Posted by on in NEJM Highlights

Calendaring care The length of our sidereal year is an accident – we happen to be circling a G2 star from which the habitable zone where free surface liquid water can exist lies at around 150,000,000 km; by Newton’s laws this in turn corresponds to an orbital period that is our year.  Even if it is not particularly strongly connected to the underlying human biology, a lot of healthcare cycles are aligned to the Earth Year for convenience but is it effective and efficient? Individuals with diabetes are at risk for diabetic retinopathy which can cause blindness and for which… Read More

Posted by on in Biopharma, Payers, Population Health

Summary Drug companies are naturally incentivized to price their drugs under assumptions of optimal clinical value, i.e. as high as possible.  Payers react to this by setting stringent conditions for patient eligibility for coverage of those therapies. As a consequence, patients who do not meet these conditions do not receive those drugs even though they could derive benefit, albeit not of a magnitude that would justify the cost.  Here we lay out a population health based scheme by which payers and drug companies can design a system that ensures access to a drug to a larger group who could benefit… Read More

Posted by on in NEJM Highlights

Gene therapy for sickle cell disease Typical diseases targeted by gene therapy are those for which there is a defect that prevents the production of a functional protein needed for normal life; remediation is achieved by inserting functioning copies of the gene, and fortunately, it is usually the case that expression at a low level is sufficient to greatly improve outcomes. The situation is different in sickle cell where the defective hemoglobin is actually harmful, and where success of gene therapy requires not only production normal hemoglobin, but replacement of the defective hemoglobin. In an N-of-1 study, a French group… Read More

Posted by on in NEJM Highlights

A knock at the door of a monster franchise Adalimumab (Humira, Abbvie) is the best-selling drug on the planet with the bulk of sales coming from patients suffering from rheumatoid arthritis (RA). It is therefore quite a coup for Lilly/Incyte to have shown in a double blind controlled study that baricitinib, an inhibitor of JAK (an important intracellular signaling molecule), performed better in relieving the symptoms of patients with RA than adalimumab. It was all the more surprising given that another JAK inhibitor, tofacitinib (Xeljanz, Pfizer, now also approved for RA) did not outperform adalimumab in a similarly designed… Read More

Posted by on in NEJM Highlights

An innovative modality to suppress PCSK9 Antisense technology relies on the concept that it is possible to interfere with the cellular genetic machinery in very specific ways by deploying short RNA sequences that are complementary to the message that one wants to suppress. The idea has been around for a while, but has only achieved limited success in very niche indications (see here for the two latest). This is what makes the publication of phase 1 trial of the antisense agent inclisiran (Alnylam and the Medicines Company) targeting the synthesis of PCSK9 so exciting: one subcutaneous injection appears to… Read More

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Successful use of CAR-T therapy in a solid tumor Chimeric Antigen Reception T-cells (CAR-T) are immune cells molecularly engineered to seek out and destroy cancer cells; the push to develop them into a scalable generally usable treatment is likely the most exciting challenge in cancer right now.  Successful CAR-T use has so far been generally confined to hematological tumors.  In a brief report, a group from City of Hope reports on the use of CAR-T in a patient who was dying from an advanced, aggressive form of brain cancer, which led to a regression of the tumors for several months. Read More

Posted by on in NEJM Highlights

“My name is T-Cell…, James T-Cell” Immune T-cells are licensed to kill other cells through a quick molecular kiss of death, and as such are potentially powerful allies in controlling a tumor. For obvious reasons this killing power is under strict regulatory control and in particular T-cells display PD-1 proteins on their surface, which when engaged by the ligand PD-L1 on another cell, protects that cell from being killed. Tumors often display high levels of PD-L1 so that disrupting the interaction between PD-L1 and PD-1 can enhance the effectiveness of immune killing of tumor cells. Amplifying results from last year… Read More

Posted by on in NEJM Highlights, Providers

I am not sure how many docs continue to do this, but I still read the actual hard copy of my NEJM, and that means I flip past ad pages with smiling grandfathers playing with grandchildren thanks to supercalifragilistic products on my way to scholarly papers with tables and figures.  But this time, I stopped in puzzlement when I came across exhibit 1; Intermountain is a health system based in Utah, very highly respected for its sound approach to quality and cost control[1], but not broadly well known for cancer care in the way of centers like Dana Farber… Read More

Posted by on in NEJM Highlights

Continued progress in multiple myeloma About 25,000 patients are diagnosed with multiple myeloma yearly in the US. Despite being initially treatable, typically this disease is ultimately lethal. Following a highly successful phase 1-2 study a monoclonal antibody against a marker of myeloma cells (daratumumab, Janssen) underwent phase 3 studies in combinations with established mainstays of therapy (the proteasome inhibitor bortezomib and the immune modulator lenalinomide) in a patient population several years out from their initial diagnosis.  Results were stellar, with the inclusion of daratumumab decreasing the disease progression rate by half at 1 year.  Daratumumab, Lenalidomide, and Dexamethasone… Read More

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Taking a page from HIV to build a response to opioid abuse A couple of perspectives on the challenges of treating individuals who suffer from opioid dependence. The first highlights the importance of integrating medication assisted treatment (e.g. methadone or buprenorphine) into hospital and post-hospital care – plausibly an ED visit or a hospital stay for an event triggered by opioid abuse (such as an overdose) is a significant opportunity to go beyond treating the acute issue and starting patients on long term treatments. In the second, the author recalls the tremendous progress in treating HIV/AIDS in the early 90s… Read More