An opinionated take on NEJM highlights for September 2017


A new drug to address hard-to-treat severe asthma

In ~10% of people with asthma, traditional therapies do not work well and they have recurrent exacerbations leading them to the ED. Over the past few years, a number of biologics (mAbs) have been developed to treat such patients, but each of these agents is targeted to a small subgroup with specific biomarker characteristics for which it has been shown to be effective, resulting in ultra-niche therapies with limited uptake.  For broader penetration of those modalities, what is needed is a drug that has more general applicability to the non-responders with severe asthma, and it looks like tezepelumab (Medimmune/Astra Zeneca) may be it. In a phase 2 RCT of more than 400 patients with severe asthma unresponsive to classic therapies (but who were not selected based on biomarkers such as eosinophilia), the treatment arm had a decrease of two thirds in exacerbations compared to placebo. Given that the drug is obviously hitting a powerful inflammatory target (known as thymic stromal lymphopoeitin), it will be important to verify in phase 3 if the benign side effect profile is confirmed. If it is, one can well imagine the severe asthma segment developing into its own multibillion market. Tezepelumab in Adults with Uncontrolled Asthma; Moving Upstream — Anti-TSLP in Persistent Uncontrolled Asthma (subscriber access)


Another twist in the fascinating story of gastric bypass surgery

Gastric bypass surgery is a wondrous thing – for many it immediately induces a remission of diabetes, and greatly improves their cardiovascular risk profile. The long-term benefits are strongly confirmed by a study that enrolled 3 cohorts and followed them for 12 years: a group who received surgery; a group who wanted surgery but could not get it, largely for reasons of insurance coverage; and a control group with severe obesity who did not seek surgery. The results are unambiguous. The cohort who got surgery is much healthier at 12 years, but there is a qualification that you won’t find in the abstract or the tables, but need to read in the details of the text and the supplementary materials – people who have undergone bariatric surgery are much more likely to kill themselves. There were 5 suicides (out of 418) in the surgery group, 2 among those who wanted surgery but could not get it at the time but both suicides in this group occurred after the patients managed to get gastric bypass surgery, and none in the control group who did not seek surgery. Whether this is from self-selection for surgery or a result of the profound physiologic changes that follow surgery is unclear. But given that this has been observed in other studies too it’s clear that patients need to be counseled about this risk to be weighed against the undeniable benefits of the surgery.  Finally, it is an interesting thought-experiment to consider what would happen if instead of a surgical procedure, we had the same data for a drug. Somehow it seems likely that the discussion would be very different, but it is unclear why it should be. This is less of a theoretical concept that it might seem – less than a decade ago the weight loss drug rimonabant (Acomplia, Sanofi) was pulled from the EU market and denied approval in the US in large part because it caused suicidal ideation in a fraction of patients who took it.  Weight and Metabolic Outcomes 12 Years after Gastric Bypass (subscriber access)


Understanding prematurity

Prematurity is a tremendous health burden – in terms of child mortality, long-term disability, and tremendous associated costs – but it is unpredictable and fundamentally not understood. In a genomic study of two sets of women with a history of pregnancy, investigators have identified three genetic loci that are significantly associated with preterm birth. That is the first step to addressing this scourge. Interestingly, the 43,568 women in the discovery set were participants enrolled through 23andMe. Genetic Associations with Gestational Duration and Spontaneous Preterm Birth (free access)


The New England Journal of Medicine is a premier weekly medical journal covering many topics of interest to the health sector. In this monthly series we offer an opinionated perspective on selected highlights that might be of interest to our clients and others.