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Immunology and Allergy Clinics of North... Aug 2023The spondyloarthritides are a diverse group of distinct yet interrelated disease processes with overlapping clinical features. They are ankylosing spondylitis, reactive... (Review)
Review
The spondyloarthritides are a diverse group of distinct yet interrelated disease processes with overlapping clinical features. They are ankylosing spondylitis, reactive arthritis, inflammatory bowel disease-associated arthritis, and psoriatic arthritis. Genetically, these disease processes have been linked by the presence of HLA-B27. They manifest with axial and peripheral symptoms, such as inflammatory back pain, enthesitis, oligoarthritis, and dactylitis. The onset of symptoms can begin before the age of 45; however, because of the wide range of signs and symptoms, diagnosis can be delayed, leading to unchecked inflammation, structural damage, and later, restriction in physical mobility.
Topics: Humans; Spondylarthritis; Spondylitis, Ankylosing; Arthritis, Psoriatic; Arthritis, Reactive; Inflammatory Bowel Diseases
PubMed: 37394262
DOI: 10.1016/j.iac.2022.10.001 -
Clinical and Experimental Rheumatology Nov 2023Axial spondyloarthritides (axSpA) are a group of systemic autoimmune diseases, characterised by an inflammatory involvement of the axial skeleton, which, in the earlier... (Review)
Review
Axial spondyloarthritides (axSpA) are a group of systemic autoimmune diseases, characterised by an inflammatory involvement of the axial skeleton, which, in the earlier phases, cannot be detected by conventional radiology, but only by magnetic resonance imaging, thus defining the so-called non-radiographic axSpA (nr-axSpA). The initial osteitis then tends to complicate into bone reabsorption and aberrant bone deposition, which then determines the ankylosis of the axial skeleton in the latest phases of the disease.Peripheral joints may also be affected, enthesitis being its more characteristic manifestation. The radiographic form corresponds to ankylosing spondylitis which, with psoriatic arthritis, is the best-known subtype of SpA. AxSpA are rarely associated to laboratory abnormalities and are usually complicated by the presence of both extra-articular manifestations (particularly acute anterior uveitis, psoriasis and inflamatory bowel disease) and comorbidities, with a subsequent higher risk for patients of an impaired quality of life.In this paper we reviewed the literature on axSpA of 2021 and 2022 (Medline search of articles published from 1st January 2021 to 31st December 2022).
Topics: Humans; Spondylarthritis; Quality of Life; Spondylitis, Ankylosing; Arthritis, Psoriatic; Psoriasis
PubMed: 37965699
DOI: 10.55563/clinexprheumatol/9fhz98 -
Nature Reviews. Rheumatology Dec 2023Since the original description of spondyloarthritis 50 years ago, results have demonstrated similarities and differences between ankylosing spondylitis (AS) and axial... (Review)
Review
Since the original description of spondyloarthritis 50 years ago, results have demonstrated similarities and differences between ankylosing spondylitis (AS) and axial psoriatic arthritis (PsA). HLA-B27 gene carriage in axial inflammation is linked to peri-fibrocartilaginous sacroiliac joint osteitis, as well as to spinal peri-entheseal osteitis, which is often extensive and which provides a crucial anatomical and immunological differentiation between the AS and PsA phenotypes. Specifically, HLA-B27-related diffuse bone marrow oedema (histologically an osteitis) and bone marrow fatty corners detected via magnetic resonance imaging, as well as radiographic changes such as sacroiliitis, vertebral squaring, corner erosions and Romanus lesions, all indicate initial bone phenotypes in HLA-B27 axial disease. However, in much of PsA with axial involvement, enthesitis primarily manifests in ligamentous soft tissue as 'ligamentitis', with characteristic lesions that include para-syndesmophytes and sacroiliac joint bony sparing. Like axial PsA, diffuse idiopathic skeletal hyperostosis phenotypes, which can be indistinguishable from PsA, exhibit a thoracic and cervical spinal ligamentous soft-tissue tropism, clinically manifesting as syndesmophytosis that is soft-tissue-centric, including paravertebral soft-tissue ossification and sacroiliac soft-ligamentous ossification instead of joint-cavity fusion. The enthesis bone and soft tissues have radically different immune cell and stromal compositions, which probably underpins differential responses to immunomodulatory therapy, especially IL-23 inhibition.
