112 research outputs found
The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases
The Supplementary Material for this article can be found online
at: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1191782/
full#supplementary-materialInterleukin-17 family (IL-17s) comprises six structurally related members (IL-17A to IL-17F); sequence homology is highest between IL-17A and IL-17F, displaying certain overlapping functions. In general, IL-17A and IL-17F play important roles in chronic inflammation and autoimmunity, controlling bacterial and fungal infections, and signaling mainly through activation of the nuclear factor-kappa B (NF-κB) pathway. The role of IL-17A and IL-17F has been established in chronic immune-mediated inflammatory diseases (IMIDs), such as psoriasis (PsO), psoriatic arthritis (PsA), axial spondylarthritis (axSpA), hidradenitis suppurativa (HS), inflammatory bowel disease (IBD), multiple sclerosis (MS), and asthma. CD4+ helper T cells (Th17) activated by IL-23 are well-studied sources of IL-17A and IL-17F. However, other cellular subtypes can also produce IL-17A and IL-17F, including gamma delta (γδ) T cells, alpha beta (αβ) T cells, type 3 innate lymphoid cells (ILC3), natural killer T cells (NKT), or mucosal associated invariant T cells (MAIT). Interestingly, the production of IL-17A and IL-17F by innate and innate-like lymphocytes can take place in an IL-23 independent manner in addition to IL-23 classical pathway. This would explain the limitations of the inhibition of IL-23 in the treatment of patients with certain rheumatic immune-mediated conditions such as axSpA. Despite their coincident functions, IL-17A and IL-17F contribute independently to chronic tissue inflammation having somehow non-redundant roles. Although IL-17A has been more widely studied, both IL-17A and IL-17F are overexpressed in PsO, PsA, axSpA and HS. Therefore, dual inhibition of IL-17A and IL-17F could provide better outcomes than IL-23 or IL-17A blockade.UCB Pharma S
Sponyloarthritis features forecasting the presence of HLA-B27 or sacroiliitis on magnetic resonance imaging in patients with suspected axial spondyloarthritis: Results from a cross-sectional study in the ESPeranza Cohort
Introduction: Chronic back pain (CBP) is frequently the presenting symptom in patients with suspected axial
spondyloarthritis (axSpA). Presence of sacroiliitis on magnetic-resonance-imaging (MRI) or HLA-B27 adds to
diagnostic certainty. However, these costly tests cannot be applied in all patients with CBP. This study aims to
investigate which SpA features increase the likelihood of a positive HLA-B27 or positive MRI of the sacroiliac-joints
(MRI-SI) in patients with suspected axSpA.
Methods: Data from 665 patients with CBP within the ESPeranza Programme were analysed. Diagnostic utility
measures (LR+, LR−) for a positive MRI-SI or HLA-B27 were calculated for various definitions of inflammatory back
pain (IBP), their separate items and for other SpA features.
Results: Pretest probabilityies of a positive result was 41 % for MRI-SI and 40 % for HLA-B27. For a positive MRI-SI
result the most useful IBP characteristic was alternating buttock pain (LR + =2.6). Among the IBP-criteria, fulfillment
of the ‘ASAS criteria’ (LR + =2.1) was most contributory. Interestingly, the addition of alternating buttock pain to the
Calin/ASAS-IBP criteria (LR + =6.0 and 5.5, respectively) or the addition of awakening at second half of night to the
Calin-IBP criteria (LR + =5.5) increased the pre-test probability of MRI-sacroiliitis from 41 % to 79–80 %. Dactylitis
(LR + =4.1) and inflammatory bowel disease (IBD) (LR + =6.4) increased this probability to 73 % and 81 %, respectively.
To forecast HLA-B27 positivity, awakening at the second half of the night, fulfillment of the ASAS-IBP definition and
uveitis were the most useful, but only marginally predictive (LR + = 1.3, 1,6 and 2.6, respectively).
Conclusions: If patients with suspected axial SpA have either 1) IBP according to Calin/ASAS definition plus alternating
buttock pain, or 2) IBP according to Calin definition plus awakening at night, or 3) dactylitis or 4) IBD, the probability of
finding a positive MRI-SI increases significantlyVNC received one of the ASAS research
grants on call 2013 to perform this study. The Spanish Foundation of
Rheumatology received funding from Pfizer to develop the Esperanza
Programme. Nowadays, the programme is supported by a restricted grant of
the Institute Carlos III (FIS PI13/02034)
Pain and inflammation as mediators of tofacitinib treatment effect on fatigue in patients with ankylosing spondylitis: a mediation analysis
Introduction:Â Tofacitinib is an oral Janus kinase inhibitor for treatment of ankylosing spondylitis (AS). Using mediation modelling, we describe interrelationships between fatigue, pain, morning stiffness, C-reactive protein (CRP) and tofacitinib treatment in patients with AS.
Methods: Data from phase 2 (NCT01786668)/phase 3 (NCT03502616) studies of patients receiving tofacitinib 5 mg twice daily (BID) or placebo were used. Initial models included treatment as the independent binary variable (tofacitinib 5 mg BID versus placebo); fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F; model A] or Bath AS Disease Activity Index [BASDAI] Q1 [model B]) as the dependent variable; and pain (total back pain/nocturnal spinal pain [model A] or pain measured by BASDAI Q2/3 [model B]), morning stiffness (BASDAI Q5/6) and CRP as mediator variables.
