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Objectives: The objective of this study was to evaluate the real-world drug survival, adherence, and discontinuation risk of biologics disease-modifying anti-rheumatic drugs (bDMARDs) among patients with ankylosing spondylitis (AS). Methods: This was a retrospective study using a computerized database. Biologic-naïve and biologic-experienced AS patients who initiated treatment with bDMARDs (tumor necrosis factor alpha inhibitors {TNF-αis} or interleukin-17 inhibitor {IL-17i}) during 2015-2018 were included. Adherence was assessed using the proportion of days covered (PDC) method. Drug survival was analyzed using Kaplan-Meier estimates. Risk of discontinuation was estimated by the Cox proportional hazard model. Results: We identified 343 eligible patients utilizing 481 lines of therapy. The mean age was 44.6 years (SD ± 13.4), 57.7% were males, and 69.7% were biologic-naïve at baseline. The proportion of highly adherent patients (PDC ≥ 0.8) in the biologic-naïve group was 63.5% for golimumab, 69.2% for etanercept, and 71.6% for adalimumab (p > 0.9). Among the biologic-experienced group, secukinumab had the highest proportion of adherent patients (75.7%) and etanercept the lowest (50.0%) reaching statistical difference (p < 0.001). The Kaplan-Meier analysis did not show a significant difference in drug survival in either the biologic-naïve or the biologic-experienced groups (p = 0.85). Multivariable analysis demonstrated a similar risk for discontinuation for etanercept, golimumab, and secukinumab compared with adalimumab, regardless of biologic-experience status. Conclusions: Adherence, drug survival, and risk for discontinuation were similar for all TNF-αis and the IL-17i SEC, regardless of biologic-experience status. As drug survival is an indirect measure of drug efficacy, n, in real-world settings, we believe caregivers can integrate these results into treatment considerations.
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BACKGROUND AND AIMS: Emerging evidence suggests an arrhythmogenic effect of Anti-Ro/SSA (anti-Ro) and anti-La/SSB (anti-La) antibodies in adults, potentially involving a subclinical intracardiac inflammatory process. Despite the established association between inflammation and ischemic heart disease (IHD), it is noteworthy that as of now no study has delved into the potential link between these antibodies and IHD. This population-based study aimed to examine the association between anti-Ro/La seropositivity and IHD in the general adult population. METHODS: We conducted a retrospective study using electronic medical records from the largest health maintenance organization in Israel. Patients with positive serology for either or both anti-Ro and anti-La antibodies were included, along with matched controls. Multivariate logistic regression models were utilized to assess the odds of IHD in seropositive patients compared to controls. RESULTS: Among 17,231 seropositive patients and 84,368 controls, the rate of IHD was significantly higher in the seropositive group (9.7 % vs. 8.1 %,OR = 1.23; 95%CI 1.14-1.31; p<0.001). The association was more pronounced in younger patients [<40 years old (OR = 3.36; 95%CI 1.66-6.82; p<0.001), 40-49 years old (OR = 1.85; 95%CI 1.26-2.73; p<0.01), 50-59 years old (OR = 1.87; 95%CI 1.55-2.26; p<0.001), 60-69 years old (OR = 1.26; 95%CI 1.11-1.42; p<0.001), ≥70 years old (OR = 1.11; 95%CI 1.03-1.20; p<0.01)], as well as in patients with fewer traditional cardiovascular risk-factors (none:OR = 1.29; 95 % CI 1.09 to 1.77; p<0.01, 1-2:OR = 1.30; 95 % CI 1.19 to 1.41; p<0.001, ≥3:OR = 1.09; 95 % CI 0.99 to 1.21; p=0.076). CONCLUSIONS: Our study demonstrates for the first time a positive association between anti-Ro/La seropositivity and IHD in the general adult population, especially among younger individuals with fewer traditional cardiovascular risk factors.
