Exploring the Link Between Ankylosing Spondylitis and Inflammatory Bowel Disease: A Retrospective Cohort Study.

BACKGROUND: Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are chronic conditions with overlapping pathogenic mechanisms. The genetic predisposition and inflammatory pathways common to both diseases suggest a syndemic relationship. While some evidence points to a connection between the two conditions, other reports do not support this link. OBJECTIVES: To investigate the association between AS and the subsequent incidence of IBD. To identify potential risk factors and effect modifiers that contribute to this relationship. METHODS: Utilizing the Chronic Disease Registry of Clalit Health Services, we conducted a retrospective cohort study of individuals diagnosed with AS between January 2002 and December 2018. We compared these patients with age- and sex-matched controls, excluding those with a prior diagnosis of IBD. Statistical analyses included chi-square and t-tests for demographic comparisons, and Cox proportional hazards models for evaluating the risk of IBD development, with adjustments for various co-morbidities and demographic factors. RESULTS: The study included 5825 AS patients and 28,356 controls. AS patients demonstrated a significantly higher incidence of IBD with hazard ratios of 6.09 for Crohn's disease and 2.31 for ulcerative colitis, after multivariate adjustment. The overall incidence of IBD in the AS cohort was significantly higher compared to controls. CONCLUSIONS: AS patients exhibit a markedly increased risk of developing IBD. These findings advocate for heightened clinical vigilance for IBD symptoms in AS patients and suggest the need for a multidisciplinary approach to patient care. Further research into the shared pathogenic pathways is needed to develop personalized treatment strategies and improve patient management.

The Risk and Predictors of Malignancies in Ankylosing Spondylitis Patients in Israel-A Retrospective Electronic Data-Based Study.

BACKGROUND: Previous studies demonstrated unclear and vast variability in the association between Ankylosing Spondylitis (AS) and the risk of cancer. OBJECTIVES: To assess the risk of overall and site-specific malignancies for AS patients in Israel, while examining the role of comorbidities and immunomodulatory therapy. METHODS: We conducted a retrospective electronic data-based study including all AS patients diagnosed between 2002 and 2018, with no history of cancer prior to enrollment, with 5:1 ratio matched-control by age, gender, and place of residence. The odds Ratios (OR) for site-specific malignancies, comparing AS patients and controls, were calculated using logistic regression. Risk factors for malignancies within the AS cohort were evaluated in the same manner. RESULTS: This study comprised 5825 AS patients and 28,356 matched controls. There was a higher overall risk of cancer in AS patients compared to controls (OR = 1.4, 95% CI 1.24-1.6), specifically for solid malignancies (OR = 1.5, 95% CI 1.3-1.7), CNS (OR = 3.72, 95% CI 1.29-10.7), kidney (OR = 2.06, 95% CI 1.12-3.8), and malignancy of unknown primary (OR = 3.06, 95% CI 2.35-3.98). Regarding predictors for malignancy within AS patients, older age at diagnosis (OR = 1.31, 95%,CI 1.25-2.36), diabetes (OR = 1.52, 95% CI 1.18-1.97), IBD (OR = 2.61, 95% CI 1.75-3.89), and treatment with DMARDs (OR = 2.17, 95% CI 1.65-2.83) were associated with a higher risk of solid malignancies, while NSAIDs treatment alone had a protective effect for solid malignancies (OR = 0.78, 95% CI 0.61-0.99). No significant association was found between anti-TNF therapy and the risk of solid or hematologic malignancies within the AS group. CONCLUSION: AS is associated with an increased risk of overall and site-specific malignancies, with independently higher risk for older age, comorbidity of DM, IBD, and treatment with DMARDs.

Increased risk for stroke in patients with familial Mediterranean fever: results from a large population-based study.

