[HLA genotypes associated with gastrointestinal symptoms in patients with spondyloarthritis without inflammatory bowel disease]. / Genotipos HLA asociados a síntomas gastrointestinales en pacientes con espondiloartritis sin enfermedad inflamatoria intestinal.

OBJECTIVE: This study aimed to establish the association between HLA-A, B, DR genotypes and gastrointestinal variables in patients with SpA without inflammatory bowel disease (IBD). METHODS: Retrospective study of 91 patients with SpA and 401 healthy controls, with typing by Illumina Sequencing/PacBio and LIFECODES HLA-PCR/SSO multiplex sequencing technology. The presence of gastrointestinal symptoms was evaluated by administering a survey, and those who presented 2 or more symptoms were taken for clinical evaluation by rheumatology and gastroenterology, colonoscopy and histopathological study. (Ethics committee approval). RESULTS: The 59,3% of the patients were men, with a mean age of 43,9±11.4 years; 80,2% were classified as ankylosing spondylitis. 14, 28 and 19 genotypes for the HLA-A*, HLA-B* and HLA-DR* loci were identified in both groups, of which a relationship with gastrointestinal symptoms was identified: A*26, A*29 and B*27 were associated to abdominal pain, DRB1*11 and DRB1*16 with abdominal distention, A*30, B*38, DRB1*13 and DRB1*14 with weight loss, B*40 with diarrhea >4 weeks, and presence of mucus in the stools with A*02 and DRB1*11 (p<0.05). Furthermore, the presence of B*15 had a statistical relationship with intolerance to some food, highlighting the B*27 genotype in relation to grains and dairy products, A*23 with grains, vegetables and meats, and B*49 with vegetables and dairy (p<0.05). Regarding the endoscopic variables, macroscopic changes were found in the ileum mucosa related to A*02, B*48, DRB1*14 and the relationship between B*27 and ulcers at this level should be highlighted. Macroscopic changes in the sigmoid colon with B*48 and the rectum with A*30. In microscopic changes, inflammatory alterations of the ileum are mentioned with genotypes DRB1*07, DRB1*13 and DRB1*14, a genotype that is related to changes in the ileum both endoscopically and histologically (p<0.05). CONCLUSIONS: These findings indicate a potential genetic predisposition related to HLA genotypes that may increase the likelihood of food intolerance, gastrointestinal symptoms, and even visible and microscopic changes, specifically in the ileal tissue. The study highlights the presence of B*27 and other noteworthy HLA class I and class II genes (such as DRB1*14) in the diverse Colombian population.

OBJETIVO: Establecer la asociación entre genotipos HLA-A, B, DR y variables gastrointestinales en pacientes con EspA, sin enfermedad inflamatoria intestinal (EII). MÉTODOS: Estudio retrospectivo de 91 pacientes con EspA y 401 controles sanos, con tipificación por tecnología de secuenciación Illumina Sequencing/PacBio, y LIFECODES HLA-PCR/SSO multiplex. Se evaluó la presencia de síntomas gastrointestinales por aplicación de una encuesta, y, aquellos que presentaran dos o más síntomas, fueron llevados a valoración clínica por reumatología y gastroenterología, colonoscopia y estudio histopatológico. (Aprobación del Comité de Ética, HMC, 2022 - 2020). RESULTADOS: El 59,3% de los pacientes fueron hombres, con edad media de 43,9 ± 11,4 años. El 80,2% se clasificó como espondilitis anquilosante. Se identificaron en ambos grupos 14, 28 y 19 genotipos para los loci HLA-A*, HLA-B* y HLA-DR*, de los cuales se identificó relación con síntomas gastrointestinales: A*26, A*29 y B*27, con dolor abdominal; DRB1*11 y DRB1*16, con distensión abdominal; A*30, B*38, DRB1*13 y DRB1*14, con pérdida de peso; B*40, con diarrea >4 semanas y presencia de moco en las deposiciones con A*2 y DRB1*11 (p<0,05). Además, la presencia de B*15, tuvo relación estadística con intolerancia a algún tipo de alimento, a resaltar el genotipo B*27, en relación con granos y lácteos; A*23 con granos, verduras y carnes; y el B*49, con verduras y lácteos (p<0,05). Frente a las variables endoscópicas, se encontraron cambios macroscópicos en la mucosa de íleon relacionados con A*02, B*48, DRB1*14 y, a destacar, la relación B*27 con úlceras a este nivel. Cambios macroscópicos en colon sigmoides con B*48 y en recto con A*30. En cambios microscópicos, se mencionan alteraciones inflamatorias de íleon con genotipos DRB1*07, DRB1*13 y DRB1*14, genotipos que se relaciona a cambios en íleon tanto endoscópica e histológicamente (p<0,05). CONCLUSIONES: Estos resultados sugieren una posible susceptibilidad genética asociada al HLA, con genotipos que pueden predisponer a intolerancia alimentaria, síntomas gastrointestinales, e incluso, a cambios macroscópicos e histológicos, particularmente en tejido de íleon, entre los cuales está presente el B*27, pero resaltan otros interesantes en HLA clase I, como clase II (DRB1*14), en una población de alto mestizaje como la colombiana.

