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Arquivos de Gastroenterologia 2024Monoclonal antibodies have proven efficacy in the management of several conditions and infliximab (IFX) is one of the most important drugs of the class. Some recent data... (Observational Study)
Observational Study
BACKGROUND
Monoclonal antibodies have proven efficacy in the management of several conditions and infliximab (IFX) is one of the most important drugs of the class. Some recent data have shown low rates of both persistence and adherence to several available biologics.
OBJECTIVE
The objective of this study was to describe adherence and persistence rate to IFX treatment and also persistence in the patient support program (PSP), among patients diagnosed with inflammatory bowel diseases (IBD) or rheumatic diseases (RD) enrolled in the program of a large pharmaceutical company in Brazil.
METHODS
Retrospective observational analysis using the PSP database. IBD or RD patients using IFX enrolled on the PSP database between September 2015 and August 2019 were retrospectively evaluated to identify the persistence rate and adherence and followed up until March 1, 2020. Patients were excluded if treatment start date was prior to program entry; first infusion prior to September 1st, 2015 or after August 31st, 2019; the patients did not started treatment; and patients with "OTHERS" in "Indication" field. Persistence was assessed considering both persistence in the program ("PSP persistence") and persistence on IFX in the PSP ("IFX persistence in the PSP"). PSP persistence was defined as the proportion of patients remaining in the program at 6, 12, 24, 36 and 48 months after initiating IFX. To determine IFX persistence in the PSP, censoring was defined at the time the patient left the program, died, or was lost to follow-up. Adherence to treatment was measured by medication possession ratio ((MPR) - All days supply / elapsed days from first prescription to last day of medication possession)). Descriptive statistics were initially used. Kaplan-Meier curve, the median time estimated by the survival function, Cox regression model, and restricted mean survival time (RMST) were used to evaluate the treatment persistence time at 24 months and the logistic regression model was performed aiming to identify variables associated with adherence (MPR ≥80%).
RESULTS
A total of 10,233 patients were analyzed, 5,826 (56.9%) with the diagnosis of RD and 4,407 (43.1%) of IBD. At the end of the follow-up (median 9.1 months from PSP entry to the last infusion), persistence in the PSP was 65.6%, 48.2%, 31.0%, 20.7% and 13.1% at 6, 12, 24, 36 and 48 months, respectively. Considering persistence on IFX in the PSP, estimates were 93.7%, 87.8%, 77.0%, 62.4% and 53.0% at 6, 12, 24, 36 and 48 months, respectively. Variables associated with the risk of non-persistence were gender, country region and diagnosis of rheumatoid arthritis and ankylosing spondylitis. Median MPR was 94.2%, while the percentage of patients with MPR ≥80% was 91.0%. Variables associated with MPR≥80% were country region and diagnosis of Crohn's disease.
CONCLUSION
Many patients leave the program without discontinuing IFX, since the 12-month persistence were very different between program and medication estimates, while high adherence rates were observed among patients enrolled in the PSP. Data highlights the benefits of a PSP.
Topics: Humans; Infliximab; Medication Adherence; Female; Retrospective Studies; Male; Adult; Brazil; Middle Aged; Gastrointestinal Agents; Inflammatory Bowel Diseases; Rheumatic Diseases; Time Factors
PubMed: 38775584
DOI: 10.1590/S0004-2803.24612023-149 -
Frontiers in Immunology 2024To date, an increasing number of epidemiological evidence has pointed to potential relationships between Parkinson's disease (PD) and various autoimmune diseases (AIDs),...
BACKGROUND
To date, an increasing number of epidemiological evidence has pointed to potential relationships between Parkinson's disease (PD) and various autoimmune diseases (AIDs), however, no definitive conclusions has been drawn about whether PD is causally related to AIDs risk.
METHODS
By employing summary statistics from the latest and most extensive genome-wide association studies (GWAS), we performed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between PD and a variety of 17 AIDs, encompassing multiple sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis, asthma, inflammatory bowel disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome, celiac disease, primary biliary cirrhosis, primary sclerosing cholangitis, type 1 diabetes, ankylosing spondylitis, rheumatoid arthritis, systemic lupus erythematosus, psoriasis and vitiligo. Inverse-variance weighted (IVW) was adopted as the main statistical approach to obtain the causal estimates of PD on different AIDs, supplemented by a series of complementary analyses (weighted median, MR Egger regression, and MR-PRESSO) for further strengthening the robustness of results.
RESULTS
Our MR findings suggested that genetically predicted higher liability to PD was causally associated with a decreased risk of irritable bowel syndrome (OR = 0.98; 95% CI: 0.96-0.99; = 0.032). On the contrary, IVW analysis showed a potential positive correlation between genetically determined PD and the incidence of type 1 diabetes (OR = 1.10; 95%CI: 1.02-1.19; = 0.010). Subsequent MR tests ended up in similar results, confirming our findings were reliable. Additionally, in the reverse MR analyses, we did not identify any evidence to support the causal relationship of genetic predisposition to AIDs with PD susceptibility.
