Did you know that the live version of #GeriMedJC runs for an hour and is broadcast to several different hospitals in four different cities via the Ontario Telemedicine Network?
Toronto: Mount Sinai Hospital, Sunnybrook Hospital, St. Michael’s Hospital, Baycrest Hospital, North York General Hospital, St. Joseph’s Hospital
Mississauga: Trillium Hospital
Kitchener-Waterloo: Grand River Hospital, St. Mary's Hospital
Orillia: Soldier's Memorial Hospital
Can't join us live? No worries! Engage in the discussion on Twitter on August 28, 2015 at 08:00 EDT / 12:00 GMT and don't forget to use the hashtag #GeriMedJC.
The long article this month should provide an interesting discussion on study design and statistical methodology. This study utilizes a delayed-start, also known as randomized-start, to demonstrate disease-modification drug effect. We will take a look at this study of an investigational treatment for mild Alzheimer's disease:
Delayed-start analysis: Mild Alzheimer's disease patients in solanezumab trials, 3.5 years. Alzheimer's & Dementia: Translational Research & Clinical Interventions. In press. 2015.
Access the article here or read the abstract below:
Introduction
Solanezumab is an anti-amyloid monoclonal antibody in clinical testing for treatment of Alzheimer's disease (AD). Its mechanism suggests the possibility of slowing the progression of AD.
Methods
A possible disease-modifying effect of solanezumab was assessed using a new statistical method including noninferiority testing. Performance differences were compared during the placebo-controlled period with performance differences after the placebo patients crossed over to solanezumab in the delayed-start period.
Results
Noninferiority of the 14-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog14) and Alzheimer's Disease Cooperative Study Activities of Daily Living inventory instrumental items (ADCS-iADL) differences was met through 132 weeks, indicating that treatment differences observed in the placebo-controlled period remained, within a predefined margin, after the placebo group initiated solanezumab. Solanezumab was well tolerated, and no new safety concerns were identified.
Discussion
The results of this secondary analysis show that the mild subgroup of solanezumab-treated patients who initiated treatment early, at the start of the placebo-controlled period, retained an advantage at most time points in the delayed-start period.
The short article discussion will follow the long article discussion. The currently available live-attenuated vaccine against herpes zoster has two major limitations: diminishing efficacy against shingles with increasing age of vaccine recipients and contraindication for use in immunocompromised individuals. Could recombinant subunit vaccines fill in this gap? In this month's #GeriMedJC, the following trial will be appraised.
Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015 May 28;372(22):2087-96.
PMID: 25916341
Access the article here or read the abstract below:
BACKGROUND:
In previous phase 1-2 clinical trials involving older adults, a subunit vaccine containing varicella-zoster virus glycoprotein E and the AS01B adjuvant system (called HZ/su) had a clinically acceptable safety profile and elicited a robust immune response.
METHODS:
We conducted a randomized, placebo-controlled, phase 3 study in 18 countries to evaluate the efficacy and safety of HZ/su in older adults (≥50 years of age), stratified according to age group (50 to 59, 60 to 69, and ≥70 years). Participants received two intramuscular doses of the vaccine or placebo 2 months apart. The primary objective was to assess the efficacy of the vaccine, as compared with placebo, in reducing the risk of herpes zoster in older adults.
RESULTS:
A total of 15,411 participants who could be evaluated received either the vaccine (7698 participants) or placebo (7713 participants). During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001). Vaccine efficacy was between 96.6% and 97.9% for all age groups. Solicited reports of injection-site and systemic reactions within 7 days after vaccination were more frequent in the vaccine group. There were solicited or unsolicited reports of grade 3 symptoms in 17.0% of vaccine recipients and 3.2% of placebo recipients. The proportions of participants who had serious adverse events or potential immune-mediated diseases or who died were similar in the two groups.
CONCLUSIONS:
The HZ/su vaccine significantly reduced the risk of herpes zoster in adults who were 50 years of age or older. Vaccine efficacy in adults who were 70 years of age or older was similar to that in the other two age groups.
