic; Arthritis, Reactive; HLA-B27 Antigen; Humans; Inflammation; Inflammatory Bowel Diseases; Joints; Spine; Spondylarthritis; Spondylitis, Ankylosing; Unfolded Protein Response
PubMed: 33092023
DOI: 10.3390/biom10101461 -
Frontiers in Immunology 2022Spondyloarthritis (SpA) refers to a group of diseases with inflammation in joints and spines. In this family, ankylosing spondylitis (AS) is a rare but classic form that... (Review)
Review
Spondyloarthritis (SpA) refers to a group of diseases with inflammation in joints and spines. In this family, ankylosing spondylitis (AS) is a rare but classic form that mainly involves the spine and sacroiliac joint, leading to the loss of flexibility and fusion of the spine. Compared to other diseases in SpA, AS has a very distinct hereditary disposition and pattern of involvement, and several hypotheses about its etiopathogenesis have been proposed. In spite of significant advances made in Th17 dynamics and AS treatment, the underlying mechanism remains concealed. To this end, we covered several topics, including the nature of the immune response, the microenvironment in the articulation that is behind the disease's progression, and the split between the hypotheses and the evidence on how the intestine affects arthritis. In this review, we describe the current findings of AS and SpA, with the aim of providing an integrated view of the initiation of inflammation and the development of the disease.
Topics: Humans; Spondylitis, Ankylosing; Spondylarthritis; Sacroiliac Joint; Inflammation; Th17 Cells
PubMed: 36325352
DOI: 10.3389/fimmu.2022.996103 -
Journal of Clinical Rheumatology :... Dec 2021Axial spondyloarthritis (axSpA) is a chronic, rheumatic disease characterized by inflammation of the sacroiliac joint, spine, and entheses. Axial spondyloarthritis... (Review)
Review
BACKGROUND
Axial spondyloarthritis (axSpA) is a chronic, rheumatic disease characterized by inflammation of the sacroiliac joint, spine, and entheses. Axial spondyloarthritis affects up to 1.4% of adults in the United States and is associated with decreased quality of life, increased mortality, and substantial health care-related costs, imposing a high burden on patients, their caregivers, and society.
SUMMARY OF WORK
Diagnosing axSpA can be difficult. In this review, we seek to help rheumatologists in recognizing and diagnosing axSpA.
MAJOR CONCLUSIONS
A discussion of challenges associated with diagnosis is presented, including use and interpretation of imaging, reasons for diagnostic delays, differences in disease presentation by sex, and differential diagnoses of axSpA.
FUTURE RESEARCH DIRECTIONS
The early diagnosis of axSpA and advances in available therapeutic options have improved patient care and disease management, but delays in diagnosis and treatment remain common. Additional research and education are critical for recognizing diverse axSpA presentations and optimizing management early in the course of disease.
Topics: Adult; Humans; Quality of Life; Rheumatologists; Sacroiliac Joint; Spine; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 33105312
DOI: 10.1097/RHU.0000000000001575 -
Seminars in Arthritis and Rheumatism Aug 2021Psoriatic arthritis (PsA) is a heterogenous, chronic, inflammatory musculoskeletal disease that can lead to peripheral and axial damage and loss of function. Axial... (Review)
Review
Psoriatic arthritis (PsA) is a heterogenous, chronic, inflammatory musculoskeletal disease that can lead to peripheral and axial damage and loss of function. Axial involvement occurs in 25% to 70% of patients with PsA, varying greatly depending on its definition, with the key manifestations being sacroiliitis and/or spondylitis. However, there are no agreed-upon classification or diagnostic criteria for axial involvement in PsA and no consensus on treatment paradigms, which complicates management of PsA. There have only been a few studies assessing biologics in patients with PsA with axial involvement, and most treatment plans are based on evidence from patients with axial spondyloarthritis. Rheumatologists therefore face many challenges in the management of axial PsA, including diagnosis, differential diagnosis, and choice of appropriate treatment. In this review, we summarize the clinical presentation, imaging characteristics, differential diagnoses, treatment options, and prognosis of axial PsA, with the aim of increasing rheumatologists' knowledge of this phenotype of PsA and thereby aiding its optimal management.
