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Archives of Rheumatology Mar 2024This study aimed to evaluate the frequency of fibromyalgianess, fibromyalgia syndrome (FS), and widespread pain in patients with rheumatoid arthritis (RA) and ankylosing...
OBJECTIVES
This study aimed to evaluate the frequency of fibromyalgianess, fibromyalgia syndrome (FS), and widespread pain in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and their relationship with clinical and demographic parameters.
PATIENTS AND METHODS
This cross-sectional multicenter trial was performed in 14 centers across Türkiye between June 2018 and November 2019. Out of 685 patients recruited from the accessible population, 661 patients (342 RA, 319 AS; 264 males, 397 females; mean age: 48.1±12.9 years; range, 17 to 88 years) met the selection criteria. In these cohorts, those who did not meet the criteria for FS and had widespread pain (widespread pain index ≥7) were evaluated as a separate group. Clinical status and demographic parameters of patients in both cohorts were evaluated as well as the evaluations of RA and AS patients with widespread pain (widespread pain index ≥7) and RA and AS patients with FS groups. In addition, correlations between polysymptomatic distress scale (PSD) scores and Visual Analog Scale (VAS), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and Disease Activity Score using 28 joint counts for RA patients and VAS, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Ankylosing Spondylitis Disease Activity Score (ASDAS) for AS patients were analyzed.
RESULTS
Frequencies of patients with FS and patients who had PSD scores ≥12 were 34.1% and 44.4% in all RA patients, respectively. Moreover, FS and PSD scores ≥12 were found in 29.2% and 36.9% of all AS patients, respectively. PSD scores of RA patients with FS were higher than all RA patients and RA patients with widespread pain. SDAI and CDAI scores of RA patients with FS were higher than all RA patients and RA patients with widespread pain. Similarly, PSD scores of AS patients with FS were higher than all AS patients and AS patients with widespread pain. ASDAS-erythrocyte sedimentation rate and BASDAI scores of AS patients with FS were found higher than all AS patients and AS patients with widespread pain.
CONCLUSION
Disease activity scores, including pain in RA and AS, were higher in the presence of FS or fibromyalgianess. It may be related to clinical parameters, but cohort studies with long-term follow-up are needed to reveal causality. Additionally, to avoid overtreatment, coexistence of fibromyalgianess should be kept in mind in patients who have inflammatory diseases such as RA and AS, particularly with intractable widespread pain.
PubMed: 38774695
DOI: 10.46497/ArchRheumatol.2023.9925 -
Archives of Rheumatology Mar 2024This study compared the secukinumab treatment responses and adverse effects in psoriatic arthritis patients who received secukinumab as second-line with those that...
OBJECTIVES
This study compared the secukinumab treatment responses and adverse effects in psoriatic arthritis patients who received secukinumab as second-line with those that received secukinumab after two or more tumor necrosis factor-alpha (TNF-α) inhibitors.
PATIENTS AND METHODS
The retrospective study included 68 psoriatic arthritis patients followed up between October 2018 and October 2021. The patients were divided into two groups according to their anti-TNF-α treatment history. Group 1 consisted of 29 patients (11 males, 18 females; mean age: 45.3±13.3 years; range, 21 to 69 years) who had previously received one anti-TNF-α agent, while Group 2 included 39 patients (18 males, 21 females; mean age: 46.4±13.0 years; range, 24 to 70 years) who had been treated with two or more anti-TNF-α agents. Treatment responses of the groups were measured and compared using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Visual Analog Scale (VAS). A posttreatment BASDAI score ≤4 was used as a criterion for remission.
RESULTS
The mean duration of secukinumab treatment was 16.6±12.7 months for Group 1 and 16.0±11.6 months for Group 2 (p=0.84). Both groups responded significantly to secukinumab in terms of BASDAI and VAS scores (p<0.001 and p<0.001, respectively). Group 1 had a greater decline in BASDAI and VAS scores than Group 2 (p=0.045 and p=0.032, respectively). Furthermore, the remission rate was greater in Group 1 compared to Group 2 (58% 34%, p=0.03). The adverse effects of secukinumab treatment were an allergic reaction in Group 1 and one case of ulcerative colitis in Group 2.
