Ankylosing Spondylitis Disease Activity Research Articles

Quantitative proteomic screening uncovers candidate diagnostic and monitoring serum biomarkers of ankylosing spondylitis

BackgroundWe sought to discover serum biomarkers of ankylosing spondylitis (AS) for diagnosis and monitoring disease activity.MethodsWe studied biologic-treatment-naïve AS and healthy control (HC) patients’ sera. Eighty samples matched by age, gender, and race (1:1:1 ratio) for AS patients with active disease, inactive disease, and HC were analyzed with SOMAscan™, an aptamer-based discovery platform. T-tests tests were performed for high/low-disease activity AS patients versus HCs (diagnosis) and high versus low disease activity (Monitoring) in a 2:1 and 1:1 ratio, respectively, to identify differentially expressed proteins (DEPs).We used the Cytoscape Molecular Complex Detection (MCODE) plugin to find clusters in protein–protein interaction networks and Ingenuity Pathway Analysis (IPA) for upstream regulators. Lasso regression analysis was performed for diagnosis.ResultsOf the 1317 proteins detected in our diagnosis and monitoring analyses, 367 and 167 (317 and 59, FDR-corrected q < .05) DEPs, respectively, were detected. MCODE identified complement, IL-10 signaling, and immune/interleukin signaling as the top 3 diagnosis PPI clusters. Complement, extracellular matrix organization/proteoglycans, and MAPK/RAS signaling were the top 3 monitoring PPI clusters. IPA showed interleukin 23/17 (interleukin 22, interleukin 23A), TNF (TNF receptor-associated factor 3), cGAS-STING (cyclic GMP-AMP synthase, Stimulator of Interferon Gene 1), and Jak/Stat (Signal transducer and activator of transcription 1), signaling in predicted upstream regulators. Lasso regression identified a Diagnostic 13-protein model predictive of AS. This model had a sensitivity of 0.75, specificity of 0.90, a kappa of 0.59, and overall accuracy of 0.80 (95% CI: 0.61–0.92). The AS vs HC ROC curve was 0.79 (95% CI: 0.61–0.96).ConclusionWe identified multiple candidate AS diagnostic and disease activity monitoring serum biomarkers using a comprehensive proteomic screen. Enrichment analysis identified key pathways in AS diagnosis and monitoring. Lasso regression identified a multi-protein panel with modest predictive ability.

Interferon-alpha 1 expression indicates the disease activity and response of patients with ankylosing spondylitis to anti-TNF-α treatment.

This study aimed to investigate whether interferon-alpha 1 (IFNA1) is predictive of Ankylosing spondylitis (AS) progression and treatment response to Tumour necrosis factor inhibitors (TNFis). Data of 50 AS patients receiving TNFi for 24 weeks were retrospectively analysed. AS patients who reached the Assessment of Spondyloarthritis International Society 40 response at the W24 were classified as responders to TNFi treatment; otherwise, they were classified as nonresponders. Human fibroblast-like synoviocytes (HFLS) isolated from AS patients (AS-HFLS) were used for in vitro validation. When the IFNA1 expression level was used to diagnose AS patients, an area under the curve of 0.895 was yielded (P < .001). Pearson correlation analysis showed negative correlations between IFNA1 expression, C-reactive protein (CRP) level, Bath AS Disease Activity Index scores, AS Disease Activity Score with CRP, and the production of inflammatory cytokines. An increased IFNA1 expression level was found to be associated with a better treatment response to TNFi. IFNA1 overexpression could protect HFLS against inflammatory response in the setting of AS. Blood IFNA1 deficiency is correlated with inflammatory cytokine production and disease activity and is indicative of unsatisfied response to TNFi treatment in AS patients.