[Faecal microbiota study reveals specific dysbiosis in spondyloarthritis according to subtype, disease activity and treatment]. / Estudio de microbiota fecal revela disbiosis específica en espondiloartritis, según subtipo, actividad de la enfermedad y tratamiento.

OBJECTIVE: To compare the diversity and composition of the gastrointestinal microbiome of patients with SpA. METHODS: MiSeq sequencing of the V3-V4 region of the 16S ribosomal RNA gene was performed on DNA isolated from stool. Patients with concurrent SpA and IBD were excluded. Differences were assessed for richness and diversity indices by QIIME 2™. Differences between means >0,2% with a p-value<0,05 were assumed significant. Institutional Ethics Committee endorsement. RESULTS: 69 individuals included, 49 with SpA (ankylosing spondylitis-AS 72,9%, psoriatic arthritis-PsA 18,8%, reactive arthritis-ReA 8,3%) 5 positive controls-dysbiosis and 15 controls-eubiosis. Conventional treatment in 42,9%, anti-IL-17 16,3% and anti-TNF 40,8%. By subtype, statistically significant differences in favour of AS were found for the diversity indices. AS vs PsA there was a difference in favour of AS for Clostridium clostridioforme (p=0,002), Gemmiger formicilis (p=0,009), Roseburia inulivorans (p=0,008) and Lachnospira pectinoschiza. AS vs ReA there was a difference in favour of AS for L. pectinoschiza (p=0,009), Ruminococcus callidus (p=0.006), Clostridium ruminantium (p=0.031); G. formicilis (p=0,034). Diversity and richness showed differences in patients with high activity for Simpson's and Pielou's indices. In high activity, lower enrichment of Bacteroides eggerthii (p= 0,0003), C. ruminantium (p= 0,026) and Alistipes putredinis (p=0,035) was found. The number of ASV was higher in the anti-IL-17 vs conventional group (p=0.025) and a trend between anti-IL-17 vs anti-TNF (p=0.09). In anti-TNF there was a lower proportion for C. clostridioforme (p=0.023), G. formicilis (p=0.030) and R. callidus (p= 0.003). In anti IL-17, Alistipes indistinctus (p= 0.012) was decreased. CONCLUSIONS: There are differences in microbial diversity for SpA subtypes. The level of disease activity is plausible to influence the composition of the faecal microbiota. Anti-TNFα treatment may influence the microbiome environment favouring restoration of the gut microbiota, while anti-IL-17 may maintain an inflammatory environment.

OBJETIVO: Comparar la diversidad y composición del microbioma gastrointestinal de pacientes con EspA. MÉTODOS: La secuenciación MiSeq de la región V3-V4 del gen ARN ribosomal 16, se realizó en ADN aislado de heces. Se excluyeron pacientes con EspA y EII simultánea. Se evaluaron diferencias para los índices de riqueza y diversidad por medio de QIIME 2™. Las diferencias entre medias> 0,2%, con un valor de p< 0,05, se asumieron significativas. Aval del Comité de Ética Institucional. RESULTADOS: 69 individuos incluidos, 49 con EspA (espondilitis anquilosante-EA 72,9%, artritis psoriásica-APs 18,8%, artritis reactiva-ARe 8,3%), cinco controles positivos-disbiosis y 15 controles-eubiosis. El tratamiento convencional en 42,9%, anti-IL-17 16,3%, y anti-TNF 40,8%. Por subtipo-EasP, se encontraron diferencias estadísticamente significativas a favor de EA para los índices de diversidad. Entre EA vs APs, hubo diferencia a favor de EA para Clostridium clostridioforme (p=0,002), Gemmiger formicilis (p=0,009), Roseburia inulivorans (p=0,008) y Lachnospira pectinoschiza. Entre EA vs ARe hubo diferencia a favor de EA para L. pectinoschiza (p=0,009), Ruminococcus callidus (p = 0,006), Clostridium ruminantium (p=0,031); G. formicilis (p=0,034). La diversidad y riqueza mostraron diferencias en pacientes con alta actividad para los índices de Simpson y Pielou. En alta actividad, se encontró menor enriquecimiento de Bacteroides eggerthii (p=0,0003), C. ruminantium (p= 0,026) y Alistipes putredinis (p= 0,035). El número de ASV fue superior en el grupo de anti IL-17 vs convencional (p=0.025), y una tendencia entre anti IL-17 vs anti-TNF (p=0,09). En anti TNF hubo menor proporción para C. clostridioforme (p=0,023), G. formicilis (p=0,030) y R. callidus (p= 0,003). Y en anti IL-17, Alistipes indistinctus (p= 0,012), estuvo disminuida. CONCLUSIONES: Existen diferencias en la diversidad microbiana para los subtipos de EspA. El nivel de actividad de la enfermedad es plausible para influir en la composición de microbiota fecal. El tratamiento con anti-TNFα, puede influenciar el ambiente del microbioma favoreciendo la restauración de la microbiota intestinal, mientras los anti IL-17 podrían mantener un ambiente inflamatorio.

Tuberculosis and Nontuberculous Mycobacterial Infections in Patients with Spondyloarthritis: A Population-Based Study.

