BACKGROUND: Alzheimer 's disease is a progressive, irreversible, and fatal disease for which accumulation of amyloid beta is thought to play a key role in pathogenesis. Aducanumab is a human monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta. OBJECTIVES: We evaluated the efficacy and safety of aducanumab in early Alzheimer's disease. DESIGN: EMERGE and ENGAGE were two randomized, double-blind, placebo-controlled, global, phase 3 studies of aducanumab in patients with early Alzheimer's disease. SETTING: These studies involved 348 sites in 20 countries. PARTICIPANTS: Participants included 1638 (EMERGE) and 1647 (ENGAGE) patients (aged 50-85 years, confirmed amyloid pathology) who met clinical criteria for mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease dementia, of which 1812 (55.2%) completed the study. INTERVENTION: Participants were randomly assigned 1:1:1 to receive aducanumab low dose (3 or 6 mg/kg target dose), high dose (10 mg/kg target dose), or placebo via IV infusion once every 4 weeks over 76 weeks. MEASUREMENTS: The primary outcome measure was change from baseline to week 78 on the Clinical Dementia Rating Sum of Boxes (CDR-SB), an integrated scale that assesses both function and cognition. Other measures included safety assessments; secondary and tertiary clinical outcomes that assessed cognition, function, and behavior; and biomarker endpoints. RESULTS: EMERGE and ENGAGE were halted based on futility analysis of data pooled from the first approximately 50% of enrolled patients; subsequent efficacy analyses included data from a larger data set collected up to futility declaration and followed prespecified statistical analyses. The primary endpoint was met in EMERGE (difference of −0.39 for highdose aducanumab vs placebo [95% CI, −0.69 to −0.09; P=.012; 22% decrease]) but not in ENGAGE (difference of 0.03, [95% CI, −0.26 to 0.33; P=.833; 2% increase]). Results of biomarker substudies confirmed target engagement and dose-dependent reduction in markers of Alzheimer's disease pathophysiology. The most common adverse event was amyloid-related imaging abnormalities-edema. CONCLUSIONS: Data from EMERGE demonstrated a statistically significant change across all four primary and secondary clinical endpoints. ENGAGE did not meet its primary or secondary endpoints. A dose-and time-dependent reduction in pathophysiological markers of Alzheimer 's disease was observed in both trials.

Background Aducanumab is a human monoclonal antibody that selectively targets aggregated forms of Aβ, including soluble oligomers and insoluble fibrils. EMERGE and ENGAGE are two 18‐month, randomized, double‐blind, placebo‐controlled, global Phase 3 studies with identical design that evaluated the efficacy and safety of aducanumab in patients aged 50–85 years with early Alzheimer’s disease (MCI due to AD or mild AD dementia). Method Key inclusion criteria included positive amyloid PET, MMSE score of 24–30, CDR Global score of 0.5, and an RBANS‐DMI score ≤85. During the 18‐month placebo‐controlled period, patients were randomized 1:1:1 to low‐dose aducanumab, high‐dose aducanumab, or placebo, administered via IV infusion every 4 weeks. The primary endpoint for EMERGE and ENGAGE was change from baseline at Week 78 on the CDR‐SB. Secondary endpoints included change from baseline on MMSE, ADAS‐Cog13, and ADCS‐ADL‐MCI. Result Following pre‐planned futility analysis, analysis of the data from the final database lock showed that EMERGE met its primary endpoint, based on the pre‐specified statistical analysis plan. Patients treated with high dose aducanumab showed a significant reduction of clinical decline from baseline in CDR‐SB scores at 78 weeks (22% versus placebo, P = 0.01). ENGAGE did not meet its primary endpoint. However, data from patients in ENGAGE who achieved sufficient exposure to high dose aducanumab supported the findings of EMERGE. Conclusion EMERGE met its primary endpoint, based on the pre‐specified statistical analysis plan. Data from a subset of patients in ENGAGE support the results of EMERGE. The safety and tolerability profile of aducanumab in EMERGE and ENGAGE was consistent with previous studies of aducanumab.

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Aims: The study investigates the effectiveness and safety of methotrexate (MTX) versus leflunomide (LEF) in 12-month treatment of Takayasu arteritis (TAK). Methods: This was a cohort study. Patients diagnosed with TAK between 1 January 2013 and 1 January 2019 were enrolled from First Hospital of China Medical University and Zhongshan Hospital of Fudan University. Patients had active disease and were treated with glucocorticoid combined with LEF or MTX. Treatment response, imaging assessment and side-effects were evaluated during 12-month follow-up. Results: In total, 68 patients were enrolled (40 cases treated with LEF and 28 treated with MTX). At baseline, age, sex, disease duration and disease activity index showed no significant differences between groups. Prevalence of complete remission (CR) at 6 months was significantly higher in the LEF group than that in the MTX group (LEF versus MTX: 72.50% versus 53.57%, p = 0.04), though the CR prevalence at 9 months and 12 months showed no significant differences between groups. At 9 months, the prevalence of treatment resistance was much lower in the LEF group compared with MTX group (5.41% versus 11.54%, p = 0.03). Furthermore, prevalence of disease relapse in the LEF group was lower than that in MTX group at 12 months (7.24% versus 16.67%, p = 0.03). Patients with high baseline C-reactive protein levels (⩾15 mg/L) carried a higher risk of treatment resistance (OR = 1.36, 95% CI 1.07–13.41, p = 0.06) and disease relapse (HR = 2.51, 95% CI 1.36–12.98, p = 0.04). Conclusion: LEF might provide a quicker treatment response with lower prevalence of disease relapse compared with that elicited in MTX during 12 months follow-up for TAK.