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Annals of the Rheumatic Diseases Dec 2021Axial spondyloarthritis (axSpA) encompasses both radiographic and non-radiographic axSpA. It is a chronic inflammatory disease with a predilection for involving the... (Review)
Review
Axial spondyloarthritis (axSpA) encompasses both radiographic and non-radiographic axSpA. It is a chronic inflammatory disease with a predilection for involving the axial skeleton. The most common presenting symptoms are chronic back pain and spinal stiffness but peripheral and extra-musculoskeletal manifestations occur also frequently. The diagnosis of axSpA relies on the recognition of a clinical pattern of the disease, based on clinical, laboratory and imaging features. The Assessment in SpondyloArthritis international Society classification criteria for axSpA are valid and well implemented for research purposes. Sustained disease activity, measured by validated tools such as the Ankylosing Spondylitis Disease Activity Score, leads to irreversible structural damage and poor functioning and therefore should be abrogated. As part of the management algorithm, non-steroidal anti-inflammatory drugs remain as the first line of pharmacological treatment besides physiotherapy. As a second line, tumour necrosis factor inhibitor and interleukin-17 inhibitor are available but recently Janus kinase inhibitors have also shown efficacy in improving symptoms of the disease.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Axial Spondyloarthritis; Humans; Interleukin Inhibitors; Interleukin-17; Janus Kinase Inhibitors; Non-Radiographic Axial Spondyloarthritis; Physical Therapy Modalities; Tumor Necrosis Factor Inhibitors
PubMed: 34615639
DOI: 10.1136/annrheumdis-2021-221035 -
BMJ (Clinical Research Ed.) Jan 2021Axial spondyloarthritis (axSpA) is an inflammatory disease of the axial skeleton associated with significant pain and disability. Previously, the diagnosis of ankylosing... (Review)
Review
Axial spondyloarthritis (axSpA) is an inflammatory disease of the axial skeleton associated with significant pain and disability. Previously, the diagnosis of ankylosing spondylitis required advanced changes on plain radiographs of the sacroiliac joints. Classification criteria released in 2009, however, identified a subset of patients, under the age of 45, with back pain for more than three months in the absence of radiographic sacroiliitis who were classified as axSpA based on a positive magnetic resonance imaging or HLAB27 positivity and specific clinical features. This subgroup was labeled non-radiographic (nr)-axSpA. These patients, compared with those identified by the older New York criteria, contained a larger percentage of women and demonstrated less structural damage. However, their clinical manifestations and response to biologics were similar to radiographic axSpA. The discovery of the interleukin (IL) IL-23/IL-17 pathway revealed key molecules involved in the pathophysiology of axSpA. This discovery propelled the generation of antibodies directed toward IL-17A, which are highly effective and demonstrate treatment responses in axSpA that are similar to those observed with anti-TNF agents. The finding that agents that block IL-23 were not effective in axSpA came as a surprise and the potential underlying mechanisms underlying this lack of response are discussed. New agents with dual inhibition of the IL-17A and F isoforms and some oral small molecule agents that target the Jak-STAT pathway, have also shown efficacy in axSpA.
