NEJM Year In Review Flashcards
NEJM: Benefit of Semaglutide in patients with HFpEF and Obesity
Improved weight loss
Greater reduction in heart failure related symptoms
Not powered to show difference in clinical events or mortality
NEJM Mechanism and Benefit of Dupilumab in COPD
IL-4 and IL-13 blockade → reduced Type 2 inflammation.
In patients with raised eosinophils, and already on maximal COPD therapy (i.e. triple therapy with LAMA/LABA/ICS), addition of Dupilumab reduced exacerbations, improved quality of life
NOTE: Mepolizumab and Benralizumab have previously been studied and not shown benefit. These agents block IL-5.
NEJM: What is Resmetiron, and what is it used for?
Oral liver directed thyroid hormone receptor beta selective agonist → for treatment of NASH with liver fibrosis
Improves resolution of NASH and fibrosis compared to placebo. Also lowers LDLs.
Diarrhoea, nausea as side effects.
NEJM: Omalizumab and Food Allergy
Omalizumab (anti IgE)
Oncreases reaction threshold for multiple common food allergens
NEJM Semaglutide in CKD + T2DM
Reduced risk of cardiovascular death, and adverse kidney outcomes.
Renal function declined more slowly
NEJM: Tirzepatide in MASH
Tirzepatide (GLP-1) more effective than placebo for resolution of MASH without worsening fibrosis
Not powered to evaluate effect on fibrosis, and too short to assess effect on major liver outcomes.
Patients with cirrhosis not included
NEJM Lencapavir mechanism and use
Lencapavir is a multistage HIV-1 capsid inhibitor with long half life → can be given 6 monthly
6 monthly administration as PrEP is more effective than daily emtricitabine-tenofovir disoproxil fumarate in preventing HIV infection in cisgender young women.
NEJM Nivolumab + AVD in Hodgkin’s Lymphoma
Nivolumab: PD-1 inhibitor
AVD: Doxorubicin, vinblastine, dacarbazine
Brentuximab vedotin (CD-30 directed ADC) typically used with AVD, but high toxicity and relapse risks.
This study used Nivo in its place for stage III and IV patients: improved PFS, fewer side effects.
However short follow up duration, so durability of treatment not known.
NEJM Finerenone in HFmrEF and HFpEF
Finerenone is a non steroidal MRA
Reduced composite of worsening heart failure and deaths.
Does not reduce cardiovascular mortality as a stand alone outcome, so benefit really from reduction in heart failure events.
Associated with increased risk of hyperkalaemia
NEJM Pembrolizumab in triple negative breast cancer
Pembrolizumab: PD-1 inhibitor
Multiple groups:
Pembro + paclitaxel/carboplatin then pembro + doxorubicin/cyclophosphamide for neuadjuvant
Then Pembro monotherapy post op.
Compared to a placebo group with same chemo use.
Outcome: Addition of neoadjuvant + adjuvant Pembro leads to better OS compared to neoadjuvant chemo alone
NEJM Vutrisiran for ATTR
Nutrisiran: RNA interference agent → inhibits hepatic transthyretin production
Outcome: For patients with ATTR cardiomyopathy, Vutrisiran reduced risk of death from any cause, as well as cardiovascular events. Also preserved functional capacity and quality of life.
NEJm Ponsegromab for Cancer Cachexia
Pnsegromab: GDF-15 inhibitor
Increased weight gain, increased overall activity levels, reduced cachexia symptoms.
In patients with cancer cachexia and raised GDF-15.
NEJM CRISPR and Hereditary Angioedema
Reduction in angioedema attacks, sustained reduction in total plasma kallikrein levels
NEJM Tirzepatide for HFpEF and Obesity
Lower risk of composite of cardiovascular death and worsening heart failure.
Improved health status in patients with HFpEF and obesity.
However benefit still mostly from symptom improvement rather than actually improving mortality.
High rate of GI side effects
NEJM Kidney Disease and APOL1
APOL1 is a gene on Ch22
Linked to ESRF
Most common in patients from sub saharan Africa
Also protects against Trypanosoma brucei rhodesiense and T brucei gambiense (hence likely natural selected as protective against sleeping sickness).
Probasbly the explanation for increased FSGS.
Inaxaplin vcan inhibit APOL1 activity and potentially improve outcomes.
