ELBASVIR-GRAZOPREVIR

HCV-infected kidneys may be viable for transplant

Even though wait times for kidney transplants are 3 to 5 years in some areas, more than 500 high-quality kidneys from deceased donors are discarded annually because the donor had hepatitis C virus (HCV) infection. However, high HCV cure rates associated with direct-acting antiviral drugs have created the possibility that these kidneys could be suitable for transplant in HCV-negative people, potentially increasing the number of donor kidneys substantially. To explore that possibility, researchers designed a small pilot study to determine the safety and efficacy of transplanting kidneys from HCV genotype 1-viremic donors into HCV-negative recipients, followed by treatment with elbasvir-grazoprevir, a combination antiviral drug approved to treat HCV genotype 1 and 4 in adults.

Ten adult patients received HCV-infected kidneys. Half were male and two were Black Americans. All were undergoing dialysis and anticipated long wait times for a kidney transplant.

Each patient's HCV viral load was measured on post-op day 3. Therapy with elbasvir-grazoprevir was initiated when results became positive and continued for 12 weeks.

After 12 weeks of treatment, all recipients were cured of HCV. A cure was defined as a sustained virologic response 12 weeks after the end of treatment. The researchers conclude, "This pilot trial showed that transplantation of HCV genotype 1-infected kidneys into HCV-negative recipients, followed by the use of direct-acting antiviral agents, can provide potentially excellent allograft function with a cure of HCV infection."

Source: Goldberg DS, Abt PL, Blumberg EA, et al. Trial of transplantation of HCV-infected kidneys into uninfected recipients. N Engl J Med. [e-pub Apr. 30, 2017]

PREGNANCY

Antibiotics linked to miscarriage risk

Antibiotics are widely prescribed during pregnancy, but little research has been done to determine fetal risks. To study the relationship between antibiotic exposure in early pregnancy and spontaneous abortion, researchers conducted a nested case-control study within the Quebec Pregnancy Cohort (1998-2009). Spontaneous abortion was defined as having a diagnosis or procedure related to spontaneous abortion before the 20th week of pregnancy. Ten controls per case were randomly selected and matched by gestational age and year of pregnancy.

The study showed that "use of macrolides (excluding erythromycin), quinolones, tetracyclines, sulfonamides, and metronidazole during early pregnancy was associated with an increased risk of spontaneous abortion." The researchers suggest that their finding might be useful for updating guidelines on treating infections during pregnancy.

Source: Muanda FT, Sheehy O, Berard A. Use of antibiotics during pregnancy and risk of spontaneous abortion. CMAJ. 2017;189(17):E625-E633.

GENERIC VS. BRAND-NAME DRUGS

Do gifts influence prescriptive behavior?

A new study indicates that in 2015, about 48% of U.S. physicians received payments and/or gifts from pharmaceutical and biomedical industries amounting to an estimated $2.4 billion. A second study focusing on physician prescribing behavior in academic medical centers indicates that physicians were more likely to prescribe generic rather than brand-name drugs after their facilities adopted rules restricting pharmaceutical sales visits. Both studies were published by the Journal of the American Medical Association in a theme issue on conflicts of interest in medicine.

An accompanying editorial notes that other recent studies have shown that pharmaceutical marketing, usually in the form of a free meal accompanied by an educational presentation, is associated with higher rates of prescribing brand-name drugs rather than generic equivalents. "Such overuse of brand-name drugs cost the United States about $73 billion between 2010 and 2012, one third of which was borne by patients."

In an interview, editorial coauthor R. Adams Dudley, MD, MBA, commented, "Many doctors would say they can't be bought for the low amounts we're talking about, but the amounts actually aren't that low. Many, many doctors are getting thousands of dollars. It's hard to imagine that is not influential."

Sources: Tringale KR, Marshall D, Mackey TK, Connor M, Murphy JD, Hattangadi-Gluth JA. Types and distribution of payments from industry to physicians in 2015. JAMA. 2017;317(17):1774-1784. Larkin I, Ang D, Steinhart J, et al. Association between academic medical center pharmaceutical detailing policies and physician prescribing. JAMA. 2017;317(17):1785-1795. DeJong C, Dudley RA. Reconsidering physician-pharmaceutical industry relationships. JAMA. 2017;317(17):1772-1773. Half of U.S. docs get payments from drug, device industries: study. HealthDay. May 2, 2017.

PERIPHERAL VASCULAR DISEASE

How helpful is aspirin?

Aspirin use in patients with peripheral vascular disease (PVD) has been endorsed by the American College of Cardiology/American Heart Association, but evidence of its safety and effectiveness in treating patients with PVD is conflicting. To investigate the issue, researchers conducted an electronic search of databases to identify randomized trials comparing aspirin with either placebo or control (no aspirin) in patients with PVD. Eleven trials and 6,560 patients were included in the study. The primary efficacy outcome was all-cause mortality; the primary safety outcome was major bleeding. Other outcomes of interest were major adverse cardiac and cerebrovascular events, myocardial infarction, stroke, and intracranial hemorrhage.

Researchers found that the incidence of all-cause mortality and major adverse cardiac and cerebrovascular events was similar between both groups across a wide range of aspirin dosages. In addition, aspirin use wasn't associated with an increased risk of either major bleeding or intracranial hemorrhage. They conclude that "aspirin use in PVD might not be associated with improved cardiovascular outcomes or worse bleeding outcomes....Guideline recommendations regarding the use of aspirin among patients with PVD need to be updated."

Source: Mahmoud AN, Elgendy AY, Rambarat C, Mahtta D, Elgendy IY, Bavry AA. Efficacy and safety of aspirin in patients with peripheral vascular disease: an updated systematic review and meta-analysis of randomized controlled trials. PLoS One. 2017;12(4):e0175283.

RYDAPT

Newly approved drug targets acute AML

The FDA has approved Rydapt (midostaurin) for adults with newly diagnosed acute myeloid leukemia (AML) who have a specific genetic mutation called FLT3, to be used in combination with chemotherapy. A kinase inhibitor, Rydapt works by blocking several enzymes that promote leukemic cell growth. It's approved for use with a companion diagnostic assay for detecting the FLT3 mutation in patients with AML. Rydapt isn't indicated as a single-agent induction therapy for the treatment of patients with AML. Rydapt is also approved to treat adults with aggressive systemic mastocytosis, systemic mastocytosis with associated hematologic neoplasm, and mast cell leukemia.

Rydapt is taken orally twice a day, about 12 hours apart, with food. Common adverse reactions in patients treated for AML include febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, and musculoskeletal pain.

Tell patients to take the drug exactly as prescribed and warn them not to open, crush, or chew the capsules. If they vomit after taking a dose, they shouldn't take an extra dose. Instead, they should take the next dose at the scheduled time.

Sources: Food and Drug Administration. FDA approves new combination treatment for acute myeloid leukemia. News release. April 28, 2017. Rydapt Treatment Information. http://www.us.rydapt.com.