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INTRODUCTION: Biologic therapies are licensed for both psoriasis (PsO) and psoriatic arthritis (PsA) with some electronic medical record data suggest that IL (Interleukin)-23 blockers might be more protective in PsA prevention than TNF blockers; however, the findings have been inconsistent. Higher Psoriasis Area and Severity Index (PASI) scores have also been linked to an increased PsA risk. To clarify these unresolved issues we investigated biologic agents, methotrexate, phototherapy, and topical therapy for PsA prevention in patients with psoriasis. METHODS: This retrospective cohort study analyzed data from 58,671 patients with psoriasis from the Israeli Meuhedet Health Services Organization database was evaluated for incident PsA. Patients were categorized on the basis of treatment: group 1, topical therapy; group 2, phototherapy; group 3, conventional disease-modifying antirheumatic drugs (cDMARDs; methotrexate); group 4, biologic DMARDs which was also stratified according to biologic class. RESULTS: The PsA incidence rate was lower in the biologic agents' group versus the methotrexate group (HR 0.46 [95% CI 0.35-0.62]). The incidence rates per 100 person-years varied across biologic treatment groups, with the antiIL12/23 or antiIL23p19 group at 4.57, the anti-IL-17 group at 4.35, and the TNF inhibitor group at 2.55. No differences were found between various biological agents in terms of preventing PsA. The phototherapy group exhibited a higher PsA development rate than the topical therapy group (HR 1.85 [95% CI 1.65-2.07]). CONCLUSION: Biological agents are more effective than methotrexate in reducing incident PsA in patients with psoriasis. This lower rate of PsA on topical therapy compared to phototherapy supports the importance of psoriasis severity as a risk factor.
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Background: Axial spondyloarthropathy(AS) is a chronic inflammatory disease primarily affecting the axial skeleton, often characterized by sacroiliitis. While pulmonary embolism (PE), a potentially lethal condition, has been linked to several autoimmune diseases, limited data exist regarding PE risk among patients with AS. Methods: This retrospective cohort study utilized the Clalit Healthcare Services (CHS) database, including 5825 patients with AS and 28,356 matched controls. Follow-up began at the date of first AS diagnosis for patients and at the matched patient's diagnosis date for controls and continued until PE diagnosis, death, or study end date. Results: Prevalence of PE before AS diagnosis in patients compared to controls was 0.4% vs. 0.2% (p < 0.01). The incidence rate of PE was 11.6 per 10,000 person-years for patients with AS and 6.8 per 10,000 person-years for controls. The adjusted hazard ratio (HR) for PE in patients with AS was 1.70 (p < 0.001). Subgroup analysis demonstrated excess risk for PE in patients with AS regardless of gender and age, with variations among AS treatment categories. Discussion: Our findings highlight a significant association between AS and PE, indicating an increased risk in patients with AS independent of age and sex and suggests a subclinical level of inflammation. Preliminary results suggest a protective role of immunosuppressing drugs. Further research into the impact of treatment strategies should be conducted and could inform clinical management and reduce the life-threatening risk of PE in Patients with AS.
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OBJECTIVE: Obesity and age are strongly linked to severe COVID-19 pneumonia where immunomodulatory agents including Janus kinase inhibitors have shown benefits but the efficacy of such therapy in viral pneumonia is not well understood. We evaluated the impact of obesity and age on survival following baricitinib therapy for severe COVID-19. METHODS: A post hoc analysis of the COV-BARRIER multicentre double-blind randomised study of baricitinib versus placebo (PBO) with an assessment of 28-day mortality was performed. All-cause mortality by day 28 was evaluated in a Cox regression analysis (adjusted to age) in three different groups according to body mass index (BMI) (<25 kg/m2, 25-30 kg/m2 and >30 kg/m2) and age <65 years and ≥65 years. RESULTS: In the high BMI group (>25 kg/m2), baricitinib therapy showed a significant survival advantage compared with PBO (incidence rate ratio (IRR) for mortality by day 28 0.53 (95% CI 0.32 to 0.87)) and 0.66 (95% CI 0.46 to 0.94) for the respective <65 years and ≥65 years, respectively. The 28-day all-cause-mortality rates for BMI over 30 were 5.62% for baricitinib and 9.22% for PBO (HR=0.6, p<0.05). For BMI under 25 kg/m2, irrespective of age, baricitinib therapy conferred no survival advantage (IRR of 1.89 (95% CI 0.49 to 7.28) and 0.95 (95% CI 0.46 to 1.99) for <65 years and ≥65 years, respectively) ((mortality 6.6% baricitinib vs 8.1 in PBO), p>0.05). CONCLUSION: The efficacy of baricitinib in COVID-19 pneumonia is linked to obesity suggesting that immunomodulatory therapy benefit is associated with obesity-associated inflammation.