OBJECTIVE: The association between chronic inflammatory conditions and cardiovascular disease is well established. Considering FMF, few studies exist investigating the risk of ischaemic heart disease, and none address the risk of stroke. We aimed to evaluate the incidence and risk for stroke in FMF patients compared with the general population. METHODS: A retrospective cohort study using the electronic database of Clalit Health Services (CHS), the largest health organization in Israel. All FMF patients diagnosed between 2000 and 2016 were included and matched with control according to age, gender and place of residence. Follow-up continued until the first diagnosis of stroke or death. The incidence of stroke was compared between the groups using univariate and multivariate models adjusting for cardiovascular risk-factors. RESULTS: A total of 9769 FMF patients and a similar number of controls were followed up for a median period of 12.5 years. The mean age at the beginning of the follow-up was 25.7 years. In total, 208 FMF patients were diagnosed with stroke compared with 148 controls, resulting in an incidence rate (per 10 000 persons-years) of 19.8 (95% CI 17.2, 22.7) and 13.9 (95% CI 11.8, 16.4), respectively, and a crude HR of 1.42 (95% CI 1.15-1.76; P < 0.001). In a multivariate analysis, FMF patients who developed amyloidosis with related or non-related renal failure demonstrated significant stroke risk (HR = 2.16; 95% CI 1.38, 3.38; P < 0.001), as well as for those who did not develop these complications (HR = 1.32; 95% CI 1.04, 1.67; P < 0.05). CONCLUSION: FMF patients are at increased risk for stroke regardless of known complications.

Possible Association Between Anti-Trisulfated-Heparin-Disaccharide (TS-HDS) Immunoglobulin M Autoantibody and Fibromyalgia Syndrome.

BACKGROUND: Fibromyalgia syndrome (FMS) is estimated to affect 2-4% of the general population. While FMS has some known environmental and genetic risk factors, the disorder has no clear etiology. A common coexisting disorder with FMS is small fiber neuropathy (SFN). High levels of serum immunoglobulin M (IgM) binding to trisulfated-heparin-disaccharide (TS-HDS) were recently found to be associated with SFN. OBJECTIVES: To evaluate potential differences in anti-TS-HDS antibody titers in women with FMS compared to healthy controls. METHODS: In this cross-sectional study, we evaluated 51 female participants: 30 with a diagnosis of FMS and 21 healthy controls who had been recruited at the Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Israel. All of the participants were older than 18 years of age. Anti-TS-HDS IgM levels were measured in their sera using the enzyme immunoassay technique. RESULTS: The mean anti-TS-HDS IgM levels were significantly lower in the FMS group, compared with the control group (7.7 ± 5 vs. 13.2 ± 8.6 U/ml, respectively; P = 0.013). CONCLUSIONS: There is a possible association between FMS and anti-TS-HDS IgM. This association might be the missing link for the coexistence of SFN and FMS, but further study should be performed to assess this association and this auto-antibody characteristic.

The association between ankylosing spondylitis and psychiatric disorders: Insights from a population based cross-sectional database.

BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease involving the axial skeleton ultimately resulting in physical disability and psychological sequalae. The current study aims to evaluate the link between AS and psychiatric disorders, and to investigate the impact of different disease modifying drugs on such link. METHODS: A large retrospective, population-based, cross-sectional study utilizing the Clalit-Health-Service (CHS) database was conducted on 5825 AS patients and 25,984 age- and sex-matched control individuals. The prevalence of psychiatric morbidity was compared between AS patients and age- and gender-matched controls. Predictors for psychiatric disorders in AS patients were also investigated. RESULTS: The prevalence of psychiatric morbidity was higher in AS patients compared to controls (13.8 % vs. 9.8 %, p < 0.001). Similarly, major depression was positively associated with AS (OR 1.60, 95 % CI 1.43-1.79, p < 0.001), however, schizophrenia was negatively associated with AS (OR 0.60, 95 % CI 0.42-0.89, p < 0.011). Conventional DMARDs (cDMARDs) and anti-TNF used for management of AS were not shown to be predictors for psychiatric illnesses in AS patients. CONCLUSIONS: Patients with AS are at a higher risk of developing psychiatric disorders, with increased risk of depression and lower risk of schizophrenia. cDMARDs and TNF-inhibitors are not predictors of psychiatric disorders in AS patients.

