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Aim: Patients with relapsing–remitting multiple sclerosis (RRMS) treated with natalizumab have anecdotally reported a ‘feel-good experience’ (FGE). The authors characterized the FGE using survey data from patients with RRMS treated with natalizumab or other disease-modifying therapies (other-DMT). Methods: Questionnaire data from RRMS patients who use MyMSTeam, an online patient social network, were analyzed. Results: The survey included 347 patients (95 natalizumab; 252 other-DMT). More natalizumab than other-DMT patients self-reported having an FGE (62.1 vs 44.8%; p = 0.001) as well as other physical, emotional and cognitive benefits. Conclusion: This study demonstrates that physical, emotional and cognitive benefits were more commonly reported by patients treated with natalizumab than those treated with other disease-modifying therapies and helps characterize patient-reported factors associated with the FGE.

The two-stage process of propensity score analysis (PSA) includes a design stage where propensity scores (PSs) are estimated and implemented to approximate a randomized experiment and an analysis stage where treatment effects are estimated conditional on the design. This article considers how uncertainty associated with the design stage impacts estimation of causal effects in the analysis stage. Such design uncertainty can derive from the fact that the PS itself is an estimated quantity, but also from other features of the design stage tied to choice of PS implementation. This article offers a procedure for obtaining the posterior distribution of causal effects after marginalizing over a distribution of design-stage outputs, lending a degree of formality to Bayesian methods for PSA that have gained attention in recent literature. Formulation of a probability distribution for the design-stage output depends on how the PS is implemented in the design stage, and propagation of uncertainty into causal estimates depends on how the treatment effect is estimated in the analysis stage. We explore these differences within a sample of commonly used PS implementations (quantile stratification, nearest-neighbor matching, caliper matching, inverse probability of treatment weighting, and doubly robust estimation) and investigate in a simulation study the impact of statistician choice in PS model and implementation on the degree of between- and within-design variability in the estimated treatment effect. The methods are then deployed in an investigation of the association between levels of fine particulate air pollution and elevated exposure to emissions from coal-fired power plants.

Extended interval dosing (EID; average dosing interval approximately every 6 weeks) of natalizumab is associated with significantly lower risk of progressive multifocal leukoencephalopathy than standard interval dosing (SID; every 4 weeks) in patients with relapsing-remitting multiple sclerosis (MS). Real-world studies, though limited, suggest that natalizumab effectiveness is generally maintained in patients who switch to EID after initiation of stable treatment with SID. MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions) is a collaborative, multicenter learning health system that generates real-world clinical and MRI data using highly standardized acquisition protocols. We compared MRI outcomes in MS PATHS patients treated with natalizumab EID versus SID. We also compared MRI outcomes in patients treated with natalizumab (EID and/or SID) versus injectable MS platform therapy.Natalizumab infusion data from the TOUCH Prescribing Program database and MS PATHS MRI assessment data from seven US sites as of July 23, 2020, were used to identify patients with relapsing-remitting MS who had received natalizumab EID or SID in the interval between two MRI scans (an MRI segment). Patients who received injectable platform MS therapy between two MRI scans were also identified. MRI data were used to determine the incidence rate and odds of developing new or enlarging T2 lesions, annualized percentage change in T2 lesion volume (T2LV), and annualized percentage change in brain parenchymal fraction (BPF). MRI outcomes were compared for 1) natalizumab EID treatment versus natalizumab SID treatment, 2) natalizumab treatment (EID + SID) versus platform therapy, and 3) natalizumab EID versus platform therapy. Propensity score-based weighting or matching were used to balance covariates at the start of MRI segments for all comparisons.The MRI outcomes observed with natalizumab EID treatment did not differ significantly from those observed with natalizumab SID treatment. The odds ratio for any new or enlarging T2 lesion was 1.07 (95% confidence interval [CI]: 0.93, 1.24; p = 0.355), and the rate ratio (95% CI) for new or enlarging T2 lesions was 1.62 (0.93, 2.82; p = 0.090). Differences (95% CI) between EID and SID patients in mean annualized percentage change in T2LV and BPF were 1.56% (-3.77%, 6.90%; p = 0.566) and -0.11% (-0.25%, -0.10%; p = 0.096), respectively. Conversely, when MRI outcomes in natalizumab and platform therapy patients were compared, there were significant differences favoring natalizumab in all assessments: the odds of any new or enlarging T2 lesion (odds ratio: 0.69 [95% CI: 0.64, 0.75]; p0.001), the incidence rate of new or enlarging T2 lesions (rate ratio: 0.47 [95% CI: 0.37, 0.61]; p0.001), annualized percentage change (decrease) in T2LV (difference: -3.68% [95% CI: -7.06%, -0.30%]; p = 0.033), and annualized percentage change (increase) in BPF (difference: 0.22% [95% CI: 0.16%, 0.29%]; p0.001). Results of the subgroup comparison of natalizumab EID patients with platform therapy patients were similar to those of the overall-natalizumab-group-versus-platform-therapy comparison.The results indicate that natalizumab EID and SID provide comparable real-world effectiveness on quantitative MRI metrics. These data further demonstrate that natalizumab EID can provide superior real-world effectiveness to injectable platform therapy on quantitative MRI metrics.