Background and Objectives: Tuberculosis is caused by Mycobacterium tuberculosis (MTB), while nontuberculous mycobacteria (NTM) encompass a group of mycobacterial species that are distinct from the MTB complex and leprae. Spondyloarthritis (SpA) is a group of chronic inflammatory diseases with shared clinical characteristics and is treated with biological agents; however, their use may elevate the risk of MTB and NTM infections. This study aimed to compare the incidence and risk of MTB and NTM infections in patients with SpA, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), using a population-based approach. Materials and Methods: This study included 2333 patients with SpA and 9332 age- and sex-matched controls from the Korea National Health Insurance Service-National Sample Cohort database from 2002 to 2019. The patients were identified using the International Classification of Diseases-10 codes for AS, PsA, MTB, and NTM. Results: The results showed that a negligible percentage of patients with SpA developed NTM (0.002%) and MTB (0.016%), with no significant difference in the incidence rate ratio (IRR) compared to controls. Among patients with SpA treated with biologics, the IRRs for NTM and MTB were 5.66 and 3.069, respectively; however, these were not statistically significant. No cases of NTM or MTB infection were reported in female patients with SpA treated with biologics. In both the SpA patient group and the control group, the incidence of MTB was higher in individuals over 60 years old compared to those under 60 years old. Cox proportional hazard analysis revealed a significant adjusted hazard ratio of 1.479 for MTB in patients with SpA after adjusting for age, sex, smoking history, insurance level, and comorbidities. However, this significance was not maintained when biological therapy was further adjusted. Conclusions: Our study indicated that the risks of NTM and MTB infection are not elevated in patients with SpA. Although biological use may potentially increase the risk of MTB infection, it does not lead to a significant increase in incidence rates. Proactive screening for latent tuberculosis and adequate prophylaxis using biologics can effectively manage the risk of NTM and MTB infections.

Efficacy and safety of gut microbiota-based therapies in autoimmune and rheumatic diseases: a systematic review and meta-analysis of 80 randomized controlled trials.

BACKGROUND: Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is lacking. METHODS: Pubmed, EMbase, Sinomed, and other databases were searched for RCTs related to the treatment of autoimmune diseases with probiotics from inception to June 2022. RevMan 5.4 software was used for meta-analysis after 2 investigators independently screened literature, extracted data, and assessed the risk of bias of included studies. RESULTS: A total of 80 RCTs and 14 types of autoimmune disease [celiac sprue, SLE, and lupus nephritis (LN), RA, juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia syndrome, MS, systemic sclerosis, type 1 diabetes mellitus (T1DM), oral lichen planus (OLP), Crohn's disease, ulcerative colitis] were included. The results showed that gut microbiota-based therapies may improve the symptoms and/or inflammatory factor of celiac sprue, SLE and LN, JIA, psoriasis, PSS, MS, systemic sclerosis, Crohn's disease, and ulcerative colitis. However, gut microbiota-based therapies may not improve the symptoms and/or inflammatory factor of spondyloarthritis and RA. Gut microbiota-based therapies may relieve the pain of fibromyalgia syndrome, but the effect on fibromyalgia impact questionnaire score is not significant. Gut microbiota-based therapies may improve HbA1c in T1DM, but its effect on total insulin requirement does not seem to be significant. These RCTs showed that probiotics did not increase the incidence of adverse events. CONCLUSIONS: Gut microbiota-based therapies may improve several autoimmune diseases (celiac sprue, SLE and LN, JIA, psoriasis, fibromyalgia syndrome, PSS, MS, T1DM, Crohn's disease, and ulcerative colitis).

Factors associated with acute anterior uveitis history in patients with axial spondyloarthritis: Results of a longitudinal study.

BACKGROUNDS: Acute anterior uveitis (AAU) is the most common extra-musculoskeletal manifestation in axial spondyloarthritis (axSpA). OBJECTIVES: The aim of the study is to evaluate the factors associated with AAU attacks in patients with axSpA during a 36-month follow-up period. METHODS: In total, 469 patients with axSpA were included in this observational study. Demographic data, clinical characteristics, disease activity measurements, and treatment patterns were compared between patients with and without a history of AAU. The development of AAU and its related factors were investigated using generalized estimating equations, which is a technique for longitudinal data analysis. RESULTS: Overall, 99 (21%) out of 469 patients experienced at least one AAU attack, with 77 patients (78%) having a history of AAU and 53 patients (58% of whom had a history of AAU) experiencing AAU attacks during the follow-up period. At baseline, patients with a history of AAU were found to be older (p = .001), be more likely to have peripheral arthritis (p < .001), have higher serum CRP levels (p = .016), have a higher frequency of sulfasalazine (SLZ) and tumor necrosis factor inhibitors (TNFi) use (p < .001 and p < .001, respectively). In the longitudinal analysis, having a history of AAU was identified as the only independent determinant of the development of AAU. CONCLUSIONS: AAU history might be a risk factor for the development of AAU attacks in patients with axSpA. Although TNFi and SLZ were prescribed more frequently to patients with a history of AAU, the effectiveness of these agents in preventing further AAU attacks was not demonstrated.