CONCLUSION
Second-line secukinumab treatment resulted in a greater decline in BASDAI and VAS scores. Moreover, secukinumab achieved a significantly higher rate of remission when it was used as second-line therapy after one anti-TNF-α agent.
PubMed: 38774692
DOI: 10.46497/ArchRheumatol.2024.10050 -
Scandinavian Journal of Rheumatology Jul 2024To explore the registration of enthesitis among biologic-naïve patients with psoriatic arthritis (PsA) initiating tumour necrosis factor inhibitor (TNFi) treatment...
Enthesitis in a European registry-based cohort of patients with psoriatic arthritis treated with tumour necrosis factor inhibitors: clinical burden, patient-reported outcomes, and treatment response.
OBJECTIVE
To explore the registration of enthesitis among biologic-naïve patients with psoriatic arthritis (PsA) initiating tumour necrosis factor inhibitor (TNFi) treatment across 12 European registries, compare the disease burden and patient-reported outcomes (PROs) between patients with and without enthesitis, and assess the enthesitis treatment response.
METHOD
Demographics, clinical characteristics, and PROs at first TNFi (TNFi-1) initiation (baseline) were assessed in patients with PsA, diagnosed by a rheumatologist, with versus without assessment of entheses and between those with versus without enthesitis. Enthesitis scores and resolution frequency were identified at follow-up.
RESULTS
Of 10 547 patients in the European Spondyloarthritis (EuroSpA) Research Collaboration Network initiating TNFi, 1357 underwent evaluation for enthesitis. Eight registries included a validated scoring system for enthesitis. At baseline, 874 patients underwent entheses assessment [Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 485 patients, Spondyloarthritis Research Consortium of Canada (SPARCC) 389 patients]. Enthesitis was detected by MASES in 170/485 (35%, mean score ± sd 3.1 ± 2.4) and by SPARCC in 236/389 (61%, 4 ± 3.4). Achilles enthesitis was most frequent, by both MASES (unilateral/bilateral 28%/9%) and SPARCC (48%/18%). MASES/SPARCC baseline and follow-up scores for TNFi-1 were available for 100/105 patients. Of these, 63 patients (63%) (MASES) and 46 (43.8%) (SPARCC) achieved resolution of enthesitis. The site-specific enthesitis resolution was overall lower at SPARCC sites (peripheral; 63-80%) than at MASES sites (mainly axial; 82-100%) following TNFi-1. Disease activity and PROs were worse in patients with versus without enthesitis.
CONCLUSION
Entheseal assessments are only registered in a minority of patients with PsA in routine care. When assessed, enthesitis was common, and a substantial proportion demonstrated resolution following treatment with TNFi-1.
Topics: Humans; Arthritis, Psoriatic; Patient Reported Outcome Measures; Male; Registries; Female; Middle Aged; Europe; Adult; Enthesopathy; Treatment Outcome; Antirheumatic Agents; Cost of Illness; Tumor Necrosis Factor Inhibitors; Severity of Illness Index; Cohort Studies; Tumor Necrosis Factor-alpha
PubMed: 38771017
DOI: 10.1080/03009742.2024.2336743 -
Frontiers in Medicine 2024To explore the expression characteristics and regulatory patterns of RBPs in different immune cell types of AS, and to clarify the potential key role of RBPs in the...
OBJECTIVE
To explore the expression characteristics and regulatory patterns of RBPs in different immune cell types of AS, and to clarify the potential key role of RBPs in the occurrence and development of AS disease.
METHODS
PBMC sample data from scRNA-seq (HC*29, AS*10) and bulk RNA-seq (NC*3, AS*5) were selected for correlation analysis.
