Background: We previously investigated low doses (105 or 225 mg) of gantenerumab, a fully human monoclonal antibody that binds and removes aggregated amyloid-β by Fc receptor-mediated phagocytosis, in the SCarlet RoAD (SR) and Marguerite RoAD (MR) phase 3 trials. Several lines of evidence suggested that higher doses may be necessary to achieve clinical efficacy. We therefore designed a positron emission tomography (PET) substudy to evaluate the effect of gantenerumab uptitrated to 1200 mg every 4 weeks on amyloid-β plaques as measured using florbetapir PET in patients with prodromal to moderate Alzheimer’s disease (AD). Methods: A subset of patients enrolled in the SR and MR studies who subsequently entered the open-label extensions (OLEs) were included in this substudy. Patients were aged 50 to 90 years with a clinical diagnosis of probable prodromal to moderate AD and were included based on a visual read of the original screening scan in the double-blind phase. Patients were assigned to 1 of 5 titration schedules (ranging from 2 to 10 months) with a target gantenerumab dose of 1200 mg every 4 weeks. The main endpoint of this substudy was change in amyloid-β plaque burden from OLE baseline to week 52 and week 104, assessed using florbetapir PET. Florbetapir global cortical signal was calculated using a prespecified standard uptake value ratio method converted to the Centiloid scale. Results: Sixty-seven of the 89 patients initially enrolled had ≥ 1 follow-up scan by August 15, 2018. Mean amyloid levels were reduced by 39 Centiloids by the first year and 59 Centiloids by year 2, a 3.5-times greater reduction than was seen after 2 years at 225 mg in SR. At years 1 and 2, 37% and 51% of patients, respectively, had amyloid-β plaque levels below the amyloid-β positivity threshold. Conclusion: Results from this exploratory interim analysis of the PET substudy suggest that gantenerumab doses up to 1200 mg resulted in robust amyloid-β plaque removal at 2 years. PET amyloid levels were consistent with sparse-to-no neuritic amyloid-β plaques in 51% of patients after 2 years of therapy. Amyloid reductions were similar to those observed in other placebo-controlled studies that have suggested potential clinical benefit. Trial registration: ClinicalTrials.gov, NCT01224106 (SCarlet RoAD) and NCT02051608 (Marguerite RoAD).
Operation experiments were conducted to optimize the preparation of activated carbons from corn cob. The Cr(VI) adsorption capacity of the produced activated carbons was also evaluated. The impact of the adsorbent dosage, contact time, initial solution pH and temperature was studied. The results showed that the produced corn cob activated carbon had a good Cr(VI) adsorptive capacity, the theoretical maximum adsorption was 34.48 mg g−1 at 298 K. The Brunauer–Emmett–Teller and iodine adsorption value of the produced activated carbon could be 924.9 m2 g−1 and 1,188 mg g−1, respectively. Under the initial Cr(VI) concentration of 10 mg L−1 and the original solution pH of 5.8, an adsorption equilibrium reached after 4 h, and Cr(VI) removal rate was from 78.9 to 100% with an adsorbent's dosage increased from 0.5 to 0.7 g L−1. The kinetics and equilibrium data agreed well with the pseudo-second-order kinetics model and Langmuir isotherm model. The equilibrium adsorption capacity improved with the increment of the temperature.
Objective: To evaluate the association between health insurance coverage and disease-modifying therapy (DMT) use for multiple sclerosis (MS). Methods: In 2014, we surveyed participants in the North American Research Committee on MS registry regarding health insurance coverage. We investigated associations between negative insurance change and (1) the type of insurance, (2) DMT use, (3) use of free/discounted drug programs, and (4) insurance challenges using multivariable logistic regressions. Results: Of 6,662 respondents included in the analysis, 6,562 (98.5%) had health insurance, but 1,472 (22.1%) reported negative insurance change compared with 12 months earlier. Respondents with private insurance were more likely to report negative insurance change than any other insurance. Among respondents not taking DMTs, 6.1% cited insurance/financial concerns as the sole reason. Of respondents taking DMTs, 24.7% partially or completely relied on support from free/discounted drug programs. Of respondents obtaining DMTs through insurance, 3.3% experienced initial insurance denial of DMT use, 2.3% encountered insurance denial of DMT switches, and 1.6% skipped or split doses because of increased copay. For respondents with relapsing-remitting MS, negative insurance change increased their odds of not taking DMTs (odds ratio [OR] 1.50; 1.16–1.93), using free/discounted drug programs for DMTs (OR 1.89; 1.40–2.57), and encountering insurance challenges (OR 2.48; 1.64–3.76). Conclusions: Insurance coverage affects DMT use for persons with MS, and use of free/discounted drug programs is substantial and makes economic analysis that ignores these supplements potentially inaccurate. The rising costs of drugs and changing insurance coverage adversely affect access to treatment for persons with MS.