Cross-sectional analysis of cardiovascular disease and risk factors in patients with spondyloarthritis: a real-life evidence from biostar nationwide registry.

The association between spondyloarthritis and cardiovascular (CV) diseases is complex with variable outcomes. This study aimed to assess the prevalence rates of CV diseases and to analyze the impact of CV risk factors on CV disease in patients with spondyloarthritis. A multi-center cross-sectional study using the BioSTAR (Biological and Targeted Synthetic Disease-Modifying Antirheumatic Drugs Registry) database was performed on patients with spondyloarthritis. Socio-demographic, laboratory, and clinical data were collected. Patients with and without major adverse cardiovascular events (MACE) were grouped as Group 1 and Group 2. The primary outcome was the overall group's prevalence rates of CV disease and CV risk factors. The secondary outcome was the difference in socio-demographic and clinical characteristics between the groups and predictive risk factors for CV disease. There were 1457 patients with a mean age of 45.7 ± 10.9 years. The prevalence rate for CV disease was 3% (n = 44). The distribution of these diseases was coronary artery disease (n = 42), congestive heart failure (n = 4), peripheral vascular disorders (n = 6), and cerebrovascular events (n = 4). Patients in Group 1 were significantly male (p = 0.014) and older than those in Group 2 (p < 0.001). There were significantly more patients with hypertension, diabetes mellitus, chronic renal failure, dyslipidemia, and malignancy in Group 1 than in Group 2 (p < 0.05). Smoking (36.7%), obesity (24.4%), and hypertension (13.8%) were the most prevalent traditional CV risk factors. Hypertension (HR = 3.147, 95% CI 1.461-6.778, p = 0.003), dyslipidemia (HR = 3.476, 95% CI 1.631-7.406, p = 0.001), and cancer history (HR = 5.852, 95% CI 1.189-28.810, p = 0.030) were the independent predictors for CV disease. A multi-center cross-sectional study using the BioSTAR (Biological and Targeted Synthetic Disease-Modifying Antirheumatic Drugs Registry) database was performed on patients with spondyloarthritis. Socio-demographic, laboratory, and clinical data were collected. Patients with and without major adverse cardiovascular events (MACE) were grouped as Group 1 and Group 2. The primary outcome was the overall group's prevalence rates of CV disease and CV risk factors. The secondary outcome was the difference in socio-demographic and clinical characteristics between the groups and predictive risk factors for CV disease. There were 1457 patients with a mean age of 45.7 ± 10.9 years. The prevalence rate for CV disease was 3% (n = 44). The distribution of these diseases was coronary artery disease (n = 42), congestive heart failure (n = 4), peripheral vascular disorders (n = 6), and cerebrovascular events (n = 4). Patients in Group 1 were significantly male (p = 0.014) and older than those in Group 2 (p < 0.001). There were significantly more patients with hypertension, diabetes mellitus, chronic renal failure, dyslipidemia, and malignancy in Group 1 than in Group 2 (p < 0.05). Smoking (36.7%), obesity (24.4%), and hypertension (13.8%) were the most prevalent traditional CV risk factors. Hypertension (HR = 3.147, 95% CI 1.461-6.778, p = 0.003), dyslipidemia (HR = 3.476, 95% CI 1.631-7.406, p = 0.001), and cancer history (HR = 5.852, 95% CI 1.189-28.810, p = 0.030) were the independent predictors for CV disease. The prevalence rate of CV disease was 3.0% in patients with spondyloarthritis. Hypertension, dyslipidemia, and cancer history were the independent CV risk factors for CV disease in patients with spondyloarthritis.

Ultrasonographic Evaluation of Nail Involvement in Patients With Axial Spondyloarthritis.

OBJECTIVES: This study aimed to evaluate the nail units of patients with axial spondyloarthritis (ax-SpA) using ultrasound and to identify any subclinical changes. We also aimed to examine the relationship between clinical enthesitis scores and nail involvement in patients with ax-SpA. METHODS: The study included 40 patients with ax-Spa, 40 patients with psoriatic arthritis (PsA), and 40 healthy controls. The thickness of the nail plates, morphological changes, the thickness of the proximal nail units, the thickness of the nail beds, and power Doppler signal intensities were evaluated and compared. Maastricht Ankylosing Spondylitis Enthesitis Score and Spondyloarthritis Research Consortium of Canada Enthesitis Index were also evaluated in patients with ax-SpA. RESULTS: There was no significant difference between the thickness of the nail plates of the three groups (P > .05). The first nail bed thickness of ax-SpA cases was significantly higher than the control group (P = .046), and the fourth and fifth nail proximal unit thicknesses of the control group were significantly lower than the ax-SpA and PsA groups (P = .023, P = .017). We also found that the Wortsman scores of the cases with PsA were significantly higher than the ax-SpA and control groups (P = .0001). CONCLUSION: The thickness of the proximal nail unit adjacent to the insertion of the digital extensor tendon, which is considered as the enthesis area, is similar to the patients with PsA in patients with ax-SpA, especially in the fourth and fifth fingers compared to the control group. On the other hand, almost no structural changes in nail plates were observed in patients with ax-SpA group.