CONCLUSION
In general, a bifunctional role that PD exerted on the risk of developing AIDs was detected in our studies, both protecting against irritable bowel syndrome occurrence and raising the incidence of type 1 diabetes. Future studies, including population-based observational studies and molecular experiments and , are warranted to validate the results of our MR analyses and refine the underlying pathological mechanisms involved in PD-AIDs associations.
Topics: Humans; Parkinson Disease; Mendelian Randomization Analysis; Autoimmune Diseases; Genome-Wide Association Study; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38774879
DOI: 10.3389/fimmu.2024.1370831 -
Archives of Rheumatology Mar 2024The study aimed to evaluate the correlation between the clinical disease activity of axial spondyloarthropathy (axSpA) and magnetic resonance imaging findings of the...
OBJECTIVES
The study aimed to evaluate the correlation between the clinical disease activity of axial spondyloarthropathy (axSpA) and magnetic resonance imaging findings of the sacroiliac joint.
PATIENTS AND METHODS
Thirty-two patients (21 males, 11 females; mean age: 39.3±9.2 years; range, 18 to 55 years) who were diagnosed with axSpA according to the Assessment in Spondyloarthritis International Society classification criteria between November 2015 and August 2017 were included in this cross-sectional study. Visual Analog Scale (VAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS)-erythrocyte sedimentation rate (ESR), and ASDAS-C-reactive protein (CRP) were used as the indicators of clinical activity. Magnetic resonance imaging of the sacroiliac joint was performed and the Spondyloarthritis Research Consortium of Canada (SPARCC) score was evaluated by a radiologist who was blinded to the clinical and laboratory parameters of the patients.
RESULTS
The mean duration of symptom onset was 9.3±7.7 years, and the mean duration of diagnosis was 3.6±2.8 years. Human leukocyte antigen (HLA)-B27 was positive in 16 (50%) patients. There was no correlation between the SPARCC score and VAS, BASDAI, MASES, BASFI, ASDAS-CRP, ASDAS-ESR, ESR, and CRP values (p>0.05). In the HLA-B27 subgroup analyses, a statistically significant correlation was found between HLA-B27-negative patients and SPARCC score (r=0.639, p=0.008).
CONCLUSION
No relationship was found between other clinical disease parameters and sacroiliac joint imaging findings, except for the relationship between the SPARCC and BASDAI in HLA-B27- negative patients with axSpA.
PubMed: 38774700
DOI: 10.46497/ArchRheumatol.2024.10401 -
Archives of Rheumatology Mar 2024Considering the role of T helper (Th)17 cells in the pathogenesis of ankylosing spondylitis (AS), the aim of this study was to determine the correlation between aryl...
Aryl hydrocarbon receptor gene expression in ankylosing spondylitis and its correlation with interleukin-17, RAR-related orphan receptor gamma t expression, and disease activity indices.
OBJECTIVES
Considering the role of T helper (Th)17 cells in the pathogenesis of ankylosing spondylitis (AS), the aim of this study was to determine the correlation between aryl hydrocarbon receptor (AHR) gene expression and the expression of Th17-related genes including interleukin (IL)-17 and RAR-related orphan receptor gamma t (RORγt) transcription factor.
PATIENTS AND METHODS
Thirty patients with AS (26 males, 4 females; mean age: 36.1±8.1 years) and 30 age- and sex-matched healthy individuals (26 males, 4 females; mean age: 36.2±14.6 years) were recruited for the case-control study between June 2021 and January 2022. Ribonucleic acid (RNA) was extracted from peripheral blood cells and expression levels of AHR, IL-17, RORγt, and AHR repressor (AHRR) genes were evaluated using real-time polymerase chain reaction technique. The serum level of IL-17 was evaluated with enzyme-linked immunosorbent assay.
RESULTS
The results showed a nonsignificant elevation of AHR, IL-17, and RORγt gene expression in the patient group compared to the control. There was a direct correlation between AHR gene expression and IL-17 and RORγt genes and a negative correlation between AHR and AHRR expression. Moreover, AHR gene expression showed a weak correlation with disease activity indices, including Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Global Score, and Ankylosing Spondylitis Quality of Life. Moreover, the serum level of IL-17 was higher in AS patients compared to the healthy group (p=0.02).
CONCLUSION
Upregulated expression of the AHR gene in ankylosing spondylitis and its correlation with IL-17 and ROR-γ t gene expression suggests that it could be a potential diagnostic and therapeutic target for AS.
PubMed: 38774696
DOI: 10.46497/ArchRheumatol.2023.10203 -
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