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Background: Clinical trials comparing the efficacy of ocrelizumab (OCR) with other disease-modifying therapies (DMTs) other than interferon (IFN) β-1a in relapsing multiple sclerosis (RMS) are lacking. Objectives: To compare the treatment effect of OCR vs six DMTs' (IFN β-1a, glatiramer acetate, fingolimod, dimethyl fumarate, teriflunomide, natalizumab) treatment pathways used in clinical practice by combining clinical trial and real-world data. Methods: Patient-level data from OPERA trials and open-label extension phase, and from the German NeuroTransData (NTD) MS registry, were used to build 1:1 propensity score-matched (PSM) cohorts controlling for seven baseline covariates, including brain imaging activity. Efficacy outcomes were time to first relapse and time to 24-week confirmed disability progression over 5.5 years of follow-up. Intention-to-treat analysis using all outcome data irrespective of treatment switch was applied. Results: The analyses included 611 OPERA patients and 7141 NTD patients. We built 12 paired-matched cohorts (six for each outcome, two for each DMT) to compare efficacy of OCR in OPERA with each DMT treatment pathway in NTD. Post-matching, baseline covariates and PS were well balanced (standardized mean difference <.2 for all cohorts). Over 5.5 years, patients treated with OCR showed a statistically significant reduction in the risk of relapse (hazard ratios [HRs].30 to.54) and disability progression (HRs.51 to.67) compared with all index therapies and their treatment switching pathways in NTD. Treatment switch and/or discontinuation occurred frequently in NTD cohorts. Conclusion: OCR demonstrates superiority in controlling relapses and disability progression in RMS compared with real-world treatment pathways over a 5.5-year period. These analyses suggest that high-efficacy DMTs and high treatment persistence are critical to achieve greatest clinical benefit in RMS. Registration: OPERA I (NCT01247324), OPERA II (NCT01412333) [ABSTRACT FROM AUTHOR]

Prenatal exposure to airborne particles is a potential risk factor for infant neuropsychological development. This issue is usually explored by regression analysis under the implicit assumption that all relevant confounders are accounted for. Our aim is to estimate the causal effect of prenatal exposure to high concentrations of airborne particles with a diameter < 2.5 µm (PM2.5) on children's psychomotor and mental scores in a birth cohort from Gipuzkoa (Spain), and investigate the robustness of the results to possible unobserved confounding. We adopted the propensity score matching approach and performed sensitivity analyses comparing the actual effect estimates with those obtained after adjusting for unobserved confounders simulated to have different strengths. On average, mental and psychomotor scores decreased of -2.47 (90% CI: -7.22; 2.28) and -3.18 (90% CI: -7.61; 1.25) points when the prenatal exposure was ≥17 μg/m 3 (median). These estimates were robust to the presence of unmeasured confounders having strength similar to that of the observed ones. The plausibility of having omitted a confounder strong enough to drive the estimates to zero was poor. The sensitivity analyses conferred solidity to our findings, despite the large sampling variability. This kind of sensitivity analysis should be routinely implemented in observational studies, especially in exploring new relationships.