IntroductionThe TYSABRI Observational Program (TOP) is an ongoing observational study of natalizumab treatment in relapsing-remitting multiple sclerosis (RRMS) patients. Country-specific data on relapse and disability outcomes, alongside global data, can provide information on natalizumab’s effectiveness in local practice.MethodsAnnualised relapse rate (ARR) was analysed in TOP UK (n=134) and global (N=6320) cohorts using data from July 2007 to November 2020. A subgroup analysis assessed ARR in patients with one prior disease modifying therapy (DMT) in the UK (n=64) and global (n=2795) cohorts. Cumulative probabilities of 24-week confirmed disability worsening and improvement will be presented.ResultsARR decreased in UK patients from 2.21 in the year before initiation to 0.16 on natalizumab (PConclusionsThe reduction in ARR on natalizumab was similar in the TOP UK and global cohorts, including in the subset of patients with one prior DMT. These findings support the real-world effectiveness of natalizumab.Support.Biogen. Disclosures: Included on the poster. jean.vonsy@biogen.com

Background Despite the need for mental health surveillance in humanitarian emergencies, there is a lack of validated instruments. This study evaluated a sequential screening process for major depressive disorder (MDD) using the two- and eight-item Patient Health Questionnaires (PHQ-2 and PHQ-8, respectively). Methods This study analyzed data collected during a cross-sectional survey in a Syrian refugee camp in Greece (n = 135). The response rate for each instrument was assessed, and response burden was calculated as the number of items completed. The sequential screening process was simulated to replicate the MDD classifications captured if the PHQ-2 was used to narrow the population receiving the full PHQ-8 assessment. All respondents were screened using the PHQ-2. Only respondents scoring ≥ 2 are considered at risk for symptoms of MDD and complete the remaining six items. The positive and negative percent agreement of this sequential screening process were evaluated. Results The PHQ-2, PHQ-2/8 sequential screening process, and PHQ-8 were completed by 91%, 87%, and 84% of respondents, respectively. The sequential screening process had a positive percent agreement of 89% and a negative percent agreement of 100%, and eliminated the need to complete the full PHQ-8 scale for 34 (25%) respondents. Conclusions The benefits of the sequential screening approach for the classification of MDD presented here are twofold: preserving classification accuracy relative to the PHQ-2 alone while reducing the response burden of the PHQ-8. This sequential screening approach is a pragmatic strategy for streamlining MDD surveillance in humanitarian emergencies.

Marginal structural models (MSM) with inverse probability weighting (IPW) are used to estimate causal effects of time-varying treatments, but can result in erratic finite-sample performance when there is low overlap in covariate distributions across different treatment patterns. Modifications to IPW which target the average treatment effect (ATE) estimand either introduce bias or rely on unverifiable parametric assumptions and extrapolation. This paper extends an alternate estimand, the ATE on the overlap population (ATO) which is estimated on a sub-population with a reasonable probability of receiving alternate treatment patterns in time-varying treatment settings. To estimate the ATO within an MSM framework, this paper extends a stochastic pruning method based on the posterior predictive treatment assignment (PPTA) (Zigler, C. M., and M. Cefalu. 2017. “Posterior Predictive Treatment Assignment for Estimating Causal Effects with Limited Overlap.” eprint arXiv:1710.08749.) as well as a weighting analog (Li, F., K. L. Morgan, and A. M. Zaslavsky. 2018. “Balancing Covariates via Propensity Score Weighting.” Journal of the American Statistical Association 113: 390–400, https://doi.org/10.1080/01621459.2016.1260466.) to the time-varying treatment setting. Simulations demonstrate the performance of these extensions compared against IPW and stabilized weighting with regard to bias, efficiency, and coverage. Finally, an analysis using these methods is performed on Medicare beneficiaries residing across 18,480 ZIP codes in the U.S. to evaluate the effect of coal-fired power plant emissions exposure on ischemic heart disease (IHD) hospitalization, accounting for seasonal patterns that lead to change in treatment over time.

