T. Casper
4University of UtahAuthor Of 2 Presentations
PS04.04 - Evidence for an interaction between ozone pollution and HLA-DRB1*15 alleles in pediatric multiple sclerosis
Abstract
Background
We previously reported a relationship between air pollutants and increased risk of pediatric MS (ped-MS). Environmental risk factor research in ped-MS offers the advantage of shorter duration between exposure and disease onset. Ozone, an air pollutant, is a major global health hazard thought to have a role in MS pathoetiology. Identifying gene-environment interactions advances the understanding of biological processes at play in MS susceptibility.
Objectives
We sought to examine the interaction between ozone pollution and DRB1*15 status as the main genetic variant associated with MS susceptibility.
Methods
Cases and controls enrolled in the Environmental and Genetic Risk Factors for Pediatric MS study of the US Network of Pediatric MS Centers were analysed. County-level modeled ozone data were acquired from the CDC’s Environmental Tracking Network air pollution database. Participants were assigned ozone values based on county of residence. Values were categorized into tertiles based on healthy controls. The association between ozone tertiles and having MS were assessed by logistic regression. Interaction between tertiles of ozone level and presence of DRB1*15 alleles on odds of ped-MS was evaluated. Models were adjusted for sex, race, ethnicity, age, second-hand smoke exposure, and mother’s education. Additive interaction was estimated using relative risk due to interaction (RERI) and attributable proportion of disease were calculated.
Results
355 ped-MS cases and 565 controls contributed to the analyses. Ozone levels were associated with MS with an odds ratio (OR) of 2.35 (95%CI 1.57–3.51) and 2.21 (95%CI 1.48–3.32) in the upper two tertiles, respectively, compared with the lowest tertile. DRB1 status was also independently associated with MS (OR 1.99; 95%CI 1.43–2.78). There was a significant additive interaction between ozone and DRB1, with a RERI of 2.74 (95%CI 0.50–4.98) and 2.43 (95%CI 0.36–4.5) in the upper two tertiles, respectively. Approximately 60% of the ped-MS risk in those with HLA-DRB1*15 haplotype and high ozone exposure was attributable to the interaction between these risk factors.
Conclusions
Our data revealed additive interaction between higher exposure to ozone and DRB1 alleles on ped-MS susceptibility. Further evaluation of additional genetic variants that might play a role in ozone-induced ped-MS is underway to provide mechanistic insight.
YI02.02 - Assessing No Evidence of Disease Activity in Pediatric Onset Multiple Sclerosis
Abstract
Background
Pediatric onset multiple sclerosis (POMS) account for 5-10% of all MS cases. The optimal treatment target in POMS is not known. No Evidence of Disease Activity (NEDA), defined as the lack of clinical and radiologic evidence of MS activity, has been proposed as a possible outcome measure and treatment target in MS.
Objectives
We aim to determine POMS NEDA rate, compare NEDA and evidence of disease activity (EDA) patient characteristics, and determine NEDA predictors.
Methods
Retrospective analyses of POMS cases from the Multiple Sclerosis and other Demyelinating Diseases Database (PedMSDD) were conducted. Multiple imputation was employed to reduce bias relative to complete-case methods. NEDA proportions at 12, 18, and 24 months post-diagnosis were calculated. Demographic and clinical disease characteristics between NEDA and EDA were compared. The odds of achieving NEDA at each time interval were modeled using separate univariable logistic regressions, and significant predictors were included in final multivariable models.
Results
Demographics and clinical characteristics were similar between NEDA and EDA. In patients with at least six months of follow-up (N=913), an estimated 56%, 64%, and 69% of patients achieve NEDA at months 12, 18, and 24, respectively. A significant proportion (>70%) of patients were not on disease modifying therapy (DMT) in the first 6 months. Among those on DMT, intravenous (IV) DMT was more common among the NEDA group compared to EDA. Recent DMT use was more important than initial DMT use in its ability to explain NEDA status at 18 and 24 months. Those on IV DMT had increased odds of achieving NEDA compared to those on no DMT or other DMTs.
Conclusions
A majority of POMS patients achieved NEDA at some point within 2 years of MS diagnosis, despite being treatment-naïve initially. In those on DMT, recent intravenous DMT use was associated with higher likelihood of NEDA.