Effectiveness and safety of secukinumab in ankylosing spondylitis and psoriatic arthritis: a 52-week real-life study in an Italian cohort

BackgroundSecukinumab has shown high efficacy in randomized controlled trials in both ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Here, we investigated its real-life effectiveness and tolerability in a cohort of AS and PsA patients.MethodsWe retrospectively analyzed medical records of outpatients with AS or PsA treated with secukinumab between December 2017 and December 2019. ASDAS-CRP and DAS28-CRP scores were used to measure axial and peripheral disease activity in AS and PsA, respectively. Data were collected at baseline and after 8, 24, and 52 weeks of treatment.ResultsEighty-five adult patients with active disease (29 with AS and 56 with PsA; 23 males and 62 females) were treated. Overall, mean disease duration was 6.7 years and biologic-naïve patients were 85%. Significant reductions in ASDAS-CRP and DAS28-CRP were observed at all time-points. Body weight (in AS) and disease activity status at baseline (particularly in PsA) significantly affected disease activity changes. ASDAS-defined inactive disease and DAS28-defined remission were achieved in comparable proportions between AS and PsA patients, at both 24 weeks (45% and 46%) and 52 weeks (65.5% and 68%, respectively); male sex was found an independent predictor of positive response (OR 5.16, P = 0.027). After 52 weeks, achievement of at least low disease activity and drug retention were observed in 75% of patients. Secukinumab was well-tolerated and only mild injection-site reactions were recorded in 4 patients.ConclusionIn a real-world setting, secukinumab confirmed great effectiveness and safety in both AS and PsA patients. The influence of gender on treatment response deserves further attention.

Associations of Neutrophil/lymphocyte ratio with disease activity indices in patients with ankylosing spondylitis

Background: Axial spondyloarthritis (axSpA) is a painful, inflammatory condition of the spine that usually manifests in young individuals with chronic back pain (less than 45 years of age). It may also be accompanied by extra-articular or periarticular (enthesitis, dactylitis) symptoms (uveitis, psoriasis, inflammatory bowel disease). AxSpA encompasses both ankylosing spondylitis (AS) with radiographic evidence of sacroiliitis and axSpA without radiographic evidence of sacroiliitis. Objective: to assess neutrophil/lymphocyte ratio (NLR) among AS patients and to evaluate its relation to disease activity. Methodology: The present investigation included thirty AS patients and thirty healthy controls. Disease Bath Ankylosing Spondylitis Disease Activity indicators were utilized to assess the disease activity of AS (BASDAI). Analyses were conducted on the relationship between NLR and disease activity. Results: There was a significant positive correlation between NLR and Duration of the disease (r=0.421, P=0.020), ESR (r=0.433, P=0.014), CRP (r=0.700, P< 0.001), BASDAI (r=0.433, P=0.017). There was an insignificant correlation between NLR and age. NLR had increased considerably among AS patients compared to controls (P-value <0.05). NLR can significantly predict AS disease activity (P-value <0.001, at cut off value ≥2.03 with 90% sensitivity, 88.89 % specificity, 94.7% PPV and 80% NPV). Conclusion: In conjunction with acute phase reactants, NLR might be a valuable marker for indicating inflammation.

High Baseline Neutrophil-to-Lymphocyte Ratio Could Serve as a Biomarker for Tumor Necrosis Factor-Alpha Blockers and Their Discontinuation in Patients with Ankylosing Spondylitis.

This study explores the association of neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios with the 3-month treatment response and persistence of tumor necrosis factor-alpha (TNF-α) blockers in patients with ankylosing spondylitis (AS). This retrospective cohort study investigated 279 AS patients who were newly initiated on TNF-α blockers between April 2004 and October 2019 and 171 sex- and age-matched healthy controls. Response to TNF-α blockers was defined as a reduction in the Bath AS Disease Activity Index of ≥50% or 20 mm, and persistence referred to the time interval from the initiation to discontinuation of TNF-α blockers. Patients with AS had significantly increased NLR, MLR, and PLR ratios as compared to controls. The frequency of non-response at 3 months was 3.7%, and TNF-α blockers' discontinuation occurred in 113 (40.5%) patients during the follow-up period. A high baseline NLR but not high baseline MLR and PLR showed an independently significant association with a higher risk of non-response at 3 months (OR = 12.3, p = 0.025) and non-persistence with TNF-α blockers (HR = 1.66, p = 0.01). NLR may be a potential marker for predicting the clinical response and persistence of TNF-α blockers in AS patients.

