ALZHEIMER DISEASE
New treatment may reduce amyloid beta plaque
Lecanemab-irmb (Leqembi, Eisai and Biogen Inc.) was granted accelerated approval by the FDA.1 The drug is an amyloid beta-directed antibody indicated for treating Alzheimer disease.2 Treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.
Drugs that meet an endpoint designated as "reasonably likely to predict a real clinical benefit" may be granted accelerated approval.3 These drugs must still undergo a phase 4 confirmatory trial to test whether they return a real clinical benefit, such as extending lifetime.
Lecanemab-irmb was tested in a double-blind, placebo-controlled, parallel-group, dose-finding study of 856 patients with Alzheimer disease.1 Patients that received the treatment had significant dose- and time-dependent reduction of amyloid beta plaque. Further, those receiving 10 mg/kg every 2 weeks had a statistically significant reduction in brain amyloid plaque from baseline to week 79 compared with the placebo. The latter had no reduction.
There are no contraindications for the use of lecanemab-irmb; however, the prescribing information warns of amyloid-related imaging abnormalities and infusion-related reactions.
References: 1. Office of the Commissioner. FDA grants accelerated approval for Alzheimer's disease treatment. U.S. Food and Drug Administration. 2023. http://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approv. Accessed February 5, 2023.
2. LEQEMBI Prescribing Information. 2023.
3. Office of the Commissioner. Accelerated approval. U.S. Food and Drug Administration. 2018. http://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval. Accessed February 5, 2023.
CARDIOVASCULAR
Thromboprophylaxis with aspirin for extremity fractures
Thromboprophylaxis with aspirin may be an alternative for patients with extremity fractures that had been treated surgically or with any pelvic or acetabular fracture, according to study results published in the New England Journal of Medicine.
In such patients, the treatment was found to be noninferior to low-molecular-weight heparin (LMWH) in preventing death and was associated with low incidences of deep vein thrombosis (DVT) and pulmonary embolism (PE) and low 90-day mortality.
Over 12,000 patients were included in the pragmatic, multicenter, randomized, noninferiority trial. They were randomly assigned to aspirin (6,101) at a dose of 81 mg twice daily or LMWH (enoxaparin, 6,110) at 30 mg twice daily while hospitalized. Patients were 18 years or older and had an extremity fracture (between hip to midfoot or shoulder to wrist) that had been treated surgically or who had any pelvic or acetabular fracture.
The primary endpoint for the study, death from any cause at 90 days, occurred in 47 patients (0.78%) in the aspirin group and in 45 patients (0.73%) in the LMWH group.
Secondary endpoints included nonfatal PE, DVT, and bleeding complications. DVT occurred in 2.51% of patients in the aspirin group and 1.71% in the LMWH group. The incidence of PE, bleeding complications, and other serious adverse events were similar in the two groups.
Reference: O'Toole RV, Stein DM, O'Hara NN, et al. Aspirin or low-molecular-weight heparin for thromboprophylaxis after a fracture. N Engl J Med. 2023;388(3):203-213. doi:10.1056/nejmoa2205973.
COVID-19
Convalescent plasma may reduce mortality
Transfusion of COVID-19 convalescent plasma may reduce mortality risk in patients who are immunocompromised and susceptible to refractory infection.
COVID-19 convalescent plasma transfusion is presumed to passively transfer potentially therapeutic SARS-CoV-2 antibodies to recipients.
Authors of a paper published in JAMA Network Open performed a systematic review of clinical studies involving COVID-19 convalescent plasma use in patients who are immunocompromised. The authors were specifically looking for the all-cause mortality after COVID-19 convalescent plasma transfusion.
The authors included 3 randomized clinical trials enrolling 1,487 participants and 5 controlled studies. A further 125 case series or reports enrolling 265 participants and 13 uncontrolled large case series enrolling 358 participants were included in their analysis.
From these studies, the authors found that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for both randomized clinical trials and matched cohort studies.