Topics: Humans; Arthritis, Psoriatic; Spondylitis, Ankylosing; Osteitis; HLA-B27 Antigen; Ligaments
PubMed: 37919337
DOI: 10.1038/s41584-023-01038-9 -
Arthritis Research & Therapy Sep 2023Upadacitinib, a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients with ankylosing spondylitis (AS) in the phase III... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of upadacitinib in patients with ankylosing spondylitis refractory to biologic therapy: 1-year results from the open-label extension of a phase III study.
BACKGROUND
Upadacitinib, a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients with ankylosing spondylitis (AS) in the phase III SELECT-AXIS programs. We report the 1-year efficacy and safety in patients with AS and an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR) from the SELECT-AXIS 2 study.
METHODS
Patients ≥ 18 years with active AS who met the modified New York criteria for AS and were bDMARD-IR received double-blind upadacitinib 15 mg once daily (QD) or placebo for 14 weeks. Patients who completed 14 weeks could enter an open-label extension and receive upadacitinib 15 mg QD for up to 2 years. Efficacy endpoints included the percentage of patients achieving ≥ 40% improvement in Assessment of SpondyloArthritis international Society response (ASAS40), Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity (LDA), and ASDAS inactive disease (ID); and change from baseline in total and nocturnal back pain, and Bath Ankylosing Spondylitis Functional Index (BASFI). Subgroup analyses (bDMARD lack of efficacy versus intolerance, and prior tumor necrosis factor inhibitor [TNFi] versus interleukin-17 inhibitor [IL-17i] exposure) were conducted. Binary and continuous efficacy endpoints were assessed using non-responder imputation with multiple imputation (NRI-MI) and as observed (AO) analyses; and mixed-effects model repeated measures (MMRM) and AO, respectively. Safety was assessed based on adverse events. Data through week 52 are reported.
RESULTS
Of 420 randomized patients, 366 (continuous upadacitinib: n = 181; placebo to upadacitinib: n = 185) completed 52 weeks of treatment. At week 52, in the continuous upadacitinib and placebo to upadacitinib groups, ASAS40, ASDAS LDA, and ASDAS ID were achieved by 66% and 65%, 57% and 55%, and 26% and 25% (all NRI-MI); and change from baseline in total back pain, nocturnal back pain, and BASFI was -4.5 and -4.3, -4.6 and -4.4, and -3.6 and -3.5 (all MMRM), respectively. No new safety risks were identified. Subgroup analyses were consistent with the overall study population.
CONCLUSIONS
Upadacitinib 15 mg QD demonstrated sustained improvement up to 52 weeks in bDMARD-IR patients with AS. Efficacy was generally similar in patients with lack of efficacy versus intolerance to bDMARDs and prior TNFi versus IL-17i exposure.
TRIAL REGISTRATION
NCT02049138.
Topics: Humans; Antirheumatic Agents; Biological Therapy; Heterocyclic Compounds, 3-Ring; Spondylarthritis; Spondylitis, Ankylosing; Tumor Necrosis Factor Inhibitors
PubMed: 37723577
DOI: 10.1186/s13075-023-03128-1 -
Arthritis Research & Therapy Jan 2024Ankylosing spondylitis (AS) is one of several disorders known as seronegative spinal arthritis (SpA), the origin of which is unknown. Existing epidemiological data show...
BACKGROUND
Ankylosing spondylitis (AS) is one of several disorders known as seronegative spinal arthritis (SpA), the origin of which is unknown. Existing epidemiological data show that inflammatory and immunological factors are important in the development of AS. Previous research on the connection between immunological inflammation and AS, however, has shown inconclusive results.
METHODS
To evaluate the causal association between immunological characteristics and AS, a bidirectional, two-sample Mendelian randomization (MR) approach was performed in this study. We investigated the causal connection between 731 immunological feature characteristic cells and AS risk using large, publically available genome-wide association studies.