Topics: Antibodies, Monoclonal, Humanized; Exercise Therapy; HLA-B27 Antigen; Humans; Interleukin-17; Interleukins; Magnetic Resonance Imaging; Spondylitis, Ankylosing
PubMed: 33397652
DOI: 10.1136/bmj.m4447 -
Frontiers in Immunology 2021The term spondyloarthritis pertains to both axial and peripheral arthritis including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), which is strongly linked... (Review)
Review
The term spondyloarthritis pertains to both axial and peripheral arthritis including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), which is strongly linked to psoriasis and also the arthritis associated with inflammatory bowel disease. The argument supporting the role for IL-23 across the spectrum of SpA comes from 4 sources. First, genome wide associated studies (GWAS) have shown that all the aforementioned disorders exhibit IL-23R pathway SNPs, whereas HLA-B27 is not linked to all of these diseases-hence the IL-23 pathway represents the common genetic denominator. Secondly, experimental animal models have demonstrated a pivotal role for the IL-23/IL-17 axis in SpA related arthropathy that initially manifests as enthesitis, but also synovitis and axial inflammation and also associated aortic root and cutaneous inflammation. Thirdly, the emergent immunology of the human enthesis also supports the presence of IL-23 producing myeloid cells, not just at the enthesis but in other SpA associated sites including skin and gut. Finally, drugs that target the IL-23 pathway show excellent efficacy for skin disease, efficacy for IBD and also in peripheral arthropathy associated with SpA. The apparent failure of IL-23 blockade in the AS which is effectively a spinal polyenthesitis but evidence for efficacy of IL-23 inhibition for peripheral enthesitis in PsA and preliminary suggestions for benefit in axial PsA, raises many questions. Key amongst these is whether spinal inflammation may exhibit entheseal IL-17A production independent of IL-23 but peripheral enthesitis is largely dependent on IL-23 driven IL-17 production. Furthermore, IL-23 blocking strategies in animal models may prevent experimental SpA evolution but not prevent established disease, perhaps pointing towards a role for IL-23 in innate immune disease initiation whereas persistent disease is dependent on memory T-cell responses that drive IL-17A production independently of IL-23, but this needs further study. Furthermore, IL-12/23 posology in inflammatory bowel disease is substantially higher than that used in AS trials which merits consideration. Therefore, the IL-23 pathway is centrally involved in the SpA concept but the nuances and intricacies in axial inflammation that suggest non-response to IL-23 antagonism await formal definition. The absence of comparative immunology between the different skeletal sites renders explanations purely hypothetical at this juncture.
Topics: Animals; Biomarkers; Diagnosis, Differential; Disease Management; Disease Susceptibility; Genetic Predisposition to Disease; Humans; Interleukin-17; Interleukin-23; Molecular Targeted Therapy; Signal Transduction; Spondylitis, Ankylosing; Treatment Outcome
PubMed: 33815371
DOI: 10.3389/fimmu.2021.614255 -
Lancet (London, England) Jul 2022Upadacitinib, a Janus kinase inhibitor, has been shown to be effective in patients with ankylosing spondylitis. We aimed to assess the efficacy and safety of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Upadacitinib, a Janus kinase inhibitor, has been shown to be effective in patients with ankylosing spondylitis. We aimed to assess the efficacy and safety of upadacitinib in non-radiographic axial spondyloarthritis.
METHODS
The SELECT-AXIS 2 non-radiographic axial spondyloarthritis study was a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 113 sites across 23 countries (Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, France, Germany, Hungary, Israel, Japan, Mexico, Poland, Russia, Slovakia, South Korea, Spain, Taiwan, Turkey, Ukraine, and the USA). Eligible adults had active non-radiographic axial spondyloarthritis, with objective signs of inflammation based on MRI or elevated C-reactive protein and an inadequate response to non-steroidal anti-inflammatory drugs. Patients were randomly assigned (1:1) to receive oral upadacitinib 15 mg once daily or placebo using interactive response technology. Random treatment assignment was stratified by MRI inflammation in the sacroiliac joints and screening high-sensitivity C-reactive protein status (MRI-positive and C-reactive protein-positive, MRI-positive and C-reactive protein-negative, and MRI-negative and C-reactive protein-positive) and previous exposure to biologic disease-modifying antirheumatic drugs (yes vs no). Treatment assignment was masked from patients, investigators, study site personnel, and the study sponsor. The primary endpoint was the proportion of patients with an Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Analyses were performed on the full analysis set of patients, who underwent random allocation and received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04169373.