Background: Despite the urgency of mental health surveillance and treatment in humanitarian emergencies, there has been little evaluation of instruments that keep response burden to a minimum. We aimed to evaluate a sequential screening process for the detection of major depressive disorder that improves the efficiency of screening-confirmation procedures using the two-item and eight-item Patient Health Questionnaires (PHQ-2 and PHQ-8, respectively) in a refugee population. Methods: We analysed data from a cross-sectional survey completed by Syrian refugees in a camp in Greece between January and February, 2017. All survey items were translated to and back-translated from Arabic. Face-to-face interviews took place in an area with audio privacy. We used logistic regression to measure the correlation between the PHQ-2 classification and the summed score of the remaining six items of the PHQ-8, and used empirical data to simulate the sequential screening process for major depressive disorder. The sequential process replicates the diagnoses captured if the PHQ-2 were used to narrow the population who would complete the full PHQ-8 assessment. First, respondents complete the PHQ-2; next, only respondents who score above a threshold are considered at risk for depression and complete the remaining six items. We compared the positive and negative percent agreement of the PHQ-2 and sequential screening process. Response burden was assessed through item and instrument completion. Findings: We included data from 135 respondents, representing 40% of the adult population in the refugee camp at the time of the survey. Mean age was 30 years (range 18–61 years); 41% of respondents were women. The PHQ-2 and PHQ-8 instruments were completed by 123 (91%) and 113 (84%) respondents, respectively (p=0·014). The scores of the PHQ-2 and remaining six items of the PHQ-8 were significantly correlated (p

Introduction Les patients atteints de SEP doivent souvent quitter leur emploi prematurement et un retour au travail peut s’averer difficile. Il est donc important de prevenir ces departs du marche de travail. Objectifs Evaluer le developpement de la situation professionnelle de patients sous traitement dans l’etude observationnelle de la securite et l’efficacite a long terme du natalizumab (TOP). Patients et methodes Cette analyse retrospective incluait 2004 patients de ≤ 65 ans a l’inclusion dans TOP, interroges sur leur situation professionnelle l’annee precedant leur traitement et depuis l’inclusion. Lors de l’enquete les patients devaient avoir recu ≤ 3 doses de natalizumab, mais ne devaient pas necessairement etre sous traitement continu. Une analyse logistique multivariee analysait l’association entre les variables de base et les resultats sur l’emploi. Resultats L’annee precedant le traitement avec natalizumab, 80,7 % des patients travaillaient. Au cours du traitement, 62,8 % ont ameliore/garde leur emploi alors que 12,4 % ont perdu leur emploi du a la SEP; 6,2 % ont arrete de travailler pour d’autres raisons. L’âge et le score EDSS a l’inclusion dans TOP, ainsi que le nombre de poussees l’annee precedant l’initiation du traitement avec natalizumab, avaient des effets significatifs sur le maintien/amelioration de la situation professionnelle. Discussion Parmi les patients travaillant a l’inclusion dans TOP, 77,0 % ont conserve ou ameliore leur situation professionnelle pendant un suivi moyen de 5,5 annees. Les patients plus jeunes, avec moins de poussees et un handicap moins severe lors de l’inclusion avaient de meilleures chances de conserver ou ameliorer leur emploi. Conclusion Ces resultats suggerent que l’initiation de traitement par natalizumab tot dans le processus de la maladie peut contribuer au maintien de l’emploi.

Background: Over one million Syrian asylum seekers have travelled to Greece with the ultimate aim of reaching other countries in western Europe. Depression prevalence and associated sociodemographic and displacement characteristics have been reported for resettled migrants. However, the prevalence of major depressive disorder (MDD) and its risk factors have not been described among migrants engaged in the asylum process ensuing from the Syrian crisis. This study provides new data about the mental health status of migrants in transition in the context of protracted asylum procedures. Methods: We conducted a cross-sectional survey in a Syrian refugee camp in the Attica region of Greece from January 16–31, 2017. Individuals ≥18 years of age with verbal Arabic or English language skills were eligible to participate. The Patient Health Questionnaire-8 (PHQ-8), an eight-item validated diagnostic and severity measure, was used to screen for MDD. We analysed the relationships between MDD and sociodemographic and displacement characteristics using multivariable logistic regression. Results: A total of 135 surveys were completed, representing 40% of the adult population in the refugee camp. The mean age of the participants was 30 years (18–61 years); women comprised 41% of the sample; 74% of the participants had ever married; 67% had children; and 33% of participants had not attended secondary school, including 11% who had never attended school. Median time since departing the country of origin was 12 months (