Reference: Senefeld JW, Franchini M, Mengoli C, et al. COVID-19 convalescent plasma for the treatment of immunocompromised patients: a systematic review and meta-analysis. JAMA Netw Open. 2023;6(1):e2250647. doi:10.1001/jamanetworkopen.2022.50647.
Cannabis use for pain management
About one-third of patients with chronic pain reported turning to cannabis for pain management, according to the results of a paper published in JAMA Network Open.
These patients also reported substituting cannabis for other medications, including prescription opioids.
The authors performed a cross-sectional study that consisted of a survey distributed to 1,724 individuals age 18 years or older with chronic pain who lived in the 36 states (and Washington, D.C.) with active medical cannabis programs. The authors assessed participants' self-reported use (ever, past 12 months, past 30 days) of medical cannabis; pharmacologic treatments, including prescription opioids, prescription nonopioid analgesics, and over-the-counter analgesics; common nonpharmacologic treatments, including physical therapy, meditation, cognitive behavioral therapy; and substitution of cannabis in place of these treatments for chronic pain.
Out of the 1,724 individuals who received a survey, 1,661 completed the full survey. About 31.0% reported ever using cannabis to manage pain, while 25.9% reported doing so in the past 12 months, and 23.2% reported doing so in the past 30 days.
Of those reported to use cannabis for chronic pain management, most also reported having used either at least one other pharmacologic or nonpharmacologic pain treatment.
More than half of those using cannabis for chronic pain management said doing so decreased their use of prescription opioids, prescription nonopioids, and over-the-counter pain medications. Less than 1% said it increased their use of the medications. Less than half said cannabis use changed their use of nonpharmacologic pain treatments.
Among adults with chronic pain in this study, 38.7% reported that their use of cannabis led to decreased use of physical therapy, 19.1% reported it led to decreased use of meditation, and 26.0% reported it led to decreased use of cognitive behavioral therapy.
Reference: Bicket MC, Stone EM, McGinty EE. Use of cannabis and other pain treatments among adults with chronic pain in US states with medical cannabis programs. JAMA Netw Open. 2023;6(1). doi:10.1001/jamanetworkopen.2022.49797.
ANEMIA
First oral treatment approved
Daprodustat (Jesduvroq, GSK plc) has been approved as the first oral treatment for anemia caused by chronic kidney disease (CKD), according to an FDA announcement.1
The drug is an hypoxia-inducible factor prolyl hydroxylase inhibitor indicated for the treatment of anemia due to CKD in adults who have been receiving dialysis for at least 4 months.
The approval was based on the results from a randomized study involving 2,964 adults receiving dialysis. Participants received either oral daprodustat or an injectable erythropoiesis-stimulating agent (ESA). Patients who had a hemoglobin level of 8.0 to 11.5 g/dL received daprodustat or an injectable ESA (epoetin alfa if they were receiving hemodialysis or darbepoetin alfa if they were receiving peritoneal dialysis). Daprodustat raised and maintained the hemoglobin within the target range of 10-11 g/dL, like that of an ESA.
Daprodustat prescribing information contains a boxed warning for increased risk of death, myocardial infarction, stroke, venous thromboembolism, and vascular access thrombosis.2
Daprodustat is contraindicated in those using strong cytochrome P450 2C8 (CYP2C8) inhibitors, such as gemfibrozil, and those with uncontrolled hypertension.
Other warnings and precautions listed with the use of daprodustat include the risk of hospitalization for heart failure, hypertension, gastrointestinal erosion, and malignancy. The drug is also not indicated for the treatment of anemia of CKD in patients who are not dialysis-dependent.
Adverse reactions reported with the use of daprodustat include hypertension, thrombotic vascular events, and abdominal pain.
References: 1. U.S. Food and Drug Administration. FDA approves first oral treatment for anemia caused by chronic kidney disease for adults on dialysis. 2023. http://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treat. Accessed February 7, 2023.
2. GSK. Jesduvroq prescribing information. 2023. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Be. Accessed February 7, 2023.