BackgroundSelect systemic autoimmune diseases show a predilection toAtherosclerotic and Cardiovascular Disease (ASCVD) largely attributed to proinflammatory cytokines supporting the role of the inflammatory hypothesis in endothelial dysfunction and subsequent clinical sequala. Dermatomyositis (DM) and polymyositis (PM) are polygenic autoimmune disorders involving mainly skeletal muscles. The association between DM/PM and ASCVD has not been well addressed and explored.ObjectivesTo investigate the association between DM/PM and ASCVD events by exploring incidence, mortality, and interaction with respect to disease-modifying agents, autoantibodies, and traditional CVD risk factors in a large, population-based sample.MethodsA retrospective cohort study using the electronic database of Clalit Health Services (CHS), the largest health organization in Israel. All DM and PM patients diagnosed between 2000-2016 were included with age- and sex-matched controls in a 1:5 ratio. Follow-up continued until the first diagnosis of ASCVD or death. The incidence of ASCVD was compared between the groups using univariate and multivariate models adjusting for baseline cardiovascular risk factors.ResultsThe study population included 1,567 DM/PM patients and 7,676 controls. The mean age at the index date was 32.5 years (SD±19 years), and the female proportion was 60.3%, similar for both groups. Traditional cardiovascular risk factors were similar between both groups. Median follow-up time was 8.4 (3.6-12.8) in the PM/DM group compared to 8.6 (3.7-12.9) in the control group. 47 (3.0%) PM/DM patients were diagnosed with IHD compared to 140 (1.8%) controls, yielding an Unadjusted HR of 1.66 (1.19 to 2.30). Unadjusted HR for CVA in the PM/DM group was (95%CI) 2.76 (1.86 to 4.11). Unadjusted HR for ASCVD (95%CI) was 1.88 (1.46 to 2.43). APLA-associated antibody predicted ASCVD among PM/DM groups as compared to non-ASCVD PM and DM patients (OR- 2.33, 95% CI - 1.41 to 3.86, p<0.0001).ConclusionOur study demonstrates that PM and DM are both associated with an increased risk of MI and ischemic stroke. Furthermore, PM and DM patients positive for APLA-associated antibodies were associated with excessive rates of ASCVD. Taken together, these findings support the increased need for awareness and surveillance of cardiovascular outcomes in the DM/PM cohort.Figure 1.Kaplan Meyer survival analysis comparing All atherosclerotic related cardiovascular diseases (ASCVD) outcomes between inflammatory myositis patients and controls.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
Background Treating perianal Crohn’s disease (pCD) is challenging with at least 60% of the patients not responding or relapsing after a year of 1st line biological therapy. Effectiveness data on 2nd and 3rd line in pCD is still quite limited. The aim of this study was to describe the effectiveness of 2nd and 3rd line biological therapy in pCD. Methods A retrospective cohort study of patients with pCD from a large tertiary center registry. We included all patients with pCD that were treated with >1 biologic while anti-TNF was the first one used. Primary outcome was defined as clinical failure of 2nd or 3rd line treatment (as defined by the clinician) or radiological evidence for disease progression by MRI or transrectal ultrasonography (TRUS). Secondary outcomes were relapse of perianal fistula or abscess. Results Registry included 893 patients with pCD who are being followed up routinely in a dedicated IBD clinic; 643 patients received 1 biological were excluded. Final cohort included 245 patients treated with ≥2 biologics. In 2nd line, 40/245 patients (16%) treated with infliximab (IFX), 128/245 (52%) with adalimumab (ADA), 48/245 (20%) with vedolizumab (VDZ) and 32/245 (13%) with ustekinumab (UST). 7/32 patients (22%) treated with UST failed the treatment, compared to 32/40 (80%), 101/128 (79%) , 37/48 (77%) patients treated with IFX, ADA and VDZ, respectively [Hazard Ratio(HR) 0.27 (0.1-0.69)]. Median time of 2nd line treatment with UST, anti-TNFs and VDZb was 2.5 (IQR=1-3[uk1] ), 3 (IQR=1-5) and 3 (IQR=1-4) years, respectively. Higher response rate in 2nd line therapy was associated with longer response duration to 1st line [OR (1.11-1.55), p<0.001)]. 99/245 patients (40%) required 3rd line treatment (VDZ - 52/99 , UST - 47/99 (48%)) patients). 8/47 patients (17%) under UST therapy experienced clinical failure, compared to 41/52 (78.8%) patients treated with VDZ [HR 0.32 (0.12-0.68)]. Median duration (years) of third line treatment with both UST and VDZ was 3 years (IQR=3-1). Figure A shows Kaplan-Meier survival analysis to 2nd line and 3rd line failure. Conclusion 2nd and 3rd line biological therapies may be efficacious in pCD patients. Ustekinumab appears to be effective as a 2nd or 3rd line treatment. Longer duration of treatment is associated with a higher likelihood of response to 2nd line treatment.
Objective The association between chronic inflammatory conditions and cardiovascular disease is well established. Considering Familial-Mediterranean-Fever (FMF), few studies exist investigating the risk of ischemic heart disease, and none address the risk of stroke. We aimed to evaluate the incidence and risk for stroke in FMF patients compared to 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 2000-2016 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 9,769 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. 208 FMF patients were diagnosed with stroke compared to 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 to 16.4) respectively, and a crude HR of 1.42 (95% CI 1.15 to 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 to 3.38; P < 0.001), as well as for those who did not develop these complications (HR = 1.32; 95%CI 1.04 to 1.67; P < 0.05). Conclusion FMF patients are at increased risk for stroke regardless of known complications.
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