Subject(s)
Azetidines , Body Mass Index , COVID-19 , Obesity , Purines , Pyrazoles , SARS-CoV-2 , Sulfonamides , Humans , Purines/therapeutic use , Purines/administration & dosage , Sulfonamides/therapeutic use , Azetidines/therapeutic use , Azetidines/administration & dosage , Obesity/complications , Male , Middle Aged , COVID-19/mortality , COVID-19/complications , COVID-19/epidemiology , Pyrazoles/therapeutic use , Female , Aged , Double-Blind Method , Janus Kinase Inhibitors/therapeutic use , COVID-19 Drug Treatment , Pneumonia, Viral/drug therapy , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Treatment Outcome , Betacoronavirus , Coronavirus Infections/drug therapy , Coronavirus Infections/complications , Coronavirus Infections/mortality , PandemicsABSTRACT
OBJECTIVE: Subjects with subclinical psoriatic arthritis (PsA), defined as the presence of arthralgia in psoriasis (PsO), are at higher risk of PsA but scant real-world data exist. Our aims were to (1) estimate the probability of PsA development in subclinical PsA, (2) characterise subclinical PsA symptoms and (3) determine the clinical patterns at PsA diagnosis. METHODS: Patients with PsO, mainly subclinical PsA, were evaluated longitudinally in two European cohorts. The key outcome was new-onset PsA. Musculoskeletal symptoms including inflammatory and non-inflammatory symptoms before PsA diagnosis were collected. Occurrence of PsA was analysed with survival analysis and cumulative incidence functions (CIFs). RESULTS: 384 patients with PsO were included with a mean follow-up of 33.0 (±20.9) months. 311 of 384 (80.9%) had subclinical PsA with a PsA incidence rate of 7.7 per 100 patient-years. Subclinical PsA displayed a higher risk of PsA development compared with PsO (HR=11.7 (95% CI 1.57 to 86.7), p=0.016). The probability of new-onset PsA estimated by the CIF was 9.4% (95% CI 4.7% to 10.6%) at month 12 and 22.7% (95% CI 17.2% to 28.6%) at month 36. 58.9% of cases reported inflammatory symptoms in the months immediately prior to PsA diagnosis but prior non-inflammatory symptoms were evident in 83.9% prior to PsA diagnosis. Peripheral joint swelling was the predominant PsA presentation pattern (82.1%). CONCLUSIONS: The probability of PsA development among subclinical PsA was relatively high, emphasising the importance of emergent musculoskeletal symptoms when aiming for PsA prevention. Joint swelling was the dominant feature in new-onset PsA, likely reflecting clinical confidence in recognising joint swelling.
Subject(s)
Arthritis, Psoriatic , Psoriasis , Humans , Arthritis, Psoriatic/complications , Arthritis, Psoriatic/diagnosis , Arthritis, Psoriatic/epidemiology , Psoriasis/complications , Arthralgia/epidemiology , Arthralgia/etiology , Arthralgia/diagnosisABSTRACT
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.