RESULTS
(1) Compared with the HC group, the numbers of B, DC (dendritic cells), CD14 Mono and CD8 T cells were increased in AS group, while the numbers of platelet (platelets), CD8 NKT, CD16 Mono (non-classical monocytes), Native CD4 T and NK were decreased. (2) Through the analysis of RBP genes in B cells, some RBPs were found to play an important role in B cell differentiation and function, such as , , , . (3) It may be related to B-cell receptor, IgA immunity, NOD-like receptor and other signaling pathways; Through the analysis of RBP genes in CD8 T cells, some RBPs that play an important role in the immune regulation of CD8 T were found, such as , , , , and ; It may be related to T cell receptor, TNF, IL17 and other signaling pathways. (4) Based on bulk RNA-seq, it was found that compared with HC and AS patients, differentially expressed variable splicing genes (RASGs) may play an important role in the occurrence and development of AS by participating in transcriptional regulation, protein phosphorylation and ubiquitination, DNA replication, angiogenesis, intracellular signal transduction and other related pathways.
CONCLUSION
RBPs has specific expression characteristics in different immune cell types of AS patients, and has important regulatory functions. Its abnormal expression and regulation may be closely related to the occurrence and development of AS.
PubMed: 38770048
DOI: 10.3389/fmed.2024.1369341 -
Rheumatology Advances in Practice 2024In the absence of axial psoriatic arthritis (axPsA)-specific tools, the BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS) are used to assess axial...
OBJECTIVE
In the absence of axial psoriatic arthritis (axPsA)-specific tools, the BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS) are used to assess axial symptoms in patients with PsA. Here, we assessed the performance of BASDAI and ASDAS in patients with PsA.
METHODS
Patients with active PsA in DISCOVER-1 and DISCOVER-2 (ClinicalTrials.gov: NCT03162796 and NCT03158285, respectively) with or without axPsA but with available baseline BASDAI information were analysed; those with investigator-identified axial symptoms and imaging-confirmed sacroiliitis comprised the axPsA cohort. Correlations between BASDAI/ASDAS and clinical variables were assessed with Pearson's coefficient (). Longitudinal effects of enthesitis (Leeds Enthesitis Index [LEI]), swollen joint count and presence versus absence of axPsA on BASDAI/ASDAS (normalized 0-10 scale) were analysed with mixed models for repeated measures.
RESULTS
At baseline in the axPsA ( = 312) and non-axPsA ( = 124) cohorts, BASDAI scores showed no or weak correlation with swollen joint count (0.18-0.20), tender joint count (0.12-0.29), LEI (-0.04 to 0.24) and physician global assessment (0.35-0.43); moderate correlation with fatigue (both -0.56); and strong correlation with patient global assessment of disease activity (0.62-0.69) and patient-reported pain (0.66-0.70). Similar correlations were observed for ASDAS. Axial involvement versus non-involvement was associated with higher BASDAI scores and ASDAS (all β ≥ 0.5), without differences between instruments; longitudinal associations between swollen joint count (β ≤ 0.06)/LEI (β ≤ 0.19) and BASDAI/ASDAS were clinically unimportant.
CONCLUSION
BASDAI and ASDAS performed similarly in patients with active PsA and axial involvement, independent of peripheral disease involvement, supporting their performance in assessing axial disease activity.
TRIAL REGISTRATION
ClinicalTrials.gov, http://clinicaltrials.gov, NCT03162796 and NCT03158285.
PubMed: 38765190
DOI: 10.1093/rap/rkae058 -
Global Spine Journal May 2024Bioinformatics analysis of Gene Expression Omnibus (GEO).
STUDY DESIGN
Bioinformatics analysis of Gene Expression Omnibus (GEO).