Novel regulatory role of non-coding RNAs in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a type of arthritis that primarily affects the spine and involves disorders of the immune and skeletal systems. However, the exact pathogenesis of AS is not fully understood. Non-coding RNAs (ncRNAs), particularly, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and micro RNAs (miRNAs) and their interactions have been shown to influence many biological processes such as inflammatory responses, osteogenic differentiation and apoptosis, pyroptosis, and proliferation. In addition, ncRNAs reflect the disease activity of AS. In this review, we discuss the regulatory roles of ncRNAs in AS cell functions (inflammatory responses, cellular osteogenic differentiation and apoptosis, pyroptosis, and proliferation) and their potential applications in AS diagnosis and treatment. Understanding the role of ncRNAs in the pathogenesis of AS will lay the foundation for exploring potential new therapeutic approaches for AS.

Dietary Fiber Intake Influences Changes in Ankylosing Spondylitis Disease Status

The objectives of this study were to characterize dietary fiber (DF) intake in patients with ankylosing spondylitis (AS), to assess whether DF intake affects disease activity in AS, and to investigate the effect of DF intake on disease activity in AS in the context of functional bowel disease (FBD) symptoms. We recruited 165 patients with AS and divided them into two groups according to whether they had a high DF intake > 25 g/d to investigate the characteristics of people with high DF intake. Some 72 of the 165 AS patients (43%) met the criteria for high DF intake, which was more common in patients with negative FBD symptoms (68%). Data analysis revealed that DF intake was negatively associated with AS disease activity and did not differ statistically significantly from FBD symptoms. Multivariate adjusted models were used to explore the effect of DF intake on AS disease activity. ASDAS-CRP and BASDAI were stable and negatively correlated across models in both groups with and without FBD symptoms. Thus, DF intake positively affected disease activity in patients with AS. ASDAS-CRP and BASDAI were negatively correlated with DF intake.

Dual-specificity phosphatases 22-deficient T cells contribute to the pathogenesis of ankylosing spondylitis

BackgroundDual-specificity phosphatases (DUSPs) can dephosphorylate both tyrosine and serine/threonine residues of their substrates and regulate T cell-mediated immunity and autoimmunity. The aim of this study was to investigate the potential roles of DUSPs in ankylosing spondylitis (AS).MethodsSixty AS patients and 45 healthy controls were enrolled in this study. Associations of gene expression of 23 DUSPs in peripheral T cells with inflammatory cytokine gene expression and disease activity of AS were analyzed. Finally, we investigated whether the characteristics of AS are developed in DUSP-knockout mice.ResultsThe mRNA levels of DUSP4, DUSP5, DUSP6, DUSP7, and DUSP14 in peripheral T cells were significantly higher in AS group than those of healthy controls (all p < 0.05), while DUSP22 (also named JKAP) mRNA levels were significantly lower in AS group than healthy controls (p < 0.001). The mRNA levels of DUSP4, DUSP5, DUSP6, DUSP7, and DUSP14 in T cells were positively correlated with mRNA levels of tumor necrosis factor-α (TNF-α), whereas DUSP22 was inversely correlated (all p < 0.05). In addition, inverse correlations of DUSP22 gene expression in peripheral T cells with C-reactive protein, erythrocyte sedimentation rate, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were observed (all p < 0.05). More importantly, aged DUSP22 knockout mice spontaneously developed syndesmophyte formation, which was accompanied by an increase of TNF-α+, interleukin-17A+, and interferon-γ+ CD3+ T cells.ConclusionsDUSP22 may play a crucial role in the pathogenesis and regulation of disease activity of AS.