Subject(s)
Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Spondylitis, Ankylosing , Humans , Retrospective Studies , Spondylitis, Ankylosing/epidemiology , Inflammatory Bowel Diseases/epidemiology , Crohn Disease/epidemiologyABSTRACT
BACKGROUND: Familial Mediterranean Fever (FMF) is a genetic disorder characterized by recurrent episodes of fever and inflammation in various organs, including the joints. Traditionally, the arthritis of FMF has been considered relatively harmless. However, anecdotal evidence has suggested that it may contribute to long-term joint damage, which may necessitate surgical joint replacement. This study aimed to investigate the rates of arthroplasty among FMF patients and compare it to the general population. METHODS: The study used the electronic database of the largest healthcare organization in Israel to identify 9,769 FMF patients diagnosed between 2000 and 2016. A similar number of age-, gender-, and residency-matched controls were also identified. The rates of arthroplasty were compared between the two groups. A logistic regression model predicting the need for arthroplasty within the FMF group was formed to identify potential risk factors. RESULTS: Of the 9,769 FMF patients, 114 (1.2%) underwent arthroplasty, compared with 64 (0.7%) of the control group [unadjusted odds ratio (OR)=1.79, 95% confidence interval (CI) 1.32-2.43; partially adjusted OR = 1.97, 95% CI 1.40-2.77; fully adjusted OR = 1.92, 95% CI 1.35-2.72]. Within the FMF cohort, those of North African origin had a significantly higher risk of arthroplasty (OR = 6.89, 95% CI 5.09-9.33; p< 0.001). CONCLUSION: FMF patients can experience long-term joint damage that may require arthroplasty. Although this complication is relatively uncommon in FMF patients, it occurs almost twice as frequently as compared with the general population. FMF patients of North African origin are at an even higher risk.
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Background: The skin-gut axis, characterized by bidirectional communication between the skin and gut, plays a crucial role in the pathogenesis of psoriasis and inflammatory bowel diseases (IBD). Objectives: We aimed to explore the association between psoriasis and IBD and identify predictors associated with IBD development among patients with psoriasis. Design: Retrospective cohort study. Methods: A retrospective study which utilized an electronic database from the Meuhedet Health Maintenance Organization (MHMO) in Israel. Psoriasis was categorized as severe if any systemic agent or phototherapy was administered. Univariate and multivariate logistic regressions were used to identify specific predictors for IBD, with adjustments made for potential confounders. The study received approval from the Ethical Committee of the MHMO. Results: In total, 61,003 adult patients who were diagnosed with psoriasis between 2000 and 2022 were included. Among them, 1495/61,003 patients (2.4%) were diagnosed with IBD, as compared to 3834/244,012 patients (1.6%) in the non-psoriasis group [adjusted odds ratio (OR): 1.47; 95% confidence interval (CI): 1.37-1.56; p < 0.001]. Increased age (OR: 1.01; 95% CI: 1.01-1.02; p < 0.001), male gender (OR: 1.22; 95% CI: 1.03-1.45; p = 0.024), and Jewish ethnicity (OR: 2.5; 95% CI: 1.2-4.1; p < 0.001) were identified as significant risk factors for IBD. Spondyloarthropathies, including psoriatic arthritis (OR: 2.27; 95% CI: 1.86-2.77; p < 0.001) and ankylosing spondylitis (OR: 2.82; 95% CI: 1.5-5.32; p < 0.05), were associated with a higher prevalence of IBD. Furthermore, severe psoriasis was significantly associated with a higher likelihood of IBD, compared to mild psoriasis (OR: 16.03; 95% CI: 11.02-23.34; p < 0.001). Conclusion: A significant association between psoriasis and IBD was demonstrated, including its subtypes: Crohn's disease and ulcerative colitis. Moreover, such association may depend on psoriasis severity as determined by the treatment used. This association warrants further investigation and implies a potential need for closer monitoring of patients with severe psoriasis.
Association between psoriatic disease severity and risk of inflammatory bowel diseases 1- Gut and skin barrier play an integral role in psoriasis and inflammatory bowel disease (IBD) development. 2- Shared genetic and environmental factors could explain the association between both diseases. 3- We report increased association between psoriasis and IBD, a relationship that is more pronounced in patients with severe psoriasis. 4- Patients with spondyloarthritis related diseases have a stronger association with IBD.