RESULTS
After FDR correction, two immunophenotypes were found to be significantly associated with AS risk: CD14 - CD16 + monocyte (OR, 0.669; 95% CI, 0.544 ~ 0.823; P = 1.46 × 10; P = 0.043), CD33dim HLA DR + CD11b + (OR, 0.589; 95% CI = 0.446 ~ 0.780; P = 2.12 × 10; P = 0.043). AS had statistically significant effects on six immune traits: CD8 on HLA DR + CD8 + T cell (OR, 1.029; 95% CI, 1.015 ~ 1.043; P = 4.46 × 10; P = 0.014), IgD on IgD + CD24 + B cell (OR, 0.973; 95% CI, 0.960 ~ 0.987; P = 1.2 × 10; P = 0.021), IgD on IgD + CD38 - unswitched memory B cell (OR, 0.962; 95% CI, 0.945 ~ 0.980; P = 3.02 × 10; P = 0.014), CD8 + natural killer T %lymphocyte (OR, 0.973; 95% CI, 0.959 ~ 0.987; P = 1.92 × 10; P = 0.021), CD8 + natural killer T %T cell (OR, 0.973; 95% CI, 0.959 ~ 0.987; P = 1.65 × 10; P = 0.021).
CONCLUSION
Our findings extend genetic research into the intimate link between immune cells and AS, which can help guide future clinical and basic research.
Topics: Humans; Spondylitis, Ankylosing; Genome-Wide Association Study; Mendelian Randomization Analysis; Spondylarthritis; HLA-DR Antigens
PubMed: 38229175
DOI: 10.1186/s13075-024-03266-0 -
The Journal of Rheumatology Aug 2023To report safety and efficacy of ixekizumab (IXE) from the COAST program at 3 years, including 1 year from the originating studies (COAST-V, COAST-W, and COAST-X), and 2...
OBJECTIVE
To report safety and efficacy of ixekizumab (IXE) from the COAST program at 3 years, including 1 year from the originating studies (COAST-V, COAST-W, and COAST-X), and 2 years from COAST-Y.
METHODS
In COAST-Y, patients continued with the dose received at the end of the originating study at week 52: 80 mg IXE either every 4 weeks (Q4W) or every 2 weeks (Q2W). Placebo-treated patients from COAST-X received IXE Q4W in COAST-Y. Starting at week 116 (week 64 of COAST-Y), patients receiving IXE Q4W could be escalated to Q2W. Safety for patients receiving ≥ 1 dose of IXE and efficacy for patients receiving ≥ 1 dose of IXE Q4W was assessed. Data are summarized as observed.
RESULTS
For the 932 patients who received ≥ 1 dose of IXE (Q2W or Q4W) through 3 years, treatment-emergent adverse events (TEAEs) occurred at an incidence rate (IR) of 38.0 per 100 patient-years (PYs). The most frequently reported were infections (IR 25.7 per 100 PYs) and injection site reactions (IR 7.4 per 100 PYs); the majority of TEAEs were mild or moderate in severity. In total, 7.1% of TEAEs led to discontinuation (IR 3.1 per 100 PYs). All patient groups receiving IXE Q4W assessed through 3 years saw sustained improvements in Ankylosing Spondylitis Disease Activity Score, clinically important improvement, and other efficacy end points.
CONCLUSION
The 3-year safety profile of IXE in the COAST program is consistent with the previously established long-term safety profile. IXE Q4W provided sustained improvement of disease activity in patients who received treatment through 3 years. (ClinicalTrials.gov: NCT02696785 [COAST-V], NCT02696798 [COAST-W], NCT02757352 [COAST-X], and NCT03129100 [COAST-Y]).
Topics: Humans; Treatment Outcome; Double-Blind Method; Dermatologic Agents; Spondylitis, Ankylosing
PubMed: 36792107
DOI: 10.3899/jrheum.221022 -
Nature Medicine Nov 2023Autoimmunity is intrinsically driven by memory T and B cell clones inappropriately targeted at self-antigens. Selective depletion or suppression of self-reactive T cells...
Autoimmunity is intrinsically driven by memory T and B cell clones inappropriately targeted at self-antigens. Selective depletion or suppression of self-reactive T cells remains a holy grail of autoimmune therapy, but disease-associated T cell receptors (TCRs) and cognate antigenic epitopes remained elusive. A TRBV9-containing CD8 TCR motif was recently associated with the pathogenesis of ankylosing spondylitis, psoriatic arthritis and acute anterior uveitis, and cognate HLA-B*27-presented epitopes were identified. Following successful testing in nonhuman primate models, here we report human TRBV9 T cell elimination in ankylosing spondylitis. The patient achieved remission within 3 months and ceased anti-TNF therapy after 5 years of continuous use. Complete remission has now persisted for 4 years, with three doses of anti-TRBV9 administered per year. We also observed a profound improvement in spinal mobility metrics and the Bath Ankylosing Spondylitis Metrology Index (BASMI). This represents a possibly curative therapy of an autoimmune disease via selective depletion of a TRBV-defined group of T cells. The anti-TRBV9 therapy could potentially be applicable to other HLA-B*27-associated spondyloarthropathies. Such targeted elimination of the underlying cause of the disease without systemic immunosuppression could offer a new generation of safe and efficient therapies for autoimmunity.
