ANTIMICROBIALS

Quicker administration may not increase use

Shortening the time to antibiotic use in patients with sepsis may not necessarily increase antimicrobial use, days of therapy, or broadness of antimicrobial coverage among the population at risk for sepsis, according to a study published in JAMA Internal Medicine.

Researchers performed an observational cohort study that included over 1.5 million patients from 152 hospitals in 2 health systems who were admitted via the ED with 2 or more systemic inflammatory response syndrome (SIRS) criteria. Of the 1.5 million patients included, about 1.3 million were males with a median age of 67 years. Only about 273,000 (17.5%) met the objective criteria for sepsis.

Patients were admitted between 2013 and 2018; data analysis was performed between June 10, 2021, and March 22, 2022.

The researchers found that the adjusted average time to first antimicrobial administration decreased by 37 minutes from an average of 4.7 hours in 2013 to an average of 3.9 hours in 2018. During that same period, antimicrobial use within 48 hours, days of antimicrobial therapy, and receipt of broad-spectrum coverage decreased among the broader cohort of patients with SIRS.

In-hospital mortality, 30-day mortality, length of hospitalization, new multidrug-resistant (MDR) culture positivity, and new MDR blood culture positivity also decreased over the study period among both patients with sepsis and those with SIRS.

Decreases in antimicrobial use, days of therapy, and broadness of antibacterial coverage for patients with SIRS did not differ by hospital antimicrobial timing trend for sepsis.

Reference: Prescott HC, Seelye S, Wang XQ, et al. Temporal trends in antimicrobial prescribing during hospitalization for potential infection and sepsis. JAMA Intern Med. [e-pub June 27, 2022]

COVID-19 VACCINES

No evidence of increased CRS risk in patients undergoing immunotherapy for cancer

Elevated cytokine levels are common but may not be sufficient to establish cytokine release syndrome (CRS) diagnosis in patients with cancer who are receiving immunotherapy and a COVID-19 vaccine, according to a study published in Nature Cancer.

CRS is an acute SIRS characterized by fever, with or without multiple organ dysfunction that is associated with chimeric antigen receptor-T cell therapy, other forms of immunotherapy, or haploidentical hematopoietic cell transplantation.

Researchers examined 90 patients, out of 220 originally included, in a prospectively planned, single-center, pan-tumor cohort study. Sixty-four of these patients were receiving an mRNA or viral vector-based COVID-19 vaccination while under immune-checkpoint inhibitor therapy while 26 were not receiving a vaccine.

The researchers conclude that there was no clinically relevant CRS diagnosis (grade 2 or more), after vaccination in the small cohort examined. Furthermore, within 4 weeks of vaccination, serious adverse events occurred in eight patients, six were hospitalized due to common events in cancer therapy, and two died due to conditions present before vaccination. The authors stress that this study was not powered to assess the exact frequency of adverse events after vaccination.

A set of pairwise-correlated CRS-associated cytokines including CXCL8 and interleukin-6 was greater than 1.5-fold upregulated in 40% of patients after vaccination.

Reference: Walle T, Bajaj S, Kraske JA, et al. Cytokine release syndrome-like serum responses after COVID-19 vaccination are frequent and clinically inapparent under cancer immunotherapy. Nat Cancer. [e-pub June 17, 2022]

TYPE 2 DIABETES

Dulaglutide efficacious in pediatrics

Once-weekly administration of dulaglutide, a glucagon-like peptide-1 receptor agonist, at 0.75 mg or 1.5 mg was shown to be superior to placebo at improving glycemic control through 26 weeks among pediatric patients with type 2 diabetes who were also being treated with or without metformin or basal insulin in a paper published in The New England Journal of Medicine.

Researchers performed a double-blind, placebo-controlled, 26-week trial that included 154 patients. They were randomized 1:1:1 to receive once-weekly subcutaneous injections of placebo, dulaglutide at 0.75 mg or 1.5 mg. The participants were then included in a 26-week, open-label extension in which those receiving placebo began receiving dulaglutide at a weekly dose of 0.75 mg.

The primary endpoint for the study was a change from baseline in A1C at 26 weeks. Secondary endpoints included an A1C of less than 7.0% and changes from baseline in fasting glucose concentration and body mass index (BMI).