Exploring radiographic patterns of the cervical spine, including zygapophyseal joints, in axial spondyloarthritis.

INTRODUCTION: The assessment of the cervical spine (CS) in axial spondyloarthritis (axSpA) and its radiographic characteristics, including the zygapophyseal joints (ZJ), may be helpful for an accurate diagnosis, establishing a prognosis and enhancing treatment decisions. OBJECTIVES: To describe the prevalence and characteristics of CS involvement in patients with axSpA and perform a comparison between groups according to cervical radiographic damage. METHODS: Patients who fulfilled the Assessment of SpondyloArthritis International Society classification criteria were included from January 2011 to January 2021. Sociodemographic, clinical, radiographic and treatment variables were gathered. Patients were categorised into 'CS group' (Bath Ankylosing Spondylitis Radiology Index ≥2 or De Vlam score ≥3 for ZJ) and 'no CS group' as controls. ZJ fusion and interobserver reliability in ZJ scoring were analysed. RESULTS: A total of 340 patients were included, 244 (71.7%) men, with mean age 57±15 years. CS involvement was observed in 181 (53.2%) patients. Patients in the CS group, as compared with no CS group, were predominantly men, older, had a higher body mass index, higher prevalence of smoking, showed higher disease activity, worse functionality and mobility, as well as more structural damage. Sixty-nine patients with CS involvement had ZJ fusion at some level. These patients showed worse mobility and more radiographic damage. Overall, ZJ involvement was observed in 99 patients (29.1%), 20 of whom did not present with vertebral body involvement. CONCLUSION: Radiographic evaluation of CS is relevant in patients with axSpA and should be assessed routinely. Evaluation of the ZJ is particularly significant, as it is related to higher disease activity and worse function.

Factors Associated With Treatment Pathways in Early Axial Spondyloarthritis: A Multistate Analysis of the 10-Year Follow-Up of the DESIR Cohort.

OBJECTIVE: Current recommendations for the management of patients with axial spondyloarthritis (axSpA) emphasize the need of an individualized strategy in therapeutic decision-making. The study objectives were to describe therapeutic strategies observed in axSpA, and to assess the factors associated with treatment intensification over time. METHODS: We included patients with axSpA from the French prospective cohort DESIR (Devenir des Spondylarthropathies Indifférenciées Récentes), with a scheduled 10-year follow-up. A multistate model with 4 ordered treatment states (no treatment, nonsteroidal antiinflammatory drugs [NSAIDs], conventional synthetic disease-modifying antirheumatic drugs [csDMARDs], and tumor necrosis factor inhibitors [TNFi]) was defined, with 6 possible transitions. Restricted mean sojourn times in each state were estimated. Then, predictors of those transitions were assessed by multivariable Cox models. RESULTS: A total of 686/708 (96.9%) patients who had > 1 visit were analyzed. At cohort entry, 199 (29%) were untreated, 427 (62.2%) were receiving NSAIDs, 60 (8.7%) csDMARDs, and none were receiving TNFi. Over the follow-up period, patients mostly (46.4% of the time) received NSAIDs, followed by TNFi (24.4% of the time). The presence of sacroiliitis on radiographs, inflammatory bowel disease, and articular index were jointly associated with the transition to NSAIDs. Longer duration in the previous state often decreased the hazard of the transition to csDMARDs or TNFi. Worse disease activity outcomes increased the hazard of most transitions. CONCLUSION: To our knowledge, this was the first study using a multistate model to easily represent different treatment states, detailing the transitions across them and their associated factors. Different time profiles for the management of patients with axSpA were identified, including in those abstaining from treatment up to a significant proportion of patients treated with csDMARDs.

Dose Tapering and Discontinuation of Biologic DMARDs in Axial Spondyloarthritis: A Narrative Review (2023 SPARTAN Annual Meeting Proceedings).

PURPOSE OF REVIEW: Limited data is available for tapering or discontinuation of biologic therapy in patients with axSpA who are in disease remission. The current review concentrates on published studies regarding dose tapering or withdrawal of biologics in axSpA. RECENT FINDINGS: Recent evidence in light of randomized controlled trials suggests that tapering of b-DMARDs is a feasible strategy to maintain remission or low disease activity in axSpA patients. TNF inhibitors were the studied biologics in most of these trials. The disease flare rates were comparable to those maintained on standard dose in most of these studies, although with variable tapering strategies and follow-up. Additionally, the duration of disease in remission prior to tapering, studied primary outcome, and flare definitions were heterogeneous. Female sex, HLA-B*27 negativity, high physician global score, and high CRP were negative predictors of successful tapering, but not consistently reported in all the trials. Although designed to address efficacy, there were no safety concerns with b-DMARD tapering. Withdrawal or complete discontinuation of biologics met with increased risk of flares compared to standard dosing. Tapering of TNF inhibitors may be feasible in certain axSpA patients with an acceptable disease state; however, discontinuation is not currently recommended owing to increased risk of flare. Future studies with axSpA patients with longer remission duration prior to taper and different doses and types of b-DMARDs may provide more guidance.