Patient registry data on the efficacy and tolerability of adalimumab biosimilar in ankylosing spondylitis: A retrospective multicenter observational study

Abstract: BACKGROUND: Adalimumab, a tumor necrosis factor-α inhibitor, is an approved treatment for ankylosing spondylitis (AS). In Iraq, a biosimilar of adalimumab (ABP 501; Amgevita®) has been licensed for prescription since 2021. However, there have been no previous studies on its efficacy and safety in Iraqi AS patients. Multiple studies have shown that adalimumab biosimilars are effective and well tolerated, with comparable rates of clinical response, adverse events (AEs), and immunogenicity to the reference product. OBJECTIVES: To evaluate the efficacy and safety of Amgevita in Iraqi patients with AS. PATIENTS AND METHODS: A retrospective multi-center observational study involving 72 patients with active AS for whom Amgevita 40 mg was prescribed every 2 weeks The data were collected from Amgevita registry data across multiple centers in Iraq. Patients’ entire data sets were retrieved and examined for disease activity parameters and recorded adverse reactions up to 12 months of Amgevita medication. RESULTS: The cumulative percentage of response in active AS patients treated with Amgevita was 82% after 3 months (the baseline) and 61% after 12 months. The mean change from the baseline in the Bath AS Disease Activity Index was statistically significant (−0.5 [P = 0.033; 95% confidence interval (CI): −0.87 to −0.04] and −1.14 [P = 0.0001; 95% CI: −1.68 to −0.60]) at 3 months and 12 months, respectively. On multivariate Cox regression modeling, disease activity was a predictor of a decreased response to treatment by 49%. There were no new, significant AEs. CONCLUSIONS: Adalimumab biosimilar (ABP501; Amgevita®) is clinically effective and tolerable over 12 months of follow-up in Iraqi patients with AS.

The predictability of ASDAS on drug survival in patients with ankylosing spondylitis on biologic therapy: data from the KOBIO registry.

The Ankylosing Spondylitis (AS) Disease Activity Score (ASDAS) is largely used for assessing disease activity in patients with AS. We aimed to investigate the predictability of ASDAS on drug survival in patients with low Bath AS Disease Activity Index (BASDAI) during biologic therapy. Using data from multi-center, prospective, observational prospective cohort, Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry. The study population consisted of patients enrolled in the KOBIO registry from December 2012 to December 2018. The baseline demographic data and variables such as extra-articular manifestations, HLA-B27 positivity, family history of spondyloarthritis, ASDAS C-reactive protein (CRP), BASDAI, and Bath AS Functional Index scores were collected from the database. The disease activity indices were followed yearly after initiating a tumor necrosis factor (TNF) inhibitor (TNFi). Disease activities were defined as high (ASDAS-CRP ⩾ 2.1, BASDAI ⩾ 4) and low (ASDAS-CRP < 2.1, BASDAI < 4). Data from 1773 patients were analyzed. Among 269 patients with low BASDAI at baseline, 151 (56.1%) patients had high ASDAS-CRP, yet in 142 patients with low ASDAS-CRP at baseline, only 24 (16.9%) patients had a high BASDAI. High ASDAS-CRP captured more patients who had initiated or switched to a TNFi than those with high BASDAI (92.5% versus 84.8%, respectively, p < 0.001). Moreover, among AS patients with low BASDAI after 1 year of therapy, drug persistence in the following year was significantly lower in patients with high ASDAS than in those with low ASDAS (68.7% versus 82.5%, p < 0.001). ASDAS-CRP not only has its advantages over BASDAI in assessing disease activity but also low ASDAS-CRP at 1 year can be a marker of long-term drug survival of TNFi therapy.

Platelet to albumin ratio is an independent indicator for disease activity in ankylosing spondylitis.

