GLIOMA

Oral inhibitor improves survival

Vorasidenib, an oral brain-penetrant inhibitor of mutant isocitrate dehydrogenase (IDH) enzymes IDH1 and IDH2, significantly improved progression-free survival and delayed the need for subsequent interventions in patients with grade 2 IDH-mutant gliomas, according to a paper published in the New England Journal of Medicine.

Grade 2 IDH-mutant gliomas are malignant brain tumors that cause considerable disability and premature death.

The authors randomly assigned 331 patients to receive either vorasidenib or a placebo. The primary outcome assessed was progression-free survival, measured through imaging-based evaluations; the key secondary outcome was the time for the next anticancer intervention.

The results showed that patients who received vorasidenib had significantly improved progression-free survival compared with those who received the placebo. The median progression-free survival in the vorasidenib group was 27.7 months, and 11.1 months in the placebo group. The time to the next intervention was also significantly prolonged in the vorasidenib group.

Adverse events of grade 3 or higher were observed in more patients in the vorasidenib group, including an increased alanine aminotransferase level. However, overall, the treatment was considered safe and well-tolerated.

These findings suggest that vorasidenib may be a promising treatment option for patients with IDH-mutant grade 2 gliomas, as it improves progression-free survival and delays the need for additional interventions. Nurses should be aware of this potential therapeutic option and monitor patients receiving vorasidenib for any adverse events, particularly those related to liver function.

Reference: Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al Vorasidenib in IDH1- or IDH2-mutant low-grade glioma. N Engl J Med. [e-pub June 4, 2023]

MIGRAINES

Ketamine potential acute treatment

Intranasal ketamine was an acute treatment for chronic refractory migraines that reduced headache intensity and improved quality of life in a Regional Anesthesia & Pain Medicine study.

A total of 169 patients (79.9% women) with a median age of 44 years were interviewed. These patients reported a median of 30 monthly headache days and had already tried an average of 4 classes of preventive medications. The patients used an average of 6 sprays of intranasal ketamine daily for a median of 10 days per month.

The findings showed that intranasal ketamine was considered "very effective" in 49.1% of patients. Additionally, 35.5% of patients reported significantly improved quality of life. However, it is worth noting that 74.0% of patients experienced at least one adverse event.

Further research is warranted. Clinicians should consider the potential benefits and risks of intranasal ketamine on a case-by-case basis, ensuring appropriate safety measures are in place.

Reference: Yuan H, Natekar A, Park J, Lauritsen CG, Viscusi ER, Marmura MJ. Real-world study of intranasal ketamine for use in patients with refractory chronic migraine: a retrospective analysis. Reg Anesth Pain Med. [e-pub May 30, 2023]

AMYOTROPHIC LATERAL SCLEROSIS

Parkinson's drug shows promise

A study evaluating the efficacy of ropinirole in patients with amyotrophic lateral sclerosis (ALS) using patient-derived motor neurons was published in Cell Stem Cell.

Ropinirole hydrochloride, a dopamine D2 receptor (D2R) agonist commonly used for Parkinson disease, demonstrated a dose-dependent effect, showing promising results in suppressing ALS-related damage. The tolerability of ropinirole was assessed, and doses up to 16 mg were well-tolerated, with no serious adverse reactions reported. The concentration of ropinirole in the cerebrospinal fluid reached a level effective for suppressing ALS damage.

The drug significantly slowed disease progression, with a 21% to 60% slower decline in the ALS Functional Rating Scale-Revised score. Ropinirole inhibited neuronal hyperexcitability, potentially contributing to its protective effect on ALS motor neurons.

Reference: Morimoto S, Takahashi S, Ito D, et al Phase 1/2A clinical trial in ALS with ropinirole, a drug candidate identified by IPSC drug discovery. Cell Stem Cell. 2023;30(6). doi:10.1016/j.stem.2023.04.017.

HEART FAILURE

New drug approved

Sotagliflozin, an oral tablet that lowers the risk of cardiovascular death, hospitalization for heart failure (HF), and urgent HF visits in adults with HF or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors, has been approved by the FDA.¹

The approval includes various types of patients with HF, including those with preserved or reduced ejection fraction, with or without diabetes. Sotagliflozin was evaluated in two randomized, double-blind, placebo-controlled Phase 3 studies involving nearly 12,000 patients and demonstrated a 33% reduction in the risk of hospitalizations for heart failure, urgent visits for heart failure, and cardiovascular death compared with placebo. It inhibits both sodium-glucose cotransporter type 2 and type 1.

Before initiating treatment, assess renal function and volume status.²

Contraindications include hypersensitivity to sotagliflozin.

Ketoacidosis and hypoglycemia are potential risks, especially in patients with type 1 diabetes or when combined with insulin or insulin secretagogues. Volume depletion, urinary tract infections, and genital mycotic infections may occur.

Common adverse reactions include urinary tract infection, volume depletion, diarrhea, and hypoglycemia. Nurses should monitor patients for drug interactions with digoxin, uridine 5'-diphospho-glucuronosyltransferase inducers such as rifampin, and lithium.

Sotafliglozin should be avoided during the second and third trimesters of pregnancy and is not recommended in patients with moderate or severe hepatic impairment. In patients with renal impairment, evaluate the safety profile.

References: 1. Lexxicon Pharmaceuticals. Lexicon announces FDA approval of inpefatm (sotagliflozin) for treatment of heart failure. May 26, 2023. http://www.lexpharma.com/media-center/news/2023-05-26-lexicon-announces-fda-appr. Accessed June 12, 2023.

2. Sotagliflozin Prescribing Information.

PREGNANCY

Marijuana use, fetal growth deficits

The timing of marijuana exposure during pregnancy plays a significant role in fetal growth deficits, according to a paper published in Frontiers in Pediatrics.

The study included marijuana users (109) and a control group of nonusers (171) randomly selected and confirmed through biochemical testing. Data were collected from electronic health records.

After accounting for confounding factors, the results showed that newborns exposed to marijuana during the first trimester had a significant decrease in weight (-154g) compared with the control group. Similarly, marijuana exposure throughout gestation resulted in a significant decrease in weight (-185g). Head circumference deficits were observed in newborns exposed to marijuana during the first and second trimesters (-0.83cm) and throughout pregnancy (-0.79cm) compared with the control group. However, marijuana exposure did not significantly predict newborn length.

The study suggests that the timing of marijuana exposure plays a crucial role in specific fetal growth deficits, with exposure throughout pregnancy being the most detrimental. Further studies that characterize this relationship are needed. Nevertheless, marijuana use is discouraged throughout pregnancy.

Reference: Dodge P, Nadolski K, Kopkau H, Zablocki V, Forrestal K, Bailey BA. The impact of timing of in utero marijuana exposure on fetal growth. Front Pediatr. 2023;11. doi:10.3389/fped.2023.1103749.