A Good Response to Nonsteroidal Antiinflammatory Drugs Does Not Discriminate Patients With Longstanding Axial Spondyloarthritis From Controls With Chronic Back Pain.

OBJECTIVE: To compare the response to nonsteroidal antiinflammatory drugs (NSAIDs) in patients with longstanding axial spondyloarthritis (axSpA) and controls with back pain (nonspondyloarthritis [non-SpA]). METHODS: Consecutive outpatients with chronic back pain (axSpA or non-SpA), were prospectively recruited. Any previous NSAIDs were withdrawn 2 days before study start (baseline). Back pain was assessed using a numerical rating scale (NRS; range 0-10) starting at 2 hours after baseline and several times thereafter up to 4 weeks. "Any response" to NSAIDs was defined as improvement of back pain on the NRS > 2 units, and "good response" as improvement > 50%, compared to baseline. RESULTS: Among 233 patients included, 68 had axSpA (29.2%) and 165 had non-SpA back pain (70.8%). The mean age was 42.7 (SD 10.7) vs 49.3 (SD 11.1) years, symptom duration 15.1 (SD 11.1) years vs 14.6 (SD 11.9) years, and pain score 5.9 (SD 2.3) vs 6.3 (SD 2.0), respectively. Overall, of patients with axSpA or non-SpA back pain, 30.9% vs 29.1% of patients showed any response and 23.5% vs 16.4% of patients showed a good response after 4 weeks, respectively (P value not significant). No differences were found in the rapidity of response or between subgroups of patients based on demographics, including different stages of axSpA. CONCLUSION: No major differences in the response to NSAIDs were found between patients with axSpA and those with non-SpA with longstanding chronic back pain. The item in the Assessment of SpondyloArthritis international Society classification criteria on "response to NSAIDs" needs more study.

Circulating cell-free DNA correlate to disease activity and treatment response of patients with radiographic axial spondyloarthritis.

Microdamage and its related inflammation contribute to the development of radiographic axial spondyloarthritis (r-axSpA). Inflammation and cell death in damaged tissues are associated with cell-free DNA (cfDNA) release. Here we investigated whether circulating cfDNA could be a potential biomarker for evaluating disease activity and treatment response in r-axSpA. Circulating cfDNA was detected in the discovery and validation cohort with 79 and 60 newly diagnosed r-axSpA patients respectively and 42 healthy controls using the Quant-iT PicoGreen dsDNA reagent and kit. As a result, cfDNA levels were significantly higher in r-axSpA patients compared with healthy controls in the discovery and validation cohort. Moreover, cfDNA levels were positively correlated with CRP, ASDAS-CRP and neutrophil counts. Additionally, non-steroid anti-inflammatory drugs (NSAIDs) combined with disease-modifying anti-rheumatic drugs or tumor necrosis factor inhibitors but not NSAIDs alone could reduce cfDNA levels. Moreover, a decrease of cfDNA levels after treatment was associated with an effective therapeutic response. Intriguingly, patients with higher levels of cfDNA at diagnosis responded better to combination therapy rather than NSAIDs. However, patients with lower levels of cfDNA displayed similar responses to combination or mono-NSAID treatment. In conclusion, circulating cfDNA levels showed a significant correlation with disease activity as well as treatment efficacy in patients with r-axSpA. Moreover, cfDNA at diagnosis might predict the response to different therapy. Consequently, cfDNA may serve as a useful biomarker of inflammation in r-axSpA.

Retention rate of subcutaneous TNF inhibitors in axial spondyloarthritis in a multicentre study from the RIC-FRANCE network.

The objectives of our study were to assess retention rate, safety, and predictive factors for retention of subcutaneous (SC) TNF inhibitors (TNFi) (adalimumab (ADA), etanercept (ETN), golimumab (GOL), and certolizumab pegol (CZP)) in axial spondyloarthritis (axSpA) depending on the line of treatment in real-life conditions. A multicentre retrospective observational study was conducted including 552 patients fulfilling the ASAS criteria for axSpA followed in the RIC-France register who began SC-TNFi between 01/01/13 and 08/31/2018 for a total of 824 prescriptions. Taking all lines of treatment into account, GOL had a significantly higher retention rate compared with ADA, ETN, and CZP with a mean retention length of 59 months. As first-line bDMARDs, GOL had a significantly higher retention rate compared with ADA and ETN. ETN had the best retention rate when prescribed as at least 3rd bDMARD. Taking all lines of treatment into account, female sex, peripheral disease, BASDAI at initiation, and line of treatment were predictive factors for treatment cessation. Primary inefficiency was the most frequent reason for treatment cessation. In conclusion, GOL showed the highest retention rate in axSpA. Male sex, absence of peripheral disease, and early line of prescription were associated with better SC-TNFi retention in axSpA.

Frequency of irritable bowel syndrome in spondyloarthritis: a multicentric cross-sectional study and meta-analysis.