The objective of this study is to characterize the association between platelet to albumin ratio (PAR) and disease activity in patients with ankylosing spondylitis (AS) and axial psoriatic arthritis (axPsA). Baseline platelet count, albumin, PAR, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Bath ankylosing spondylitis disease index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), and ankylosing spondylitis disease activity score (ASDAS) were collected from patients with a definitive diagnosis of AS or axPsA. Spearman's correlation analysis, quantile regression, and receiver operating characteristic (ROC) curves were performed. Four hundred forty-six patients with AS and 68 patients with axPsA were included. AS patients had higher CRP, ASDAS-CRP, and ASDAS-ESR than axPsA patients (median: CRP, 6.8 vs. 3.5mg/L, p = 0.02; ASDAS-CRP, 2.32 vs.1.93, p = 0.001; ASDAS-ESR, 2.57 vs.1.97, p = 0.007; respectively). Platelet count, albumin, PAR, ESR, BASDAI, and BASFI did not significantly differ between the two populations (all p > 0.05). In AS patients, PAR was positively correlated with BASDAI (r = 0.204, p < 0.01), BASFI (r = 0.24, p < 0.01), ASDAS-CRP (r = 0.475, p < 0.01), and ASDAS-ESR (r = 0.483, p < 0.01), while these coefficients were not significant in axPsA patients. The quantile regression further confirmed that, in AS patients, PAR was independently associated with BASDAI, BASFI, ASDAS-CRP, and ASDAS-ESR at their individual quantiles (all p < 0.01). However, in axPsA patients, PAR was not significantly associated with these disease activities. The optimal cut-off value of PAR for AS disease activity was 5.87, with an AUC of 0.745, a sensitivity of 72.4%, and a specificity of 71%. PAR could serve as an alternative indicator for AS disease activity. Key Points • Platelet to albumin ratio is independently associated with ankylosing spondylitis disease activity. • Platelet to albumin ratio could serve as an alternative indicator for ankylosing spondylitis disease activity.

Ankylosing spondylitis disease activity and serum vitamin D levels: A systematic review and meta-analysis.

To prove that serum vitamin D (VD) levels are strongly associated with ankylosing spondylitis (AS) disease activity, the association between serum VD levels and key monitoring indicators of AS disease activity has been analyzed, such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Studies published in PubMed, Cochrane Library, EMBASE, and China National Knowledge Infrastructure by August 30, 2022 were searched, and 6 studies finally met the selection criteria. Serum 25-hydroxyvitamin D (25(OH)D), ESR, CRP levels, and correlation coefficients between serum VD and BASDAI, ESR, CRP in AS, and control in these studies were extracted for the meta-analysis. When compared to controls, patients with AS had considerably lower blood 25(OH)D levels (MD = -7.53 ng/mL, 95% CI, -9.78 to -5.28, P < .001) and significantly higher ESR and CRP levels (ESR: MD = 11.75 mm/h, 95% CI, 4.20 to 19.31, P = .002; CRP: MD = 15.36 mg/L, 95% CI, 4.95 to 25.77, P = .004). Additionally, a negative correlation was discovered between serum VD levels and BASDAI, ESR, and CRP (Fisher' Z = -0.34, -0.38, -0.35, respectively). The findings of our meta-analysis demonstrated a negative correlation between serum VD levels and the main monitoring indices of disease activity in patients with AS and verified that the differences in the continent and ethnicity may be one of the major contributors to this finding.

Effectiveness and safety of electroacupuncture for ankylosing spondylitis: A protocol for a systematic reviews and meta-analysis.