Topics: Arthritis, Psoriatic; Humans; Prognosis; Rheumatologists; Sacroiliitis; Spondylarthritis
PubMed: 34198146
DOI: 10.1016/j.semarthrit.2021.06.006 -
Drug Design, Development and Therapy 2022Although the pathogenesis of spondyloarthritis (SpA) has still not been elucidated our options to treat SpA have definitely improved in the last decades. There are two... (Review)
Review
Although the pathogenesis of spondyloarthritis (SpA) has still not been elucidated our options to treat SpA have definitely improved in the last decades. There are two main types of SpA: (i) axial spondyloarthritis (axSpA), also covering the classical ankylosing spondylitis (AS) which is largely equivalent to radiographic (r)-axSpA but different from non-radiographic (nr)-axSpA, and (ii) peripheral SpA (pSpA) also covering psoriatic arthritis (PsA) as the main subtype. The subtype nr-axSpA has historically developed because the approval of drugs for AS did not cover forms without structural changes in the sacroiliac joints which is mandatory in the 1984 New York criteria. The definitions for axSpA are based on the 2009 Assessments in AxSpA International Society (ASAS) classification criteria. Several biologic disease modifying anti-rheumatic drugs (bDMARDs) such as the tumor necrosis factor alpha inhibitors (TNFi) and the interleukin-17-inhibitors (IL-17i) are approved mostly for the whole spectrum of SpA including axSpA and PsA but L-17i does not work in inflammatory bowel disease (IBD). Targeted synthetic (ts) DMARDs cover mainly the janus kinase (JAK)-inhibitors which have recently been developed to inhibit inflammation in several rheumatic and other immune mediated diseases such as IBD. Indeed, the physiologic mechanism of JAK-mediated signal transduction has been recognized as an important target because the inhibition of its actions was shown to successfully work as a therapeutic mechanism. There are now 4 small molecule JAK inhibitors (JAKi) that currently play a role in rheumatology with variable selectivity for the four different JAK isoforms: tofacitinib, baricitinib, upadacitinib and filgotinib. In this review, we summarize current clinical trial data and evaluate the use of the JAK1 selective inhibitor upadacitinib in the treatment of axSpA, including nr-axSpA and r-axSpA. Even though the efficacy and safety of upadacitinib over shorter periods of time has been convincing to date, long-term trials are needed to fully establish its performance and also evaluate the safety at higher doses, and its use in PsA.
Topics: Humans; Tumor Necrosis Factor-alpha; Axial Spondyloarthritis; Interleukin-17; Janus Kinase Inhibitors; Arthritis, Psoriatic; Spondylarthritis; Spondylitis, Ankylosing; Antirheumatic Agents; Biological Products; Inflammatory Bowel Diseases; Janus Kinases
PubMed: 36268520
DOI: 10.2147/DDDT.S330413 -
Annals of the Rheumatic Diseases Apr 2023Axial spondyloarthritis (axSpA) is a complex disease with diverse manifestations, for which new treatment options are warranted. BE MOBILE 1 (non-radiographic...
OBJECTIVES
Axial spondyloarthritis (axSpA) is a complex disease with diverse manifestations, for which new treatment options are warranted. BE MOBILE 1 (non-radiographic (nr)-axSpA) and BE MOBILE 2 (radiographic axSpA (r-axSpA)) are double-blind, phase 3 trials designed to evaluate efficacy and safety of bimekizumab, a novel dual interleukin (IL)-17A and IL-17F inhibitor, across the axSpA spectrum.
METHODS
In parallel 52-week trials, patients with active disease were randomised 1:1 (nr-axSpA) or 2:1 (r-axSpA) to bimekizumab 160 mg every 4 weeks:placebo. From week 16, all patients received bimekizumab 160 mg every 4 weeks. Primary (Assessment of SpondyloArthritis international Society ≥40% improvement (ASAS40)) and secondary endpoints were assessed at week 16. Here, efficacy and treatment-emergent adverse events (TEAEs) are reported up to week 24.
RESULTS
254 patients with nr-axSpA and 332 with r-axSpA were randomised. At week 16, primary (ASAS40, nr-axSpA: 47.7% bimekizumab vs 21.4% placebo; r-axSpA: 44.8% vs 22.5%; p<0.001) and all ranked secondary endpoints were met in both trials. ASAS40 responses were similar across TNFi-naïve and TNFi-inadequate responder patients. Improvements were observed in Ankylosing Spondylitis Disease Activity Score (ASDAS) states and objective measures of inflammation, including high-sensitivity C-reactive protein (hs-CRP) and MRI of the sacroiliac joints and spine. Most frequent TEAEs with bimekizumab (>3%) included nasopharyngitis, upper respiratory tract infection, pharyngitis, diarrhoea, headache and oral candidiasis. More fungal infections (all localised) were observed with bimekizumab vs placebo; no major adverse cardiovascular events (MACE) or active tuberculosis were reported. Incidence of uveitis and adjudicated inflammatory bowel disease was low.
CONCLUSIONS
Dual inhibition of IL-17A and IL-17F with bimekizumab resulted in significant and rapid improvements in efficacy outcomes vs placebo and was well tolerated in patients with nr-axSpA and r-axSpA.
