P506 Increased risk of anti-drug antibodies to a second anti-TNF in patients who developed antibodies to the first anti-TNF

Abstract Background Evidence regarding predisposition to develop anti-drug antibodies to a second anti-TNF in patients with inflammatory bowel diseases (IBD) who previously developed antibodies to a first anti-TNF (either infliximab or adalimumab) is conflicting. We aimed to assess the rates of such consecutive immunogenicity. Methods The medical records of all patients with IBD followed at the Rabin and Schneider Medical Centers (all ages) from 2014 to 2019, who were treated with an anti-TNF agent were reviewed. Clinical data including age at diagnosis, gender, disease type, concomitant use of immunomodulators, as well as drug trough levels (TLs) and anti-drug antibodies (ADAs) for both agents were registered. Patients who switched from one anti-TNF to another and had comprehensive clinical and pharmacokinetic data were assessed for consecutive immunogenicity. Results Overall, 1570 patients were tested for TLs and ADAs (infliximab, n = 702, 45%). Rates of positive infliximab ADAs were 31%, and positive adalimumab ADAs were 13%. We identified 55 eligible patients (Crohn’s disease = 52, ulcerative colitis = 2, IBD unclassified = 1; females = 26 [47%]; mean age at diagnosis 26.5 ± 13 years). Of 29 patients with infliximab as the first anti-TNF, 25 (86%) had positive ADAs. None of the 4 patients without ADAs against infliximab developed ADAs against consequent adalimumab, whereas 7/25 (28%) of patients with positive ADAs against infliximab developed ADAs against adalimumab, significantly higher than the overall immunogenicity rate of adalimumab (28% vs. 13%, p = 0.03). Of the 26 patients who were switched from adalimumab to infliximab, 10 (38%) had positive ADAs. Out of 16 patients with negative ADAs against adalimumab, 5 (31%) developed ADAs against consequent infliximab whereas 7/10 (70%) of patients with positive ADAs against adalimumab developed ADAs against infliximab, significantly higher than the overall immunogenicity rate of infliximab (70% vs. 31%, p = 0.008). The overall rate of immunogenicity against the second anti TNF following a switch due to immunogenic failure was 39%. Only 33% of patients were treated with concomitant immunomodulators after an immunogenicity driven switch. Clinical data, as well as TLs and ADA, were comparable in children and adults. Conclusion The rate of consecutive immunogenicity in anti-TNF treated patients is significantly higher than the overall immunogenicity against the first anti-TNF. This higher rate of consecutive immunogenicity may be associated with a predisposition to developing anti-drug antibodies to anti-TNF agents. It may also be a consequence of the relatively low rates of combination therapy following an immunogenic failure. </jats:sec

Abstract P414: Omega-3 Fatty Acids Modify the Genetic Risk of Early Onset Acute Coronary Syndrome

Background: Recent gene-environment interaction studies suggest that diet may influence an individual’s genetic predisposition to cardiovascular risk. We tested the hypothesis that omega-3 fatty acid intake may influence the risk for acute coronary syndrome (ACS) conferred by genetic polymorphisms among patients with premature ACS. Methods: Our study population consisted of 706 patients of white European descent enrolled in GENESIS PRAXY, a multicentre prospective cohort study of patients aged 18 to 55 years hospitalized with ACS. We used a case-only design to investigate gene-environment interactions between the omega-3 index (a validated biomarker of omega-3 fatty acid intake) and 30 single nucleotide polymorphisms (SNPs) that have been robustly associated with ACS. We used logistic regression to study the associations between each SNP and the omega-3 index. Interaction was also assessed between the omega-3 index and a genetic risk score generated from the 30 SNPs as a simple unweighted count of the risk alleles for each SNP. All the SNPs used in the genetic risk score were uncorrelated (r2 &lt;0.3). We further adjusted all models for age and sex. Results: The median age of our population was 49 years and 72.1% were male. Median omega-3 index was 3.35% (interquartile range 2.81-4.07%). None of the SNPs deviated from Hardy-Weinberg equilibrium. A synergistic multiplicative interaction for increased ACS risk was found between carriers of chromosome 9p21 variant rs4977574 and low omega-3 index (OR 1.57, 95% CI 1.07-2.32, p=0.02), but did not reach significance after correction for multiple testing. Similar results were obtained in the adjusted model (OR 1.55, 95% CI 1.05-2.29, p=0.03). We did not observe interaction between the genetic risk score and the omega-3 index. Conclusions: In conclusion, our results suggest that omega-3 fatty acid intake may modify the genetic risk conferred by chromosome 9p21 variation among ACS patients but require independent replication in other cohorts. Further validation research is also warranted to examine whether this interaction occurs in other ethnic groups. </jats:p

Comparison of the Effect of Thiazide Diuretics and Other Antihypertensive Drugs on Central Blood Pressure: Cross-Sectional Analysis Among Nondiabetic Patients

Thiazide diuretics (TDs) are a cost‐effective first‐line therapy for uncomplicated hypertension; however, they are less prescribed than other options. The authors aimed to assess the noninferiority of TDs relative to different classes of antihypertensive medications in relation to central blood pressure. Cross‐sectional data from the Quebec CARTaGENE project was used. Nondiabetic hypertensive participants on monotherapy for hypertension were studied. Separate adjusted models were constructed to establish noninferiority of TDs to non‐TD antihypertensive medications for central blood pressure measurements. Models included a set of potential confounders. Of the 1194 hypertensive participants, 7.4% were taking TDs. We found that TDs were comparable with non‐TD antihypertensive medications for central systolic blood pressure (adjusted regression coefficient, 0.45; 95% confidence interval, −1.61 to 2.50). No differences in other central measurements were noted. The results provide additional support that TDs are at least as effective as other first‐line medications for treating uncomplicated hypertension

Sex differences in acute coronary syndrome symptom presentation in young patients

IMPORTANCE Little is known about whether sex differences in acute coronary syndrome (ACS) presentation exist in young patients and what factors determine absence of chest pain in ACS presentation. OBJECTIVES To evaluate sex differences in ACS presentation and to estimate associations between sex, sociodemographic, gender identity, psychosocial and clinical factors, markers of coronary disease severity, and absence of chest pain in young patients with ACS. DESIGN, SETTING, PARTICIPANTS We conducted a prospective cohort study of 1015 patients (30% women) 55 years or younger, hospitalized for ACS and enrolled in the GENESIS PRAXY (Gender and Sex Determinants of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary Syndrome) study (January 2009-September 2012). MAIN OUTCOMES AND MEASURES The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey was administered during hospitalization. RESULTS The median age for both sexes was 49 years. Women were more likely to have non-ST-segment elevation myocardial infarction (37.5 vs 30.7; P = .03) and present without chest pain compared with men (19.0% vs 13.7%; P = .03). Patients without chest pain reported fewer symptoms overall and no discernable pattern of non-chest pain symptoms was found. In the multivariate model, being a woman (odds ratio [OR], 1.95 [95% CI, 1.23-3.11]; P = .005) and tachycardia (OR, 2.07 [95% CI, 1.20-3.56]; P = .009) were independently associated with ACS presentation without chest pain. Patients without chest pain did not differ significantly from those with chest pain in terms of ACS type, troponin level elevation, or coronary stenosis. CONCLUSIONS AND RELEVANCE Chest pain was the most common ACS symptom in both sexes. Although women were more likely to present without chest pain than men, absence of chest pain was not associated with markers of coronary disease severity. Strategies that explicitly incorporate assessment of common non-chest pain symptoms need to be evaluated