Ankylosing spondylitis (AS) is a type of autoimmune disease commonly characterized by joint pain and stiffness. This disease progression can exhibit common deformities and other activities with limited symptoms and significantly impacts people's work and life. Electroacupuncture (EA) as a traditional Chinese therapy, showing several advantages (e.g., safety, economy, and less side effects), has been extensively used to treat AS. However, its curative effect is supported by limited evidence. Accordingly, the present study aims to comprehensively assess the reliability of EA in AS treatment. The study will conduct a systematic review and meta-analysis. Seven databases, including the Embase, Cochrane Library, Pubmed, SinoMed, CNKI, VIP, and Wanfang Data, will be searched using predefined search terms to identify relevant studies. The primary outcomes will be the clinical efficiency, the Bath AS Disease Activity Index, and the Visual Analog Scale. Eligible studies should report at least 1 of these primary outcomes. Eligible studies designed as randomized controlled trials will be included for meta-analysis, while other related clinical studies will be reviewed. The methodological quality of the included studies will be assessed with a previously established checklist. The Cochrane Collaboration's bias risk tool will be used for assessing the bias of included randomized controlled trials. Stata 17.0 software is used for meta-analysis. The protocol will be used to assess the efficacy and safety of EA in AS treatment. This review reliably evidences whether EA is a reliable method for the intervention of AS.

Efficacy and safety of guselkumab in biologic-naïve patients with active axial psoriatic arthritis: study protocol for STAR, a phase 4, randomized, double-blinded, placebo-controlled trial

BackgroundAxial involvement constitutes a specific domain of psoriatic arthritis (PsA). Interleukin (IL)-23 inhibitors have demonstrated improvement in axial PsA (axPsA) symptoms, but have not shown efficacy in treating ankylosing spondylitis (AS), suggesting differences in axPsA processes and treatments. In a post hoc, pooled analysis of patients with investigator- and imaging-confirmed sacroiliitis in two phase 3, randomized, placebo-controlled studies (DISCOVER-1 and DISCOVER-2), patients treated with guselkumab, an IL-23p19 inhibitor, had greater axial symptom improvements compared with placebo. Confirmatory imaging at baseline was restricted to the sacroiliac (SI) joints, occurred prior to/at screening, and was locally read.MethodsThe STAR study will prospectively assess efficacy outcomes in PsA patients with magnetic resonance imaging (MRI)-confirmed axial inflammation. Eligible, biologic-naïve patients with PsA (N = 405) for ≥ 6 months and active disease (≥ 3 swollen and ≥ 3 tender joints, C-reactive protein [CRP] ≥ 0.3 mg/dL) despite prior non-biologic disease-modifying antirheumatic drugs, apremilast, and/or nonsteroidal anti-inflammatory drugs will be randomized (1:1:1) to guselkumab every 4 weeks (Q4W); guselkumab at week (W) 0, W4, then every 8 weeks (Q8W); or placebo with crossover to guselkumab at W24, W28, then Q8W. Patients will have Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4, spinal pain component score (0–10 visual analog scale) ≥ 4, and screening MRI-confirmed axial involvement (positive spine and/or SI joints according to centrally read Spondyloarthritis Research Consortium of Canada [SPARCC] score ≥ 3 in ≥ 1 region). The primary endpoint is mean change from baseline in BASDAI at W24; multiplicity controlled secondary endpoints at W24 include AS Disease Activity Score employing CRP (ASDAS), Disease Activity Index for PsA (DAPSA), Health Assessment Questionnaire – Disability Index (HAQ-DI), Investigator’s Global Assessment of skin disease (IGA), and mean changes from baseline in MRI SI joint SPARCC scores. Centrally read MRIs of spine and SI joints (scored using SPARCC) will be obtained at W0, W24, and W52, with readers blinded to treatment group and timepoint. Treatment group comparisons will be performed using a Cochran-Mantel-Haenszel or chi-square test for binary endpoints and analysis of covariance, mixed model for repeated measures, or constrained longitudinal data analysis for continuous endpoints.DiscussionThis study will evaluate the ability of guselkumab to reduce both axial symptoms and inflammation in patients with active PsA.Trial registrationThis trial was registered at ClinicalTrials.gov, NCT04929210, on 18 June 2021.Protocol version: Version 1.0 dated 14 April 2021.