FINDINGS
Between Nov 26, 2019, and May 20, 2021, 314 patients with active non-radiographic axial spondyloarthritis were enrolled into the study, and 313 received study drug (156 in the upadacitinib group and 157 in the placebo group); 295 (94%) patients (145 in the upadacitinib group and 150 in the placebo group) received treatment for the full 14 weeks. A significantly higher ASAS40 response rate was achieved with upadacitinib compared with placebo at week 14 (70 [45%] of 156 patients vs 35 [23%] of 157 patients; p<0·0001; treatment difference 22%, 95% CI 12-32). The rate of adverse events up to week 14 was similar in the upadacitinib group (75 [48%] of 156 patients) and placebo group (72 [46%] of 157 patients). Serious adverse events and adverse events leading to discontinuation of study drug occurred in four (3%) of 156 patients in the upadacitinib group and two (1%) of 157 patients in the placebo group. Few patients had serious infections or herpes zoster in either treatment group (each event occurred in two [1%] of 156 patients in the upadacitinib group and one [1%] of 157 patients in the placebo group). Five (3%) of 156 patients in the upadacitinib group had neutropenia; no events of neutropenia occurred in the placebo group. No opportunistic infections, malignancies, major adverse cardiovascular events, venous thromboembolic events, or deaths were reported with upadacitinib treatment.
INTERPRETATION
Upadacitinib significantly improved the signs and symptoms of non-radiographic axial spondyloarthritis compared with placebo at week 14. These findings support the potential of upadacitinib as a new therapeutic option in patients with active non-radiographic axial spondyloarthritis.
FUNDING
AbbVie.
Topics: Adult; Axial Spondyloarthritis; C-Reactive Protein; Double-Blind Method; Heterocyclic Compounds, 3-Ring; Humans; Inflammation; Neutropenia; Non-Radiographic Axial Spondyloarthritis; Treatment Outcome
PubMed: 35908570
DOI: 10.1016/S0140-6736(22)01212-0 -
Orthopedic Nursing
Topics: Humans; Spondylitis, Ankylosing
PubMed: 36944209
DOI: 10.1097/NOR.0000000000000938 -
Current Rheumatology Reports May 2022The differences in the epidemiology and management of patients with axial spondyloarthritis (axSpA) among regions and countries largely depend on the positivity of human... (Review)
Review
PURPOSE OF REVIEW
The differences in the epidemiology and management of patients with axial spondyloarthritis (axSpA) among regions and countries largely depend on the positivity of human leukocyte antigen (HLA)-B27 and the health care system. This review article focused on axSpA in Japan, where the prevalence of HLA-B27 is extremely low (0.3%) and the universal health insurance system typically provides a 70% or more copayment by the government.
RECENT FINDINGS
A nationwide survey was conducted in Japan in 2018, which estimated that there were 3200 patients (95% confidence interval [CI]: 2400-3900) with ankylosing spondylitis (AS), a term interchangeable with radiographic axSpA (r-axSpA), and 800 patients (95% CI: 530-1100) had non-radiographic (nr)-axSpA. These data indicate a prevalence of 2.6/100,000 or 0.0026% for AS and 0.6/100,000 or 0.0006% for nr-axSpA. Patients with AS, but not those with nr-axSpA, are designated as suffering from intractable diseases in Japan; thus, their medical expenses are reduced by grant under the Act on Medical Care for Patients with Intractable Diseases. As of February 2022, infliximab, adalimumab, secukinumab, ixekizumab, and brodalumab have been approved for AS, and secukinumab, ixekizumab, and brodalumab have been approved for nr-axSpA. An algorithm for nr-axSpA in Japan has been developed for the proper diagnosis and use of these therapeutic agents. A low prevalence of axSpA, especially that of nr-axSpA, was found in Japan. Early referral and the resultant diagnosis and appropriate treatment of these patients by rheumatologists are crucial issues in Japan, as in other countries.
Topics: Axial Spondyloarthritis; HLA-B27 Antigen; Humans; Japan; Non-Radiographic Axial Spondyloarthritis; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 35380380
DOI: 10.1007/s11926-022-01068-4 -
Best Practice & Research. Clinical... Sep 2023Over the recent years the wider availability and application of state-of-the-art immunological technologies greatly advanced the insight into the mechanisms that play an... (Review)
Review
Over the recent years the wider availability and application of state-of-the-art immunological technologies greatly advanced the insight into the mechanisms that play an important role in axial spondyloarthritis (axSpA) pathophysiology. This increased understanding has facilitated the development of novel treatments that target disease relevant pathways, hereby improving outcome for axSpA patients. In axSpA pathophysiology genetic and environmental factors as well as immune activation by mechanical or bacterial stress resulting in a chronic inflammatory response have a central role. The TNF and IL-23/IL-17 immune pathways play a pivotal role in these disease mechanisms. This review provides an outline of the immunological basis of axSpA with a focus on key genetic risk factors and their link to activation of the pathological immune response, as well as on the role of the gut and entheses in the initiation of inflammation with subsequent new bone formation in axSpA.