OBJECTIVE: To evaluate the prevalence of symptoms and factors associated with irritable bowel syndrome (IBS) in axial spondyloarthritis (ax-SpA). METHODS: In a cross-sectional multicentric study, consecutive patients with ax-SpA treated with biologics in five rheumatology departments were asked for IBS Rome IV criteria. Demographic data, lifestyle behaviours and disease characteristics were recorded. Second, a systematic literature review and meta-analysis were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Of the 500 patients with ax-SpA included, 124 reported IBS symptoms (25%). Female gender, unemployment, higher Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and worse Bath Ankylosing Spondylitis Functional Index scores, multiple lines of biologics, fibromyalgia, anxiety, depression and lower physical activity were associated with IBS symptoms. In multivariate model, the risk of IBS was associated with anxiety and physical inactivity. From the literature review, the prevalence of IBS in patients with SpA was 15.4% (8.8% to 23.3%). Meta-analysis of the five studies comparing the presence of IBS in patients with SpA (323/7292) and healthy controls (484/35587) showed a significant increase of IBS in patients with SpA (OR=1.59 (1.05 to 2.40)). CONCLUSION: The prevalence of IBS symptoms was high in the ax-SpA population and should therefore be considered in the presence of gastrointestinal disorders. The presence of IBS symptoms was associated with anxiety and low physical activity in multivariate analysis. Patients with IBS symptoms tended to have more difficult to manage disease characterised by higher activity, worse functional score and multiple lines of treatment in univariate analysis.

Prevalence of anxiety and depression and the association with self-management behaviour in >12 000 patients with inflammatory rheumatic disease: a cross-sectional nationwide study.

OBJECTIVE: To investigate the prevalence of anxiety and depression among patients with inflammatory arthritis (IA) and evaluate the association of these mental health issues with self-management behaviour. METHODS: In this nationwide cross-sectional study, we analysed data from 12 713 adult Danish patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or spondyloarthritis (SpA). Patients received an electronic questionnaire covering sociodemographics, self-management behaviour and mental health status. Questionnaire data were linked to clinical data from the Danish Rheumatology database (DANBIO) and the Danish National Patient Registry. The prevalence of anxiety and depression (by the Hospital Anxiety and Depression Scale for Anxiety (HADS-A) and Depression (HADS-D)) was estimated separately for RA/PsA/SpA. The association between mental health status and low self-management behaviour (adherence to treatment, health activation and physical activity) was estimated using multivariable logistic regression, adjusting for age, sex, educational level and comorbidity. RESULTS: The prevalence of anxiety (HADS-A≥8) was highest for patients with SpA (34.5% (95% CI 32.4% to 36.6%)) and lowest for patients with RA (22.1% (95% CI 21.2% to 23.0%)), it was higher for women, younger (<55 years) and recently diagnosed (<3 years) patients and those with basic education. Similar prevalence estimates were found for depression. Across diagnoses, the clinically relevant symptoms of anxiety and depression (HADS≥8) were significantly associated with low self-management behaviour. CONCLUSION: Patients with IA showed substantial levels of anxiety and depression. A statistically significant association between anxiety and depression and low self-management behaviour was identified. These findings call for a systematic approach to identifying mental health issues in patients with IA.

Mendelian randomization analysis reveals causal associations of inflammatory bowel disease with Spondylarthritis.

OBJECTIVE: Inflammatory bowel disease (IBD) is strongly associated with Spondylarthritis (SpA), but the causal relationship remains unclear. This study explores the causal associations between IBD (Crohn's disease [CD] and ulcerative colitis [UC]) and several common subtypes of SpA (Ankylosing Spondylitis [AS], Psoriatic Arthritis [PsA], and Reactive Arthritis [ReA]), using bidirectional two-sample Mendelian randomization (TSMR). METHODS: The causal effects of genetically predicted IBD on AS, PsA, and ReA were firstly investigated in this forward study. The causal effects from AS, PsA, and ReA on IBD were analyzed in the reverse MR. Inverse variance weighted, weighted median, and MR-Egger were applied in the MR analyses. The pleiotropic effects, heterogeneity, and leave-one-out sensitivity analysis were also evaluated. RESULTS: The forward MR analysis demonstrated that IBD increased risk for AS (OR:1.278; P = 1.273 × 10-5), PsA (OR:1.192; P = 1.690 × 10-5), and ReA (OR:1.106; P = 1.524 × 10-3). Among them, CD increased risk of AS (OR:1.196; P = 3.424 × 10-4), PsA (OR:1.101; P = 1.537 × 10-3), ReA (OR:1.079; P = 6.321 × 10-3) whereas UC increased risk of AS (OR:1.166; P = 2.727 × 10-2), PsA (OR:1.110; P = 1.944 × 10-2), and ReA (OR:1.091; P = 1.768 × 10-2). The reverse-direction MR disclosed no notable association; neither was any evidence of pleiotropy detected. CONCLUSION: Our study verifies a causal effect of IBD to AS, PsA as well as ReA, but not vice versa. This might bring new insights for the management of IBD and SpA in clinical practice.

Sex differential impact of comorbidities in spondyloarthritis: data from COMOSPA study.

