Gastroenterology & Hepatology
March 2016, Volume 12, Issue 3
Proton Pump Inhibitor Use Related to Increased Dementia Risk
Proton pump inhibitors (PPIs) are associated with an increased risk for dementia in older patients, according to a prospective cohort study published online on February 15, 2016 in JAMA Neurology. This study confirms the results of an earlier study by the same researchers, which based its connection between PPI use and dementia risk on medical records rather than on information from a pharmaceutical database, as the current study does.
For the latest study, Dr Willy Gomm and colleagues used observational data collected from 2004 to 2011 by Germany’s largest mandatory health insurer to perform data analysis from August to November 2015. A total of 73,679 patients 75 years or older and without dementia at baseline were analyzed for the diagnosis of incident dementia. A total of 2950 patients (mean age, 83.8 years; 77.9% female) were classified as regular PPI users (defined as receiving at least 1 prescription of esomeprazole, lansoprazole, omeprazole, pantoprazole, or rabeprazole per quarter during 12-month and 18-month intervals), and 70,729 patients (mean age, 83.0 years; 73.6% female) were considered nonregular users.
Over the 7-year study, 29,510 patients were diagnosed with dementia. Using time-dependent Cox regression, the researchers found a significant increased risk of incident dementia in the group receiving regular PPI medication (hazard ratio, 1.44; 95% CI, 1.36-1.52; P<.001). The risk for dementia increased with stroke, depression, diabetes, and polypharmacy.
The researchers suggest that the avoidance of PPI use may prevent the development of dementia, but say that more randomized, prospective clinical trials are needed to better evaluate and understand the connection between PPI use and dementia risk.
Infliximab Biosimilar CT-P13 Receives Support From US Food and Drug Administration Committee
On February 9, 2016, the Arthritis Drugs Advisory Committee of the US Food and Drug Administration (FDA) supported the infliximab (Remicade, Janssen Biotech) biosimilar CT-P13 (Celltrion) for the treatment of ulcerative colitis in adult patients and Crohn’s disease in adult and pediatric patients. The FDA is expected to agree with the committee’s recommendation, and a decision is expected by April. The drug, already approved in 67 countries (where it is marketed as Remsima), would be the first biosimilar monoclonal antibody approved in the United States.
The panel voted 21 to 3 that the biosimilar is highly comparable to all but 1 of infliximab’s approved indications from both structural and functional standpoints; orphan drug exclusivity protects the indication for pediatric ulcerative colitis through September 23, 2018. The 3 dissenting votes were related to concerns regarding the drug’s efficacy for inflammatory bowel disease indications, as trial data focused on patients with rheumatoid arthritis and ankylosing spondylitis. However, the 3 committee members stated that the company had proven that the biosimilar was comparable for most indications.
If approved, the biosimilar would be indicated for treatment-naive patients or as a one-time switch from infliximab, and it would not be marketed as an interchangeable treatment option. Committee members are hopeful that approval of the drug may lead to lower drug costs.
FDA Approves Expanded Use of Daclatasvir to Treat Additional Genotypes 1 and 3 Chronic Hepatitis C Virus Patients
On February 5, 2016, the FDA approved the expanded use of daclatasvir (Daklinza, Bristol-Myers Squibb) in combination with sofosbuvir (Sovaldi, Gilead Sciences), with or without ribavirin, to treat chronic hepatitis C virus (HCV) patients with genotypes 1 and 3, including those with HIV-1 coinfection, advanced cirrhosis, or postliver transplant recurrence of HCV. These 3 patient populations are considered to be challenging to treat. Daclatasvir/sofosbuvir was originally approved in July 2015 for the treatment of chronic HCV genotype 3.
Although the ALLY-1 and ALLY-2 trials previously demonstrated the efficacy and safety of daclatasvir-containing regimens, the drug is associated with a risk of serious symptomatic bradycardia when combined with sofosbuvir and amiodarone, and is contraindicated in combination with drugs that strongly induce the CYP3A gene. The recommended dosage of daclatasvir is 60 mg in combination with sofosbuvir, with or without ribavirin, for 12 weeks.