Results: Pooled data from 370/371 patients were included in models A/B. Initial models demonstrated that tofacitinib treatment affects fatigue mainly indirectly via pain and morning stiffness. As a result, initial models were respecified to exclude direct treatment effect and the indirect effect via CRP. For respecified model A, 44.0% of the indirect effect of tofacitinib treatment on fatigue was mediated via back pain/morning stiffness, 40.0% via morning stiffness alone and 16.0% via back pain alone (all P < 0.05). For respecified model B, 80.8% of the indirect effect of tofacitinib treatment on fatigue was mediated via pain/morning stiffness and 19.2% via pain alone (both P < 0.05).
Conclusions:Â In tofacitinib-treated patients with AS, improvements in fatigue were collectively mediated through combined treatment effects on morning stiffness and pain
Axial Spondyloarthritis: Patient-Reported Impact in Europe
This open access book provides an overview of the International Map of Axial Spondyloarthritis (IMAS) project -focusing on Europe-, a wide-ranging, multi-disciplinary collaboration between academic groups, Health Care Professionals (HCPs), patient organizations and Novartis. IMAS was conceived to improve knowledge of Axial Spondyloarthritis (axSpA) and raise awareness of its heavy burden globally. By asking more than 2,000 patients across Europe about the impact of axSpA on multiple aspects of their life, the full extent of this disease was investigated from a direct patient perspective. This allowed a unique understanding of how living with axSpA affects the daily lives and well-being of patients, and how this varies between European countries. Axial Spondyloarthritis: Patient-Reported Impact in Europe highlights opportunities for progressing quality patient care to be applied to health services globally. HCPs, policy makers and patients will find this book to be an indispensable resource for improving the understanding of this chronic condition, including patients’ clinical outcomes, the protection of those at risk of psychological distress, and the economic burden on patients and society
Axial Spondyloarthritis: Patient-Reported Impact in Europe
This open access book provides an overview of the International Map of Axial Spondyloarthritis (IMAS) project -focusing on Europe-, a wide-ranging, multi-disciplinary collaboration between academic groups, Health Care Professionals (HCPs), patient organizations and Novartis. IMAS was conceived to improve knowledge of Axial Spondyloarthritis (axSpA) and raise awareness of its heavy burden globally. By asking more than 2,000 patients across Europe about the impact of axSpA on multiple aspects of their life, the full extent of this disease was investigated from a direct patient perspective. This allowed a unique understanding of how living with axSpA affects the daily lives and well-being of patients, and how this varies between European countries. Axial Spondyloarthritis: Patient-Reported Impact in Europe highlights opportunities for progressing quality patient care to be applied to health services globally. HCPs, policy makers and patients will find this book to be an indispensable resource for improving the understanding of this chronic condition, including patients’ clinical outcomes, the protection of those at risk of psychological distress, and the economic burden on patients and society
Poor health and functioning in patients with axial spondyloarthritis during the COVID-19 pandemic and lockdown: REUMAVID study (phase 1)
To evaluate the overall health and functioning in patients with axial spondyloarthritis
(axSpA) and related factors affecting these during the COVID-19 pandemic and lockdown
measure
Sacroiliac joint radiographic progression - speed and determinants
Non-radiographic axial spondyloarthritis (nr-axSpA) and radiographic axial spondyloarthritis (r-axSpA) are considered to be different spectra of the same disease. Accumulating data suggest a low transition rate from nr-axSpA to r-axSpA in patients with early disease and identify inflammation, smoking and HLA-B27 positivity as factors associated with transition
Regional differences in diagnosis journey and healthcare utilization: Results from the International Map of Axial Spondyloarthritis (IMAS)
Introduction:
To assess differences in the diagnosis journey and access to care in a large sample of patients with axial spondyloarthritis (axSpA) from around the world, included in the International Map of Axial Spondyloarthritis (IMAS).
Methods:
IMAS was a cross-sectional online survey (2017–2022) of 5557 unselected patients with axSpA from 27 countries. Across five worldwide geographic regions, the patient journey until diagnosis and healthcare utilization in the last 12 months prior to survey were evaluated. Univariable and multivariable linear regression was used to analyze factors associated with higher healthcare utilization.
Results:
Of 5557 participants in IMAS, the diagnosis took an average of 7.4 years, requiring more than two visits to HCPs (77.7% general practitioner and 51.3% rheumatologist), and more than two diagnostic tests [67.5% performed human leukocyte antigen B27 (HLA-B27), 64.2% x-ray, and 59.1% magnetic resonance imaging (MRI) scans]. North America and Europe were the regions with the highest number of healthcare professional (HCP) visits for diagnosis, while the lowest number of visits was in the Asian region. In the previous 12 months, 94.9% (n = 5272) used at least one healthcare resource, with an average of 29 uses per year. The regions with the highest healthcare utilization were Latin America, Europe, and North America. In the multiple linear regression, factors associated with higher number of healthcare utilization were younger age (b = – 0.311), female gender (b = 7.736), higher disease activity (b = 1.461), poorer mental health (b = 0.624), greater functional limitation (b = 0.300), greater spinal stiffness (b = 1.527), and longer diagnostic delay (b = 0.104).
Conclusion:
The diagnosis of axSpA usually takes more than two visits to HCPs and at least 7 years. After diagnosis, axSpA is associated with frequent healthcare resource use. Younger age, female gender, higher disease activity, poorer mental health, greater functional limitation, greater spinal stiffness, and longer diagnostic delay are associated with higher healthcare utilization. Europe and North America use more HCP visits and diagnostic tests before and after diagnosis than the other regions
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