OBJECTIVE
Ossification of the ligamentum flavum (OLF) and ankylosing spondylitis (AS) represent intricate conditions marked by the gradual progression of endochondral ossification. This investigation endeavors to unveil common biomarkers associated with heterotopic ossification and explore the potential molecular regulatory mechanisms.
METHODS
Microarray and RNA-sequencing datasets retrieved from the Gene Expression Omnibus (GEO) repository were harnessed to discern differentially expressed genes (DEGs) within the OLF and AS datasets. Subsequently, Weighted Gene Co-expression Network Analysis (WGCNA) was implemented to pinpoint co-expression modules linked to OLF and AS. Common genes were further subjected to an examination of functional pathway enrichment. Moreover, hub intersection genes were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) regression, followed by an evaluation of diagnostic performance in external OLF and AS cohorts. Lastly, an analysis of immune cell infiltration was conducted to scrutinize the correlation of immune cell presence with shared biomarkers in OLF and AS.
RESULTS
A total of 1353 and 91 Differentially Expressed Genes (DEGs) were identified in OLF and AS, respectively. Using the Weighted Gene Co-expression Network Analysis (WGCNA), 2 modules were found to be notably significant for OLF and AS. The integrative bioinformatic analysis revealed 3 hub genes (MAB21L2, MEGF10, ISLR) as shared risk biomarkers, with MAB21L2 being the central focus. Receiver Operating Characteristic (ROC) analysis exhibited a strong diagnostic potential for these hub genes. Gene Ontology (GO) analysis indicated their involvement in the positive regulation of myoblast proliferation. Notably, MAB21L2 was singled out as the optimal common biomarker for OLF and AS. Furthermore, an analysis of immune infiltration demonstrated a correlation between MAB21L2 expression and changes in immune cells. Activated CD8 T cells were identified as shared differential immune infiltrating cells significantly linked to MAB21L2 in both OLF and AS.
CONCLUSION
This study represents the first instance of identifying MAB21L2 as a prospective diagnostic marker for patients contending with OLF associated with AS. The research results indicate that the ECM-receptor interaction and the cell-cell adhesion may play a role in both disease processes. This newfound knowledge not only enhances our understanding of the pathogenesis behind spinal ligament ossification but also uncovers potential targets for therapeutic interventions.
PubMed: 38757696
DOI: 10.1177/21925682241255894 -
Mediterranean Journal of Rheumatology Mar 2024Janus kinase (JAK)/signal transducers and activators of transcription (STATs) are a group of molecules responsible for signal transduction of multiple cytokines and... (Review)
Review
Janus kinase (JAK)/signal transducers and activators of transcription (STATs) are a group of molecules responsible for signal transduction of multiple cytokines and growth factors in different cell types, involved in the maintenance of immune tolerance. Thus, the dysregulation of this pathway plays a crucial role in the pathogenesis of multiple autoimmune, inflammatory, and allergic diseases and is an attractive treatment target. JAK inhibitors (JAKinibs) have been approved in the treatment of multiple autoimmune diseases including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (SPA). In SLE, there is a plethora of ongoing trials evaluating their efficacy, with tofacitinib, baricitinib and deucravacitinib showing promising results, without major safety concerns. In this review, we will discuss the rationale of targeting JAKinibs in SLE and summarize the clinical data of efficacy and safety of JAKinibs in SLE patients.
PubMed: 38756931
DOI: 10.31138/mjr.231123.jia -
Clinical Case Reports May 2024Ankylosing spondylitis (AS) presents with renal failure and proteinuria in a minority of cases, usually due to secondary amyloidosis or IgA nephropathy. While focal...
Ankylosing spondylitis (AS) presents with renal failure and proteinuria in a minority of cases, usually due to secondary amyloidosis or IgA nephropathy. While focal segmental glomerulosclerosis (FSGS) is less common, it should still be in the differential regardless of the patient's clinical profile.