Serum fibrinogen to albumin ratio in patients with ankylosing spondylitis: correlation with disease activity and severity

BackgroundThe fibrinogen to albumin ratio (FAR) has risen to prominence as a novel biomarker for various conditions, including systemic inflammation. Therefore, this study aims to assess the role of FAR in ankylosing spondylitis (AS) and its correlation with disease activity, severity, and functional status of AS patients. Thirty adult patients with AS were enrolled, along with 20 healthy age- and sex-matched subjects as controls. Bath Indices were used to determine the disease activity, severity, and functional status.ResultsThe patients’ mean age was 35.3 years, including 22 males (73.3%) and eight females (26.7%). The median disease duration was 10 years, ranging from 1 to 28 years. AS cases showed higher FAR than the control group (P < 0.001). Active cases were associated with significantly higher FAR when compared to cases in remission (P < 0.001). FAR showed significant positive correlations with Bath Indices including BASDAI, BASFI, and BASMI scores (P = 0.002, 0.002, < 0.001, 0.019, 0.022).ConclusionFAR has been increased in AS, particularly in active cases. FAR has also been associated with the impaired functional status of AS patients. FAR can represent a novel inflammatory parameter for monitoring disease activity and severity in AS.

Seropositive Neuromyelitis Optica in a Case of Undiagnosed Ankylosing Spondylitis: A Neuro-Rheumatological Conundrum

Seropositive Neuromyelitis Optica in a Case of Undiagnosed Ankylosing Spondylitis: A Neuro-Rheumatological Conundrum

Symptoms compatible with Rome IV functional bowel disorder in patients with ankylosing spondylitis.

To determine the frequency of symptoms meeting Rome IV functional bowel disorder (FBD) in patients with ankylosing spondylitis (AS), investigate factors associated with FBD symptoms, and assess whether having FBD symptoms might influence AS disease activity. In this cross-sectional study, we enrolled 153 AS patients without known colonic ulcers and 56 sex- and age-matched controls to evaluate FBD (or its subtypes) symptoms. Disease characteristics were also evaluated in the AS group. Sixty (39.2%) of 153 AS patients had FBD symptoms, which were more prevalent than controls (23.2%). Besides, symptoms compatible with irritable bowel syndrome (IBS) and chronic diarrhoea were detected in 18 and 43 AS patients, respectively. For the AS group, multivariable logistic regression analyses showed that symptoms of FBD, IBS, and chronic diarrhoea were negatively associated with using non-steroidal anti-inflammatory drugs and positively associated with comorbid fibromyalgia, respectively. In exploration about the effects of FBD (or its subtypes) symptoms on AS disease activity by multivariable linear regression analyses, FBD symptoms and chronic diarrhoea had universal positive associations with assessments of AS disease characteristics, respectively. Patients with AS had frequent symptoms compatible with FBD, IBS, and chronic diarrhoea, proportions of which were lower in those with non-steroidal anti-inflammatory drug use. The improvement of FBD symptoms and chronic diarrhoea might be conducive to the disease status of AS patients.

Defining and managing flares in axial spondyloarthritis.

Flares correspond to fluctuations in disease activity or symptoms. They should be avoided in chronic inflammatory diseases. In axial spondyloarthritis (axSpA), work is ongoing to better conceptualise and treat flares. This review highlights recent data on the definition and management of flares in axSpA. Many definitions of flares have been used in clinical trials, limiting the interpretation and comparison of studies. The expert group Assessment of SpondyloArthritis International Society (ASAS) developed a data-driven definition of flares/disease worsening: an increase in Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP) of at least 0.9 points, for use in axSpA clinical trials. Flares are more challenging to define in clinical practice because of their multifaceted nature. Qualitative studies have shown that flares from the patient's perspective are related not only to disease activity, but also to fatigue, mood, sleep and general well-being. The management of axSpA relies on a treat-to-target (T2T) strategy and aims at reaching clinical remission while monitoring closely disease activity to prevent and shorten flares. The concept of flares has been clarified, and definitions have been developed for use in trials. The T2T approach aims at minimising flares in axSpA. The early recognition of flares and their severity may lead to better management.