TNF inhibitors have a protective role in the risk of dementia in patients with ankylosing spondylitis: Results from a nationwide study.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic progressive and debilitating form of arthritis with associated extra-articular features including uveitis, intestinal and lung apical inflammation and psoriasis. Putative associations between AS and neurologic disorders has been relatively overlooked. The purpose of this study is to assess the link between AS and major neurologic disorders and whether treatment with Tumor-Necrosis-Factor inhibitors (TNFi) has an impact on that association. METHODS: A retrospective cross-sectional study was carried out based on the Clalit Health Services (CHS) computerized database. AS patients were compared to age- and gender-matched controls with respect to the proportion of Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, and multiple sclerosis (MS). The impact of AS therapy (biologic vs conventional therapy) was assessed as well. RESULTS: 4082 AS patients and 20,397 age- and gender-matched controls were identified. AS was associated with a higher prevalence of AD (odds-ratio(OR) 1.46 [95%Confidence-interval(CI) 1.13-1.87], p = 0.003), epilepsy (OR 2.33 [95%CI 1.75-3.09] p < 0.0001) and PD (OR 2.75 [95%CI 2.04-3.72], p < 0.0001), whereas no statistically significant association was found for MS. Association with PD remained significant in the multivariate analysis (OR 1.49 [95%CI 1.05-2.13],p = 0.027). Within AS patients, the use of TNFi (OR 0.10 [95%CI 0.01-0.74], p = 0.024) were associated with a lowered risk of developing AD. CONCLUSION: AS is positively associated with AD, PD, and epilepsy but not MS. AS patients treated with TNFi have lower rates of AD.

Mortality in Ankylosing Spondylitis According to Treatment: A Nationwide Retrospective Cohort Study of 5,900 Patients From Israel.

OBJECTIVE: In this large population-based study we aimed: 1) to assess mortality in patients with ankylosing spondylitis (AS) compared to the general population, considering demographics, comorbidities, and treatment, and 2) to assess factors associated with mortality within patients with AS. METHODS: This study was designed as a retrospective cohort study using the electronic database of the largest health maintenance organization in Israel. All patients with AS diagnosed between 2002 and 2018 were included. Controls were matched by age, sex, clinic, and enrollment time. Follow-up continued until death or the end of the study. RESULTS: The study comprised 5,930 AS patients and 29,018 matched controls who were followed up for a median period of 7.5 years. There were 667 deaths within the AS cohort and 2,919 deaths within controls; the mean age at death was 76.9 years and 77.1 years, respectively (P = 0.74). A total of 3,249 AS patients (54.8%) were treated only with nonsteroidal antiinflammatory drugs, 1,760 (29.7%) were treated with tumor necrosis factor inhibitors (TNFi), and 1,687 (28.4%) with disease-modifying antirheumatic drugs (DMARDs). Mortality rates were increased among AS patients compared to controls, with an age- and sex-adjusted hazard ratio (HR) of 1.19 (95% confidence interval [95% CI] 1.10-1.30). The association was significant for men (HR 1.15 [95% CI 1.04-1.27]) and women (HR 1.32 [95% CI 1.13-1.54]), and after adjusting for background comorbidities (HR 1.14 [95% CI 1.05-1.24]). AS patients treated with TNFi or with a combination of TNFi and DMARDs did not have significant difference in mortality rates compared to controls (HR 0.67 [95% CI 0.38-1.18] and HR 0.93 [95% CI 0.69-1.25], respectively). Age, male sex, mean C-reactive protein (CRP) levels and general comorbidities were predictors of mortality within the AS cohort. CONCLUSION: AS patients had an increased mortality risk compared to the general population after adjusting for age, sex, and baseline comorbidities. AS patients treated with TNFi did not demonstrate excess mortality compared to matched controls. Within the AS cohort, age, male sex, background comorbidities, and higher CRP levels were identified as risk factors for mortality.

COVID-19 associated hospitalization in 571 patients with fibromyalgia-A population-based study.