OBJECTIVES: To describe and compare the prevalence of comorbidities in female and male patients with spondyloarthritis (SpA) and to assess whether comorbidities had a different impact on disease outcomes in male and female patients. METHODS: This is a post hoc analysis of the COMOrbidities in SPondyloArthritis study. Differences in comorbidities regarding sex were assessed using logistic regression models. Comorbidities were evaluated for their impact on disease outcomes (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index, European health-related quality of life questionnaire) with linear models, which included sex and comorbidity as explanatory variables and their interaction. Age and treatment with biological synthetic disease-modifying antirheumatic drugs were included as confounders. RESULTS: We included 3982 patients with SpA (65% male, mean age 43.6 years). Male and female patients with SpA exhibited similar comorbidity profiles, except for a low prevalence of fibromyalgia in males and a higher prevalence of certain cardiovascular risk factors in males (hypertension, dyslipidaemia, renal impairment and ischaemic heart disease). Comorbidities, especially fibromyalgia, correlated with higher disease activity, decreased physical function and reduced health-related quality of life in both sexes. Some comorbidities exhibited sex-specific associations with disease outcomes. Peptic ulcers and high waist circumference had a greater impact on disease activity in females (with a higher impact in BASDAI than in ASDAS). In contrast, osteoporosis had a more pronounced effect on physical function in male patients. CONCLUSIONS: Comorbidities exert distinct influences on disease activity, physical function and health-related quality of life in male and female patients with SpA. Understanding these sex-specific effects is crucial for improving SpA management, emphasising the importance of assessing disease activity using ASDAS when comorbidities are present to mitigate sex-related disparities in disease assessment.

[Immune-mediated inflammatory diseases in Germany : A cross-sectional analysis of comorbidities and pharmacotherapy]. / Chronische Entzündungserkrankungen in Deutschland : Eine Querschnittanalyse über Begleiterkrankungen und Arzneimitteleinsatz.

BACKGROUND: Immune-mediated inflammatory diseases (IMID) can lead to a substantial disease burden for those affected, in particular by the concomitant occurrence of other IMIDs or in the presence of comorbidities. The care of patients with IMIDs is complex and involves various medical disciplines. OBJECTIVE: To describe the burden of disease and the current routine drug treatment of patients with IMID. MATERIAL AND METHODS: The retrospective cross-sectional analysis was based on statutory health insurance claims data from the InGef database. Prevalent patients with psoriasis (Pso), psoriatic arthritis (PsA), spondylarthritis (SpA), rheumatoid arthritis (RA), Crohn's disease (MC), ulcerative colitis (CU), or connective tissue disease were identified among 3,988,695 insured patients in 2018. The concomitant occurrence of different IMIDs and the extent to which patients with IMID are affected by other comorbidities compared to a reference population were investigated. The current routine drug treatment was described based on the use of predefined forms of treatment. RESULTS: In the database 188,440 patients with IMID (4.7%) were identified. Compared to the reference population the prevalence of comorbidities, such as depressive episodes and cardiovascular risk factors was higher in patients with IMID. For MC, CU, RA, and PsA disease-modifying antirheumatic drugs (DMARD) and classical systemic forms of treatment were used most commonly. In Pso, SpA, and connective tissue disease nonsteroidal anti-inflammatory drugs (NSAID) were the most frequently used treatment often in combination with other drugs. CONCLUSION: A considerable number of patients with IMIDs (16.9-27.5%) suffer from different diseases of the IMID group. They are frequently affected by accompanying illnesses and require interdisciplinary medical treatment.

Enthesitis in patients with psoriatic arthritis treated with secukinumab or adalimumab: a post hoc analysis of the EXCEED study.

OBJECTIVES: To evaluate enthesitis treatment response, including time to resolution and data from multiple enthesitis instruments, in patients with PsA treated with secukinumab or adalimumab for 52 weeks. METHODS: In this post hoc analysis of the EXCEED study, patients receiving secukinumab 300 mg or adalimumab 40 mg per the label were grouped by presence or absence of baseline enthesitis based on the Leeds Enthesitis Index (LEI) and the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Efficacy was assessed according to several enthesitis-related instruments using non-responder imputation for the achievement of enthesitis resolution (LEI/SPARCC = 0), Kaplan-Meier analysis for time to resolution, and as-observed data for other outcomes. RESULTS: Enthesitis was present at baseline in 498 of 851 patients (58.5%) as assessed by LEI and in 632 of 853 patients (74.1%) as assessed by SPARCC. Patients with baseline enthesitis generally presented with greater disease activity. Similar proportions of patients receiving secukinumab or adalimumab achieved resolution of LEI and SPARCC at weeks 24 (secukinumab: LEI/SPARCC, 49.6%/45.8%; adalimumab: LEI/SPARCC, 43.6%/43.5%) and 52 (secukinumab: LEI/SPARCC, 60.7%/53.2%; adalimumab: LEI/SPARCC, 55.3%/51.4%), with comparable mean time to enthesitis resolution. Improvements were similar for both drugs at individual enthesitis sites. Resolution of enthesitis with secukinumab or adalimumab was associated with improvements in quality of life at week 52. CONCLUSION: Secukinumab and adalimumab showed similar efficacy, including time to resolution, with respect to resolution of enthesitis. Inhibition of IL-17 with secukinumab reduced clinical enthesitis similarly to TNF-α inhibition. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02745080.