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The association between uveitis and spondyloarthropathy (SpA)-related conditions is well-established. However, evidence describing the link between uveitis and psoriasis, and psoriasis without concomitant SpA-related conditions is scarce and conflicting. This large-scale population-based study sought to describe the prevalence and features of uveitis among psoriasis patients in Israel as well as investigating the risk for uveitis in different subgroups of psoriasis patients compared to the general population. We conducted a retrospective study utilizing the electronic database of the Meuhedet Health Maintenance Organization. The study included all patients diagnosed with psoriasis between 2000 and 2020, each patient was matched with four controls based on age, sex, place of residence, and index date. Logistic regression models were employed to assess the association between psoriasis and uveitis while adjusting for the presence of SpA-related conditions. A total of 61 003 psoriasis patients and 244 012 matched controls were included. The prevalence of uveitis was 1.3% versus 1.1% respectively (OR 1.12; 95% CI 1.10-1.30; p < 0.001). When adjusting to psoriasis severity, concurrent SpA, and psoriasis treatment no significant association was found. The rates of uveitis among psoriasis patients with concurrent SpA-related conditions was 3.2% compared to 1.4% in controls without psoriasis or SpA (OR 2.38; 95% CI 2.00-2.83; p < 0.001), while in psoriasis patients without SpA, the rate of uveitis was 1.0% and was similar to controls. Although crude rates of uveitis were higher in patients with severe psoriasis compared to mild psoriasis (2.1% vs. 1.1%), after adjustment, no significant association compared to controls was found in either group. Our findings suggest that the positive association between psoriasis and uveitis is primarily mediated by the coexistence of other SpA-related conditions. These findings imply the presence of a shared pathogenetic mechanism and set the direction for a phenotypic-targeted screening strategy.
Subject(s)
Psoriasis , Uveitis , Humans , Retrospective Studies , Prevalence , Uveitis/epidemiology , Psoriasis/complications , Psoriasis/epidemiology , Risk FactorsABSTRACT
Since the original description of spondyloarthritis 50 years ago, results have demonstrated similarities and differences between ankylosing spondylitis (AS) and axial psoriatic arthritis (PsA). HLA-B27 gene carriage in axial inflammation is linked to peri-fibrocartilaginous sacroiliac joint osteitis, as well as to spinal peri-entheseal osteitis, which is often extensive and which provides a crucial anatomical and immunological differentiation between the AS and PsA phenotypes. Specifically, HLA-B27-related diffuse bone marrow oedema (histologically an osteitis) and bone marrow fatty corners detected via magnetic resonance imaging, as well as radiographic changes such as sacroiliitis, vertebral squaring, corner erosions and Romanus lesions, all indicate initial bone phenotypes in HLA-B27+ axial disease. However, in much of PsA with axial involvement, enthesitis primarily manifests in ligamentous soft tissue as 'ligamentitis', with characteristic lesions that include para-syndesmophytes and sacroiliac joint bony sparing. Like axial PsA, diffuse idiopathic skeletal hyperostosis phenotypes, which can be indistinguishable from PsA, exhibit a thoracic and cervical spinal ligamentous soft-tissue tropism, clinically manifesting as syndesmophytosis that is soft-tissue-centric, including paravertebral soft-tissue ossification and sacroiliac soft-ligamentous ossification instead of joint-cavity fusion. The enthesis bone and soft tissues have radically different immune cell and stromal compositions, which probably underpins differential responses to immunomodulatory therapy, especially IL-23 inhibition.