PubMed: 38751961
DOI: 10.1002/ccr3.8901 -
World Neurosurgery May 2024Bipedalism was a significant milestone in the evolutionary development of Homo sapiens sapiens, influencing neocortical evolution and subsequent behavioral changes....
OBJECTIVE
Bipedalism was a significant milestone in the evolutionary development of Homo sapiens sapiens, influencing neocortical evolution and subsequent behavioral changes. Coordinated visual and sensory inputs are crucial for posture, environmental interaction, and surgical planning, with horizontal gaze being a pivotal parameter. This narrative review aims to explore various geometric measures used to assess horizontal gaze in patients, highlighting their applications in surgical planning.
METHODS
A literature review was conducted in indexed databases using Mesh terms like "Cervical Vertebrae" and "Visual Fields" along with keywords such as "horizontal gaze" and "sagittal spine parameters." Among 477 initially identified articles, 41 were selected for inclusion after rigorous filtering.
RESULTS
The most recognized method for assessing horizontal gaze is the Chin Brow Vertical Angle (CBVA), initially described in patients with ankylosing spondylitis. Clinical photography is employed as a tool for CBVA calculation, while other measures like McGregor slope and Slope of the Line of Sight have been considered as alternatives to CBVA. Each method presents its unique advantages and limitations.
CONCLUSIONS
This review highlights the need for further research into horizontal gaze measurement methods. Developing novel approaches to determine horizontal gaze can significantly enhance surgical planning and, consequently, improve patient outcomes. The ongoing exploration of these geometric measures offers promising prospects for advancing the field and optimizing patient care.
PubMed: 38750886
DOI: 10.1016/j.wneu.2024.05.035 -
RMD Open May 2024To investigate lectin pathway proteins (LPPs) as biomarkers for axial spondyloarthritis (axSpA) in a cross-sectional cohort with a suspicion of axSpA, comprising newly...
OBJECTIVES
To investigate lectin pathway proteins (LPPs) as biomarkers for axial spondyloarthritis (axSpA) in a cross-sectional cohort with a suspicion of axSpA, comprising newly diagnosed axSpA and chronic low back pain (cLBP) individuals.
METHODS
Serum samples from 515 participants within the OptiRef cohort, including 151 axSpA patients and 364 cLBP patients, were measured using immunoassays for LPPs (mannan-binding lectin (MBL), collectin liver-1 (CL-L1), M-ficolin, H-ficolin and L-ficolin, MBL-associated serine proteases (MASP)-1, -2 and -3, MBL-associated proteins (MAp19 and MAp44) and the complement activation product C3dg).
RESULTS
Serum levels of L-ficolin, MASP-2 and C3dg were elevated in axSpA patients, whereas levels of MASP-3 and CL-L1 were decreased, and this remained significant for C3dg and MASP-3 after adjustment for C reactive protein (CRP). A univariate regression analysis showed serum levels of CL-L1, MASP-2, MASP-3 and C3dg to predict the diagnosis of axSpA, and MASP-3 and C3dg remained significant in a multivariate logistic regression analysis. Assessment of the diagnostic potential showed that a combination of human leukocyte antigen B27 (HLA-B27) and measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, however, with a concomitant loss of sensitivity.
CONCLUSIONS
Serum levels of complement activation, that is, C3dg, and MASP-3 differed significantly between axSpA and cLBP patients after adjustment for CRP. Although combining HLA-B27 with measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, this seems unjustified due to the concomitant loss of sensitivity. However, both C3dg and MASP-3 were associated with axSpA diagnosis in multivariate logistic regression, suggesting an involvement of complement in the inflammatory processes and possibly pathogenesis in axSpA.
Topics: Humans; Biomarkers; Male; Female; Adult; Middle Aged; Cross-Sectional Studies; Complement System Proteins; Axial Spondyloarthritis; Mannose-Binding Protein-Associated Serine Proteases; Lectins; Complement Activation
PubMed: 38749532
DOI: 10.1136/rmdopen-2024-004127