Predictors of not Achieving Remission or Low Disease Activity in Axial Spondyloarthritis Patients from Middle Eastern Countries: A Prospective, Multicenter, Real-world Study.

ObjectivesWe sought to identify the predictors of not achieving remission or low disease activity (LDA) among axial spondyloarthritis (SpA) patients in four Middle Eastern countries.MethodsIn this multicenter prospective real-world study, adult patients with axial SpA diagnosed clinically during January–June 2019, and who met the Assessment of SpondyloArthritis International Society classification criteria for axial SpA, were enrolled from the participating centers of four countries—Lebanon, Oman, Qatar, and the UAE. Patient demographics, disease history, comorbidities, treatment, and compliance data were obtained at baseline. The primary outcome was to determine the percentage of patients who did not achieve the clinical target of remission or LDA as indicated by Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP) < 2.1 after a three-month follow-up period. Secondary outcomes were assessing the demographic and clinical characteristics of ‘achievers’ and ‘non-achievers’ and to study the predictors of ASDAS-CRP ≥ 2.1 in different clinical subsets.ResultsThe participants were 309 patients of both sexes, with a median age of 43 years. Women had a slight majority (53.7%). At the end of the study, 72.2% of patients achieved the clinical target of ASDAS-CRP < 2.1. Non-achievers were significantly more likely to have enthesitis, positive human leukocyte antigen B 27 status, psoriasis, peripheral involvement, fibromyalgia, and a lower score on Compliance Questionnaire for Rheumatology (CQR). Multiple regression analysis showed that low CQR score, enthesitis, psoriasis, and family history of SpA were independent predictors of ASDAS-CRP ≥ 2.1.ConclusionsThis real-world study suggests that low compliance, positive human leukocyte antigen B 27 status, peripheral involvement, and presence of enthesitis, psoriasis, and fibromyalgia are predictors of not achieving remission or LDA in axial SpA patients.

The BASDAI Cut-Off for Disease Activity Corresponding to the ASDAS Scores in a Taiwanese Cohort of Ankylosing Spondylitis.

ObjectivesThe Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) has been widely utilized to evaluate disease activity in patients with ankylosing spondylitis (AS) by an arbitrary cut-off of ≥4 to indicate high disease activity and initiate biological therapy. The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new composite index to assess AS disease activity states that have been defined and validated. ASDAS ≥2.1 was selected as a criterion to start biological therapy. The purpose of this study was to estimate the corresponding BASDAI and ASDAS cut-off in a Taiwanese AS cohort.MethodsFrom November 2016 to October 2018, we assessed the ASDAS and the BASDAI regularly and recorded demographic data for 489 AS patients in Taichung Veterans General hospital (TCVGH) using an electronic patient-reported data system linked to electronic medical records. We used receiver operating characteristic curves with Youden's J statistic to determine the BASDAI values that correspond to ASDAS disease activity cut-offs (i.e., 1.3, 2.1, and 3.5).ResultsIn our population, the best trade-off BASDAI values corresponding to ASDAS -C-reactive protein (CRP) 1.3, 2.1, and 3.5 were 2.1, 3.1, and 3.7, respectively. The optimal BASDAI values corresponding to ASDAS-erythrocyte sedimentation rates 1.3, 2.1, and 3.5 were 2.0, 2.6, and 4.8, respectively.ConclusionWe propose a revised BASDAI cut-off based on our data, as BASDAI scores are commonly used globally. A more reasonable, lower BASDAI cut-off to initiate or change biological therapy will bring us closer to better decisions to treat AS patients.