Subject(s)
Arthritis, Psoriatic , Osteitis , Spondylitis, Ankylosing , Humans , Spondylitis, Ankylosing/diagnosis , Spondylitis, Ankylosing/genetics , HLA-B27 Antigen/genetics , Ligaments/pathologyABSTRACT
Background: Due to its apparent efficacy and safety, dupilumab, a monoclonal antibody that blocks Interleukin 4 (IL-4) and Interleukin 13 (IL-13), has been approved for treating T-helper 2 (Th2) disorders. However, adverse effects like local injection site reactions, conjunctivitis, headaches, and nasopharyngitis have been reported. Sex differences are known to influence both adaptive and innate immune responses and, thus, may have a bearing on the occurrence of these adverse effects. Nevertheless, the literature lacks a comprehensive exploration of this influence, a gap this study aims to bridge. Materials and Methods: A comprehensive data mining of VigiBase, the World Health Organization (WHO) global pharmacovigilance database which contains case safety reports of adverse drug reactions (ADRs) was performed to test for sex -specific safety response to dual IL4/IL13 blockade by dupilumab. The information component (IC), a measure of the disproportionality of ADR occurrence, was evaluated and compared between males and females to identify potential sexual dimorphism. Results: Of the 94,065 ADRs recorded in the WHO global pharmacovigilance database, 2,001 (57.4%) were reported among female dupilumab users, and 1,768 (50.7%) were among males. Immune/autoimmune T-helper 1 (Th1)-, innate- and T-helper 17 (Th17)-driven diseases and degenerative ones were consistently reported with a stronger association with Dupilumab in males than females. Some adverse events were more robustly associated with Dupilumab in females. Conclusion: Dupilumab has an excellent safety profile, even though some ADRs may occur. The risk is higher among male patients, further studies, including ad hoc studies, are needed to establish causality.
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BACKGROUND: The link between ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) is well-established, with concurrent prevalence estimates ranging from 5-10%. However, there are still significant gaps in our understanding, and a comprehensive treatment guideline for these co-diagnosed patients has yet to be established. Our objective was to explore patterns of treatment alterations following the diagnosis of AS in patients previously diagnosed with IBD, and vice versa. Additionally, we sought to determine how these modifications influence clinical outcomes in both conditions. METHODS: This retrospective data-based cohort study included patients with coexisting IBD and AS that were diagnosed between the years 2009-2022 and were followed by the gastroenterology and the rheumatology units of the Sheba Medical Center, Israel. The data were extracted from the electronic health record and included demographic information, medication history, treatment modification at the time of second diagnosis, and the characteristics and activity of both IBD and AS at the index time and at the 3-month mark. RESULTS: The study included a total of 68 patients, with a male predominance (40 patients, 59%). The median age was 43 years (IQR 31-55) and 78% had Crohn's disease (CD). The median duration between the diagnosis of the first disease to the second one was 4 years (IQR 1-9.5). A significant proportion of patients (85%) underwent treatment modification at their second diagnosis. Out of the total cohort, 28% initiated biological therapy, 17.6% switched their biologic regimen, and 16.2% discontinued NSAIDS. Patients who underwent biologic modifications at time of the second diagnosis (the initiation/switch/augmentation of a concurrent regimen) experienced significantly higher rates of clinical improvement in either IBD or AS at the 90-day follow-up compared to patients who did not (68% vs. 32%, p = 0.004), and biologic modification was found to be an independent predictor for clinical improvement (OR 3.69, CI 1.08-12.58, p = 0.037). CONCLUSIONS: Our findings suggest that biologic therapy modification at the time of the second diagnosis was associated with a higher rate of improvement in AS/IBD at the 90-day follow-up.