Topics: Humans; Epitopes; HLA-B Antigens; Immunotherapy; Receptors, Antigen, T-Cell; Spondylitis, Ankylosing; T-Lymphocytes; Tumor Necrosis Factor Inhibitors
PubMed: 37872223
DOI: 10.1038/s41591-023-02613-z -
Nature Reviews. Rheumatology Aug 2023Spondyloarthritis (SpA) is characterized by the infiltration of innate and adaptive immune cells into entheses and bone marrow. Molecular, cellular and imaging evidence... (Review)
Review
Spondyloarthritis (SpA) is characterized by the infiltration of innate and adaptive immune cells into entheses and bone marrow. Molecular, cellular and imaging evidence demonstrates the presence of bone marrow inflammation, a hallmark of SpA. In the spine and the peripheral joints, bone marrow is critically involved in the pathogenesis of SpA. Evidence suggests that bone marrow inflammation is associated with enthesitis and that there are roles for mechano-inflammation and intestinal inflammation in bone marrow involvement in SpA. Specific cell types (including mesenchymal stem cells, innate lymphoid cells and γδ T cells) and mediators (Toll-like receptors and cytokines such as TNF, IL-17A, IL-22, IL-23, GM-CSF and TGFβ) are involved in these processes. Using this evidence to demonstrate a bone marrow rather than an entheseal origin for SpA could change our understanding of the disease pathogenesis and the relevant therapeutic approach.
Topics: Humans; Immunity, Innate; Bone Marrow; Lymphocytes; Spondylarthritis; Inflammation; Axial Spondyloarthritis
PubMed: 37407716
DOI: 10.1038/s41584-023-00986-6 -
Best Practice & Research. Clinical... Sep 2023With back pain as one of the most common complaints in the population and with no single disease feature with sufficient sensitivity and specificity to diagnose axial... (Review)
Review
With back pain as one of the most common complaints in the population and with no single disease feature with sufficient sensitivity and specificity to diagnose axial spondyloarthritis (axSpA) on its own, diagnosing axSpA can be challenging. In this article, we discuss clinical, laboratory, and imaging spondyloarthritis features that can be used in diagnosis and explain the general principles underlying an axSpA diagnosis. Moreover, we discuss three pitfalls to avoid when diagnosing axSpA: i) using classification criteria as diagnostic criteria, ii) making a diagnosis by simple counting of spondyloarthritis features, and iii) over-reliance on imaging findings. Finally, we have some advice on how to build diagnostic skills and discuss new developments that may help facilitate the diagnosis of axSpA in the future.
Topics: Humans; Spondylarthritis; Back Pain; Axial Spondyloarthritis; Spondylitis, Ankylosing; Magnetic Resonance Imaging
PubMed: 37714776
DOI: 10.1016/j.berh.2023.101871 -
Best Practice & Research. Clinical... Sep 2023The treatment of patients with axial spondyloarthritis (axSpA) is characterized by non-pharmacological and pharmacological treatment options. It may depend on the type... (Review)
Review
The treatment of patients with axial spondyloarthritis (axSpA) is characterized by non-pharmacological and pharmacological treatment options. It may depend on the type and extent of musculoskeletal and extramusculoskeletal manifestations. Recent data on non-pharmacological treatment options, such as physical activity, physiotherapy, and modification of lifestyle factors, are summarized in this review. Moreover, we have provided an overview on non-steroidal anti-inflammatory drugs and the ever-expanding number of biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs, respectively). In addition to data on efficacy and safety, the review also encompasses data on switching/cycling, tapering, and treatment selection for specific patient subgroups to optimize treatment outcomes.
Topics: Humans; Antirheumatic Agents; Spondylitis, Ankylosing; Anti-Inflammatory Agents, Non-Steroidal; Axial Spondyloarthritis; Treatment Outcome; Spondylarthritis
PubMed: 37673758
DOI: 10.1016/j.berh.2023.101858