Topics: Humans; Interleukin-17; Non-Radiographic Axial Spondyloarthritis; Treatment Outcome; Spondylitis, Ankylosing; Spondylarthritis; Double-Blind Method; Randomized Controlled Trials as Topic
PubMed: 36649967
DOI: 10.1136/ard-2022-223595 -
Mayo Clinic Proceedings Nov 2020Axial spondyloarthritis (axSpA) is an important cause of chronic low back pain and affects approximately 1% of the US population. The back pain associated with axSpA has... (Review)
Review
Axial spondyloarthritis (axSpA) is an important cause of chronic low back pain and affects approximately 1% of the US population. The back pain associated with axSpA has a characteristic pattern referred to as inflammatory back pain (IBP). Features of IBP include insidious onset before age 45 years, association with morning stiffness, improvement with exercise but not rest, alternating buttock pain, and good response to treatment with nonsteroidal anti-inflammatory drugs. In patients with IBP, it is essential to look for other features associated with spondyloarthritis (SpA), such as enthesitis, dactylitis, peripheral arthritis, extra-articular manifestations (eg, psoriasis, uveitis, or inflammatory bowel disease), human leukocyte antigen B27 positivity, and a family history of SpA. Axial SpA is underrecognized, and a delay of several years between symptom onset and diagnosis is common. However, with new and effective therapies available for the treatment of active axSpA, early recognition and diagnosis are of critical importance. For this narrative review, we conducted a literature search of English-language articles using PubMed. Individual searches were performed to identify potential articles of interest related to axSpA (search terms: ["axSpA" OR "axial SpA" OR "axial spondyloarthritis" OR "ankylosing spondylitis"]) in combination with terms related to IBP ("inflammatory back pain" OR "IBP" OR "chronic back pain" OR "CBP" OR "lower back pain" OR "LBP"), diagnosis (["diagn∗" OR "classification"] AND ["criteria" OR "recommend∗" OR "guidelines"]), and referral ("refer∗"). No date range was formally selected, as we were interested in providing an overview of the evolution of these concepts in clinical practice. We supplemented the review with insights based on our clinical expertise. Patients with chronic back pain should be screened for IBP and other SpA features; suspicion for axSpA should trigger referral to a rheumatologist for further evaluation.
Topics: Back Pain; Humans; Primary Health Care; Spondylarthritis
PubMed: 32736944
DOI: 10.1016/j.mayocp.2020.02.007 -
Rheumatology (Oxford, England) Oct 2020In recent years, significant progress has been made in improving the early diagnosis of spondyloarthritides (SpA), including axial SpA. Nonetheless, there are still... (Review)
Review
In recent years, significant progress has been made in improving the early diagnosis of spondyloarthritides (SpA), including axial SpA. Nonetheless, there are still issues related to the application of classification criteria for making the primary diagnosis of SpA in the daily practice. There are substantial conceptional and operational differences between the diagnostic vs classification approach. Although it is not possible to develop true diagnostic criteria for natural reasons as discussed in this review, the main principles of the diagnostic approach can be clearly defined: consider the pre-test probability of the disease, evaluate positive and negative results of the diagnostic test, exclude other entities, and estimate the probability of the disease at the end. Classification criteria should only be applied to patients with an established diagnosis and aimed at the identification of a rather homogeneous group of patients for the conduction of clinical research.
Topics: Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Spondylarthritis; Spondylitis, Ankylosing; Tomography, X-Ray Computed
PubMed: 33053191
DOI: 10.1093/rheumatology/keaa250 -
Annals of the Rheumatic Diseases Sep 2019Although the pathogenic mechanisms underlying axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) are not fully elucidated, several lines of evidence suggest... (Review)
Review
Although the pathogenic mechanisms underlying axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) are not fully elucidated, several lines of evidence suggest that immune responses mediated by interleukin 17A (IL-17A) play a pivotal role in both diseases. This is best highlighted by the significant clinical efficacy shown with inhibitors of IL-17A in treating axSpA and PsA. Nevertheless, a number of knowledge gaps exist regarding the role of IL-17A in the pathophysiology of spondyloarthritis in man, including its cellular origin, its precise role in discrete disease processes such enthesitis, bone erosion, and bone formation, and the reasons for the discrepant responses to IL-17A inhibition observed in certain other spondyloarthritis manifestations. In this review, we focus on the latest data from studies investigating the role of IL-17A in ankylosing spondylitis (AS) and PsA that build on existing and emerging scientific knowledge in the field. Key remaining research questions are also highlighted to guide future research.
Topics: Antibodies, Monoclonal, Humanized; Arthritis, Psoriatic; Biomarkers; Humans; Interleukin-17; Spondylarthritis
PubMed: 31278139
DOI: 10.1136/annrheumdis-2019-215356