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OBJECTIVES: The direct impact of inflammatory conditions and their therapy with corticosteroids both contribute to an increased risk of osteoporosis with associated fractures. Familial-Mediterranean-Fever (FMF) is an autoinflammatory disorder not commonly treated with corticosteroids. Evidence regarding FMF association with osteoporosis and femur fractures is anecdotal. We aimed to evaluate the incidence and risk of osteoporosis and femoral neck fracture in FMF patients compared with the general population. METHODS: A retrospective cohort study using the electronic database of Clalit Health Services of all FMF patients first diagnosed between 2000-2016 and controls was evaluated including age and sex matched controls in 1:1 ratio. Follow-up continued until the first diagnosis of osteoporosis or fracture. Risk for these conditions was compared using univariate and multivariate cox-regression models. RESULTS: 9,769 FMF patients were followed for a median period of 12.5 years. 304 FMF patients were diagnosed with osteoporosis compared with 191 controls, resulting in an incidence rate (per 10 000 persons-years) of 28.8 and 17.8 respectively, and a crude HR of 1.62 (95%CI 1.35-1.93; p< 0.001). Patients were diagnosed with osteoporosis at a considerably younger age than controls (60.1 ± 12.4 vs 62.5 ± 11.0 years; p= 0.028). 56 FMF patients were diagnosed with femoral neck fracture compared with 35 controls, resulting in an incidence rate of 5.3 and 3.3 respectively, and a crude HR of 1.60 (95%CI 1.05-2.44; p< 0.05). CONCLUSION: FMF patients are at increased risk for osteoporosis and consequently femur fracture. Our findings emphasize the importance of considering bone health in the management of FMF patients.
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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.
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BACKGROUND: Polymyositis (PM) and dermatomyositis (DM) are inflammatory mediated myopathies characterized by progressive symmetric proximal muscle weakness and associated with extra-muscular involvement. Central nervous system complications are rarely reported with these diseases. OBJECTIVES: To investigate the association between dementia and PM/DM. METHODS: A retrospective cohort study was conducted using a database from Clalit Health Care, the largest health maintenance organization in Israel. Patients with a first recorded diagnosis of PM/DM were included and were compared with age- and sex-matched controls by a ratio of 1:5. The prevalence of dementia among PM/DM patients compared to controls was assessed using a univariate and a multivariable model. Binary logistic regression analysis was conducted to assess the association of different factors with dementia within the PM/DM cohort. RESULTS: The study included 2085 PM/DM cases (17.0%) and 10,193 age- and sex-matched controls (83.0%). During the follow-up time, 36 PM/DM patients were diagnosed with dementia compared to 160 controls, with a univariate hazard ratio (HR) of 1.10 (95% confidence interval [95%CI] 0.77-1.58). Within the PM/DM cohort, significant predictors for the development of dementia included increased age at diagnosis (5 years increment; OR 1.86, 95%CI 1.57-2.21, P < 0.001) and treatment with glucocorticoids (OR 5.40, 95%CI 1.67-17.67, P = 0.005). CONCLUSIONS: In our cohort, inflammatory myopathies were not associated with dementia. Age and treatment with glucocorticoids were associated with dementia. If dementia is diagnosed in patients with inflammatory myopathies, other systemic causes should be investigated.
Subject(s)
Dementia , Dermatomyositis , Polymyositis , Humans , Child, Preschool , Dermatomyositis/complications , Dermatomyositis/epidemiology , Dermatomyositis/diagnosis , Retrospective Studies , Glucocorticoids , Prevalence , Polymyositis/complications , Polymyositis/epidemiology , Polymyositis/diagnosis , Dementia/epidemiology , Dementia/etiologyABSTRACT
BACKGROUND: The transition from psoriasis (PsO) to psoriatic arthritis (PsA) and the early diagnosis of PsA is of considerable scientific and clinical interest for the prevention and interception of PsA. OBJECTIVE: To formulate EULAR points to consider (PtC) for the development of data-driven guidance and consensus for clinical trials and clinical practice in the field of prevention or interception of PsA and for clinical management of people with PsO at risk for PsA development. METHODS: A multidisciplinary EULAR task force of 30 members from 13 European countries was established, and the EULAR standardised operating procedures for development for PtC were followed. Two systematic literature reviews were conducted to support the task force in formulating the PtC. Furthermore, the task force proposed nomenclature for the stages before PsA, through a nominal group process to be used in clinical trials. RESULTS: Nomenclature for the stages preceding PsA onset, 5 overarching principles and 10 PtC were formulated. Nomenclature was proposed for three stages towards PsA development, namely people with PsO at higher risk of PsA, subclinical PsA and clinical PsA. The latter stage was defined as PsO and associated synovitis and it could be used as an outcome measure for clinical trials evaluating the transition from PsO to PsA. The overarching principles address the nature of PsA at its onset and underline the importance of collaboration of rheumatologists and dermatologists for strategies for prevention/interception of PsA. The 10 PtC highlight arthralgia and imaging abnormalities as key elements of subclinical PsA that can be used as potential short-term predictors of PsA development and useful items to design clinical trials for PsA interception. Traditional risk factors for PsA development (ie, PsO severity, obesity and nail involvement) may represent more long-term disease predictors and be less robust for short-term trials concerning the transition from PsO to PsA. CONCLUSION: These PtC are helpful to define the clinical and imaging features of people with PsO suspicious to progress to PsA. This information will be helpful for identification of those who could benefit from a therapeutic intervention to attenuate, delay or prevent PsA development.