Topics: Humans; Spondylarthritis; HLA-B27 Antigen; Spondylitis, Ankylosing; Axial Spondyloarthritis; Inflammation
PubMed: 38030467
DOI: 10.1016/j.berh.2023.101897 -
Expert Opinion on Pharmacotherapy 2023Axial spondyloarthritis (axSpA) refers to an inflammatory rheumatic disease that mainly affects the axial skeleton and leads to progressive radiographic changes of the... (Review)
Review
INTRODUCTION
Axial spondyloarthritis (axSpA) refers to an inflammatory rheumatic disease that mainly affects the axial skeleton and leads to progressive radiographic changes of the sacroiliac joints and spine. axSpA is currently subdivided into the radiographic (r-axSpA) and non-radiographic (nr-axSpA) form. Both forms are associated with musculoskeletal pain, restriction of spinal mobility, specific extra-musculoskeletal manifestations, and overall, altered quality of life. The therapeutic management of axSpA is currently well standardized.
AREAS COVERED
We reviewed available literature (by using PubMed search) on non-pharmacological and pharmacological treatment options that may be used in axSpA, including r-axSpA and nr-axSpA, as well as the role of non-steroidal anti-inflammatory drugs (NSAIDs), biological agents including TNFalpha (TNFi) and IL-17 (IL-17i) inhibitors. New treatment options such as Janus kinase inhibitors are also reviewed.
EXPERT OPINION
NSAIDs remain the mainstay of initial therapy, and subsequently, biological agents (TNFi and IL-17i) may be envisaged. Four TNFi are licensed for the treatment of both r-axSpA and nr-axSpA, while IL-17i are approved in each indication. The choice between a TNFi and an IL-17i is mainly guided by the presence of extra-articular manifestations. JAKi were more recently introduced for the treatment of r-axSpA, but their use is restricted to specific patients with a safe cardiovascular profile.
Topics: Humans; Spondylitis, Ankylosing; Spondylarthritis; Quality of Life; Non-Radiographic Axial Spondyloarthritis; Anti-Inflammatory Agents, Non-Steroidal; Axial Spondyloarthritis
PubMed: 37318776
DOI: 10.1080/14656566.2023.2226328 -
Arthritis & Rheumatology (Hoboken, N.J.) Dec 2019
Topics: Ankylosis; Biological Therapy; Humans; Magnetic Resonance Imaging; Sacroiliac Joint; Spondylarthritis
PubMed: 31328427
DOI: 10.1002/art.41049 -
Seminars in Immunology Dec 2021The spondyloarthritides are a cluster of inflammatory rheumatic diseases characterized by different diagnostic entities with heterogeneous phenotypes. The current... (Review)
Review
The spondyloarthritides are a cluster of inflammatory rheumatic diseases characterized by different diagnostic entities with heterogeneous phenotypes. The current classification system groups spondyloarthritis patients in two main categories, axial and peripheral spondyloarthritis, providing a framework wherein the clinical picture guides the treatment. However, the heterogeneity of the clinical manifestations of the pathologies, even when residing in the same group, highlights the importance of analyzing the smallest features of each entity to understand how different cellular subsets evolve, what the underlying mechanisms are and what biological markers can be identified and validated to evaluate the stage of disease and the corresponding efficacy of treatments. In this review, we will focus mostly on axial spondyloarthritis, report current knowledge concerning the cellular populations involved in its pathophysiology, and their molecular diversity. We will discuss the implications of such a diversity, and their meaning in terms of patients' stratification.
Topics: Humans; Spondylitis, Ankylosing; Spondylarthritis
PubMed: 34763975
DOI: 10.1016/j.smim.2021.101521