OBJECTIVE: To identify predicators of patients with fibromyalgia (FM) that are associated with a severe COVID-19 disease course. METHODS: We utilized the data base of the Clalit Health Services (CHS); the largest public organization in Israel, and extracted data concerning patients with FM. We matched two subjects without FM to each subject with FM by sex and age and geographic location. Baseline characteristics were evaluated by t-test for continuous variables and chi-square for categorical variables. Predictors of COVID-19 associated hospitalization were identified using univariable logistic regression model, significant variables were selected and analyzed by a multivariable logistic regression model. RESULTS: The initial cohort comprised 18,598 patients with FM and 36,985 matched controls. The mean age was 57.5± 14.5(SD), with a female dominance of 91%. Out of this cohort we extracted the study population, which included all patients contracted with COVID-19, and consisted of 571 patients with FM and 1008 controls. By multivariable analysis, the following variables were found to predict COVID-19 associated hospitalization in patients with FM: older age (OR, 1.25; CI, 1.13-1.39; p<0.001), male sex (OR, 2.63; CI, 1.18-5.88; p<0.05) and hypertension (OR, 1.75; CI, 1.04-2.95; p<0.05). CONCLUSION: The current population-based study revealed that FM per se was not directly associated with COVID-19 hospitalization or related mortality. Yet classical risk factors endangering the general population were also relevant among patients with FM.

The Incidence and Predictors of Solid- and Hematological Malignancies in Patients with Giant Cell Arteritis: A Large Real-World Database Study.

BACKGROUND: The association between giant cell arteritis (GCA) and malignancies had been widely investigated with studies reporting conflicting results. Therefore, in this study, we aimed to investigate this association using a large nationwide electronic database. METHODS: This study was designed as a retrospective cohort study including GCA patients first diagnosed between 2002-2017 and age, sex and enrollment time-matched controls. Follow-up began at the date of first GCA-diagnosis and continued until first diagnosis of malignancy, death or end of study follow-up. RESULTS: The study enrolled 7213 GCA patients and 32,987 age- and sex-matched controls. The mean age of GCA diagnosis was 72.3 (SD 9.9) years and 69.1% were women. During the follow-up period, 659 (9.1%) of GCA patients were diagnosed with solid malignancies and 144 (2.0%) were diagnosed with hematologic malignancies. In cox-multivariate-analysis the risk of solid- malignancies (HR = 1.12 [95%CI: 1.02-1.22]), specifically renal neoplasms (HR = 1.60 [95%CI: 1.15-2.23]) and sarcomas (HR = 2.14 [95%CI: 1.41-3.24]), and the risk of hematologic malignancies (HR = 2.02 [95%CI: 1.66-2.47]), specifically acute leukemias (HR = 1.81 [95%CI: 1.06-3.07]), chronic leukemias (HR = 1.82 [95%CI: 1.19-2.77]), Hodgkin's lymphomas (HR = 2.42 [95%CI: 1.12-5.20]), non-Hodgkin's-lymphomas (HR = 1.66: [95%CI 1.21-2.29]) and multiple myeloma(HR = 2.40 [95%CI: 1.63-3.53]) were significantly increased in GCA patients compared to controls. Older age at GCA-diagnosis (HR = 1.36 [95%CI: 1.25-1.47]), male-gender (HR = 1.46 [95%CI: 1.24-1.72]), smoking (HR = 1.25 [95%CI: 1.04-1.51]) and medium-high socioeconomic status (HR = 1.27 [95%CI: 1.07-1.50]) were independently associated with solid malignancy while age (HR = 1.47 [95%CI: 1.22-1.77]) and male-gender (HR = 1.61 [95%CI: 1.14-2.29]) alone were independently associated with hematologic- malignancies. CONCLUSION: our study demonstrated higher incidence of hematologic and solid malignancies in GCA patients. Specifically, leukemia, lymphoma, multiple myeloma, kidney malignancies, and sarcomas. Age and male gender were independent risk factors for hematological malignancies among GCA patients, while for solid malignancies, smoking and SES were risk factors as well.