Subject(s)
Arthritis, Psoriatic , Psoriasis , Humans , Arthritis, Psoriatic/diagnosis , Psoriasis/diagnostic imaging , Nails , Risk Factors , EuropeABSTRACT
The association between the clinical picture of symptomatic women with silicone breast implants (SBI) and dysregulated immunity was in dispute for decades. In the current study, we describe for the first time the functional activity of purified IgG antibodies derived from symptomatic women with SBIs (suffering from subjective/autonomic-related symptoms), both in vitro and in vivo. We found that IgGs, derived from symptomatic women with SBIs, dysregulate inflammatory cytokines (TNFα, IL-6) in activated human peripheral blood mononuclear cells, compared to healthy-women-derived IgGs. Importantly, behavioral studies conducted following intracerebroventricular injection of IgGs derived from symptomatic women with SBIs (who have dysregulated circulating level of IgG autoantibodies directed against autonomic nervous system receptors) into mice brains demonstrated a specific and transient significant increment (about 60%) in the time spent at the center of the open field arena compared with mice injected with IgG from healthy women (without SBIs). This effect was accompanied with a strong trend of reduction of the locomotor activity of the SBI-IgG treated mice, indicating an overall apathic-like behavior. Our study is the first to show the potential pathogenic activity of IgG autoantibodies in symptomatic women with SBIs, emphasizing the importance of these antibodies in SBI-related illness.
Subject(s)
Breast Implants , Female , Humans , Animals , Mice , Breast Implants/adverse effects , Leukocytes, Mononuclear , Autoantibodies , Silicones , Carrier Proteins , Immunoglobulin GABSTRACT
BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory arthritis primarily affecting the sacroiliac joint and axial skeleton with associated extra-articular involvement including cardiovascular system disease including aortic valve disease with variable reported prevalence. The aim of this study is to determine the prevalence of heart valve disorders in AS patients. METHODS: This was a retrospective, population-based, cross-sectional study that retrieved data from the Clalit Health Services registry. Cases were defined as having AS, whereas controls were frequency matched by age and sex in a ratio of 5:1. The prevalence of valvular heart diseases was compared between the two groups; a multivariate logistic regression model was applied to estimate the association after controlling for potential confounders. RESULTS: We included 4082 AS patients and 20 397 controls frequency matched by age and sex. AS patients had a significantly higher prevalence of cardiovascular risk factors (P < .001) and a higher prevalence of valvular heart disease. In the multivariate logistic regression model, adjusting for multiple confounding factors, AS was independently associated with aortic stenosis [odds ratio (OR): 2.25, 95% confidence interval (CI): 1.57-3.23, P < 0.001], aortic insufficiency (OR: 2.44, 95% CI: 1.50-3.94, P < 0.001), and mitral insufficiency (OR: 1.75, 95% CI: 1.17-2.61, P < 0.001) but not mitral stenosis (OR: 1.31, 95% CI: 0.60-2.70, P = 0.47). CONCLUSIONS: Our study reports the increased risk of valvular heart diseases in patients with AS, possibly due to the inflammatory milieu associated with the disease process and the result of biomechanical stress affecting the enthesis-like valvular structures.