The mean A1C in the placebo group increased (0.6 percentage points), whereas it decreased (-0.6 percentage points) in the 0.75-mg group and (-0.9 percentage points) in the 1.5-mg group.

Fasting glucose concentration in the placebo group increased (17.1 mg/dL), whereas it decreased in the pooled dulaglutide groups (-18.9 mg/dL).

There were no group differences in the change in BMI.

Gastrointestinal adverse events were higher in the dulaglutide group than in the placebo group. The safety profile was consistent with that reported in adults.

Reference: Arslanian SA, Hannon T, Zeitler P, et al. Once-weekly dulaglutide for the treatment of youths with type 2 diabetes. N Engl J Med. 2022. doi:10.1056/nejmoa2204601.

INSULIN ACCESS

Global society announces support for new bill

The Endocrine Society has announced support of a bipartisan bill that would take steps to reduce out-of-pocket costs of insulin, the escalating price of insulin, and formulary management for people with diabetes.

The Endocrine Society is a global community with 18,000 members devoted to advancing hormone research, excellence in the clinical practice of endocrinology, broadening understanding of the role hormones play in health, and advocating for the global endocrinology community.

The bill that they are now officially supporting would take steps to reduce out-of-pocket costs of insulin, the escalating price of insulin, and formulary management for people with diabetes.

"This bill is about our patients and making insulin affordable for them. The Endocrine Society urges the Senate to pass this bill quickly. People with diabetes who rely on insulin cannot wait any longer," said Joshua Joseph, MD, clinical affairs core committee chair of The Endocrine Society.

The bill proposes ensuring insurance plans and pharmacy benefit managers cannot collect rebates on insulins that limit list price to the 2021 net prices for Medicare Part D or equivalent levels, which would significantly reduce insulin's price tag for both the insured and the uninsured; making insulin eligible for cost-sharing protections, including waiving any applicable deductible and limiting copays or coinsurance to no more than $35 per month, or 25% of list price; supporting patient access to insulin by ensuring coverage and that prior authorization, step therapy, or other medical management requirements cannot be imposed to limit beneficiary use; making sure group and individual health plans waive any deductible and limit cost-sharing to no more than $35 per month or 25% of list price, for at least one insulin of each type and dosage form.

Reference: Endocrine Society. Endocrine society urges Congress to pass bill to make insulin more affordable for people with diabetes. Endocrine Society. 2022. http://www.endocrine.org/news-and-advocacy/news-room/2022/endocrine-society-urge.

POLYNEUROPATHY

AMVUTTRA approved by FDA

The FDA has approved AMVUTTRA (vutrisiran; Alnylam Pharmaceuticals, Inc.) for the treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults. hATTR amyloidosis is a rare, inherited, rapidly progressive, and fatal disease with debilitating polyneuropathy manifestations, for which there are few treatment options.

AMVUTTRA is a transthyretin-directed small interfering RNA, one of the molecules that mediate RNA interference by potently silencing mRNA, thereby preventing the production of disease-causing proteins.

Approval was granted based upon the results of a 9-month HELIOS-A phase 3 study that showed significant improvement in signs and symptoms of polyneuropathy. More than 50% of patients in the study experienced a halting or reversal of their disease.

The primary endpoint for the study was an improvement in the mean change from baseline in a modified Neuropathy Impairment score. This was compared with placebo results from the landmark APOLLO Phase 3 study that evaluated the efficacy and safety of patisiran in a similar patient population.

All secondary endpoints were met at 9 months, including the improvement in quality of life, as measured by the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy instrument and compared with an external placebo; and an improvement in gait speed, as measured by a timed 10-meter walk test.

Efficacy results at 18 months were consistent with 9-month data. AMVUTTRA is recommended at 25 mg administered via subcutaneous injection once every 3 months, only by a healthcare provider. There are reportedly no contraindications.

The most common adverse reactions reported with the use of the drug include arthralgia, dyspnea, and a decrease in vitamin A levels.

Reference: Helios-A: A study of vutrisiran (ALN-TTRSC02) in patients with hereditary transthyretin amyloidosis (hATTR amyloidosis) - full text view. 2022. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03759379.